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Sample records for suspected active tuberculosis

  1. Challenges with diagnosing and investigating suspected active tuberculosis disease in military trainees.

    Science.gov (United States)

    Chang, David; Webber, Bryant J; Hetrick, Steven M; Owen, Jerry B; Blasi, Audra A; Steele, Bernadette M; Yun, Heather C

    2017-08-01

    Between 1 January 2010 and 31 December 2016, a total of 14 U.S. and international military personnel in training at Joint Base San Antonio-Lackland, TX, were hospitalized due to suspected pulmonary tuberculosis (TB); of these, five personnel were diagnosed with active TB disease. Only one TB case had pulmonary symptoms, but these symptoms were not suggestive of TB. The incidence rate in the training population was 1.89 per 100,000 population (95% CI: 0.81, 4.42), with a higher rate when restricted to international military students attending the Defense Language Institute English Language Center. No instances of TB transmission were identified. The variety of atypical presentations and their resulting diagnostic and public health challenges prompted this retrospective review of all hospitalized cases. This case series highlights both the importance of a high index of clinical suspicion when TB is being considered in close congregate settings as well as the risk of overreliance on acid-fast bacilli staining and nucleic acid amplification testing for ruling out active pulmonary disease in young, otherwise healthy trainees. Practical solutions are suggested.

  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. 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

  5. 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...... reaction (PCR) can guide isolation. Methods. We retrospectively evaluated sputum samples analyzed for M. tuberculosis complex at the International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark in 2002–2011. We selected culture-confirmed tuberculosis cases with ≥3 samples within 14 days...... before or after the initial culture-positive sample. We repeated the process for those with ≥2 samples within 28 days. The primary outcome was PCR-negative, smear-positive patients. Results. We included 53 533 sputum samples from 20 928 individuals; 1636 had culture-confirmed tuberculosis. Of these, 856...

  6. Molecular Identification of Mycobacterium Tuberculosis and Analysis of Its Resistance to Rifampin in Sputa from Tuberculosis Suspected Patients

    International Nuclear Information System (INIS)

    Syaifudin, M.

    2010-01-01

    An accurate identification of different species of Mycobacterium provides to allow appropriate treatment for Mycobacterium tuberculosis infection. Beside that, drug resistance of M. tuberculosis strains to rifampin is not clearly understood in contributing to the spread of tuberculosis in Indonesia. To assess the molecular mechanism of rifampin resistance, a number of clinical specimens of M. tuberculosis were analyzed their molecular nature of a part of the rpoB gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) methods. DNA's extracted from sputum samples were amplified and 32 P-labeled by PCR with the specific primers and the product was analyzed their mutation conferring resistance by MDE gel electrophoresis. Of the 70 specimens tested, 57 specimens were positive for M. tuberculosis organism only, three specimens contained a mixture of M. tuberculosis and non tuberculosis mycobacteria (NTM), and 10 specimens were negative approved by Duplex PCR. Of these sixty DNA positive samples (thus the sensitivity of PCR was 85.71%), 5 (8.3%) of them suspected to contain mutations in rpoB which were associated with rifampin resistance. Even though the frequency of mutation was low, the results from our study clearly indicate that the molecular mechanism of rifampin resistance in M. tuberculosis isolates from Indonesia involves alterations in the rpoB gene. Molecular diagnosis by PCR which is fast and easy to perform is useful for early and rapid detection of TB in sputum specimen. (author)

  7. High prevalence of smoking among patients with suspected tuberculosis in South Africa.

    Science.gov (United States)

    Brunet, L; Pai, M; Davids, V; Ling, D; Paradis, G; Lenders, L; Meldau, R; van Zyl Smit, R; Calligaro, G; Allwood, B; Dawson, R; Dheda, K

    2011-07-01

    There is growing evidence that tobacco smoking is an important risk factor for tuberculosis (TB). There are no data validating the accuracy of self-reported smoking in TB patients and limited data about the prevalence of smoking in TB patients from high-burden settings. We performed a cross-sectional analysis of 500 patients with suspected TB in Cape Town, South Africa. All underwent comprehensive diagnostic testing. The accuracy of their self-reported smoking status was determined against serum cotinine levels. Of the 424 patients included in the study, 56 and 60% of those with active and latent TB infection (LTBI), respectively, were current smokers. Using plasma cotinine as a reference standard, the sensitivity of self-reported smoking was 89%. No statistically significant association could be found between smoking and active TB or LTBI. In Cape Town, the prevalence of smoking among patients with suspected and confirmed TB was much higher than in the general South African population. Self-reporting is an accurate measure of smoking status. These results suggest the need to actively incorporate tobacco cessation programmes into TB services in South Africa.

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

    OpenAIRE

    Tegegne, Yalewayker; Wondmagegn, Tadelo; Worku, Ligabaw; Jejaw Zeleke, Ayalew

    2018-01-01

    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 wa...

  9. Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia.

    Science.gov (United States)

    Ahmad, Riris Andono; Matthys, Francine; Dwihardiani, Bintari; Rintiswati, Ning; de Vlas, Sake J; Mahendradhata, Yodi; van der Stuyft, Patrick

    2012-02-15

    Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

  10. The frequency of peritoneal tuberculosis using diagnostic laparoscopy in clinically suspected cases

    International Nuclear Information System (INIS)

    Sattar, Z.; Iqbal, M.

    2014-01-01

    Introduction: Diagnostic laparoscopy allows the visual examination and documentation of intra-abdominal organs in order to detect any pathology. It is an important tool for final minimally invasive exploration of patients with abdominal tuberculosis, the diagnosis of which remains uncertain despite employing the requisite laboratory and non-invasive imaging investigations. Objective: To determine the frequency of peritoneal tuberculosis using diagnostic laparoscopy in clinically suspected cases of peritoneal tuberculosis. Study Design: Cross sectional survey. Setting: The study was conducted in all the four Surgical Wards on surgical floor of Mayo Hospital Lahore. Duration of Study with Dates: Six months (1st July 2009 to 31st December 2009). Material and Methods: 35 Patients aged between 13-60 years with clinical suspicion of peritoneal tuberculosis were selected. The patients underwent the procedure accordingly. Per operative diagnosis of peritoneal tuberculosis made on the basis of presence of any or all of the operative (laparoscopic) findings such as multiple peritoneal adhesions, fibrous bands, whitish peritoneal tubercles, omental thickening and ascites. Diagnosis was confirmed with histopathology of peritoneal tissue biopsy. Also the biochemical analysis and culture sensitivity of ascetic fluid was routinely performed if any ascites is present. Results: Out of 35 patients, 40% were males and 60% females with mean age of 24.91+-6.69 years. The Laparoscopic findings of peritoneal tuberculosis were whitish peritoneal tubercles (57.2%) peritoneal adhesions (28.6%), ascites (17.2%), omental thickening (14.3%), fibrous bands (11.4%) and swollen edematous appendix (5.7%). Eighty percent were labeled with diagnosis of peritoneal tuberculosis on basis of diagnostic laparoscopy. These patients were confirmed to have peritoneal tuberculosis on histopathology of tissue biopsy. Conclusion: Diagnostic laparoscopy is useful in patients with suspected peritoneal

  11. Suspected pulmonary tuberculosis in rural South Africa - Sputum ...

    African Journals Online (AJOL)

    Three (125%) of the 24 patients with a discharge diagnosis other than TB (17 pneumonia, 3 old TB, 2 carcinoma of the lung, 1 bronchiectasis) turned out to have TB within the follow-up period; 2 of those had extrapulmonary TB Conclusion, SI produced a positive smear result in 29% of patients with suspected TB who had ...

  12. Prevalence of pulmonary TB and spoligotype pattern of Mycobacterium tuberculosis among TB suspects in a rural community in Southwest Ethiopia

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    Deribew Amare

    2012-03-01

    Full Text Available Abstract Background In Ethiopia where there is no strong surveillance system and state of the art diagnostic facilities are limited, the real burden of tuberculosis (TB is not well known. We conducted a community based survey to estimate the prevalence of pulmonary TB and spoligotype pattern of the Mycobacterium tuberculosis isolates in Southwest Ethiopia. Methods A total of 30040 adults in 10882 households were screened for pulmonary TB in Gilgel Gibe field research centre in Southwest Ethiopia. A total of 482 TB suspects were identified and smear microscopy and culture was done for 428 TB suspects. Counseling and testing for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize the Mycobacterium tuberculosis isolates. Results Majority of the TB suspects were females (60.7% and non-literates (83.6%. Using smear microscopy, a total of 5 new and 4 old cases of pulmonary TB cases were identified making the prevalence of TB 30 per 100,000. However, using the culture method, we identified 17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed pulmonary TB cases for every TB case who was diagnosed through the passive case detection mechanism in the health facility. Eleven isolates (64.7% belonged to the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS. Six new spoligotype patterns of Mycobacterium tuberculosis, not present in the international database (SpolDB4 were identified. None of the rural residents was HIV infected and only 5 (5.5% of the urban TB suspects were positive for HIV. Conclusion The prevalence of TB in the rural community of Southwest Ethiopia is low. There are large numbers of undiagnosed TB cases in the community. However, the number of sputum smear-positive cases was very low and therefore the risk of transmitting the infection to others may be limited. Active case finding through health extension workers in the community can improve the low case detection rate

  13. Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

    Directory of Open Access Journals (Sweden)

    Ahmad Riris

    2012-02-01

    Full Text Available Abstract Background Early and accurate diagnosis of pulmonary tuberculosis (TB is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. Methods We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results, and final diagnosis were collected. Results Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC. Diagnostic delays were significantly longer in health centres compared to lung clinics. Conclusions The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

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

    Science.gov (United States)

    Tegegne, Yalewayker; Wondmagegn, Tadelo; Worku, Ligabaw; Jejaw Zeleke, Ayalew

    2018-01-01

    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. To assess the prevalence of intestinal parasites among pulmonary tuberculosis suspected patients. 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 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%). The prevalence of intestinal parasites and their coinfection rate with pulmonary tuberculosis among pulmonary tuberculosis suspected patients were considerable.

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

    Directory of Open Access Journals (Sweden)

    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. Sex disparities in tuberculosis suspect evaluation: a cross-sectional analysis in rural Uganda.

    Science.gov (United States)

    Miller, C R; Davis, J L; Katamba, A; Sserwanga, A; Kakeeto, S; Kizito, F; Cattamanchi, A

    2013-04-01

    Six primary health care centers in rural Uganda. To compare the quality of tuberculosis (TB) evaluation for men and women presenting to primary health care facilities in high-burden settings. Cross-sectional study using indicators derived from the International Standards of Tuberculosis Care (ISTC) to compare the quality of TB evaluation services provided to men and women. Of 161 230 patient visits between January 2009 and December 2010, 112 329 (69.7%) were women. We considered 3308 (2.1%) patients with cough ≥2 weeks as TB suspects, of whom 1871 (56.6%) were women. Female TB suspects were less likely to be referred for sputum smear examination (45.9% vs. 61.6%, P ISTC (33.0% vs. 45.6%, P ISTC-recommended care (RR 0.79, 95%CI 0.72-0.86, P < 0.001). Strategies to ensure that women receive appropriate TB evaluation could provide a valuable opportunity for increasing case detection while also promoting equitable and universal access to care.

  17. 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....

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  20. Should all suspected tuberculosis cases in high income countries be tested with GeneXpert?

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    Vella, Venanzio; Broda, Agnieszka; Drobniewski, Francis

    2018-05-01

    In countries with a low incidence of multidrug-resistant tuberculosis (MDR-TB), universal testing with GeneXpert might not be always cost-effective. This study provides hospital managers in low MDR-TB incidence countries with criteria on when decentralised universal GeneXpert testing would make sense. The alternatives taken into consideration include: universal microbiological culture and drug susceptibility testing (DST) only (comparator); as above but with concurrent centralized GeneXpert in a referral laboratory vs a decentralized GeneXpert system in every hospital to test smear-positive cases only; as above but testing all samples with GeneXpert regardless of smear status. The parameters were from the national TB statistics for England and from a systematic review. Decentralised GeneXpert to test any suspected TB case was the most cost-effective option when 6% or more TB patients belonged to the high-risk group, defined as previous TB diagnosis and or being born in countries with a high MDR-TB incidence. Hospital managers in England and other low MDR-TB incidence countries could use these findings to decide when to invest in GeneXpert or other molecular diagnostics with similar performance criteria for TB diagnostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Factors associated to referral of tuberculosis suspects by private practitioners to community health centres in Bali Province, Indonesia.

    Science.gov (United States)

    Artawan Eka Putra, I Wayan Gede; Utami, Ni Wayan Arya; Suarjana, I Ketut; Duana, I Made Kerta; Astiti, Cok Istri Darma; Putra, I W; Probandari, Ari; Tiemersma, Edine W; Wahyuni, Chatarina Umbul

    2013-10-28

    The contrast between the low proportion of tuberculosis (TB) suspects referred from private practitioners in Bali province and the high volume of TB suspects seeking care at private practices suggests problems with TB suspect referral from private practitioners to the public health sector. We aimed to identify key factors associated with the referral of TB suspects by private practitioners. We conducted a case-control study conducted in Bali province, Indonesia. The cases were private practitioners who had referred at least one TB suspect to a community health centre between 1 January 2007 and the start of data collection, while the controls were private practitioners who had not referred a single TB suspect in the same time. The following factors were independently associated with referral of TB suspects by private practitioners: having received information about the directly observed treatment short-course (DOTS) strategy (OR 2.0; 95% CI 1.1-3.8), ever having been visited by a district TB program officer (OR 2.1; 95% CI 1.0-4.5), availability of TB suspect referral forms in the practice (OR 2.8; 95% CI 1.5-5.2), and less than 5 km distance between the private practice and the laboratory for smear examination (OR 2.2; 95% CI 1.2-4.0). Education and exposure of private practitioners to the TB program improves referral of TB suspects from private practitioners to the national TB program. We recommend that the TB program provides all private practitioners with information about the DOTS strategy and TB suspect referral forms, and organizes regular visits to private practitioners.

  2. 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...

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

    International Nuclear Information System (INIS)

    Lee, H. J.; Jeon, D. S.; Yoo, S. D.; Lee, M. K.; Park, S. K.; Kim, S. J.; Kim, I. J.; Kim, Y. K.

    1998-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Drug-resistance patterns of Mycobacterium tuberculosis strains and associated risk factors among multi drug-resistant tuberculosis suspected patients from Ethiopia.

    Science.gov (United States)

    Mesfin, Eyob Abera; Beyene, Dereje; Tesfaye, Abreham; Admasu, Addisu; Addise, Desalegn; Amare, Miskir; Dagne, Biniyam; Yaregal, Zelalem; Tesfaye, Ephrem; Tessema, Belay

    2018-01-01

    Multidrug drug-resistant tuberculosis (MDR-TB) is a major health problem and seriously threatens TB control and prevention efforts globally. Ethiopia is among the 30th highest TB burden countries for MDR-TB with 14% prevalence among previously treated cases. The focus of this study was on determining drug resistance patterns of Mycobacterium tuberculosis among MDR-TB suspected cases and associated risk factors. A cross-sectional study was conducted in Addis Ababa from June 2015 to December 2016. Sputum samples and socio-demographic data were collected from 358 MDR-TB suspected cases. Samples were analyzed using Ziehl-Neelsen technique, GeneXpert MTB/RIF assay, and culture using Lowenstein-Jensen and Mycobacterial growth indicator tube. Data were analyzed using SPSS version 23. A total of 226 the study participants were culture positive for Mycobacterium tuberculosis, among them, 133 (58.8%) participants were males. Moreover, 162 (71.7%) had been previously treated for tuberculosis, while 128 (56.6%) were TB/HIV co-infected. A majority [122 (54%)] of the isolates were resistant to any first-line anti-TB drugs. Among the resistant isolates, 110 (48.7%) were determined to be resistant to isoniazid, 94 (41.6%) to streptomycin, 89 (39.4%) to rifampicin, 72 (31.9%) to ethambutol, and 70 (30.9%) to pyrazinamide. The prevalence of MDR-TB was 89 (39.4%), of which 52/89 (58.4%) isolates were resistance to all five first-line drugs. Risk factors such as TB/HIV co-infection (AOR = 5.59, p = 0.00), cigarette smoking (AOR = 3.52, p = 0.045), alcohol drinking (AOR = 5.14, p = 0.001) hospital admission (AOR = 3.49, p = 0.005) and visiting (AOR = 3.34, p = 0.044) were significantly associated with MDR-TB. The prevalence of MDR-TB in the study population was of a significantly high level among previously treated patients and age group of 25-34. TB/HIV coinfection, smoking of cigarette, alcohol drinking, hospital admission and health facility visiting were identified as risk factors

  6. Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

    NARCIS (Netherlands)

    R.A. Ahmad (Riris); F. Matthys (Francine); B. Dwihardiani (Bintari); N. Rintiswati (Ning); S.J. de Vlas (Sake); Y. Mahendradhata (Yodi); P. van der Stuyft (Patrick)

    2012-01-01

    textabstractBackground: Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the

  7. 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

  8. Tuberculosis.

    Science.gov (United States)

    Tabbara, Khalid F

    2007-11-01

    The purpose of this report is to present an update on the manifestations and management of ocular tuberculosis. Tuberculosis affects one-third of the world's population. The incidence of tuberculosis has increased with the increase in the HIV infected population. Following a resurgence of the disease in the US, the incidence has recently declined. Patients may develop scleritis that can be focal, nodular or diffuse with or without keratitis. Anterior granulomatous uveitis may occur. The posterior segment reveals vitritis, choroiditis, and can mimic serpiginous choroiditis and other entities. Patients who are immunosuppressed or HIV infected may develop active mycobacterial disease in the eye leading to rapid destruction of the ocular structures. The diagnosis of ocular tuberculosis is made by isolation of Mycobacterium tuberculosis on Löwestein-Jensen medium or by PCR. The diagnosis is supported by the clinical findings, imaging techniques including optical coherence tomography, fluorescein angiography, indocyanine green and ultrasonography. Tuberculin skin test helps to confirm the diagnosis. Ocular tuberculosis may occur in the absence of pulmonary disease. Patients present with a spectrum of clinical signs. The disease may mimic several clinical entities. Early diagnosis and prompt treatment of ocular tuberculosis may prevent ocular morbidity and blindness.

  9. Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis.

    Science.gov (United States)

    Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

    2017-01-01

    We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.

  10. Prevalence of Pulmonary Tuberculosis among Household Contacts in Hyderabad, Sindh: Active Contact Tracing in Children with Tuberculosis

    International Nuclear Information System (INIS)

    Sheikh, M.A.; Shah, S.A.A.

    2017-01-01

    Background: Tuberculosis (TB) in children is clearly linked to TB in adults therefore active household contact tracing is an important method of early diagnosis and treatment particularly in high-TB-burden countries. Objectives: To estimate the prevalence of TB among household contacts of children suffering from tuberculosis using active contact tracing and linking them to TB program for treatment. Subjects and Methods: A total of 125 children suffering from active tuberculosis (index cases)aged 12 years or less were randomly selected from the outpatient department of a tertiary care hospital of Hyderabad. Using their home address, all house hold members of the index cases (sharing one kitchen) were identified. The households were visited by a team including a doctor and the supported staff and were screened for TB using history, physical examination, sputum for AFB and X-ray of chest. Clinical suspects were divided in to two populations, equal to or less than 12 years of age and greater than this age. All suspected cases were brought to outpatient's department of the hospital where children were examined and diagnosed by pediatrician and adults were examined by the pulmonologist. Results: There were 125 children and 1365 household members. Prevalence of active TB in adult household contacts was 8.1 percent and among children was 5.7 percent. Mother, father, grand parents or siblings were the source of disease spread in children. Family history of TB was present in 95 percent (pulmonary 78 percent, extra-pulmonary 22 percent). Conclusion: Tuberculosis in children is mostly spreading from household member hence deeply required to undertake active contact tracing in each new case that is diagnosed or being treated. Policy message: National and Provincial TB programs should advocate and undertake active screening of all household contacts of all TB cases. (author)

  11. Protective activity of Lentinan in experimental tuberculosis.

    Science.gov (United States)

    Markova, Nadya; Kussovski, Vesselin; Drandarska, Ivanka; Nikolaeva, Sascha; Georgieva, Neli; Radoucheva, Tatyana

    2003-10-01

    Protective effects of Lentinan (Ajinomoto, Japan) against Mycobacterium tuberculosis infection were studied by in vitro and in vivo mouse models. The effectiveness of Lentinan administrated intraperitoneally (i.p.) before infection at a dose of 1 mg/kg three times at 2-day intervals was monitored in vivo by several parameters (body temperature; spleen weight; CFU counts of M. tuberculosis in spleen, liver and lung; and histomorphological observations). Peritoneal macrophages obtained from animals treated with Lentinan were greatly stimulated, as assayed by establishing their number, acid phosphatase activity, H2O2 production and killing ability against M. tuberculosis in vitro. The in vivo model demonstrated that administration of Lentinan before infection can mobilize host defense potential and reduce mycobacterial infection.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Evaluation of basophil activation test in suspected food hypersensitivity.

    Science.gov (United States)

    Pignatti, Patrizia; Yacoub, Mona-Rita; Testoni, Claudia; Pala, Gianni; Corsetti, Maura; Colombo, Giselda; Meriggi, Antonio; Moscato, Gianna

    2017-07-01

    Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

  15. [Clinical evaluation on causes of death in patients with active pulmonary tuberculosis].

    Science.gov (United States)

    Kuba, M; Nakasone, K; Miyagi, S; Kyan, K; Shinzato, T; Kohagura, N; Futenma, M; Genka, K

    1996-04-01

    Seventy one patients with active pulmonary tuberculosis who died during the past 5 years (1989 to 1993) were evaluated on their causes of death. Twenty two patients (31%) died directly of tuberculosis, and among them, 18 patients (81%) of 22 patients who died of tuberculosis) had very advanced tuberculosis. The majority of them (64%) were old age over 70 years and were bedridden due mostly to cerebrovascular injuries. The serum level of albumin was low in all 17 patients in whom it was measured. Establishment of diagnosis of tuberculosis was delayed over one month after the onset of symptoms in 59% of patients who died of severe disease. Sixty one percent (11/18) of patients died within the first month after the initiation of chemotherapy and about 90% (16/18) died within 3 months. Two patients died from massive hemoptysis and other patients died of either respiratory failure or tuberculosis meningitis. From these observations it was found that very advanced tuberculosis was the major cause of death in patients who died of tuberculosis and that the advanced disease was chiefly caused by the delay on the establishment of diagnosis, and it was most important to detect tuberculosis as early as possible, with regular check up of chest X-ray and frequent examination for AFB (acid-fast bacilli) for tuberculosis suspected patients. On the other hand, the majority of patients (49/71) died of complicating medical problem unrelated to tuberculosis. Seventeen patients died from malignancy (seven lung cancer, four lymphoma, two laryngeal cancer, etc). Ten deaths were the result of bacterial superinfection. Other patients died from respiratory failure due to COPD, arteiosclerotic heart disease, or cerebrovascular injuries, etc. Two patients of old age died of hepatic failure possibly caused by adverse reaction of TB chemotherapy. It was found that diseases unrelated to tuberculosis were the cause of death in approximately 70% of patients with active tuberculosis, and it should

  16. Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical, diagnostic and epidemiological characteristics.

    Science.gov (United States)

    Bruchfeld, Judith; Aderaye, Getachew; Palme, Ingela Berggren; Bjorvatn, Bjarne; Britton, Sven; Feleke, Yewenhareg; Källenius, Gunilla; Lindquist, Lars

    2002-01-01

    In a setting with a high prevalence of HIV we studied (i) the prevalence of pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological characteristics of PTB; and (iii) the usefulness of standard procedures for diagnosing PTB. Of 509 consecutive outpatients evaluated on clinical suspicion of PTB in Addis Ababa, 33.0% were culture-verified as having PTB. PTB patients, non-TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases, respectively. Predictors for culture-verified PTB were age infection. Diagnosis of PTB based on clinical symptoms, sputum microscopy for acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific (64.1%). In HIV-positive patients both sensitivity and specificity were significantly lower (p infections are often misinterpreted as smear-negative PTB. HIV screening is therefore warranted not only in cases of verified TB but also as part of the diagnostic work-up in patients with respiratory symptoms suggestive of PTB. Also, increased awareness of, and improved diagnostic tools for, HIV-related pulmonary infections other than PTB are required, together with algorithms for patients with suspected PTB.

  17. Comparison of Overnight Pooled and Standard Sputum Collection Method for Patients with Suspected Pulmonary Tuberculosis in Northern Tanzania

    Directory of Open Access Journals (Sweden)

    Stellah G. Mpagama

    2012-01-01

    Full Text Available In Tanzania sputum culture for tuberculosis (TB is resource intensive and available only at zonal facilities. In this study overnight pooled sputum collection technique was compared with standard spot morning collection among pulmonary TB suspects at Kibong’oto National TB Hospital in Tanzania. A spot sputum specimen performed at enrollment, an overnight pooled sputum, and single morning specimen were collected from 50 subjects and analyzed for quality, quantity, and time to detection in Bactec MGIT system. Forty-six (92% subjects’ overnight pooled specimens had a volume ≥5 mls compared to 37 (37% for the combination of spot and single morning specimens (P<0.001. Median time to detection was 96 hours (IQR 87–131 for the overnight pooled specimens compared to 110.5 hours (IQR is 137 right 137–180 for the combination of both spot and single morning specimens (P=0.001. In our setting of limited TB culture capacity, we recommend a single pooled sputum to maximize yield and speed time to diagnosis.

  18. Molecular diagnosis of suspected tuberculosis from archived smear slides from the Balimo region, Papua New Guinea.

    Science.gov (United States)

    Guernier, Vanina; Diefenbach-Elstob, Tanya; Pelowa, Daniel; Pollard, Sandra; Burgess, Graham; McBryde, Emma S; Warner, Jeffrey

    2018-02-01

    Tuberculosis (TB) is a serious health problem in Papua New Guinea (PNG) with an estimated 30000 new cases and 3800 deaths each year. In the Balimo region of the Western Province, diagnosis relies on clinical manifestations and on the microscopic detection of acid-fast bacilli (AFB) in sputum smears, a technique with limited sensitivity. A molecular diagnosis assay targeting DNA extracted from archived sputum smear slides collected from the Balimo region (2012-2014) was conducted, without the need for a viable culture. The presence of Mycobacterium sp on 1162 slides prepared from 345 sputum samples was assessed using a real-time PCR (qPCR) approach. The qPCR technique identified the presence of mycobacteria in 35.4% of the smear slides and 59.7% of the tested sputum samples. Poor agreement was observed between the two diagnosis methods (smear AFB microscopy versus qPCR), with 100 AFB-positive sputum samples compared to 206 qPCR-positive sputum samples overall. Treatment was initiated in 90.2% of the smear-positive cases. Unnecessary treatment of 'false-positive' TB cases (AFB-negative/qPCR-negative) was very low (8.6%) and was even lower when the nine patients diagnosed with extrapulmonary TB were excluded from the analysis. However, the prevalence of false-negatives (AFB-negative/qPCR-positive) was high (28.5%). Undetected smear-negative TB is occurring in the Balimo region of PNG, as well as some unnecessary empirical treatment. Molecular methods of diagnosis could greatly reduce the frequency of inappropriate clinical assessment, as well as providing point-of-care diagnosis. This may provide substantial patient and programmatic benefits, including lowering the economic burden on patients from rural areas seeking medical diagnosis in Balimo. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. 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.

  20. 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

    8(+) T cell proliferation assays (CFSE dilution) in 41 M. tuberculosis-responsive donors identified 70 new M. tuberculosis epitopes. Using HLA/peptide tetramers for the 18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides, recognition by cured TB patients' CD8(+) T cells......-epitope/Ag repertoire for human CD8(+) T cells is much broader than hitherto suspected, and the newly identified M. tuberculosis Ags are recognized by (poly) functional CD8(+) T cells during control of infection. These results impact on TB-vaccine design and biomarker identification. The Journal of Immunology, 2011...

  1. Tuberculosis

    International Nuclear Information System (INIS)

    Aleksandrova, A.V.

    1983-01-01

    Classification of clinical forms of tuberculosis of respiratory organs is m ade. It is shown, that diagnosis, determination of the clinical form of pulmona ry tuberculosis, extent and phase of the process are mainly based on the data of roentgenologic studies and in certain cases tomography is preferable. Roentgenologic picture of primary tuberculosis, tuberculosis of intrathoracis l ymp nodes, dissemenated tuberculosis, focal and infiltrative tuberculosis of lungs, tuberculomas of lungs, cavernous and fibrocavernous form of pulmonary tub erculosis, cirrhotic tuberculosis of lungs, tuberculosis of upper respiratory tracks, tuberculous pleurite and tuberculosis of respiratory organs, combined wi th dust occupational diseases, has been described

  2. Mathematical Modeling of Tuberculosis Granuloma Activation

    Directory of Open Access Journals (Sweden)

    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.

  3. Identification of Mycobacterium tuberculosis in 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

  4. Changing patterns in pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Tytle, T.L.; Johnson, T.H.

    1984-01-01

    The authors reviewed the initial chest roentgenograms of 182 consecutive adult patients with proven active tuberculosis. Less than 50% of all cases were known or suspected at the time of initial presentation. There is a low degree of correlation between radiologically discernible active pulmonary tuberculosis and extrapulmonary tuberculosis. A high percentage of cases represent uncommon pulmonary locations. The frequency of occurrence of four common pulmonary patterns is presented. 21 references, 4 figures, 5 tables

  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

    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...

  6. Evaluation of the efficiency of nested q-PCR in the detection of Mycobacterium tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem macroscopic inspections of bovine carcasses slaughtered in the state of Mato Grosso, Brazil.

    Science.gov (United States)

    Carvalho, Ricardo César Tavares; Furlanetto, Leone Vinícius; Maruyama, Fernanda Harumy; Araújo, Cristina Pires de; Barros, Sílvia Letícia Bomfim; Ramos, Carlos Alberto do Nascimento; Dutra, Valéria; Araújo, Flábio Ribeiro de; Paschoalin, Vânia Margaret Flosi; Nakazato, Luciano; Figueiredo, Eduardo Eustáquio de Souza

    2015-08-01

    Bovine tuberculosis (BTB) is a zoonotic disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). The quick and specific detection of this species is of extreme importance, since BTB may cause economic impacts, in addition to presenting imminent risks to human health. In the present study a nested real-time PCR test (nested q-PCR) was used in post-mortem evaluations to assess cattle carcasses with BTB-suspected lesions. A total of 41,193 cattle slaughtered in slaughterhouses located in the state of Mato Grosso, were examined. Of the examined animals, 198 (0.48%) showed BTB-suspected lesions. M. bovis was isolated in 1.5% (3/198) of the samples. Multiplex-PCR detected MTC in 7% (14/198) of the samples. The nested q-PCR test detected MTC in 28% (56/198) of the BTB-suspected lesions, demonstrating higher efficiency when compared to the multiplex-PCR and conventional microbiology. Nested q-PCR can therefore be used as a complementary test in the national program for control and eradication of bovine tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 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...

  8. Tc-99m-MIBI Uptake in Active Pulmonary Tuberculosis: A Case Report

    International Nuclear Information System (INIS)

    Lee, Chang Ho; Park, Chan Hee; Hwang, Hee Sung; Bae, Moon Sun

    1996-01-01

    Technetium-99m MIBI was developed as a myocardiac perfusion imagine agent and has been used effectively in the detection and post-therapeutic evaluation of various neoplasm such as thyroid, lung, bone and breast tumors. As an infrequent findings, Tc-99m MIBI agent has shown in non-neoplastic pulmonary conditions including fibroding alveolitis, pulmonary actinomycosis, active pulmonary sarcoidosis, pulmonary interstitial fibrosis in progressive systemic sclerosis and active osteomyelitis. In a recent report conducted by Cetin Oncel, Tc-99m MIBI imaging is an effective method in the detection and follow-up of pulmonary tuberculosis. We have also experienced Tc-99m-MIBI uptake in active pulmonary tuberculosis incidentally found in a patient with suspected proliferative villonodular synovitis of the left ankle.

  9. Prevalence of Tuberculosis among Household Contacts in Pondicherry: Active Case Finding Among New Smear Positive Cases

    Directory of Open Access Journals (Sweden)

    Kumar VA

    2016-05-01

    Full Text Available Introduction: The risk of transmission from the index case to its contacts is more in case of smear positive Pulmonary Tuberculosis cases. Any delay in diagnosis and treatment increases the risk of disease transmission to their contacts. Contact screening is important for early detection of transmission of infection. Thus, active case finding of TB is needed to identify the case yield among household contacts. This study will yield the burden of Tuberculosis among the household contact. Objective: To identify the TB suspect and estimate the prevalence of TB among household contacts. Material and Methods: A two stage cross study was done in 472 households of 157 ‘Index cases’ registered in the State Tuberculosis Unit, Puducherry. The study duration was one year and eight months. Data was entered and analyzed by using Epi_Info (Version 3.4.3 software package. Results: A total of 96 (20.3% symptomatic was found from the 472 households contacts who participated in this study. Out of 90 symptomatics, 70 (72.9% were symptomatic within two months of visit and 26 (27.1% were found to have symptoms after eight months. The overall prevalence of tuberculosis in symptomatic household contacts was 4.3% and all tuberculosis confirmed cases were found at the end of in second month only. Conclusion: Considering the prevalence tuberculosis among the symptomatic of household contact to be 4.3%, their investigation to rule out TB in earlier stages is a need. It may help prevent further spread of M. tuberculosis infection in the local community.

  10. 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

    countries do not, even if the chest radiograph suggests tuberculosis. Nearly all countries (49 out of 50) use tuberculin skin testing (TST); 27 (54%) out of 50 countries also perform chest radiography irrespective of the TST result. Interpretation of the TST varies widely. All countries use 6-9 months...... 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...

  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. 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...... with suspicion of TB and 39 healthy BCG-vaccinated persons were enrolled. Forty-eight had active TB, 25 did not, and 9 were excluded. Sensitivity and specificity of the test for active TB were evaluated in a prospective blinded manner in patients suspected of TB. The sensitivity of the QFT-RD1 was 85% (40......% (5/12) by culture (P test, sensitivity increased to 96% (CI, 90 to 102). Ten of 25 (40%) non-TB patients were QFT-RD1 positive, resulting...

  13. Tuberculosis

    OpenAIRE

    C. Robert Horsburgh, Jr

    2014-01-01

    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.

  14. Tuberculosis

    OpenAIRE

    Mochammad, Hatta

    2008-01-01

    This book chapter for medical students and researcher Tuberculosis is still one of the leading causes of death by infectious diseases with 2 million deaths per year and 9.2 million new cases of tuberculosis disease annually [1-3]. Besides, more than 2 milliard people are infected with latent tuberculosis infection (LTBI) [1-3]. Despite continuous effort in the prevention, monitoring and treatment of tuberculosis, the disease remains a major health problem in many countries [4-6...

  15. 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.

  16. The relationship between chitotriosidase activity and tuberculosis.

    Science.gov (United States)

    Chen, M; Deng, J; Li, W; Su, C; Xia, Y; Wang, M; Li, X; Abuaku, B K; Tan, H; Wen, S W

    2015-11-01

    Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future.

  17. Tuberculosis

    International Nuclear Information System (INIS)

    Latorre Tortello, Pablo

    1998-01-01

    The tuberculosis is an infection bacterial chronicle of world distribution. Three organisms of the family of the mycobacterium, the m. tuberculosis, the m. bovis and m. africanum, phenotypic and genetically similar, produce it, but only the m. tuberculosis has importance; the others rarely produce illness in the human. By definition, the lung tuberculosis is the localization of the m. tuberculosis in the breathing tract, the most common and main form in the affection and the only able to contaminate to other people. The koch bacillus, transmits the illness directly person to person. The paper Includes topics like pathogenesis, natural history, epidemiology, diagnose, symptomatology and treatment

  18. Clinical value of whole-blood interferon-gamma assay in patients with suspected pulmonary tuberculosis and AFB smear- and polymerase chain reaction-negative bronchial aspirates.

    Science.gov (United States)

    Lee, Jaehee; Lee, Shin Yup; Yoo, Seung Soo; Cha, Seung Ick; Won, Dong Il; Park, Jae Yong; Lee, Won-Kil; Kim, Chang Ho

    2012-07-01

    Combining a polymerase chain reaction (PCR) test with bronchoscopy is frequently performed to allow a rapid diagnosis of smear-negative pulmonary tuberculosis (PTB). However, limited data are available concerning clinical judgment in patients with suspected PTB and AFB smear- and PCR-negative bronchial aspirates (BA). The present study evaluated the usefulness of whole-blood QuantiFERON-TB Gold In-Tube (QFT) testing in these patients. Of 166 patients with suspected PTB who had undergone bronchoscopy because of smear-negative sputum or inadequate sputum production, 93 (56%) were diagnosed with culture-positive PTB. Seventy-four patients were either AFB smear- or PCR-positive. In the 75 patients whose BA AFB smear and PCR results were both negative, 19 were finally diagnosed with PTB by culture. The QFT test had a negative predictive value of 91% for PTB. The QFT test may be useful for excluding PTB in patients with suspected PTB whose BA AFB smear and PCR results are both negative. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. TUBERCULOSIS

    OpenAIRE

    Tarik Bajrović; Mahmud Nurkić; Šukrija Zvizdić

    2013-01-01

    Tuberculosis, known as the "White Plague" in the early 19th century, is the infectious disease, which is being researched today even in some of the most developed countries in the world. Epidemiological- epizootiological research points to the importance of pasteurizing milk as well as the transmission in aerosolized droplets in humans and animals. Mycobacterium tuberculosis (Mtb), M. bovis, M. africanum and M. microti are the mycobacteria that cause tuberculosis. Other mycobacteria cause dis...

  20. Tuberculosis

    NARCIS (Netherlands)

    Ankrah, Alfred O; Glaudemans, Andor W J M; Maes, Alex; Van de Wiele, Christophe; Dierckx, Rudi A J O; Vorster, Mariza; Sathekge, Mike M

    Tuberculosis (TB) is currently the world's leading cause of infectious mortality. Imaging plays an important role in the management of this disease. The complex immune response of the human body to Mycobacterium tuberculosis results in a wide array of clinical manifestations, making clinical and

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

    International Nuclear Information System (INIS)

    Khalil, K.F.; Ambreen, A.; Butt, T.

    2013-01-01

    Objective: To compare the sensitivity of tuberculin skin test (TST) and quantiFERON-TB gold test (QFT-G) in active pulmonary tuberculosis. Study Design: Analytical study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2011 to January 2012. Methodology: QuantiFERON-TB gold test (QFT-G) was evaluated and compared it with tuberculin skin test (TST) in 50 cases of active pulmonary tuberculosis, in whom tuberculous infection was suspected on clinical, radiological and microbiological grounds. Sensitivity was determined against positive growth for Mycobacterium tuberculosis. Results: Out of 50 cases, 43 were females and 7 were males. The mean age was 41.84 A+- 19.03 years. Sensitivity of QFT-G was 80% while that of TST was 28%. Conclusion: QFT-G has much higher sensitivity than TST for active pulmonary tuberculosis. It is unaffected by prior BCG administration and prior exposure to atypical mycobacteria. A positive QFT-G result can be an adjunct to diagnosis in patients having clinical and radiological data compatible with pulmonary tuberculosis. (author)

  2. Tuberculosis

    Science.gov (United States)

    Friend, Milton

    1999-01-01

    Avian tuberculosis is usually caused by the bacterium Mycobacterium avium. At least 20 different types of M. avium have been identified, only three of which are known to cause disease in birds. Other types of Mycobacterium rarely cause tuberculosis in most avian species; however, parrots, macaws, and other large perching birds are susceptible to human and bovine types of tuberculosis bacilli. Avian tuberculosis generally is transmitted by direct contact with infected birds, ingestion of contaminated feed and water, or contact with a contaminated environment. Inhalation of the bacterium can cause respiratory tract infections. Wild bird studies in the Netherlands disclosed tuberculosis-infected puncture-type injuries in birds of prey that fight at the nest site (kestrels) or on the ground (buteo-type buzzards), but tuberculosisinfected injuries were not found in accipiters (falco

  3. Risk for latent and active tuberculosis in Germany.

    Science.gov (United States)

    Herzmann, Christian; Sotgiu, Giovanni; Bellinger, Oswald; Diel, Roland; Gerdes, Silke; Goetsch, Udo; Heykes-Uden, Helga; Schaberg, Tom; Lange, Christoph

    2017-06-01

    Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

  4. Dendritic Cells Activate and Mature after Infection with Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Mamo Gezahagne

    2011-07-01

    Full Text Available Abstract Background Dendritic cells (DCs can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Findings To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation. Conclusion These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.

  5. Circulating microRNAs in patients with active pulmonary tuberculosis.

    Science.gov (United States)

    Fu, Yurong; Yi, Zhengjun; Wu, Xiaoyan; Li, Jianhua; Xu, Fuliang

    2011-12-01

    Emerging evidence shows that microRNAs (miRNAs) play an important role in pathogen-host interactions. Circulating miRNAs have been repeatedly and stably detected in blood and hold promise to serve as molecular markers for diverse physiological and pathological conditions. To date, the relationship between circulating miRNAs and active pulmonary tuberculosis (TB) has not been reported. Using microarray-based expression profiling followed by real-time quantitative PCR validation, the levels of circulating miRNAs were compared between patients with active pulmonary tuberculosis and matched healthy controls. The receiver operating characteristic curve was used to evaluate the diagnostic effect of selected miRNA. Bioinformatic analysis was used to explore the potential roles of these circulating miRNAs in active pulmonary tuberculosis infection. Among 92 miRNAs significantly detected, 59 miRNAs were downregulated and 33 miRNAs were upregulated in the TB serum compared to their levels in the control serum. Interestingly, only two differentially expressed miRNAs were increased not only in the serum but also in the sputum of patients with active pulmonary tuberculosis compared to the levels for the healthy controls. Upregulated miR-29a could discriminate TB patients from healthy controls with reasonable sensitivity and specificity. A number of significantly enriched pathways regulated by these circulating miRNAs were predicted, and most of them were involved in acute-phase response, inflammatory response, and the regulation of the cytoskeleton. In all, for the first time our results revealed that a number of miRNAs were differentially expressed during active pulmonary tuberculosis infection, and circulating miR-29a has great potential to serve as a marker for the detection of active pulmonary tuberculosis infection.

  6. 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...

  7. TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    Tarik Bajrović

    2013-10-01

    Full Text Available Tuberculosis, known as the "White Plague" in the early 19th century, is the infectious disease, which is being researched today even in some of the most developed countries in the world. Epidemiological- epizootiological research points to the importance of pasteurizing milk as well as the transmission in aerosolized droplets in humans and animals. Mycobacterium tuberculosis (Mtb, M. bovis, M. africanum and M. microti are the mycobacteria that cause tuberculosis. Other mycobacteria cause diseases commonly known as mycobacteriosae. Pathogenesis of tuberculosis includes both host- related and mycobacterium-related factors (virulence. Mtb acts through the expression of various genes and their proteins that are detectable in the serums of the diseased only, proving these proteins are formed in the course of the disease. In humans, a diagnosis is established by the detection of antigens (and antibodies, and in animals, with the allergy tests. As far as the bovine tuberculosis is concerned, the combination of skin tuberculin and blood gamma interferon test is recommended. Sequential genome (Mtb analysis has given the basis for further research of the new vaccines.Key words: Tuberculosis, pathogenesis, immunity

  8. 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...

  9. 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

  10. Anti-mycobacterium tuberculosis activity of polyherbal medicines used for the treatment of tuberculosis in Eastern Cape, South Africa.

    Science.gov (United States)

    Famewo, Elizabeth B; Clarke, Anna M; Wiid, Ian; Ngwane, Andile; van Helden, Paul; Afolayan, Anthony J

    2017-09-01

    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. To evaluate the anti-tubercular activity of polyherbal medicines used for the treatment of tuberculosis. The remedies were screened against Mycobacterium tuberculosis H37Rv using Middlebrook 7H9 media and MGIT BACTEC 960 system. They were liquid preparations from King Williams Town site A (KWTa), King Williams Town site B (KWTb), King Williams Town site C (KWTc), Hogsback first site (HBfs), Hogsback second site (HBss), Hogsback third site (HBts), East London (EL), Alice (AL) and Fort Beaufort (FB). The susceptibility testing revealed that all the remedies contain anti-tubercular activity with KWTa, KWTb, KWTc, HBfs, HBts, AL and FB exhibiting more activity at a concentration below 25 µl/ml. Furthermore, MIC values exhibited inhibitory activity with the most active remedies from KWTa, HBfs and HBts at 1.562 µg/ml. However, isoniazid showed more inhibitory activity against M. tuberculosis at 0.05 µg/ml when compare to the polyherbal remedies. This study has indicated that these remedies could be potential sources of new anti-mycobacterial agents against M. tuberculosis . However, the activity of these preparations and their active principles still require in vivo study in order to assess their future as new anti-tuberculosis agents.

  11. 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

  12. 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

  13. MicroRNA-365 in macrophages regulates Mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6.

    Science.gov (United States)

    Song, Qingzhang; Li, Hui; Shao, Hua; Li, Chunling; Lu, Xiao

    2015-01-01

    The present study is to investigate the relationship between microRNA (miR)-365 expression and the levels of interleukin (IL)-6 mRNA and protein in patients with active tuberculosis. From June 2011 to June 2014, 48 patients with active pulmonary tuberculosis induced by Mycobacterium tuberculosis were included in the study. In addition, 23 healthy subjects were enrolled as control. Macrophages were collected by pulmonary alveolus lavage. In addition, serum and mononuclear cells were isolated from peripheral blood. The levels of miR-365 and IL-6 in macrophages, mononuclear cells and serum were determined using quantitative real-time polymerase chain reaction. The protein expression of IL-6 in macrophages and mononuclear cells was measured using Western blotting, while that in serum was detected by enzyme-linked immunoabsorbent assay. Expression of IL-6 mRNA and protein was significantly enhanced in patients with active pulmonary tuberculosis. Increase of IL-6 protein concentration in serum was probably due to the release of IL-6 protein from mononuclear cells in the blood. In addition, miR-365 levels were significantly lowered in patients with active pulmonary tuberculosis. Up-regulated IL-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of miR-365, suggesting that miR-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via IL-6.

  14. Nutritional supplements for people being treated for active tuberculosis

    African Journals Online (AJOL)

    2018-01-17

    Jan 17, 2018 ... review assessing the effects of oral nutritional supplements in people with active tuberculosis who are receiving antituberculosis drug therapy. The review ... 2 Cochrane Nutrition, hosted jointly by the Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch. University ...

  15. Tuberculosis

    OpenAIRE

    Latorre Tortello, Pablo

    2011-01-01

    Por definición, la tuberculosis pulmonar es la localizaci6n del M. tuberculosis en el tracto respiratorio, la forma más común y principal de la afección y la única capaz de contagiar a otras personas. El M. tuberculosis, descubierto por Robert Koch en 1882, el bacilo de Koch, es un bacilo delgado, inmóvil, de 4 micras de longitud media, aerobio obligado, que se tiñe de rajo por la tinción de Ziehl-Neelsen. Debido a la coraza lipídica de su pared, lo hace resistente a la decoloración con ácido...

  16. Tuberculosis

    Directory of Open Access Journals (Sweden)

    Pablo Latorre Tortello

    1998-10-01

    Full Text Available Por definición, la tuberculosis pulmonar es la localizaci6n del M. tuberculosis en el tracto respiratorio, la forma más común y principal de la afección y la única capaz de contagiar a otras personas. El M. tuberculosis, descubierto por Robert Koch en 1882, el bacilo de Koch, es un bacilo delgado, inmóvil, de 4 micras de longitud media, aerobio obligado, que se tiñe de rajo por la tinción de Ziehl-Neelsen. Debido a la coraza lipídica de su pared, lo hace resistente a la decoloración con ácidos y alcohol, de ahí el nombre de bacilos ácido-alcohol resistente (BAAR. Su transmisión es directa, de persona a persona.

  17. Tuberculosis

    OpenAIRE

    Pablo Latorre Tortello

    1998-01-01

    Por definición, la tuberculosis pulmonar es la localizaci6n del M. tuberculosis en el tracto respiratorio, la forma más común y principal de la afección y la única capaz de contagiar a otras personas. El M. tuberculosis, descubierto por Robert Koch en 1882, el bacilo de Koch, es un bacilo delgado, inmóvil, de 4 micras de longitud media, aerobio obligado, que se tiñe de rajo por la tinción de Ziehl-Neelsen. Debido a la coraza lipídica de su pared, lo hace resistente a la decoloración con ácido...

  18. 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

  19. Tuberculosis

    OpenAIRE

    Mendoza Zuñiga, Marleny; Bastidas Párraga, Gustavo; León Untiveros, Paúl Albert

    2013-01-01

    La tuberculosis es una enfermedad infectocontagiosa producida por el bacilo de Koch, que ataca a los pulmones pero puede ser difuminada por todo el cuerpo. El siguiente artículo de información nos da una visión amplia de la detección, diagnóstico y tratamiento de la misma.

  20. 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

  1. Increased complement C1q level marks active disease in human tuberculosis.

    Directory of Open Access Journals (Sweden)

    Yi Cai

    Full Text Available BACKGROUND: Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. METHODS: Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. RESULTS: C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. CONCLUSIONS: C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

  2. 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.)

  3. Interobserver variability in the detection of mediastinal and hilar lymph nodes on CT in children with suspected pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Andronikou, Savvas; Brauer, Barbara; Brachmeyer, Steven; Lucas, Susan; Joseph, Elaine; Galpin, Jackie; DuToit, George; Swingler, George

    2005-01-01

    The presence of mediastinal or hilar adenopathy is critical for the diagnosis of pulmonary TB. Interobserver variability in the detection of lymphadenopathy on CT in children affects the usefulness of CT as a gold standard. To determine the interobserver variability for the detection of hilar and mediastinal adenopathy on CT in children. One hundred children with clinically suspected pulmonary TB were prospectively recruited for CT scanning of the chest. Four observers reviewed the scans independently for the presence of lymphadenopathy at predetermined sites. Overall Kappa statistic was determined for each recognised site of mediastinal and hilar lymphadenopathy. Kappa statistics showed that observers only agreed moderately in their detection of lymphadenopathy. The site of best agreement was the right hilum followed by the subcarinal, right paratracheal and precarinal locations. Observers differed most at the anterior mediastinum and left hilum. The best Kappa statistic was for the overall presence of lymphadenopathy taking all sites into account. Imaging techniques that are considered the gold standard for particular diseases must be validated pathologically, and if this is not possible, interobserver variability should be evaluated. CT is considered the gold standard for detecting lymphadenopathy, but we have shown only moderate agreement between readers. Readers had difficulty in distinguishing lymphadenopathy from normal thymus and were unable to distinguish normal from pathological nodes without a predetermined size threshold for abnormality. The right hilum and the sites around the carina are the most reliable for the reported presence of lymphadenopathy. (orig.)

  4. Tuberculosis

    OpenAIRE

    Juan Carlos Rodríguez, D.

    2014-01-01

    La tuberculosis sigue constituyendo un problema de salud pública a nivel mundial con casi nueve millones de casos nuevos en 2012 y se estima que un tercio de la humanidad está infectada. A nivel nacional, si bien las tasas son alentadoras, la variación regional es muy importante. En los últimos años se han registrado progresos importantes tanto en el conocimiento de la conducta del bacilo de Koch, el causante de la enfermedad, como en los métodos para detectarlo. Así los IGRAS (Interferon G R...

  5. 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.

  6. Soluble Urokinase Plasminogen Activator Receptor Levels in Tuberculosis Patients at High Risk for Multidrug Resistance

    Directory of Open Access Journals (Sweden)

    Tri Yudani Mardining Raras

    2012-01-01

    Full Text Available The soluble urokinase plasminogen activator receptor (suPAR has been shown to be a strong prognostic biomarker for tuberculosis (TB. In the present study, the profiles of plasma suPAR levels in pulmonary TB patients at high risk for multidrug resistance were analyzed and compared with those in multidrug resistant (MDR-TB patients. Forty patients were prospectively included, consisting of 10 MDR-TB patients and 30 TB patients at high risk for MDR, underwent clinical assesment. Plasma suPAR levels were measured using ELISA (SUPARnostic, Denmark and bacterial cultures were performed in addition to drug susceptibility tests. All patients of suspected MDR-TB group demonstrated significantly higher suPAR levels compared with the healthy TB-negative group (1.79 ng/mL. Among the three groups at high risk for MDR-TB, only the relapse group (7.87 ng/mL demonstrated suPAR levels comparable with those of MDR-TB patients (7.67 ng/mL. suPAR levels in the two-month negative acid-fast bacilli conversion group (9.29 ng/mL were higher than positive control, whereas levels in the group consisting of therapy failure patients (5.32 ng/mL were lower. Our results strongly suggest that suPAR levels enable rapid screening of suspected MDR-TB patients, but cannot differentiate between groups.

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

    International Nuclear Information System (INIS)

    Chung, Myung Hee; Lee, Hae Giu; Yu, Won Jong; Chung, Hong Jun; Yang, Bo Sung; Kwon, Soon Suck; Park, Seog Hee

    2000-01-01

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

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

    International Nuclear Information System (INIS)

    Rokayan, S.A

    2003-01-01

    Objective: Increased serum adenosine deaminase (ADA) activity, mainly associated with tuberculosis can also occur in a number of other diseases thus negatively affecting the diagnostic utility of ADA measurements in tuberculosis. The aim of the study was to determine whether or not the combined use of the activity of ADA, its isoenzymes and differential cell counts would provide a more efficient means of diagnosing tuberculosis than the use of ADA levels alone. Results: Data suggested significant (p 0.75) of ADA/sub 2/ADA was found to be better indicator of tuberculosis. Lymphocyte neutrophil ratio (L/N)> 0.69 gave additional benefit to increase the sensitivity and specificity for the use of ADA as marker in diagnosing tuberculosis. Conclusion: The combined use of activity of ADA, its isoenzymes and total and differential cell counts is a better indicator and gives better understanding to diagnose and evaluate tuberculosis and response to therapy. (author)

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Belinda Brust

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

  12. 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.

  13. 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.

  14. Tuberculosis among atomic bomb survivors

    International Nuclear Information System (INIS)

    Hamada, Tadao; Matsushita, Hiroshi.

    1980-01-01

    Effects of atomic bomb on tuberculosis among atomic bomb survivors necropsied after 1956 when Atomic Bomb Hospital was opened were observed statistically and the following results were obtained. The morbidity of tuberculosis in the group exposed within 2 km from the hypocenter was higher than that of the control group, but there was not a significant difference between the both groups. The morbidity of all types of tuberculosis was significantly higher in the group exposed within 2 km from the hypocenter than in the control group. The morbidity of tuberculosis tended to decrease in both exposed and non-exposed groups with time. However, the morbidity of miliary or active tuberculosis has tended to rise in the exposed since 1975. The morbidity in young a-bomb survivors exposed within 2 km was higher than that in those of other groups, but there was not a difference in the morbidity among the aged. The higher the rate of complication of active tuberculosis with stomach cancer or acute myelocytic leukemia or liver cirrhosis, the nearer the places of exposure were to the hypocenter. Out of 26 patients with miliary tuberculosis, 6 were suspected to have leukemia while they were alive and were suggested to have leukemoid reaction by autopsy. They all were a-bomb survivors, and 4 of them were exposed within 2 km from the hypocenter. (Tsunoda, M.)

  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.

    Directory of Open Access Journals (Sweden)

    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.

  16. 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...

  17. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Science.gov (United States)

    2010-07-01

    ... pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.378 Changes from activity in pulmonary tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will not...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Factors influencing quality of life in patients with active tuberculosis.

    Science.gov (United States)

    Marra, Carlo A; Marra, Fawziah; Cox, Victoria C; Palepu, Anita; Fitzgerald, J Mark

    2004-10-20

    With effective treatment strategies, the focus of tuberculosis (TB) management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL) experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4) and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." Despite the ability to cure TB, there remains a significant impact on QOL. Since much

  20. Factors influencing quality of life in patients with active tuberculosis

    Directory of Open Access Journals (Sweden)

    Cox Victoria C

    2004-10-01

    Full Text Available Abstract Background With effective treatment strategies, the focus of tuberculosis (TB management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. Methods English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. Results 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4 and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." Conclusion Despite the ability to

  1. [Morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis].

    Science.gov (United States)

    Elipashev, A A; Nikolsky, V O; Shprykov, A S

    to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis. The material taken from 310 patients operated on in 2010-2015 were retrospectively examined. The patients underwent economical lung resections of limited extent (typical and atypical ones of up to 3 segments) for circumscribed forms of tuberculosis with bacterial excretion. A study group consisted of 161 (51.9%) patients with drug-resistant variants of pulmonary tuberculosis. A control group included 149 (48.1%) patients with preserved susceptibility of Mycobacterium tuberculosis to anti-TB drugs. The activity of specific changes in tuberculosis was morphologically evaluated in accordance with the classification proposed by B.M. Ariel in 1998. The highest activity of fourth-to-fifth degree specific inflammation, including that outside the primary involvement focus, was obtained in the drug-resistant pulmonary tuberculosis group due to the predominance of patients with cavernous and fibrous-cavernous tuberculosis versus those in whom the susceptibility to chemotherapeutic agents was preserved. A macroscopic study showed that the primary lesion focus had a median size in one-half of the all the examinees; but large tuberculomas, caverns, and fibrous caverns over 4 cm in diameter were multiple and detected in the drug-resistant pulmonary tuberculosis group. Multidrug resistance was observed in more than 60% of the patients with fibrous-cavernous pulmonary tuberculosis, extensive drug resistance was seen in those with cavernous tuberculosis, which is an aggravating factor. The data obtained from the morphological study of the intraoperative material can specify the clinical form of tuberculosis and evaluate the efficiency of preoperative specific therapy. The highest activity of specific inflammation was observed in patients with multiple drug-resistant pulmonary tuberculosis, the prevalence of third-to-fourth degree

  2. [Telomerase in lung cancer. Testing the activity of the "immortaligy enzyme" bronchial biopsies increases the diagnostic yield in cases of suspected peripheral bronchogenic carcinomas].

    Science.gov (United States)

    Freitag, L; Litterst, P; Obertrifter, B; Velehorschi, V; Kemmer, H P; Linder, A; Brightman, I

    2000-11-01

    The proliferative capability is time-limited in normal somatic cells by the shortening of their chromosomal ends, the telomeres (Hayflick limit). An important feature of malignant cells is their immortality. The probably most common mechanism of tumour cells to achieve unlimited replicability is the activation of the enzyme telomerase. The reverse transcriptase can compensate the loss of telomeres. Using a PCR-based TRAP assay we found telomerase activity in tumour biopsies, exsudates and bronchial washings in various thoracic malignancies. In 38 of 47 patients with suspected peripheral lung cancer eventually surgery or invasive procedures proved a malignancy. In fluoroscopically guided bronchial brushings from 25 of these 38 patients (66%) the TRAP assay revealed telomerase activity. There was a single false positive case (tuberculosis) and with a single exception, the simultaneously taken brushes of the contralateral lobes were all telomerase negative. In 23 patients (61%) tumour cells were found in the cytological examination. In 33 patients at least one marker was positive. Thus the combination of cytology and telomerase test in bronchial brush biopsies attained a diagnostic yield of 87%.

  3. 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.

  4. 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.

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

    International Nuclear Information System (INIS)

    Sharma, Madhurima; Sandhu, Manavjit Singh; Gorsi, Ujjwal; Gupta, Dheeraj; Khandelwal, Niranjan

    2015-01-01

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

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

    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

  7. 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.

  8. 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.

  9. Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis

    DEFF Research Database (Denmark)

    Schön, T; Elias, D; Moges, F

    2003-01-01

    Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO produ......Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal...... virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide....

  10. Nutritional supplements for people being treated for active tuberculosis

    African Journals Online (AJOL)

    Journal Home > Vol 108, No 1 (2018) > ... Altered metabolism and loss of appetite associated with tuberculosis may result in undernutrition, ... increased cure rates at 6 and 12 months), but it probably improves weight gain in some settings.

  11. THE ANTI-TB DRUG SENSITIVITY OF MYCOBACTERIUM TUBERCULOSIS FROM CEREBROSPINAL FLUID AND BONE TISSUE BIOPSY SPECIMENS OF PATIENTS SUSPECTED TUBERCULOUS MENINGITIS AND SPINAL TB IN DR SOETOMO HOSPITAL INDONESIA

    Directory of Open Access Journals (Sweden)

    Ni Made Mertaniasih

    2014-09-01

    Full Text Available Tuberculous meningitis (TBM is an infection of meningens which potentially life threatening with significant morbidity and mortality. Spinal TB has the same problem with TBM, infection in bone and joint, the delayed diagnosis worsens the prognosis. The rapid and accurate diagnosis plus promt adequate treatment is essential for the good outcome. The aim of this research is to study the first line drug sensitivity of Mycobacterium tuberculosis isolated from specimens of cerebrospinal fluid from suspected tuberculous meningitis patients and bone tissue biopsy from suspected spinal TB patients. The method of this research is TB Laboratory examination in Department of Clinical Microbiology – Dr. Soetomo General Hospital, Indonesia, using the gold standard liquid culture method MGIT 960 System (Becton Dickinson and solid culture method with Lowenstein-Jensen medium. The specimens CSF from 50 TBM patients at January 2013 until May 2014. Positive isolate detection of Mycobacterium tuberculosis complex were 11 isolates (22%, which sensitivity 100% (11/11 isolates to Rifampin (R, Pyrazinamide (Z, Ethambutol (E, and Streptomycin (S; one isolate resistant to Isoniazid, sensitivity to Isoniazid 90,90% (10/11; and received 21 specimens of bone tissue biopsy which positive 5 isolates (23%, all isolates sensitive 100% (5/5 isolates to Rifampin and Pyrazinamide, and 1 isolates resistant to Isoniazid, Ethambutol, and Streptomycin, in which sensitivity 80% (4/5 isolates to Isoniazid, Ethambutol, and Streptomycin. The conclusion of this research is positivity detection 22% of CSF specimens, and 23% of bone tissue biopsy were low. All isolates sensitive 100% to Rifampin and Pyrazinamide, and 80-90% sensitive to Isoniazid.

  12. [Tuberculosis and mycobacteriosis important opportunistic disease in AIDS patients].

    Science.gov (United States)

    Zalewska-Schönthaler, N; Schönthaler-Humiecka, J; Podlasin, R; Cholewińska, G; Rzeszkowicz, T; Mikuła, T; Horban, A

    2001-01-01

    The aim of the search was investigation of tuberculosis in AIDS patients. Each year 8-9 mln people fall ill of tuberculosis and one third of them die. To the infection of tuberculosis and fast development into active state are especially exposed people with AIDS. 696 people were examined on tuberculosis most of which were AIDS patients hospitalized and cured in Hospital of Infection Diseases and Prison Hospital. 159 patients were women and 537 were men. The average age was between 25 and 45 (70%). The investigated population was characterized according to age, social and living conditions, using drugs and former contact with tuberculosis. All patients suspected of tuberculosis had chest X-rayed, sputum, BAL and pleural liquor were taken to bacteriological examination when extrapulmonary tuberculosis was suspected. The material was taken adequately to the disease process: CSF, urine, lymph nodes, peritoneal fluids, blood, stool, swabs and other. Bacteriological investigations have been carried out by fast cultivating method since 1998 and rapid genetic method since 1999. Apart from modern, fast diagnostic methods, routine bacteriological procedures were applied in tuberculosis diagnosis. More than 30% of the examined population were from bad social-living conditions, 78% had risk factors, 65% were drug users. The analysis of the tuberculosis illness from 1997 to July 2001 shows growing tendency. Nowadays it is 20% cases proved by bacteriological diagnosis. The structure of falling ill with tuberculosis has changed. Considerable increase of extrapulmonary tuberculosis was observed, 20 patients died due to tuberculosis and 8 patients due to mycobacteriosis. Resistance of M.tub.complex occurred within the range of 10% cases.

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

    OpenAIRE

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

    2016-01-01

    Background 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. Methods People treated...

  14. Altered microRNA signatures in sputum of patients with active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zhengjun Yi

    Full Text Available Role of microRNA (miRNA has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differentially expressed between tuberculosis group and controls. More miRNAs (52 out of 95 miRNAs were underexpressed than overexpressed during tuberculosis infection. Overexpression of miR-3179, miR-147 and underexpression of miR-19b-2* in TB group compared with controls were confirmed in the validation cohort. TNF-α and IL-6 levels were not significantly altered between TB group and controls. For the first time, differential expression of miRNAs in sputum was found in active pulmonary tuberculosis. The study provides rationale for identifying the role of miRNAs in the pathogenesis of pulmonary tuberculosis and indicates potential for miRNA-based therapeutic strategies.

  15. Altered microRNA signatures in sputum of patients with active pulmonary tuberculosis.

    Science.gov (United States)

    Yi, Zhengjun; Fu, Yurong; Ji, Rui; Li, Ruifang; Guan, Zhiyu

    2012-01-01

    Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differentially expressed between tuberculosis group and controls. More miRNAs (52 out of 95 miRNAs) were underexpressed than overexpressed during tuberculosis infection. Overexpression of miR-3179, miR-147 and underexpression of miR-19b-2* in TB group compared with controls were confirmed in the validation cohort. TNF-α and IL-6 levels were not significantly altered between TB group and controls. For the first time, differential expression of miRNAs in sputum was found in active pulmonary tuberculosis. The study provides rationale for identifying the role of miRNAs in the pathogenesis of pulmonary tuberculosis and indicates potential for miRNA-based therapeutic strategies.

  16. HRCT in the evaluation and diagnosis of the early/active pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Tan Gao; Liu Xueguo; Zhang Qingwen; Wang Ying; Li Zhanjun; Zhang Cuiyun; Wang Jian; He Yanli; Hong Guobin

    2003-01-01

    Objective: To evaluate the HRCT findings of early/active pulmonary tuberculosis before and after antituberculous chemotherapy. Methods: One hundred tuberculous patients were studied prospectively and they were divided into 2 groups according to the history. The diagnosis of early active pulmonary tuberculosis was based on positive acid-fast bacilli in sputum (75 patients) and changes on serial radiographs obtained during treatment (25 patients). The correlation between pathology and imaging was done in the lungs from the cadavers of five other patients who died of pulmonary tuberculosis. Results: Comparing with the presence of other HRCT findings, the presence of centrilobular lesions (93.0%), tree-in-bud appearance (76.0%), and wall thickening of bronchioles (70.0%) were most common signs in both the first group consisting of 66 patients with newly diagnosed pulmonary tuberculosis and the second group consisting of 34 patients with recent reactivation of pulmonary tuberculosis at examination by HRCT, and there was significant difference between the presence of those signs and other signs (P<0.001). Conclusion: Centrilobular lesion appeared to be the most commonly seen characteristic HRCT features of early active tuberculosis, and it may be helpful to the diagnosis and (or ) differential diagnosis if combined with other commonly seen characteristic HRCT features as well as clinical information

  17. 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...

  18. 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.

  19. Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis

    Science.gov (United States)

    Chapman, Timothy M.; Bouloc, Nathalie; Buxton, Roger S.; Chugh, Jasveen; Lougheed, Kathryn E.A.; Osborne, Simon A.; Saxty, Barbara; Smerdon, Stephen J.; Taylor, Debra L.; Whalley, David

    2012-01-01

    A high-throughput screen against PknB, an essential serine–threonine protein kinase present in Mycobacterium tuberculosis (M. tuberculosis), allowed the identification of an aminoquinazoline inhibitor which was used as a starting point for SAR investigations. Although a significant improvement in enzyme affinity was achieved, the aminoquinazolines showed little or no cellular activity against M. tuberculosis. However, switching to an aminopyrimidine core scaffold and the introduction of a basic amine side chain afforded compounds with nanomolar enzyme binding affinity and micromolar minimum inhibitory concentrations against M. tuberculosis. Replacement of the pyrazole head group with pyridine then allowed equipotent compounds with improved selectivity against a human kinase panel to be obtained. PMID:22469702

  20. 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

  1. 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

  2. In vitro and in vivo activities of the nitroimidazole TBA-354 against Mycobacterium tuberculosis.

    Science.gov (United States)

    Upton, A M; Cho, S; Yang, T J; Kim, Y; Wang, Y; Lu, Y; Wang, B; Xu, J; Mdluli, K; Ma, Z; Franzblau, S G

    2015-01-01

    Nitroimidazoles are a promising new class of antitubercular agents. The nitroimidazo-oxazole delamanid (OPC-67683, Deltyba) is in phase III trials for the treatment of multidrug-resistant tuberculosis, while the nitroimidazo-oxazine PA-824 is entering phase III for drug-sensitive and drug-resistant tuberculosis. TBA-354 (SN31354[(S)-2-nitro-6-((6-(4-trifluoromethoxy)phenyl)pyridine-3-yl)methoxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine]) is a pyridine-containing biaryl compound with exceptional efficacy against chronic murine tuberculosis and favorable bioavailability in preliminary rodent studies. It was selected as a potential next-generation antituberculosis nitroimidazole following an extensive medicinal chemistry effort. Here, we further evaluate the pharmacokinetic properties and activity of TBA-354 against Mycobacterium tuberculosis. TBA-354 is narrow spectrum and bactericidal in vitro against replicating and nonreplicating Mycobacterium tuberculosis, with potency similar to that of delamanid and greater than that of PA-824. The addition of serum protein or albumin does not significantly alter this activity. TBA-354 maintains activity against Mycobacterium tuberculosis H37Rv isogenic monoresistant strains and clinical drug-sensitive and drug-resistant isolates. Spontaneous resistant mutants appear at a frequency of 3 × 10(-7). In vitro studies and in vivo studies in mice confirm that TBA-354 has high bioavailability and a long elimination half-life. In vitro studies suggest a low risk of drug-drug interactions. Low-dose aerosol infection models of acute and chronic murine tuberculosis reveal time- and dose-dependent in vivo bactericidal activity that is at least as potent as that of delamanid and more potent than that of PA-824. Its superior potency and pharmacokinetic profile that predicts suitability for once-daily oral dosing suggest that TBA-354 be studied further for its potential as a next-generation nitroimidazole. Copyright © 2015, American

  3. 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

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

    African Journals Online (AJOL)

    Summary: Tuberculosis (TB) is of great public health burden globally especially in developing countries of Africa and Asia . Current TB regimen involves multiple therapies and of long duration leading to poor patient adherence. There is also the challenge of multidrug resistant TB. Hence, there is a need for discovery of new ...

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

    African Journals Online (AJOL)

    olayemitoyin

    standard drugs. The petri dishes were sealed with a carbon-dioxide permeable tape, left overnight in biosafety hood to allow diffusion of the extract, fractions. It was then incubated at 370C in a carbon- dioxide incubator for 4 weeks. The susceptibility of. M. tuberculosis isolates to the extract and the drugs was determined by ...

  6. Altered microRNA Signatures in Sputum of Patients with Active Pulmonary Tuberculosis

    OpenAIRE

    Yi, Zhengjun; Fu, Yurong; Ji, Rui; Li, Ruifang; Guan, Zhiyu

    2012-01-01

    Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differenti...

  7. Seroprevalence of toxoplasma-specific antibodies in patients suspected to have active toxoplasmosis: A cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Abbas Ali Eskandarian

    2014-01-01

    Full Text Available Background: The aim of this study was to investigate the presence and distribution of anti-toxoplasma-specific IgM and IgG tantibodies in patients suspected to have toxoplasmosis and investigate for any association between IgM and IgG antibodies and some toxoplasmosis risk factors as well. Materials and Methods: In a comparative cross-sectional study, 70 patients suspected to had active toxoplasmosis and 30 control volunteers, who gave informed consent, entered the study. In each group, patient age, sex, signs of appearance, education level, residency status (urban / rural, occupation, frequency of toxoplasma-specific IgG and IgM antibodies, abortion history, and some risk factors (Direct cat exposure, Occupational exposure to raw meat, and Raw vegetable consumption were recorded. The enzyme-linked immunosorbent assay (ELISA kits (EUROIMMUN®, United Kingdom were used for the evaluation of anti-toxoplasma IgG and IgM antibodies according to the manufacturer›s instructions. All analyses were done using SPSS-20. Results: The frequency of toxoplasma-specific IgG and IgM antibodies like: Direct cat exposures, Occupational exposure to raw meat, and Raw vegetable consumption were not statistically significant between the two groups (P > 0.05. The history of previous abortions in women in the toxoplasmosis-suspected group was significantly higher than that in the controls (31.4% versus 6.7%; P = 0.009. Conclusion: The frequency of specific IgM and IgG antibodies in toxoplasmosis suspected in the toxoplasmosis and control groups was not statistically significant.

  8. Impaired CXCR1-dependent oxidative defence in active tuberculosis patients.

    Science.gov (United States)

    Alaridah, Nader; Winqvist, Niclas; Håkansson, Gisela; Tenland, Erik; Rönnholm, Anna; Sturegård, Erik; Björkman, Per; Godaly, Gabriela

    2015-12-01

    Much of the pronounced host inflammatory response that occurs in tuberculosis (TB) is related to failed immunity against the invading pathogen. The G-protein coupled receptors CXCR1 and CXCR2 are implicated in important signal transduction pathways in lung inflammatory responses. We investigated the expression and function of these receptors in a simple whole blood model from 24 patients with pulmonary TB and in subjects with latent TB infection (LTBI). Healthy controls were recruited from close contacts to the pulmonary index patients. We found that pulmonary TB patients had significantly increased CXCR1 expression on blood cells compared to LTBI subjects and controls (p microRNA-223 was increased in pulmonary TB patients compared to LTBI (p tuberculosis (Mtb). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Primary isolated hepatic tuberculosis

    International Nuclear Information System (INIS)

    Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

    2013-01-01

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

  10. A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis.

    Science.gov (United States)

    Dey, Bappaditya; Dey, Ruchi Jain; Cheung, Laurene S; Pokkali, Supriya; Guo, Haidan; Lee, Jong-Hee; Bishai, William R

    2015-04-01

    Detection of cyclic-di-adenosine monophosphate (c-di-AMP), a bacterial second messenger, by the host cytoplasmic surveillance pathway (CSP) is known to elicit type I interferon (IFN) responses, which are crucial to antimicrobial defense. However, the mechanisms and role of c-di-AMP signaling in Mycobacterium tuberculosis virulence remain unclear. Here we show that resistance to tuberculosis requires CSP-mediated detection of c-di-AMP produced by M. tuberculosis and that levels of c-di-AMP modulate the fate of infection. We found that a di-adenylate cyclase (disA or dacA)-overexpressing M. tuberculosis strain that secretes excess c-di-AMP activates the interferon regulatory factor (IRF) pathway with enhanced levels of IFN-β, elicits increased macrophage autophagy, and exhibits substantial virulence attenuation in mice. We show that c-di-AMP-mediated IFN-β induction during M. tuberculosis infection requires stimulator of interferon genes (STING)-signaling. We observed that c-di-AMP induction of IFN-β is independent of the cytosolic nucleic acid receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), but cGAS nevertheless contributes substantially to the overall IFN-β response to M. tuberculosis infection. In sum, our results reveal c-di-AMP to be a key mycobacterial pathogen-associated molecular pattern (PAMP) driving host type I IFN responses and autophagy. These findings suggest that modulating the levels of this small molecule may lead to novel immunotherapeutic strategies against tuberculosis.

  11. Essential and toxic metals in serum of individuals with active pulmonary tuberculosis in an endemic region

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    Zahra Sepehri

    2017-01-01

    Full Text Available Trace elements play an important role in tuberculosis infection because their deficiencies can be associated with impaired immunity. Blood samples were collected from a total of 320 active pulmonary tuberculosis patients and healthy individuals. The serum concentrations of Zinc, Iron, Copper, Calcium, lead, Arsenic and Selenium were analyzed by atomic absorption spectrometry. The levels of trace elements were measured after 2, 4 and 6 months of anti-TB treatment initiation in TB infected groups. Compared to the control group, the concentrations of Zinc, Selenium, and Iron were significantly lower (P< 0.001 in tuberculosis patients; however, that of Arsenic, Lead, and copper was significantly higher (P< 0.001 in the serum of patients. Cu/Zn and Cu/Se ratios were also significantly higher (P< 0.001 in TB patients compared to the control group. In addition, serum concentration calcium was similar in both TB patients and healthy controls. Our results indicated that trace elements concentrations in tuberculosis patients are related to each element role in immune system. Wherever the element is essential for the pathogenesis of bacteria, its concentration will remain low; and contrariwise, when the element is toxic for the bacteria, its level will be regulated up to provide a perfect condition for bacterial growth. Keywords: Trace elements, Blood, Atomic absorption spectroscopy, Sistan, Pulmonary tuberculosis, Trace elements, Graphite furnace atomic absorption spectrometry, Sistan

  12. Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of Mycobacterium tuberculosis MazF Toxins

    Science.gov (United States)

    Nigam, Akanksha; Kumar, Sathish

    2018-01-01

    ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. PMID:29717013

  13. 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....

  14. The role of receptor-mediated T-cells activation disorders in pulmonary tuberculosis

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    Irina E. Esimova

    2017-01-01

    Full Text Available Aim. To analyze the peculiarities and mechanisms of receptor-mediated T-lymphocytes disorders in different clinical forms of pulmonary tuberculosis.Materials and мethods. The study involved 116 patients with first diagnosed infiltrative and disseminated drug-sensitive and drug-resistant pulmonary tuberculosis. The key stages in receptor-mediated activation of T-lymphocytes, isolated from blood, after their CD3/CD28-induction in vitro with addition of intracellular transport blocker were analyzed. Their immunotyping was carried out with the method of two- and threecolor flow cytofluorometry. The obtained results were statistically analyzed.Results. The breach of extracellular and intracellular stages of T-lymphocytes activation, shown by reduction in total number of CD3- and CD28-positive cells, and CD3+CD28+IL2+, CD3+CD28+IL2–, CD3+NF-kB+, CD3+NFAT2+ lymphocytes, and increase in number of CD3+CTLA4+ cells, was identified with most of their manifestations in disseminated drug-resistant pulmonary tuberculosis. It was shown that the content of CD3+AP-1+ lymphocytes is variable in drug-resistant pulmonary tuberculosis: it increases in the infiltrative form and decreases in the disseminated form.Conclusion. The results showed different mechanisms leading to a deficiency of IL-2-positive lymphocytes and T-lymphocytopenia: from “functional reserve” exhaustion of T-cells in drug-sensitive pulmonary tuberculosis to immunosuppression under the influence of suppressive cytokines (in case of the infiltrative form and inhibitory protein CTLA4 (in case of the disseminated form in drug-resistant pulmonary tuberculosis

  15. Activity of Scottish plant, lichen and fungal endophyte extracts against Mycobacterium aurum and Mycobacterium tuberculosis.

    Science.gov (United States)

    Gordien, Andréa Y; Gray, Alexander I; Ingleby, Kevin; Franzblau, Scott G; Seidel, Véronique

    2010-05-01

    With tuberculosis the leading bacterial killer worldwide and other mycobacterial diseases on the increase, the search for new antimycobacterial agents is timely. In this study, extracts from plants, lichens and fungal endophytes of Scottish provenance were screened for activity against Mycobacterium aurum and M. tuberculosis H(37)Rv. The best activity against M. aurum was observed for extracts of Juniperus communis roots and Cladonia arbuscula (MIC = 4 microg/mL), and a fungal endophyte isolated from Vaccinium myrtillus (MIC = 8 microg/mL). The best activity against M. tuberculosis was observed for extracts of C. arbuscula, Empetrum nigrum, J. communis roots, Calluna vulgaris aerial parts, Myrica gale roots and stems (93 to 99% inhibition at 100 microg/mL). Potent antitubercular activity (90 to 96% inhibition at 100 microg/mL) was also observed for the ethanol extracts of Xerocomus badius, Chalciporus piperatus, Suillus luteus and of endophytes isolated from C. vulgaris, E. nigrum, Vaccinium vitis-idaea and V. myrtillus. The results obtained this study provide, in part, some scientific basis for the traditional use of some of the selected plants in the treatment of tuberculosis. They also indicate that fungal endophytes recovered from Scottish plants are a source of antimycobacterial agents worthy of further investigation. Copyright (c) 2009 John Wiley & Sons, Ltd.

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

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    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.

  17. M. tuberculosis induces potent activation of IDO-1, but this is not essential for the immunological control of infection.

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    Antje Blumenthal

    Full Text Available Indoleamine 2,3-dioxygenesae-1 (IDO-1 catalyses the initial, rate-limiting step in tryptophan metabolism, thereby regulating tryptophan availability and the formation of downstream metabolites, including picolinic and quinolinic acid. We found that Mycobacterium tuberculosis infection induced marked upregulation of IDO-1 expression in both human and murine macrophages in vitro and in the lungs of mice following aerosol challenge with M. tuberculosis. The absence of IDO-1 in dendritic cells enhanced the activation of mycobacteria-specific T cells in vitro. Interestingly, IDO-1-deficiency during M. tuberculosis infection in mice was not associated with altered mycobacteria-specific T cell responses in vivo. The bacterial burden of infected organs, pulmonary inflammatory responses, and survival were also comparable in M. tuberculosis-infected IDO-1 deficient and wild type animals. Tryptophan is metabolised into either picolinic acid or quinolinic acid, but only picolinic acid inhibited the growth of M. tuberculosis in vitro. By contrast macrophages infected with pathogenic mycobacteria, produced quinolinic, rather than picolinic acid, which did not reduce M. tuberculosis growth in vitro. Therefore, although M. tuberculosis induces robust expression of IDO-1 and activation of tryptophan metabolism, IDO-1-deficiency fails to impact on the immune control and the outcome of the infection in the mouse model of tuberculosis.

  18. Plants and Fungal Products with Activity Against Tuberculosis

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    Marcus Vinicius Nora De Souza

    2005-01-01

    Full Text Available Tuberculosis (TB is becoming an ever more serious worldwide problem. This contagious disease kills four people every minute somewhere in the world and accounts for more than 2 million deaths per year. Due to the rapid spread of TB strains resistant to all the major anti-TB drugs on the market, and the association of TB with human immunodeficiency virus (HIV infection in AIDS, we urgently need to develop new drugs to fight against TB. In this context, due to the importance of nature in the development of new drugs, the aim of the present review is to highlight a series of new and promising anti-TB agents derived from plants and fungi discovered between 2001 and 2005.

  19. 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. ...

  20. Potential of DosR and Rpf antigens from Mycobacterium tuberculosis to discriminate between latent and active tuberculosis in a tuberculosis endemic population of Medellin Colombia.

    Science.gov (United States)

    Arroyo, Leonar; Marín, Diana; Franken, Kees L M C; Ottenhoff, Tom H M; Barrera, Luis F

    2018-01-08

    Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB. The T-cell response to a group of so-called latency (DosR-regulon-encoded) and Resuscitation Promoting (Rpf) antigens of Mtb has been proved to be significantly higher in LTBI compared to active TB across many populations, suggesting their potential use as biomarkers to differentiate latent from active TB. PBMCs from a group LTBI (n = 20) and pulmonary TB patients (PTB, n = 21) from an endemic community for TB of the city of Medellín, Colombia, were in vitro stimulated for 7 days with DosR- (Rv1737c, Rv2029c, and Rv2628), Rpf- (Rv0867c and Rv2389c), the recombinant fusion protein ESAT-6-CFP10 (E6-C10)-, or PPD-antigen. The induced IFNγ levels detectable in the supernatants of the antigen-stimulated cells were then used to calculate specificity and sensitivity in discriminating LTBI from PTB, using different statistical approaches. IFNγ production in response to DosR and Rpf antigens was significantly higher in LTBI compared to PTB. ROC curve analyses of IFNγ production allowed differentiation of LTBI from PTB with areas under the curve higher than 0.70. Furthermore, Multiple Correspondence Analysis (MCA) revealed that LTBI is associated with higher levels of IFNγ in response to the different antigens compared to PTB. Analysis based on decision trees showed that the IFNγ levels produced in response to Rv2029c was the leading variable that best-classified disease status. Finally

  1. 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.

  2. 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.

  3. 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.

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

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    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.

  5. Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

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    Kiyohiko Izumi

    Full Text Available Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots.Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed.Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2% were general inhabitants, 42 (6.5% were foreign-born people, and 184 were homeless people (28.6%. The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households.Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission

  6. Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

    Science.gov (United States)

    Izumi, Kiyohiko; Ohkado, Akihiro; Uchimura, Kazuhiro; Murase, Yoshiro; Tatsumi, Yuriko; Kayebeta, Aya; Watanabe, Yu; Ishikawa, Nobukatsu

    2015-01-01

    Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed. Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission dynamics in an

  7. Activation of MMPs in Macrophages by Mycobacterium tuberculosis via the miR-223-BMAL1 Signaling Pathway.

    Science.gov (United States)

    Lou, Jun; Wang, Yongli; Zhang, Zhimin; Qiu, Weiqiang

    2017-12-01

    An interaction between Mycobacterium tuberculosis and macrophages constitutes an essential step in tuberculosis development, as macrophages exert both positive and negative effects on M. tuberculosis-triggered organ lesions. In this study, we focused on the regulation of the expression of matrix metalloproteinases (MMPs), which is responsible for lung matrix degradation and bacteria dissection, in macrophages following M. tuberculosis infection. Female BALB/c mice were intravenously injected with the M. tuberculosis strain H37Rv at 0 h zeitgeber time (ZT0) or 12 h zeitgeber time (ZT12). The expression and activity of MMP-1, -2, -3, and -9 in lungs and spleens were then evaluated. In vitro, peritoneal macrophages were harvested at ZT0 or at ZT12 and infected with 10 MOI M. tuberculosis. The expression of MMPs, microRNA-223 and BMAL1 was analyzed by qRT-PCR and/or Western blot. The binding of BMAL1 3'-UTR by miR-223 was confirmed by luciferase activity assay. Additionally, wild-type BMAL1 or NLS mut BMAL1 plasmids were transfected to evaluate the effect of BMAL1 on MMPs. The results showed a differential expression of MMPs in mice tissues infected at different times. M. tuberculosis infection caused enhanced MMP-1, -9, and miR-223 expression, with inhibited BMAL1 expression. MiR-223 modulated BMAL1 expression via the direct binding of BMAL1 3'-UTR. Furthermore, wild-type BMAL1 other than NLS mut BMAL1 attenuated MMPs expression in M. tuberculosis-infected macrophages. Overall, this study demonstrated a potential involvement of circadian rhythm in MMP activation by M. tuberculosis in macrophages. J. Cell. Biochem. 118: 4804-4812, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Tuberculosis among atomic bomb survivors. Study of autopsy cases

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, T [H.ma Atomic Bomb Hospital (Japan); Matsushita, Hiroshi

    1980-03-01

    Effects of atomic bomb on tuberculosis among atomic bomb survivors necropsied after 1956 when Atomic Bomb Hospital was opened were observed statistically and the following results were obtained. The morbidity of tuberculosis in the group exposed within 2 km from the hypocenter was higher than that of the control group, but there was not a significant difference between the groups. The morbidity of all types of tuberculosis was significantly higher in the group exposed within 2 km from the hypocenter than in the control group. The morbidity of tuberculosis tended to decrease in both exposed and non-exposed groups with time. However, the morbidity of miliary or active tuberculosis has tended to rise in the exposed since 1975. The morbidity in young a-bomb survivors exposed within 2 km was higher than that in those of other groups, but there was not a difference in the morbidity among the aged. The higher the rate of complication of active tuberculosis with stomach cancer or acute myelocytic leukemia or liver cirrhosis, the nearer the places of exposure were to the hypocenter. Out of 26 patients with miliary tuberculosis, 6 were suspected to have leukemia while they were alive and were suggested to have leukemoid reaction by autopsy. They all were a-bomb survivors, and 4 of them were exposed within 2 km from the hypocenter.

  9. Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.

    Science.gov (United States)

    Fu, Yurong; Yi, Zhengjun; Li, Jianhua; Li, Ruifang

    2014-03-01

    The mechanisms of latent tuberculosis (TB) infection remain elusive. Roles of microRNA (miRNA) have been highlighted in pathogen-host interactions recently. To identify miRNAs involved in the immune response to TB, expression profiles of miRNAs in CD4(+) T cells from patients with latent TB, active TB and healthy controls were investigated by microarray assay and validated by RT-qPCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyse the significant functions and involvement in signalling pathways of the differentially expressed miRNAs. To identify potential target genes for miR-29, interferon-γ (IFN-γ) mRNA expression was measured by RT-qPCR. Our results showed that 27 miRNAs were deregulated among the three groups. RT-qPCR results were generally consistent with the microarray data. We observed an inverse correlation between miR-29 level and IFN-γ mRNA expression in CD4(+) T cells. GO and KEGG pathway analysis showed that the possible target genes of deregulated miRNAs were significantly enriched in mitogen-activated protein kinase signalling pathway, focal adhesion and extracellular matrix receptor interaction, which might be involved in the transition from latent to active TB. In all, for the first time, our study revealed that some miRNAs in CD4(+) T cells were altered in latent and active TB. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in TB. The study might help to improve understanding of the relationship between miRNAs in CD4(+) T cells and TB, and laid an important foundation for further identification of the underlying mechanisms of latent TB infection and its reactivation. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. DNA repair systems and the pathogenesis of Mycobacterium tuberculosis: varying activities at different stages of infection

    OpenAIRE

    Gorna, AE; Bowater, RP; Dziadek, J

    2010-01-01

    Mycobacteria, including most of all MTB (Mycobacterium tuberculosis), cause pathogenic infections in humans and, during the infectious process, are exposed to a range of environmental insults, including the host's immune response. From the moment MTB is exhaled by infected individuals, through an active and latent phase in the body of the new host, until the time they reach the reactivation stage, MTB is exposed to many types of DNA-damaging agents. Like all cellular organisms, MTB has effici...

  11. Diterpenes Synthesized from the Natural Serrulatane Leubethanol and Their in Vitro Activities against Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Ricardo Escarcena

    2015-04-01

    Full Text Available Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity against the H37Rv strain of Mycobacterium tuberculosis. Some compounds showed antimycobacterial selectivity indices higher than leubethanol.

  12. 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

    2018-04-01

    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.

  13. 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 tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without 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. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. 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.

  15. Urease Activity Represents an Alternative Pathway for Mycobacterium tuberculosis Nitrogen Metabolism

    Science.gov (United States)

    Lin, Wenwei; Mathys, Vanessa; Ang, Emily Lei Yin; Koh, Vanessa Hui Qi; Martínez Gómez, Julia María; Ang, Michelle Lay Teng; Zainul Rahim, Siti Zarina; Tan, Mai Ping; Pethe, Kevin

    2012-01-01

    Urease represents a critical virulence factor for some bacterial species through its alkalizing effect, which helps neutralize the acidic microenvironment of the pathogen. In addition, urease serves as a nitrogen source provider for bacterial growth. Pathogenic mycobacteria express a functional urease, but its role during infection has yet to be characterized. In this study, we constructed a urease-deficient Mycobacterium tuberculosis strain and confirmed the alkalizing effect of the urease activity within the mycobacterium-containing vacuole in resting macrophages but not in the more acidic phagolysosomal compartment of activated macrophages. However, the urease-mediated alkalizing effect did not confer any growth advantage on M. tuberculosis in macrophages, as evidenced by comparable growth profiles for the mutant, wild-type (WT), and complemented strains. In contrast, the urease-deficient mutant exhibited impaired in vitro growth compared to the WT and complemented strains when urea was the sole source of nitrogen. Substantial amounts of ammonia were produced by the WT and complemented strains, but not with the urease-deficient mutant, which represents the actual nitrogen source for mycobacterial growth. However, the urease-deficient mutant displayed parental colonization profiles in the lungs, spleen, and liver in mice. Together, our data demonstrate a role for the urease activity in M. tuberculosis nitrogen metabolism that could be crucial for the pathogen's survival in nutrient-limited microenvironments where urea is the sole nitrogen source. Our work supports the notion that M. tuberculosis virulence correlates with its unique metabolic versatility and ability to utilize virtually any carbon and nitrogen sources available in its environment. PMID:22645285

  16. Serological diagnosis for active tuberculosis in Malaysian population: Comparison of four protein candidate

    Directory of Open Access Journals (Sweden)

    Siti Suraiya

    2012-05-01

    Full Text Available Objective: To asses the ability of 4 types of Mtb proteins-ESAT6, SCWP, MAN and Ag85 to serve as indicator for active tuberculosis among Malaysian population. Methods: Sera from 90 individuals, 60 from confirmed pulmonary tuberculosis patients and 30 healthy PPD negative individuals were tested for presence of anti-IgG and anti IgA by ELISA assay. Result: Mean concentration of IgG and IgA were higher in patients compared to healthy Positivity of the ELISA test were calculated, taking the cut off value at mean +2 SD of healthy sera. The sensitivity of the ELISA IgA assay for ESAT 6, SCWP, MAN and Ag85 were 81.1%, 83.3%, 11.7% and 53.3% respectively. The sensitivity of the ELISA IgG asay for ESAT 6, SCWP, MAN and Ag85 were 71.0%, 71.0%, 71.0% and 21.0% respectively. Conclusion: Detectionof IgA against SCWP promised a good indicator for active tuberculosis infection among Malaysian.

  17. Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide

    Directory of Open Access Journals (Sweden)

    Isidro Palos

    2018-06-01

    Full Text Available Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the efficacy of this compound, this study evaluates methyl, ethyl, isopropyl, and n-propyl esters of quinoxaline 1,4-di-N-oxide derivatives in vitro against Mycobacterium tuberculosis (pansusceptible and monoresistant strains. Additionally, the inhibitory effect of esters of quinoxaline 1,4-di-N-oxide on M. tuberculosis gyrase supercoiling was examined, and a stability analysis by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS was also carried out. Results showed that eight compounds (T-007, T-018, T-011, T-069, T-070, T-072, T-085 and T-088 had an activity similar to that of the reference drug isoniazid (minimum inhibitory concentration (MIC = 0.12 µg/mL with an effect on nonreplicative cells and drug monoresistant strains. Structural activity relationship analysis showed that the steric effect of an ester group at 7-position is key to enhancing its biological effects. Additionally, T-069 showed a high stability after 24 h in human plasma at 37 °C.

  18. Evaluation of coexistence of cancer and active tuberculosis; 16 case series

    Directory of Open Access Journals (Sweden)

    Beyhan Çakar

    Full Text Available Introduction: Tuberculosis is an important risk factor for cancer. Pulmonary TB and lung cancer(LC may mimic each other especially in the aspect of the clinical and radiological features. The aim of the study was to evaluate the features and risk factors of cases with coexistence cancer and active TB. Methodology: We retrospectively reviewed the medical records of patients with coexisting TB and cancer a period from 2009 to 2014. We evaluated demographic data, the ways diagnosis of TB cases, the location of TB and cancer, TB treatment results of the cases. Results: We recorded 374 TB cases in our dyspensary at this study period. In 16 (4% of these cases, a coexistence of cancer and TB was detected. The male/female ratio was 12/4. The mean age was 62,12 ± 15,13 years. There were TST results except three cases. There were ten pulmonary TB and six extra-pulmonary TB (four peripheral lymphadenopathy TB, one abdominal TB lymphadenopathy and one salivary gland TB. Cancer types were as follows; eight lung cancer, two breast cancer, one base of tongue, one endometrium cancer, one hypopharyngeal cancer, one stomach cancer, one bladder cancer and one maxillary cancer. Diagnosis of all cases was confirmed by bacteriologic and/or histopathological examination. Squamous cell carcinoma was the most common type of cancers. This rate was 9/16. All TB cases were new. There were risk factors out of two case in the cases. Five cases were died during TB treatment. Others completed TB treatment without any complication. Conclusions: In our study, the coexistence of LC and pulmonary TB was more common. The local immunity is deteriorated in cancer cases. If there is pulmonary infiltrates in lung or peripheral lymphadenopathy, we must search tuberculosis too out of metastatic lesion and other infectious diseases. We should not make delay in the diagnosis of active TB in cancer cases. Keywords: Coexistent, Cancer, Tuberculosis, Tuberculosis treatment

  19. Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bingfen Yang

    Full Text Available CD244 (2B4 is a member of the signaling lymphocyte activation molecule (SLAM family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+ T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+ T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M. tuberculosis antigen-specific CD4(+ T cells compared with latent infection individuals. The frequencies of CD244/2B4-expressing antigen-specific CD4(+ T cells were significantly higher in retreatment active TB patients than in new active TB patients. Compared with CD244/2B4-dull and -middle CD4(+ T cells, CD244/2B4-bright CD4(+ T cell subset had significantly reduced expression of IFN-γ, suggesting that CD244/2B4 expression may modulate IFN-γ production in M. tuberculosis antigen-responsive CD4(+ T cells. Activation of CD244/2B4 signaling by cross-linking led to significantly decreased production of IFN-γ. Blockage of CD244/2B4 signaling pathway of T cells from patients with active TB resulted in significantly increased production of IFN-γ, compared with isotype antibody control. In conclusion, CD244/2B4 signaling pathway has an inhibitory role on M. tuberculosis antigen-specific CD4(+ T cell function.

  20. The prevalence of pulmonary tuberculosis in Jeonbug Province

    International Nuclear Information System (INIS)

    Rhee, S. J.; Moon, M. C.; Song, H. Y.; Choi, K. C.

    1981-01-01

    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%

  1. Assessment of an ELISA for serodiagnosis of active pulmonary tuberculosis in a Cuban population

    Directory of Open Access Journals (Sweden)

    Julio Cesar Ayala

    2015-10-01

    Full Text Available Objective: To explore the serodiagnostic potential of the five recombinant Mycobacterium tuberculosis antigens CFP-10 (Rv3874, ESAT-6 (Rv3875, APA (Rv1860, PstS-1 (Rv0934, Ag85A (Rv3804c and their combination in a Cuban population with active pulmonary tuberculosis. Methods: The serodiagnostic potential of the recombinant antigens rESAT-6, rCFP-10, rAPA, rPstS-1 produced in Escherichia coli, rAg85A produced in Streptomyces lividans and the combination of the five proteins was evaluated by an indirect ELISA. Humoral immune response was analysed in a group of 140 patients with active pulmonary tuberculosis (smear-, Mantoux- and culture-positive and in a control group consisting of 34 bacillus CalmetteGuerin vaccinated, Mantoux-negative, healthy subjects. Results: With the exception of CFP-10, the use of the separate recombinant antigens or the antigenic cocktail in ELISA-based serodiagnosis resulted in a significant difference in the mean optical densitiy values between sera of patients and healthy subjects. The highest sensitivity of the assay using single antigens, being 58.57%, was achieved with rPstS-1 compared to 27.14% with rCFP-10, 31.65% with Ag85A, 42.86% with rAPA and 44.29% with rESAT-6. Single antigen ELISAs provided high specificity values ranging from 94.12% to 97.06%. A cocktail of the aforementioned antigens increased the sensitivity to 87.14% and the specificity to 97.06%. Conclusions: An ELISA using a multi-antigen mix containing recombinant immuno-dominant antigens of Mycobacterium tuberculosis, namely, rCFP-10, rESAT-6, rAPA, rPstS-1 and rAg85, increases the sensitivity and specificity compared with that using the single antigens and shows potential as a complementary tool for the diagnosis of active pulmonary tuberculosis in Cuba.

  2. 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.

  3. Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates.

    Science.gov (United States)

    Balganesh, Meenakshi; Dinesh, Neela; Sharma, Sreevalli; Kuruppath, Sanjana; Nair, Anju V; Sharma, Umender

    2012-05-01

    Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in Mycobacterium tuberculosis, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and l-phenylalanyl-l-arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by Rv1218c, and the SMR (small multidrug resistance) class, encoded by Rv3065, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by Rv0849 and Rv1258c also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT M. tuberculosis cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of M. tuberculosis play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of Rv0849, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.

  4. [Cost-benefit analysis of the active screening of pulmonary tuberculosis in a recluse population entering prison].

    Science.gov (United States)

    Martín, V; Domínguez, A; Alcaide, J

    1997-01-01

    In spanish prisons, tuberculosis is a serious problem of public health and health authorities don't take it seriously. To prove the efficiency of pulmonary tuberculosis case-finding on arrival at prison in order to get location resources in this activity. Cost-benefit analysis of a case-finding program compared with to wait for diagnostic to illness. The sensitivity of test was fixed in 80% and the specificity in 99.99%. The cost was based on market prices. Sensitivity analysis was done in every variables as well as tridimensional analysis in those one of more influence. The case-finding was efficient on prevalences of tuberculosis over 5 per mil. Its efficiency was hardly affected by discount social rates or the sensitivity of diagnostic tests. The prevalence of illness, the cost of diagnostic activities as well as the success of treatment and the specificity of diagnostic tests used had as influence on the efficiency model. The tridimensional analysis proved that the case-finding of pulmonary tuberculosis has efficiency on low prevalences (1 per thousand), provided the number of people cured is a 5% higher than the alternative one and the costs of case-finding less than 1,000 pesetas per subject. The case-finding pulmonary tuberculosis on arrival at prisons is of high efficiency. In a cost-opportunity situation (location of available resources, penitentiary and extrapenitentiary) the program is very efficacious taking into account the fact of higher prevalence of pulmonary tuberculosis in this people.

  5. 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.

  6. Preliminary study on fractions' activities of red betel vine (Piper crocatum Ruiz & Pav) leaves ethanol extract toward Mycobacterium tuberculosis

    Science.gov (United States)

    Rachmawaty, Farida Juliantina; Julianto, Tatang Shabur; Tamhid, Hady Anshory

    2018-04-01

    This research aims to identify the antimycobacterial activity of fraction of red betel vine leaves ethanol extract (methanol fraction, ethyl acetate, and chloroform) toward M. tuberculosis. Red betel vine leaves ethanol extract was made with maceration method using ethanol solvent 70%. Resulted extract was then fractionated using Liquid Vacuum Chromatography (LVC) with methanol, ethyl acetate, and chloroform solvent. Each fractionation was exposed to M. tuberculosis with serial dilution method. Controls of fraction, media, bacteria, and isoniazid as standard drug were included in this research. The group of compound from the most active fraction was then identified. The research found that the best fraction for antimycobacterial activity toward M. tuberculosisis chloroform fraction. The compound group of chloroform fraction was then identified. The fraction contains flavonoid, tannin, alkaloid, and terpenoid. The fraction of methanol, ethyl acetate, and chloroform from red betel vine leaves has antimycobacterial activity toward M. tuberculosis. Chloroform fraction has the best antimycobacterial activity and it contains flavonoid, tannin, alkaloid, and terpenoid.

  7. Anti-tuberculosis activity of -lactam antibiotics: prospects for the ...

    African Journals Online (AJOL)

    This review is prepared to show results on the anti-TB activity of -lactam antibiotics. -Lactams are among the oldest drugs with little or no side effects. Both in vitro studies and clinical data indicate that -lactams have a promising activity for use in the management of MDR-TB. More studies are required to define the interaction ...

  8. Analysis of Factors Influencing Diagnostic Accuracy of T-SPOT.TB for Active Tuberculosis in Clinical Practice.

    Science.gov (United States)

    Zhang, Lifan; Shi, Xiaochun; Zhang, Yueqiu; Zhang, Yao; Huo, Feifei; Zhou, Baotong; Deng, Guohua; Liu, Xiaoqing

    2017-08-10

    T-SPOT.TB didn't perform a perfect diagnosis for active tuberculosis (ATB), and some factors may influence the results. We did this study to evaluate possible factors associated with the sensitivity and specificity of T-SPOT.TB, and the diagnostic parameters under varied conditions. Patients with suspected ATB were enrolled prospectively. Influencing factors of the sensitivity and specificity of T-SPOT.TB were evaluated using logistic regression models. Sensitivity, specificity, predictive values (PV), and likelihood ratios (LR) were calculated with consideration of relevant factors. Of the 865 participants, 205 (23.7%) had ATB, including 58 (28.3%) microbiologically confirmed TB and 147 (71.7%) clinically diagnosed TB. 615 (71.7%) were non-TB. 45 (5.2%) cases were clinically indeterminate and excluded from the final analysis. In multivariate analysis, serous effusion was the only independent risk factor related to lower sensitivity (OR = 0.39, 95% CI: 0.18-0.81) among patients with ATB. Among non-TB patients, age, TB history, immunosuppressive agents/glucocorticoid treatment and lymphocyte count were the independent risk factors related to specificity of T-SPOT.TB. Sensitivity, specificity, PV+, PV-, LR+ and LR- of T-SPOT.TB for diagnosis of ATB were 78.5%, 74.1%, 50.3%, 91.2%, 3.0 and 0.3, respectively. This study suggests that influencing factors of sensitivity and specificity of T-SPOT.TB should be considered for interpretation of T-SPOT.TB results.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Mycobacterium tuberculosis: Active disease and latent infection in a renal transplant cohort.

    Science.gov (United States)

    Rafiei, Nastaran; Williams, Jackie; Mulley, William R; Trauer, James M; Jenkin, Grant A; Rogers, Benjamin A

    2018-04-16

    Tuberculosis (TB) is a serious opportunistic infection in renal transplant recipients associated with high mortality. Screening and treatment of latent Mycobacterium tuberculosis infection (LTBI) offers an opportunity to prevent subsequent active disease. We retrospectively reviewed the records of all adult patients who underwent renal transplantation at our centre from 2005 to 2014 to assess current screening practices, the risks for and burden of active TB. A total of 660 individuals underwent renal transplantation during this period, totalling 3647 person years of follow up. Three patients were diagnosed with active TB after renal transplant, resulting in an incidence of 82 per 100,000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in high TB incidence countries and 89 (13.5%) had an interferon gamma release assay (IGRA) at any point. Individuals born in high TB risk countries had a much higher incidence of active TB (530 per 100,000 person-years). Ten individuals had positive IGRA tests, of whom two were treated for active TB, two received chemoprophylaxis and six were not treated. In the absence of formal guidelines, IGRA-based screening for LTBI was infrequently performed. Our data suggests that screening and treatment of renal transplant recipients born in high incidence countries is an important preventive measure. This article is protected by copyright. All rights reserved.

  11. [Managment of tuberculosis in an University of Campania].

    Science.gov (United States)

    Uccello, R; Monaco, M G L; Feola, D; Garzillo, E M; Muoio, M; Sannolo, N; Lamberti, M

    2012-01-01

    Tuberculosis (TBC) is an infectious disease with the highest mortality and morbidity by single pathogen, affecting about one third of worldwide population. Although Mantoux test is the most used, IGRA (Interferon-gamma Release Assays) tests seem to give good results for presumptive diagnosis of active or latent tuberculosis. From June 2011 to June 2012 we made about 1,000 visits for TBC prevention among the exposed to biological risks of our University. The management of suspected latent or active tuberculosis infection was carried out in collaboration with the pulmonologist, assessing the risk of contagion among exposed or affected operators. Health surveillance protocol and judgements of suitability for specific task were made not only in consideration of worker health, but also considerating the possible risk for patients, since this disease is a major problem for public health.

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

    Science.gov (United States)

    Soh, Avril Zixin; Pan, An; Chee, Cynthia Bin Eng; Wang, Yee-Tang; Yuan, Jian-Min; Koh, Woon-Puay

    2017-05-25

    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.

  13. The role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs.

    Science.gov (United States)

    Bax, Hannelore I; Bakker-Woudenberg, Irma A J M; de Vogel, Corné P; van der Meijden, Aart; Verbon, Annelies; de Steenwinkel, Jurriaan E M

    2017-07-01

    Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. A novel clinical sign in intraocular tuberculosis: Active chorioretinitis within chorioretinal atrophy

    OpenAIRE

    Avinash Pathengay; Bhavik Panchal; Himadri Choudhury; Soumyava Basu; Nidhi Relhan; Harry W. Flynn, Jr.

    2017-01-01

    Purpose: To report a novel clinical sign in patients with intraocular tuberculosis. The current study is an observational consecutive case series of patients diagnosed with intraocular tuberculosis managed at a tertiary eye care centre from June 1, 2012 to December 31, 2015. Observations: The diagnosis of intraocular tuberculosis was made in 6 patients based on ocular features suggestive of tuberculosis along with a positive tuberculin skin testing and chest X-ray consistent with tuberculo...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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...

  17. Tuberculosis and nutrition

    Directory of Open Access Journals (Sweden)

    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.

  18. [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.

  19. Current features of primary tuberculosis on medical imaging based on a series of fourteen cases

    International Nuclear Information System (INIS)

    Ouzidane, L.; Adamsbaum, C.; Cohen, P.A.; Kalifa, G.; Gendrel, D.

    1995-01-01

    Active pulmonary tuberculosis, a source of contamination, is currently undergoing a recrudescence in developed countries, particularly in clinical contexts of immuno-depression. The authors report a retrospective series of 14 cases of primary tuberculosis in a paediatric population (7 girls and 7 boys) with a mean age of 3.5 years (range: 4 months - 16 years) observed over a 3-year period. After reviewing the current radiological features of patent primary tuberculosis, the authors emphasize the contribution of chest CT scan in latent forms with a normal chest x-ray and a difficult bacteriological diagnosis. Imaging remains an essential tool in early diagnosis, therapeutic management and active surveillance of this form. The authors propose a decisional flow-chart in the case of suspected primary tuberculosis in children. (authors). 20 refs., 8 figs

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins.

    Science.gov (United States)

    Talavera-Paulín, M; García-Morales, L; Ruíz-Sánchez, B P; Caamal-Ley, Á D; Hernández-Solis, A; Ramírez-Casanova, E; Cicero-Sabido, R; Espitia, C; Helguera-Repetto, C; González-Y-Merchand, J A; Flores-Mejía, R; Estrada-Parra, S; Estrada-García, I; Chacón-Salinas, R; Wong-Baeza, I; Serafín-López, J

    2016-12-01

    Mexico City, Mexico. To identify proteins synthetised by Mycobacterium tuberculosis in hypoxic culture, which resemble more closely a granuloma environment than aerobic culture, and to determine if they are recognised by antibodies from patients with active pulmonary tuberculosis (PTB). Soluble extracts from M. tuberculosis H37Rv cultured under aerobic or hypoxic conditions were analysed using two-dimensional polyacrylamide gel electrophoresis, and proteins over-expressed under hypoxia were identified by mass spectrometry. The presence of immunoglobulin (Ig) G, IgA and IgM antibodies against these proteins was determined in the serum of 42 patients with active PTB and 42 healthy controls. We selected three M. tuberculosis H37Rv proteins (alpha-crystallin protein [Acr, Rv2031c], universal stress protein Rv2623 and isocitrate lyase [ICL, RV0467]) that were over-expressed under hypoxia. Titres of anti-Acr and anti-ICL IgA antibodies were higher in patients than in healthy controls, with an area under the receiver operating characteristic curve of 0.71 for anti-ICL IgA antibodies. ICL could be used in combination with other M. tuberculosis antigens to improve the sensitivity and specificity of current serological TB diagnostic methods.

  2. A Method for Extracting Suspected Parotid Lesions in CT Images using Feature-based Segmentation and Active Contours based on Stationary Wavelet Transform

    Science.gov (United States)

    Wu, T. Y.; Lin, S. F.

    2013-10-01

    Automatic suspected lesion extraction is an important application in computer-aided diagnosis (CAD). In this paper, we propose a method to automatically extract the suspected parotid regions for clinical evaluation in head and neck CT images. The suspected lesion tissues in low contrast tissue regions can be localized with feature-based segmentation (FBS) based on local texture features, and can be delineated with accuracy by modified active contour models (ACM). At first, stationary wavelet transform (SWT) is introduced. The derived wavelet coefficients are applied to derive the local features for FBS, and to generate enhanced energy maps for ACM computation. Geometric shape features (GSFs) are proposed to analyze each soft tissue region segmented by FBS; the regions with higher similarity GSFs with the lesions are extracted and the information is also applied as the initial conditions for fine delineation computation. Consequently, the suspected lesions can be automatically localized and accurately delineated for aiding clinical diagnosis. The performance of the proposed method is evaluated by comparing with the results outlined by clinical experts. The experiments on 20 pathological CT data sets show that the true-positive (TP) rate on recognizing parotid lesions is about 94%, and the dimension accuracy of delineation results can also approach over 93%.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. High utility of active tuberculosis case finding in an Ethiopian prison.

    Science.gov (United States)

    Merid, Y; Woldeamanuel, Y; Abebe, M; Datiko, D G; Hailu, T; Habtamu, G; Assefa, G; Kempker, R R; Blumberg, H M; Aseffa, A

    2018-05-01

    Hawassa Prison, Southern Region of Ethiopia. To determine the burden of pulmonary tuberculosis (TB) using active case finding among prisoners. In this cross-sectional study, prisoners were screened for TB using a symptom screen. Those with cough of 2 weeks had spot and morning sputum samples collected for acid-fast bacilli (AFB) smear microscopy and molecular diagnostic testing (Xpert® MTB/RIF). Among 2068 prisoners, 372 (18%) had a positive cough screen. The median age of these 372 persons was 23 years, 97% were male and 63% were from urban areas. Among those with a positive symptom screen, 8 (2%) were AFB sputum smear-positive and 31 (8%) were Xpert-positive. The point prevalence of pulmonary TB at the prison was 1748 per 100 000 persons. In multivariate analysis, persons with cough >4 weeks were more likely to have TB (OR 3.34, 95%CI 1.54-7.23). A high prevalence of TB was detected among inmates at a large Ethiopian prison. Active case finding using a cough symptom screen in combination with Xpert had high utility, and has the potential to interrupt transmission of Mycobacterium tuberculosis in correctional facilities in low- and middle-income, high-burden countries.

  6. 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.

  7. How to optimize tuberculosis case finding: explorations for Indonesia with a health system model

    Directory of Open Access Journals (Sweden)

    Mahendradhata Yodi

    2009-06-01

    Full Text Available Abstract Background A mathematical model was designed to explore the impact of three strategies for better tuberculosis case finding. Strategies included: (1 reducing the number of tuberculosis patients who do not seek care; (2 reducing diagnostic delay; and (3 engaging non-DOTS providers in the referral of tuberculosis suspects to DOTS services in the Indonesian health system context. The impact of these strategies on tuberculosis mortality and treatment outcome was estimated using a mathematical model of the Indonesian health system. Methods The model consists of multiple compartments representing logical movement of a respiratory symptomatic (tuberculosis suspect through the health system, including patient- and health system delays. Main outputs of the model are tuberculosis death rate and treatment outcome (i.e. full or partial cure. We quantified the model parameters for the Jogjakarta province context, using a two round Delphi survey with five Indonesian tuberculosis experts. Results The model validation shows that four critical model outputs (average duration of symptom onset to treatment, detection rate, cure rate, and death rate were reasonably close to existing available data, erring towards more optimistic outcomes than are actually reported. The model predicted that an intervention to reduce the proportion of tuberculosis patients who never seek care would have the biggest impact on tuberculosis death prevention, while an intervention resulting in more referrals of tuberculosis suspects to DOTS facilities would yield higher cure rates. This finding is similar for situations where the alternative sector is a more important health resource, such as in most other parts of Indonesia. Conclusion We used mathematical modeling to explore the impact of Indonesian health system interventions on tuberculosis treatment outcome and deaths. Because detailed data were not available regarding the current Indonesian population, we relied on expert

  8. 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....

  9. Vitamin D status did not related to calcium status in active tuberculosis patients in North Sumatera, Indonesia

    Science.gov (United States)

    Keumala Sari, Dina; Khairina Arrasyid, Nurfida

    2018-03-01

    Background: Tuberculosis is one of the highest mortality caused in a tropical country with abundant sunlight such Indonesia. Vitamin D and calcium plays important roles in tuberculosis pathogenesis. Objective:We sought to determine whether there is an association between vitamin D status and calcium status in tuberculosis patients. Design: We conducted a cross-sectional study of 32 man and women aged 18-60 years with active tuberculosis in North Sumatera, Indonesia. Parameters were 25(OH)D and calcium serum level, body mass index, fat mass, and others lifestyles factors also assessed. The association was analysis using chi-square or fischer test. Results: the mean of study subjects age were 37.2±14.9 years old and BMI were 20.8±4.4 kg/m2 There were 81.2% subjects categorized into vitamin D deficiency-insufficiency and 18.8% categorized into vitamin D sufficiency. There were 29% subjects categorized into normal calcium level, and 3% were hypocalcemia. Based on food recall analysis, there were found lower vitamin D and calcium intake. There is no association between vitamin D and calcium classification. Conclusions: based on this result, although there is no association between vitamin D and calcium, but there could be altered by lower food intake and tuberculosis progression.

  10. Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

    Science.gov (United States)

    Scordo, Julia M; Knoell, Daren L; Torrelles, Jordi B

    2016-01-01

    Tuberculosis (TB) is a disease that kills one person every 18 s. TB remains a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure, which influence the extent of infection. We further discuss how the M.tb-alveolar epithelium interaction instigates cell-to-cell crosstalk that regulates the immune balance between a proinflammatory and an immunoregulatory state, thereby prohibiting or allowing the establishment of infection. We propose that consideration of alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. © 2015 S. Karger AG, Basel.

  11. Alveolar epithelial cells in Mycobacterium tuberculosis infection: Active Players or Innocent Bystanders

    Science.gov (United States)

    Scordo, Julia M.; Knoell, Daren L.; Torrelles, Jordi B.

    2015-01-01

    Tuberculosis (TB) is a disease that kills one person every 18 seconds. TB remains a global threat due to the emergence of drug resistance Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following sero-conversion and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure that influence the extent of infection. We further discuss how the M.tb-alveolar epithelia interaction instigate cell to cell crosstalk that regulates immune balance between a pro-inflammatory or immunoregulatory state thereby prohibiting or allowing the establishment of infection. We propose that consideration of the alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. PMID:26384325

  12. 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.

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

    International Nuclear Information System (INIS)

    Pavan, Fernando Rogerio; Leite, Clarice Queico Fujimura

    2009-01-01

    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 μg/mL) and their fractions (MIC values ranging from 39 to above 250 μg/mL). The better MIC result of 39 μg/mL was associated with two fractions that contain bigger amounts of 5,7-dihydroxy-6, 8-di-C-methylflavanone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone. These compounds exhibited MICs >250 and 62.5 μg/mL, respectively, while their mixtures showed values ranging from 62.5 to 7.8 μg/mL, demonstrating a synergism between them. (author)

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

    International Nuclear Information System (INIS)

    Uzum, Kazim; Karahan, Okkes I.; Dogan, Sukru; Coskun, Abdulhakim; Topcu, Faik

    2003-01-01

    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

  15. Low sputum smear positive tuberculosis among pulmonary ...

    African Journals Online (AJOL)

    Low sputum smear positive tuberculosis among pulmonary tuberculosis suspects in a tertiary hospital in Mwanza, Tanzania. ... The risk factors among smear positive TB patients were co-illness (32.5%), previous history of TB (7.5%) and history of positive TB contact (4.7%). These findings also show that as CD4+ T Cells ...

  16. The endothelial protein C receptor and activated protein C play a limited role in host defense during experimental tuberculosis

    NARCIS (Netherlands)

    Kager, Liesbeth M.; Roelofs, Joris J. T. H.; de Vos, Alex F.; Wieland, Catharina W.; Schouten, Marcel; Meijers, Joost C. M.; Isermann, Berend; van't Veer, Cornelis; Esmon, Charles T.; van der Poll, Tom

    2013-01-01

    The protein C (PC) system is an important regulator of both coagulation and inflammation. Activated PC (APC), together with its receptor the endothelial protein C receptor (EPCR), has anticoagulant and anti-inflammatory properties. During tuberculosis (TB), a devastating chronic pulmonary disease

  17. 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

  18. 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.

  19. 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 ...

  20. Tuberculosis (TB)

    Science.gov (United States)

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

  1. The capsule endoscopy "suspected blood indicator" (SBI) for detection of active small bowel bleeding: no active bleeding in case of negative SBI.

    Science.gov (United States)

    Tal, Andrea Oliver; Filmann, Natalie; Makhlin, Konstantin; Hausmann, Johannes; Friedrich-Rust, Mireen; Herrmann, Eva; Zeuzem, Stefan; Albert, Jörg G

    2014-09-01

    Capsule endoscopy (CE) is the gold standard to diagnose small bowel bleeding. The "suspected blood indicator" (SBI) offers an automated detection of active small bowel bleeding but validity of this technique is unknown. The objective was to analyze specificity and sensitivity of the SBI using the second small bowel capsule generation for the detection of active bleeding. This is a retrospective analysis of all patients (199) who attended our clinic for CE from June 2008 through March 2013. The second-generation PillCam SB 2 capsule was used for detection of (1) luminal blood content and (2) potentially responsible small bowel lesions. The findings of an independent investigator were correlated to SBI findings and a number of SBI markings were analyzed by a receiver operating characteristic (ROC). In 157/199 cases, no sign of active bleeding or altered blood was detected. One hundred and thirty-seven of these 157 cases provided at least one SBI marking and a mean of 18.4 positive SBI markings per record were found. In 20 cases, neither SBI nor the human investigator detected abnormalities. Thirteen patients showed investigator-detected minor bleeding with mean SBI findings of 36 positive screenshots per record. When major bleeding was diagnosed by the investigator (n = 29), SBI detected a mean of 46.6 SBI-positive markings. SBI turned positive in 179 patients, whereas the investigator detected active bleeding in 42 cases. All patients with active bleeding were detected by SBI (sensitivity 100%, specificity 13%). ROC analysis revealed 51.0 SBI markings being the optimal cutoff for active versus no bleeding (sensitivity 79.1%, specificity 90.4%, misclassification of 15.3%). The new SBI software is a reliable tool to exclude active bleeding and/or major lesions but analysis of the CE video by a trained investigator is still important for the detection of lesions responsible for past bleeding.

  2. Suspected Motor Problems and Low Preference for Active Play in Childhood Are Associated with Physical Inactivity and Low Fitness in Adolescence

    Science.gov (United States)

    Kantomaa, Marko T.; Purtsi, Jarno; Taanila, Anja M.; Remes, Jouko; Viholainen, Helena; Rintala, Pauli; Ahonen, Timo; Tammelin, Tuija H.

    2011-01-01

    Background This prospective longitudinal study investigates whether suspected motor problems and low preference for active play in childhood are associated with physical inactivity and low cardiorespiratory fitness in adolescence. Methodology/Principal Findings The study sample consisted of the Northern Finland Birth Cohort 1986 (NFBC 1986) composed of 5,767 children whose parents responded to a postal inquiry concerning their children's motor skills at age 8 years and who themselves reported their physical activity at age 16 years. Cardiorespiratory fitness was measured with a cycle ergometer test at age 16 years. Odds ratios (OR) and their 95% confidence intervals (95% CI) for the level of physical activity and fitness were obtained from multinomial logistic regression and adjusted for socio-economic position and body mass index. Low preference for active play in childhood was associated with physical inactivity (boys: OR 3.31, 95% CI 2.42–4.53; girls: OR 1.79, 95% CI 1.36–2.36) and low cardiorespiratory fitness (boys: OR 1.87, 95% CI 1.27–2.74; girls: OR 1.52, 95% CI 1.09–2.11) in adolescence. Suspected gross (OR 2.16, 95% CI 1.33–3.49) and fine (OR 1.88, 95% CI 1.35–2.60) motor problems were associated with physical inactivity among boys. Children with suspected motor problems and low preference for active play tended to have an even higher risk of physical inactivity in adolescence. Conclusions/Significance Low preference for active play in childhood was associated with physical inactivity and low cardiorespiratory fitness in adolescence. Furthermore, children with suspected motor problems and low preference for active play tended to have an even higher risk of physical inactivity in adolescence. Identification of children who do not prefer active play and who have motor problems may allow targeted interventions to support their motor learning and participation in active play and thereby promote their physical activity and fitness in later life

  3. miR-30c is specifically repressed in patients with active pulmonary tuberculosis.

    Science.gov (United States)

    Spinelli, Silvana V; Fernández, Rocío Del V; Zoff, Luciana; Bongiovanni, Bettina; Díaz, Ariana; D'Attilio, Luciano; Santucci, Natalia; Alvarez, Tomás; Marchesini, Marcela M; Bogue, Cristina; Bay, Maria L; Bottasso, Oscar A

    2017-07-01

    Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators. In this work, we explored whether expression of the active isoform of the glucocorticoid receptor (hGRα) in the context of the inflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels. As expected, the inflammatory response triggered in patients coexists with increased circulating cortisol and altered hGRα levels in the peripheral blood mononuclear cells. However, while hGRα expression is significantly downregulated in PLTB, its levels in pTB patients are higher within the control values. These results point out to the existence of an additional mechanism tending to preserve hGRα levels probably to deal with the chronic inflammation observed in pTB. In this regard, we found that miR-30c is strongly downregulated in mononuclear cells of pTB patients compared to PLTB cases, showing an expression profile opposite to that seen with hGRα. Interestingly, low levels of miR-30c are specific for this active form of TB, as its expression is not altered in mononuclear cells from either healthy controls or patients with tuberculous or non-tuberculous pleurisy. Moreover, miR-30c and hGRα also showed an inverse expression pattern in M. tuberculosis-stimulated THP-1 macrophage cultures. In sum, our studies identify miR-30c as a specific correlate of pulmonary manifestations of TB, potentially involved in the altered glucocorticoid sensitivity observed in these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Isolated Optic Disc Tuberculosis

    Science.gov (United States)

    Mansour, Ahmad M.; Tabbara, Khalid F.; Tabbarah, Zuhair

    2015-01-01

    We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation. PMID:26483675

  5. Isolated Optic Disc Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2015-09-01

    Full Text Available We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation.

  6. 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.

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

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    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.

  8. 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.

  9. Tuberculosis among Children in Alaska.

    Science.gov (United States)

    Gessner, Bradford D.

    1997-01-01

    The incidence of tuberculosis among Alaskan children under 15 was more than twice the national rate, with Alaska Native children showing a much higher incidence. Children with household exposure to adults with active tuberculosis had a high risk of infection. About 22 percent of pediatric tuberculosis cases were identified through school…

  10. 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.)

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

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    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.

  12. 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; Granados-Montiel, Julio; Yunis, Maria; 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; Fridkis-Hareli, Masha; Frindkis-Hareli, Masha; Terreros, Daniel; Fernandez-Viña, Marcelo; Yunis, Edmond J

    2010-02-01

    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 anti-tuberculin IgG 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. Published by Elsevier Ltd.

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

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    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.

  14. 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.

  15. 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.

  16. Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection

    OpenAIRE

    Wu, Lawrence Shih-Hsin; Lee, Shih-Wei; Huang, Kai-Yao; Lee, Tzong-Yi; Hsu, Paul Wei-Che; Weng, Julia Tzu-Ya

    2014-01-01

    Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs ...

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

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    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

  18. Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study.

    Science.gov (United States)

    Ronald, Lisa A; Campbell, Jonathon R; Balshaw, Robert F; Romanowski, Kamila; Roth, David Z; Marra, Fawziah; Cook, Victoria J; Johnston, James C

    2018-02-26

    Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. We included all individuals ( n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18-64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized. © 2018 Joule Inc. or its licensors.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Urgent Living-Donor Liver Transplantation in a Patient With Concurrent Active Tuberculosis: A Case Report.

    Science.gov (United States)

    Jung, B-H; Park, J-I; Lee, S-G

    2018-04-01

    Although active tuberculosis (TB) is considered a contraindication for liver transplantation (LT), this is the only treatment in patients with liver failure and concurrent active TB. We report a case with successful urgent living-donor LT for irreversible liver failure in the presence of active TB. A 48-year-old man, with a history of decompensated alcoholic liver cirrhosis, was presented with stupor. At admission, his consciousness had deteriorated to semi-coma, and his renal function also rapidly deteriorated to hepatorenal syndrome. A preoperative computed tomography scan of the chest revealed several small cavitary lesions in both upper lobes, and acid-fast bacillus stain from his sputum was graded 2+. Adenosine deaminase levels from ascites were elevated, suggesting TB peritonitis. A first-line anti-TB drug regimen was started immediately (rifampin, isoniazid, levofloxacin, and amikacin). An urgent living-donor LT was performed 2 days later. After LT, the regimen was changed to second-line anti-TB drugs (amikacin, levofloxacin, cycloserine, and pyridoxine). The sputum acid-fast bacillus stain tested negative on postoperative day 10. His liver function remained well preserved, even after the reversion to first-line anti-TB treatment. The patient recovered without any anti-TB medication-related complications and was discharged. LT can be prudently performed as a life-saving option, particularly for patients with liver failure and concurrent active TB. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Modifiable factors associated with active pulmonary tuberculosis in a Kenyan prison.

    Science.gov (United States)

    Amwayi, A S; Kikuvi, G M; Muchiri, E M

    2010-02-01

    To establish modifiable factors associated with active pulmonary tuberculosis (PTB) among prisoners. Retrospective matched case-control study. Nakuru GK prison in Kenya. A total of 144 subjects (48 cases and 96 controls) were recruited into the study. Cases were adult prisoners who had at least two initial sputum specimens being Acid Fast Bacilli-positive (AFB+) on direct smear microscopy and hence recruited to PTB WHO DOTS Programme. Controls were adults with no chronic cough and not on PTB treatment six months prior to the study. Independent factors significantly associated with active PTB disease were: self reported HIV+ status (OR=11; 95% CI = 2.42-47.77), evidence of BCG vaccination (OR = 0.20; 95% CI = 0.05-0.60), contact with PTB case (OR = 7.0; 95% CI = 1.17-38.23), unemployment (OR = 9.0; 95% CI = 1.84-43.97) and sharing linen (OR = 4.32; 95%CI = 1.08-17.29). 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 hygiene of prisoners.

  3. Reverse translation in tuberculosis: neutrophils as clues for development of active disease

    Directory of Open Access Journals (Sweden)

    Anca eDorhoi

    2014-02-01

    Full Text Available Tuberculosis (TB is a major health issue globally. Although typically the disease can be cured by chemotherapy and prevented – at least in part, in newborn by vaccination, general consensus exists that development of novel intervention measures requires better understanding of disease mechanisms. Human TB is characterized by polarity between host resistance as seen in 2 billion individuals with latent TB infection and susceptibility occurring in 9 million individuals who develop active TB disease every year. Experimental animal models often do not reflect this polarity adequately, calling for a reverse translational approach. Gene expression profiling has allowed identification of biomarkers that discriminate between latent infection and active disease. Functional analysis of most relevant markers in experimental animal models can help to better understand mechanisms driving disease progression. We have embarked on in-depth characterization of candidate markers of pathology and protection hereby harnessing mouse mutants with defined gene deficiencies. Analysis of mutants deficient in miR223 expression and CXCL5 production allowed elucidation of relevant pathogenic mechanisms. Intriguingly, these deficiencies were linked to aberrant neutrophil activities. Our findings point to a detrimental potential of neutrophils in TB. Reciprocally, measures that control neutrophils should be leveraged for amelioration of TB in adjunct to chemotherapy.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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....

  7. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

    Science.gov (United States)

    Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

    2013-07-15

    C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

  8. Tomographic Aspects of Advanced Active Pulmonary Tuberculosis and Evaluation of Sequelae following Treatment

    Directory of Open Access Journals (Sweden)

    Rafael Barcelos Capone

    2017-01-01

    Full Text Available Objectives. To evaluate tomographic changes in pulmonary tuberculosis (TB, degree of agreement among three radiologists regarding tomographic diagnoses, and sequelae following treatment. Methods. Cross-sectional and descriptive study of 74 TB patients confirmed by sputum culture and chest computed tomography before (CT1 and 6 months after (CT2 drug therapy. Results were performed by three radiologists blinded to clinical and laboratory results. Results. Main findings in CT1 included nodules indicating the presence of a tree-in-bud pattern in 93% of cases, ill-defined nodules in 84% of cases, consolidation in 77% of cases, architectural distortion in 71% of cases, cavitary lesions in 62% of cases, and ground glass opacities in 37% of cases. Airway involvement, characterized by increased thickness and dilatation of the bronchial walls, occurred in 93% of cases. Pleural involvement occurred in 54%. There was an agreement on active TB among the three radiologists in 85% of cases. The results in CT2 indicated the presence of architectural distortion in 91% of cases and cylindrical bronchiectasis in 86%. Conclusions. The study established a tomographic pattern for diagnosis of active TB characterized by the presence of airway nodules, consolidation, architectural distortion, and cavitary lesions, and an almost complete degree of agreement (Kappa was observed among the radiologists (0.85. CT after treatment assists in defining the cure.

  9. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

    Directory of Open Access Journals (Sweden)

    Xiyuan Bai

    Full Text Available Nuclear factor-kappa B (NFκB is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB. However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

  10. Active tuberculosis among homeless persons, Toronto, Ontario, Canada, 1998-2007.

    Science.gov (United States)

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

    2011-03-01

    While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998-2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The proportion of homeless persons who were foreign-born increased from 24% in 1998-2002 to 39% in 2003-2007. Among foreign-born homeless persons with TB, 56% of infections were caused by strains not known to circulate among homeless persons in Toronto. Only 2% of infections were resistant to first-line TB medications. The rise in foreign-born homeless persons with TB strains likely acquired overseas suggests that the risk for drug-resistant strains entering the homeless shelter system may be escalating.

  11. Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network.

    Science.gov (United States)

    Keegan, Caroline; Krutzik, Stephan; Schenk, Mirjam; Scumpia, Philip O; Lu, Jing; Pang, Yan Ling Joy; Russell, Brandon S; Lim, Kok Seong; Shell, Scarlet; Prestwich, Erin; Su, Dan; Elashoff, David; Hershberg, Robert M; Bloom, Barry R; Belisle, John T; Fortune, Sarah; Dedon, Peter C; Pellegrini, Matteo; Modlin, Robert L

    2018-05-01

    Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-γ, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70. Copyright © 2018 by The American Association of Immunologists, Inc.

  12. Active pulmonary tuberculosis case detection and treatment among floating population in China: an effective pilot.

    Science.gov (United States)

    Li, Xinxu; Zhang, Hui; Jiang, Shiwen; Wang, Jia; Liu, Xiaoqiu; Li, Weibin; Yao, Hongyan; Wang, Lixia

    2010-12-01

    China has more and more floating population because of reform and opening-up. As one of the high burden countries in tuberculosis (TB) control in the world, China has to face more challenges about the TB case detection and treatment among floating population in China. Aim to evaluate the effect of case detection and treatment of the Floating Population TB Control Pilot Project from Global Fund Round Five (GFR5) TB Control Program in China. During October 2006 to September 2008, the pilot project was implemented gradually in 60 counties in Tianjin, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong and Guangdong. All quarterly reports of the pilot project were collected, and these materials were summarized and analyzed. In seven coastal provinces, 19,584 active pulmonary TB (PTB) cases were registered among floating population in 2 years. Among the active PTB cases, 87.2% were 15-45 years old, and 62.8% were male. In second year, 15,629 active PTB cases were registered, and the overall registration rate was 68 per 100,000 people. DOT treatments were provided for 18,125 active PTB cases in 2 years, and overall DOT treatment rate was 92.6%. There were 3,955 active PTB cases registered in first year, and the overall cure rate was 86.0%. Through the implementation of the pilot project, the TB case detection and treatment among floating population have been enhanced in pilot areas of China. The useful experience and results from the pilot project have been being gradually generalized nationally.

  13. Prothrombin fragment 1+2 in urine as a marker on coagulation activity in patients with suspected pulmonary embolism.

    Science.gov (United States)

    Wexels, Fredrik; Dahl, Ola E; Pripp, Are H; Seljeflot, Ingebjørg; Borris, Lars C; Haslund, Anniken; Gudmundsen, Tor E; Lauritzen, Trine; Lassen, Michael R

    2014-07-01

    We have recently reported that increased levels of urine prothrombin fragment 1+2 reflected radiologically verified deep vein thrombosis. In this study we evaluated whether urine prothrombin fragment 1+2 was associated with pulmonary embolism in non-selected patients. Patients with clinical suspected pulmonary embolism were interviewed on comorbidities and medications. Urine was collected from each patient before radiological examination and snap frozen until analysed on urine prothrombin fragment 1+2 with an ELISA kit. Imaging of the pulmonary arteries were conducted with contrast enhanced computer tomography. Pulmonary embolism was diagnosed in 44/197 patients. Non-significantly higher urine prothrombin fragment 1+2 levels were found in non-selected patients with pulmonary embolism vs. those without (p=0.324). Significantly higher urine prothrombin fragment 1+2 levels were found in the pulmonary embolism positive patients without comorbidities (n=13) compared to the control group (n=28) (p=0.009). The calculated sensitivity, specificity and negative predictive value using the lowest detectable urine prothrombin fragment 1+2 level was 82%, 34% and 87%, respectively. There was no significant urine prothrombin fragment 1+2 level difference in patients with and without pulmonary embolism. In non-comorbide pulmonary embolism positive patients the urine prothrombin fragment 1+2 levels were significantly higher compared to the control group. The negative predictive value found in this study indicates that uF1+2 has the potential to identify patients with a low risk of PE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis in combination with potentiator drugs verapamil, timcodar, colistin and SQ109.

    Science.gov (United States)

    de Knegt, Gerjo J; van der Meijden, Aart; de Vogel, Corné P; Aarnoutse, Rob E; de Steenwinkel, Jurriaan E M

    2017-03-01

    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 with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and SQ109. Using a time-kill kinetics assay, the activities of moxifloxacin, linezolid, verapamil, timcodar, colistin and SQ109 as single drugs against Mycobacterium tuberculosis were evaluated. In addition, the activity of the moxifloxacin + linezolid backbone in combination with one of the potentiator drugs was assessed. As little as 0.125 mg/L moxifloxacin achieved 99% killing of M. tuberculosis after 6 days of exposure. Linezolid showed moderate killing but 99% killing was not achieved. Verapamil, timcodar and colistin only resulted in killing with the highest concentrations tested but 99% killing was not achieved. SQ109 resulted in complete elimination after 1 day of exposure to 256 mg/L and in 99% elimination after 6 days of exposure to 1 mg/L. Furthermore, colistin added to the moxifloxacin + linezolid backbone resulted in increased elimination, whereas verapamil, timcodar and SQ109 showed no added value to the backbone. This finding that colistin potentiates the activity of the moxifloxacin + linezolid backbone against M. tuberculosis suggests its potential role in further studies on the applicability of a moxifloxacin + linezolid treatment of MDR-TB. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  15. Tuberculosis abdominal Abdominal tuberculosis

    OpenAIRE

    T. Rubio; M. T. Gaztelu; A. Calvo; M. Repiso; H. Sarasíbar; F. Jiménez Bermejo; A. Martínez Echeverría

    2005-01-01

    La tuberculosis abdominal cursa con un cuadro inespecífico, con difícil diagnóstico diferencial respecto a otras entidades de similar semiología. Presentamos el caso de un varón que ingresa por presentar dolor abdominal, pérdida progresiva y notoria de peso corporal y fiebre de dos meses de evolución. El cultivo de la biopsia de colon mostró presencia de bacilo de Koch.Abdominal tuberculosis develops according to a non-specific clinical picture, with a difficult differential diagnosis with re...

  16. Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis DNA helicase XPB.

    Science.gov (United States)

    Balasingham, Seetha V; Zegeye, Ephrem Debebe; Homberset, Håvard; Rossi, Marie L; Laerdahl, Jon K; Bohr, Vilhelm A; Tønjum, Tone

    2012-01-01

    XPB, also known as ERCC3 and RAD25, is a 3' → 5' DNA repair helicase belonging to the superfamily 2 of helicases. XPB is an essential core subunit of the eukaryotic basal transcription factor complex TFIIH. It has two well-established functions: in the context of damaged DNA, XPB facilitates nucleotide excision repair by unwinding double stranded DNA (dsDNA) surrounding a DNA lesion; while in the context of actively transcribing genes, XPB facilitates initiation of RNA polymerase II transcription at gene promoters. Human and other eukaryotic XPB homologs are relatively well characterized compared to conserved homologs found in mycobacteria and archaea. However, more insight into the function of bacterial helicases is central to understanding the mechanism of DNA metabolism and pathogenesis in general. Here, we characterized Mycobacterium tuberculosis XPB (Mtb XPB), a 3'→5' DNA helicase with DNA-dependent ATPase activity. Mtb XPB efficiently catalyzed DNA unwinding in the presence of significant excess of enzyme. The unwinding activity was fueled by ATP or dATP in the presence of Mg(2+)/Mn(2+). Consistent with the 3'→5' polarity of this bacterial XPB helicase, the enzyme required a DNA substrate with a 3' overhang of 15 nucleotides or more. Although Mtb XPB efficiently unwound DNA model substrates with a 3' DNA tail, it was not active on substrates containing a 3' RNA tail. We also found that Mtb XPB efficiently catalyzed ATP-independent annealing of complementary DNA strands. These observations significantly enhance our understanding of the biological roles of Mtb XPB.

  17. Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis DNA helicase XPB.

    Directory of Open Access Journals (Sweden)

    Seetha V Balasingham

    Full Text Available XPB, also known as ERCC3 and RAD25, is a 3' → 5' DNA repair helicase belonging to the superfamily 2 of helicases. XPB is an essential core subunit of the eukaryotic basal transcription factor complex TFIIH. It has two well-established functions: in the context of damaged DNA, XPB facilitates nucleotide excision repair by unwinding double stranded DNA (dsDNA surrounding a DNA lesion; while in the context of actively transcribing genes, XPB facilitates initiation of RNA polymerase II transcription at gene promoters. Human and other eukaryotic XPB homologs are relatively well characterized compared to conserved homologs found in mycobacteria and archaea. However, more insight into the function of bacterial helicases is central to understanding the mechanism of DNA metabolism and pathogenesis in general. Here, we characterized Mycobacterium tuberculosis XPB (Mtb XPB, a 3'→5' DNA helicase with DNA-dependent ATPase activity. Mtb XPB efficiently catalyzed DNA unwinding in the presence of significant excess of enzyme. The unwinding activity was fueled by ATP or dATP in the presence of Mg(2+/Mn(2+. Consistent with the 3'→5' polarity of this bacterial XPB helicase, the enzyme required a DNA substrate with a 3' overhang of 15 nucleotides or more. Although Mtb XPB efficiently unwound DNA model substrates with a 3' DNA tail, it was not active on substrates containing a 3' RNA tail. We also found that Mtb XPB efficiently catalyzed ATP-independent annealing of complementary DNA strands. These observations significantly enhance our understanding of the biological roles of Mtb XPB.

  18. DNA repair systems and the pathogenesis of Mycobacterium tuberculosis: varying activities at different stages of infection.

    Science.gov (United States)

    Gorna, Alina E; Bowater, Richard P; Dziadek, Jaroslaw

    2010-05-25

    Mycobacteria, including most of all MTB (Mycobacterium tuberculosis), cause pathogenic infections in humans and, during the infectious process, are exposed to a range of environmental insults, including the host's immune response. From the moment MTB is exhaled by infected individuals, through an active and latent phase in the body of the new host, until the time they reach the reactivation stage, MTB is exposed to many types of DNA-damaging agents. Like all cellular organisms, MTB has efficient DNA repair systems, and these are believed to play essential roles in mycobacterial pathogenesis. As different stages of infection have great variation in the conditions in which mycobacteria reside, it is possible that different repair systems are essential for progression to specific phases of infection. MTB possesses homologues of DNA repair systems that are found widely in other species of bacteria, such as nucleotide excision repair, base excision repair and repair by homologous recombination. MTB also possesses a system for non-homologous end-joining of DNA breaks, which appears to be widespread in prokaryotes, although its presence is sporadic within different species within a genus. However, MTB does not possess homologues of the typical mismatch repair system that is found in most bacteria. Recent studies have demonstrated that DNA repair genes are expressed differentially at each stage of infection. In the present review, we focus on different DNA repair systems from mycobacteria and identify questions that remain in our understanding of how these systems have an impact upon the infection processes of these important pathogens.

  19. 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.

  20. 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.

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

    International Nuclear Information System (INIS)

    Anisimova, Y.V.; Gelperina, S.I.; Peloquin, C.A.; Heifets, L.B.

    2000-01-01

    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

  2. Radiologic diagnosis of lung tuberculosis

    International Nuclear Information System (INIS)

    Eisenhuber, E.; Mostbeck, G.; Bankier, A.; Stadler, A.; Rumetshofer, R.

    2007-01-01

    The radiologic knowledge of tuberculosis-associated lung disease is an essential tool in the clinical diagnosis of tuberculosis. Chest radiography is the primary imaging method, but the importance of CT is still increasing, as CT is more sensitive in the detection of cavitation, of hilar and mediastinal lymphadenopathie, of endobronchial spread and of complications in the course of the disease. In addition, CT has been proven as a valuable technique in the assessment of tuberculosis activity, especially in patients where M. tuberculosis has not been detected in the sputum or in patients with multidrug-resistant tuberculosis. Depending on the immune status of the patient, the morphologic spectrum of tuberculosis is quite variable. Early diagnosis of tuberculosis is essential to prevent further spread of the disease. (orig.) [de

  3. Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Beatriz Beltrán-Beck

    Full Text Available Tuberculosis (TB remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV. Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.

  4. Genitourinary tuberculosis

    International Nuclear Information System (INIS)

    Matos, Maria Joao; Bacelar, Maria Teresa; Pinto, Pedro; Ramos, Isabel

    2005-01-01

    Although uncommon, genitourinary tuberculosis is the most common site of extrapulmonary tuberculosis infection. Its diagnosis is often difficult. This article provides an overview of the pathologic and radiologic findings of this disease process

  5. 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).

  6. Computed tomography of active pulmonary tuberculosis with nonvisualized cavitary lesion on plain chest film

    International Nuclear Information System (INIS)

    Ahn, Woo Hyun; Cho, Seoung Hwan; Lee, Jun Bae; Kim, Byung Soo

    1989-01-01

    The detection of cavity in pulmonary tuberculosis has important roles in its diagnosis, therapy planning and follow-up of healing process, and also means at least moderate advanced tuberculosis. The plain chest film has some limitation of detection of cavity in pulmonary tuberculosis owing to several factors. CT is superior to plain chest film and conventional tomography, in detection of cavitary lesion. Authors retrospectively analyzed CT findings of 20 cases of minimal pulmonary tuberculosis, of which the plain chest films showed no cavitary lesion from Sept. 1986 to July 1988 in Pusan National University Hospital. All cases were proven by culture or AFB test of sputum and clinical evidence. The results were as follows: 1. Sex distribution showed 10 cases (50%) in male, 10 case (50%) in female and the highest incidence in the second decade (40%). 2. All 20 cases showed no cavity on the plain chest films, but all cases showed variable sized cavities on CT. 3. The size of cavities ranged from 4 mm to 30 mm, averaged as 9.9 mm, the thickness of cavitary wall from 3 mm to 8 mm, averaged as 5.8 mm. 4. It is concluded that cavitary lesions which are not visualized on the plain chest films can be demonstrated by CT scan in minimal pulmonary tuberculosis

  7. Congenital tuberculosis

    African Journals Online (AJOL)

    Prof Ezechukwu

    2012-06-20

    Jun 20, 2012 ... Key words: Congenital tuberculo- sis, case report, miliary tuberculosis. Introduction. Congenital tuberculosis defines tuberculosis in infants of .... tary TB and otitis media, resulting in seizures, deafness, and death. It is therefore not surprising that the index case who presented at twelve weeks of age, had ...

  8. 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...

  9. 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.

  10. Hyperthermostable binding molecules on phage: Assay components for point-of-care diagnostics for active tuberculosis infection.

    Science.gov (United States)

    Zhao, Ning; Spencer, John; Schmitt, Margaret A; Fisk, John D

    2017-03-15

    Tuberculosis is the leading cause of death from infectious disease worldwide. The low sensitivity, extended processing time, and high expense of current diagnostics are major challenges to the detection and treatment of tuberculosis. Mycobacterium tuberculosis ornithine transcarbamylase (Mtb OTC, Rv1656) has been identified in the urine of patients with active TB infection and is a promising target for point-of-care diagnostics. Specific binding proteins with low nanomolar affinities for Mtb OTC were selected from a phage display library built upon a hyperthermostable Sso7d scaffold. Phage particles displaying Sso7d variants were utilized to generate a sandwich ELISA-based assay for Mtb OTC. The assay response is linear between 2 ng/mL and 125 ng/mL recombinant Mtb OTC and has a limit of detection of 400 pg/mL recombinant Mtb OTC. The assay employing a phage-based detection reagent is comparable to commercially-available antibody-based biosensors. Importantly, the assay maintains functionality at both neutral and basic pH in presence of salt and urea over the range of concentrations typical for human urine. Phage-based diagnostic systems may feature improved physical stability and cost of production relative to traditional antibody-based reagents, without sacrificing specificity and sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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.

  12. Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era.

    Science.gov (United States)

    Gupta, R K; Lipman, M; Story, A; Hayward, A; de Vries, G; van Hest, R; Erkens, C; Rangaka, M X; Abubakar, I

    2018-05-01

    Vulnerable populations, including homeless persons, high-risk drug and alcohol users, prison inmates and other marginalised populations, contribute a disproportionate burden of tuberculosis (TB) cases in low-incidence settings. Drivers of this disease burden include an increased risk of both TB transmission in congregate settings, and progression from infection to active disease. Late diagnosis and poor treatment completion further propagate the epidemic and fuel the acquisition of drug resistance. These groups are therefore a major priority for TB control programmes in low-incidence settings. Targeted strategies include active case finding (ACF) initiatives and interventions to improve treatment completion, both of which should be tailored to local populations. ACF usually deploys mobile X-ray unit screening, which allows sensitive, high-throughput screening with immediate availability of results. Such initiatives have been found to be effective and cost-effective, and associated with reductions in proxy measures of transmission in hard-to-reach groups. The addition of point-of-care molecular diagnostics and automated X-ray readers may further streamline the screening pathway. There is little evidence to support interventions to improve adherence among these risk groups. Such approaches include enhanced case management and directly observed treatment, while video-observed therapy (currently under evaluation) appears to be a promising tool for the future. Integrating outreach services to include both case detection and case-management interventions that share a resource infrastructure may allow cost-effectiveness to be maximised. Integrating screening and treatment for other diseases that are prevalent among targeted risk groups into TB outreach interventions may further improve cost-effectiveness. This article reviews the existing literature, and highlights priorities for further research.

  13. Current use and acceptability of novel diagnostic tests for active tuberculosis: a worldwide survey

    Directory of Open Access Journals (Sweden)

    Massimo Amicosante

    Full Text Available ABSTRACT Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents, followed by molecular assays (available to 70.7%. Only a small proportion of the respondents in middle- and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4% of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6% and low-income countries (76.6%. The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0% or biomarker-based serological assays (acceptable to 81.7%. Simple biomarker-based assays were more commonly deemed acceptable in middle- and low-income countries. Conclusions: Second-generation molecular assays have become more widely available in high- and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users.

  14. Using Commercial Activity Monitors to Measure Gait in Patients with Suspected iNPH: Implications for Ambulatory Monitoring.

    Science.gov (United States)

    Gaglani, Shiv; Moore, Jessica; Haynes, M Ryan; Hoffberger, Jamie B; Rigamonti, Daniele

    2015-11-17

    This study seeks to validate the use of activity monitors to detect and record gait abnormalities, potentially identifying patients with idiopathic normal pressure hydrocephalus (iNPH) prior to the onset of cognitive or urinary symptoms. This study compared the step counts of four common activity monitors (Omron Step Counter HJ-113, New Lifestyles 2000, Nike Fuelband, and Fitbit Ultra) to an observed step count in 17 patients with confirmed iNPH. Of the four devices, the Fitbit Ultra (Fitbit, Inc., San Francisco, CA) provided the most accurate step count. The correlation with the observed step count was significantly higher (p<0.009) for the Fitbit Ultra than for any of the other three devices. These preliminary findings suggest that existing activity monitors have variable efficacy in the iNPH patient population and that the MEMS tri-axial accelerometer and algorithm of the Fitbit Ultra provides the most accurate gait measurements of the four devices tested.

  15. Expanding the epidemiologic profile: risk factors for active tuberculosis in people immigrating to Ontario

    Science.gov (United States)

    Wobeser, Wendy L.; Yuan, Lilian; Naus, Monika; Corey, Paul; Edelson, Jeff; Heywood, Neil; Holness, D. Linn

    2000-01-01

    Background Many people immigrating to Canada come from countries with a high burden of tuberculosis. The aim of this study was to develop a detailed epidemiologic profile of foreign-born people with tuberculosis living in Ontario. Methods In this population-based case-control study, cases of tuberculosis diagnosed in 1994-1995 were identified from the database of the Ontario Reportable Disease Information Service and were considered eligible for analysis if a record of landing (receipt of permission to establish residence in Canada) from the period 1986-1995 was found in the Citizenship and Immigration Canada (CIC) database, if the person was at least 11 years of age at the time their visa was issued, and if the person had not been diagnosed with tuberculosis before becoming legally landed in Canada. Control subjects, who met the same criteria as the case subjects but who did not have tuberculosis in 1994-1995, were identified from a CIC database for landed immigrants. Results A total of 1341 cases of tuberculosis in foreign-born people were reported in Ontario in 1994-1995. A record of landing was found in CIC databases for 1099 of these people, 224 of whom were not legally landed at the time of diagnosis. In total, 602 cases met the inclusion criteria. The 2 strongest determinants of risk among those who had become landed within the preceding 10 years were referral for medical surveillance by immigration officials (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.6-6.0) and world region of origin (Somalia [OR 67.7, 95% CI 31.3-154.9], Vietnam [OR 25.0, 95% CI 12.5-50.0], the Philippines [OR 11.9, 95% CI 6.0-23.3], other sub-Saharan African countries [OR 11.6, 95% CI 5.7-23.2], India [OR 9.7, 95% CI 4.9-18.9], China [OR 6.1, 95% CI 3.1-12.1], other Asian countries [OR 4.7, 95% CI 2.4-9.1], the Middle East [OR 4.1, 95% CI 2.0-8.3], Latin America [OR 1.9, 95% CI 0.9-3.8), and the former socialist countries of Europe [OR 1.8, 95% CI 0.8-3.8]; the reference

  16. 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

  17. Low-Income Parents' Warmth and Parent-Child Activities for Children with Disabilities, Suspected Delays and Biological Risks

    Science.gov (United States)

    Eshbaugh, Elaine M.; Peterson, Carla A.; Wall, Shavaun; Carta, Judith J.; Luze, Gayle; Swanson, Mark; Jeon, Hyun-Joo

    2011-01-01

    Warm and responsive parenting is optimal for child development, but this style of parenting may be difficult for some parents to achieve. This study examines how parents' observed warmth and their reported frequency of parent-child activities were related to children's classifications as having biological risks or a range of disability indicators.…

  18. 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 Δ actA (LmI), rLm Δ actA Δ inlB (LmII), and rLm Δ actA Δ inlB prfA * (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.

  19. Colorectal tuberculosis

    International Nuclear Information System (INIS)

    Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.

    2003-01-01

    Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

  20. A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts

    Directory of Open Access Journals (Sweden)

    Fergal J. Duffy

    2018-04-01

    Full Text Available Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs regulate the host response to MTB and circulating miRNAs (c-miRNAs have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

  1. 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.

  2. A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.

    Science.gov (United States)

    Duffy, Fergal J; Thompson, Ethan; Downing, Katrina; Suliman, Sara; Mayanja-Kizza, Harriet; Boom, W Henry; Thiel, Bonnie; Weiner Iii, January; Kaufmann, Stefan H E; Dover, Drew; Tabb, David L; Dockrell, Hazel M; Ottenhoff, Tom H M; Tromp, Gerard; Scriba, Thomas J; Zak, Daniel E; Walzl, Gerhard

    2018-01-01

    Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

  3. Tuberculin-Specific T Cells Are Reduced in Active Pulmonary Tuberculosis Compared to LTBI or Status Post BCG Vaccination

    Science.gov (United States)

    Streitz, Mathias; Fuhrmann, Stephan; Powell, Fiona; Quassem, Ali; Nomura, Laurel; Maecker, Holden; Martus, Peter; Volk, Hans-Dieter

    2011-01-01

    Functional characteristics of tuberculosis (TB)–specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone. PMID:21186260

  4. 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 ...

  5. Living with Tuberculosis

    Science.gov (United States)

    ... Diseases > Lung Disease Lookup > Tuberculosis (TB) Living With Tuberculosis What to Expect You will need regular checkups ... XML file."); } }); } } --> Blank Section Header Lung Disease Lookup Tuberculosis (TB) Learn About Tuberculosis Tuberculosis Symptoms, Causes & Risk ...

  6. 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...

  7. risk factors of active tuberculosis in people living with hiv/aids in ...

    African Journals Online (AJOL)

    Abrham

    2011-07-02

    Jul 2, 2011 ... R, Lisse I, Samb B et al: Tuberculosis in. Bissau: incidence and risk factors in an urban community in sub-Saharan Africa. Int J. Epidemiol 2004;33(1):163-172. 10. MOH: TB, leprosy and TB/HIV prevention and control program manual. Addis Ababa,. Ethiopia. 2008. 11. Fugnudo Mbeki AG, Kuwala Lube: ...

  8. Re-thinking global health sector efforts for HIV and tuberculosis epidemic control: promoting integration of programme activities within a strengthened health system.

    Science.gov (United States)

    Maher, Dermot

    2010-07-05

    The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis control programme activities within a strengthened health system. HIV and tuberculosis share many similarities in terms of their disease burden and the recommended stratagems for their control. HIV and tuberculosis programmes implement similar sorts of control activities, e.g. case finding and treatment, which depend for success on generic health system issues, including vital registration, drug procurement and supply, laboratory network, human resources, and financing. However, the current health system approach to HIV and tuberculosis control often involves separate specialised services. Despite some recent progress, collaboration between the programmes remains inadequate, progress in obtaining synergies has been slow, and results remain far below those needed to achieve universal access to key interventions. A fundamental re-think of the current strategic approach involves promoting integrated delivery of HIV and tuberculosis programme activities as part of strengthened general health services: epidemiological surveillance, programme monitoring and evaluation, community awareness of health-seeking behavior, risk behaviour modification, infection control, treatment scale-up (first-line treatment regimens), drug-resistance surveillance, containing and countering drug-resistance (second-line treatment regimens), research and development, global advocacy and global partnership. Health agencies should review policies and progress in HIV and tuberculosis epidemic control, learn mutual lessons for policy development and scaling up interventions, and identify ways

  9. Re-thinking global health sector efforts for HIV and tuberculosis epidemic control: promoting integration of programme activities within a strengthened health system

    Directory of Open Access Journals (Sweden)

    Maher Dermot

    2010-07-01

    Full Text Available Abstract Background The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis control programme activities within a strengthened health system. Discussion HIV and tuberculosis share many similarities in terms of their disease burden and the recommended stratagems for their control. HIV and tuberculosis programmes implement similar sorts of control activities, e.g. case finding and treatment, which depend for success on generic health system issues, including vital registration, drug procurement and supply, laboratory network, human resources, and financing. However, the current health system approach to HIV and tuberculosis control often involves separate specialised services. Despite some recent progress, collaboration between the programmes remains inadequate, progress in obtaining synergies has been slow, and results remain far below those needed to achieve universal access to key interventions. A fundamental re-think of the current strategic approach involves promoting integrated delivery of HIV and tuberculosis programme activities as part of strengthened general health services: epidemiological surveillance, programme monitoring and evaluation, community awareness of health-seeking behavior, risk behaviour modification, infection control, treatment scale-up (first-line treatment regimens, drug-resistance surveillance, containing and countering drug-resistance (second-line treatment regimens, research and development, global advocacy and global partnership. Health agencies should review policies and progress in HIV and tuberculosis epidemic control, learn mutual lessons for policy

  10. Structure/activity of Pt{sup II}/N,N-disubstituted-N'-acylthiourea complexes: Anti-tumor and anti-mycobacterium tuberculosis activities

    Energy Technology Data Exchange (ETDEWEB)

    Plutín, Ana M.; Alvarez, Anislay; Mocelo, Raúl; Ramos, Raúl; Sánchez, Osmar C. [Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de La Habana (Cuba); Castellano, Euardo E. [Universidade de São Paulo (USP), São Carlos, SP (Brazil); Silva, Monize M. da; Villarreal, Wilmer; Colina-Vegas, Legna; Batista, Alzir A. [Universidade Federal de São Carlos (UFSCar), SP (Brazil); Pavan, Fernando R., E-mail: anap@fq.uh.cu, E-mail: daab@ufscar.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Faculdade de Ciências Farmacêuticas

    2018-05-01

    The syntheses, characterization, cytotoxicity against tumor cells and anti-Mycobacterium tuberculosis activity assays of Pt{sup II}/PPh{sub 3}/N,N-disubstituted-N'-acylthioureas complexes with general formulae [Pt(PPh{sub 3}){sub 2}(L)]PF{sub 6}, PPh{sub 3} = triphenylphosphine; L = N,N-disubstituted-N'-acylthiourea, are here reported. The complexes were characterized by elemental analysis, molar conductivity, infrared (IR), nuclear magnetic resonance (NMR) ({sup 1} H, {sup 13}C{1 H} and {sup 31}P{"1 H}) spectroscopy. The {sup 31}P{"1 H} NMR data are consistent with the presence of two PPh{sup 3} ligands cis to each other position, and one N,N-disubstituted-N'-acylthiourea coordinated to the metal through O and S, in a chelate form. The structures of the complexes were determined by X-ray crystallography, forming distorted square-planar structures. The complexes were tested in human cell lines carcinomas and also screened with respect to their anti-Mycobacterium tuberculosis activity (H37RvATCC 27294). It was found that complexes with N,N-disubstituted-N'-acylthiourea containing open and small chains as R2 groups show higher cytotoxic and higher anti-Mycobacterium tuberculosis activity than those containing rings in this position. (author)

  11. Identification, activity and disulfide connectivity of C-di-GMP regulating proteins in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2010-11-01

    Full Text Available C-di-GMP, a bacterial second messenger plays a key role in survival and adaptation of bacteria under different environmental conditions. The level of c-di-GMP is regulated by two opposing activities, namely diguanylate cyclase (DGC and phosphodiesterase (PDE-A exhibited by GGDEF and EAL domain, respectively in the same protein. Previously, we reported a bifunctional GGDEF-EAL domain protein, MSDGC-1 from Mycobacterium smegmatis showing both these activities (Kumar and Chatterji, 2008. In this current report, we have identified and characterized the homologous protein from Mycobacterium tuberculosis (Rv 1354c named as MtbDGC. MtbDGC is also a bifunctional protein, which can synthesize and degrade c-di-GMP in vitro. Further we expressed Mtbdgc in M. smegmatis and it was able to complement the MSDGC-1 knock out strain by restoring the long term survival of M. smegmatis. Another protein Rv 1357c, named as MtbPDE, is an EAL domain protein and degrades c-di-GMP to pGpG in vitro. Rv1354c and 1357c have seven cysteine amino acids in their sequence, distributed along the full length of the protein. Disulfide bonds play an important role in stabilizing protein structure and regulating protein function. By proteolytic digestion and mass spectrometric analysis of MtbDGC, connectivity between cysteine pairs Cys94-Cys584, Cys2-Cys479 and Cys429-Cys614 was determined, whereas the third cysteine (Cys406 from N terminal was found to be free in MtbDGC protein, which was further confirmed by alkylation with iodoacetamide labeling. Bioinformatics modeling investigations also supported the pattern of disulfide connectivity obtained by Mass spectrometric analysis. Cys406 was mutated to serine by site directed mutagenesis and the mutant MtbC406S was not found to be active and was not able to synthesize or degrade c-di-GMP. The disulfide connectivity established here would help further in understanding the structure - function relationship in MtbDGC.

  12. 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

  13. Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against Mycobacterium tuberculosis in a Series of In Vitro and In Vivo Models

    OpenAIRE

    Lenaerts, Anne J.; Gruppo, Veronica; Marietta, Karen S.; Johnson, Christine M.; Driscoll, Diane K.; Tompkins, Nicholas M.; Rose, Jerry D.; Reynolds, Robert C.; Orme, Ian M.

    2005-01-01

    This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against Mycobacterium tuberculosis. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC < 1 μg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 μg/ml, similar to that of...

  14. 1 Low sputum smear positive tuberculosis among pulmonary ...

    African Journals Online (AJOL)

    status of tuberculosis as part of the clinical case definition of AIDS in India. Postgraduate Medical Journal 81, 404–408. Bruchfeld, J., Aderaye, G., Palme, I.B., Bjorvatn, B., Britton, S., Feleke, Y., Källenius, G. & Lindquist, L. (2002) Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence ...

  15. Does trauma team activation associate with the time to CT scan for those suspected of serious head injuries?

    Science.gov (United States)

    Rados, Alma; Tiruta, Corina; Xiao, Zhengwen; Kortbeek, John B; Tourigny, Paul; Ball, Chad G; Kirkpatrick, Andrew W

    2013-11-18

    Traumatic brain injury (TBI) constitutes the leading cause of posttraumatic mortality. Practically, the major interventions required to treat TBI predicate expedited transfer to CT after excluding other immediately life-threatening conditions. At our center, trauma responses variably consist of either full trauma activation (FTA) including an attending trauma surgeon or a non-trauma team response (NTTR). We sought to explore whether FTAs expedited the time to CT head (TTCTH). Retrospective review of augmented demographics of 88 serious head injuries identified from a Regional Trauma Registry within one year at a level I trauma center. The inclusion criteria consisted of a diagnosis of head injury recorded as intubated or GCS FTA (median 50 vs. 26 minutes, p FTA). Without FTA, most delays (69%) were for emergency intubation. TTCTH after securing the airway was longer for NTTR group (median 38 vs. 26 minutes, p =0.0013). Even with no requirements for ED interventions, TTCTH for FTA was less than half versus NTTR (25 vs. 61 minutes, p =0.0013). Multivariate regression analysis indicated age and FTA with an attending surgeon as significant predictors of TTCTH, although the majority of variability in TTCTH was not explained by these two variables (R² = 0.33). Full trauma activations involving attending trauma surgeons were quicker at transferring serious head injury patients to CT. Patients with FTA were younger and more seriously injured. Discerning the reasons for delays to CT should be used to refine protocols aimed at minimizing unnecessary delays and enhancing workforce efficiency and clinical outcome.

  16. 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

  17. 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

  18. Lung scintigraphy with Tc-99m-MIBI in diagnosis of active tuberculosis

    International Nuclear Information System (INIS)

    Raziei, G.; Fotouhi, F.; Masjedi, M.R.; Neshandar, E.

    2002-01-01

    Tuberculosis is highly contagious infection and one of the most important health problems in the world today, particularly in our country. Routine diagnostic procedures are sometimes unable to differentiated active from inactive cases particularly in elderly. Children, immunomedics patients, Chronic cases with recurrent actuate infection and in the patients unable to provide sputum for microbiological studies. Several radiopharmaceuticals have been used in the evaluation of active pulmonary TB. In this study Tc 99 m-MIBI lung scan was performed using a single head ADAC gamma camera. 62 patients including 34 APTB 915 male and 19 female) and 28 IPTB 99 male and 19 female) underwent six minutes anterior and posterior chest images 20 and minutes after injection of 10 mCi (370 MBq) of Tc 99 m-MIBI. Visual grading was generated by comparing uptake of lesion with neck soft tissue (sternoleidomastoid muscle) and myocardium. For semiquantitative analysis, regions of interest were draw over the lesion (L), non lesion (NL) and neck soft tissue (SCM) and mean count value of ROIs as well as L/NL, L/SCM values were obtained. Results: From 34 patients with APTB, 4 PTS had normal lung uptake (11.7%), 14 PTs+(41, 2%), 14 PTs++41.2%) and 2 PTS +++ (5.9%), therefore 30 PTs of APTB were positive in scintigraphy (88.2%). From 28 patients with IPTB 21 PTs had normal lung uptake (75%), 6 PTs+ (21.4%) and one PT ++ (3.5%). In the semi quantitative study L/NL ratio is calculated for + about 1.35 +/-0.15 and below from this range is considered with normal limit. The sensitivity, specificity, accuracy, PPV and NPV were 88.2% 75%, 82.2%, 81.1% and 84% respectively. From 100 CXR lesion in APTB, 60 had compatible positive scan and from 86 CXR lesions in IPTB 9 had compatible positive scan, where as incompatible positive findings were 12 and 2 respectively. This study indicates Tc 99 m - MIBI lung scan can be used as a reliable complementary study in diagnosis of APTB and differentiating from

  19. 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.; Vasconcelos, Sidra E. G.; Esteves, Leonardo S.; Gomes, Harrison M.; Gomes, Lia L.; Almeida da Silva, Pedro; Perdigã o, Joã o; Portugal, Isabel; Viveiros, Miguel; McNerney, Ruth; Pain, Arnab; Clark, Taane G.; Rastogi, Nalin; Unis, Gisela; Rossetti, Maria Lucia R.; Suffys, Philip Noel

    2015-01-01

    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.

  20. 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.

  1. [Active tuberculosis in a cohort of HIV-infected inmates in a prison in Mexico City: clinical and epidemiological characteristics].

    Science.gov (United States)

    Hernández-León, Christian; Badial-Hernández, Florentino; Ponce-de-León, Alfredo; Sierra-Madero, Juan G; Martínez-Gamboa, Areli; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio; González-Aguirre, Adrián; Guerrero-Almeida, María de Lourdes; del Valle, J Miriam Bobadilla; González-Rodríguez, Andrea; Sifuentes-Osornio, José

    2012-01-01

    To determine the clinical and epidemiological characteristics of prison inmates with active tuberculosis in HIV-positive prison populations. We conducted a cohort study in HIV-infected subjects in a prison in Mexico City, with the aim of determining clinical and epidemiological characteristics of cases with active TB. We detected 172 HIV infected inmates and TB in 28 of them (16.3%) - 21 (12.2) with pulmonary TB--with an incidence rate of 7.7/100 persons/year for active TB and 4.7/100 persons/year for pulmonary TB. No drug resistance was found. Two clusters (4 and 2 subjects) were observed after RFLP-typing of 18 isolates, with a transmission rate of 11% by molecular and clinical analysis. The prevalence of active TB was found to be a thousand times greater than in the general population. Evidence of transmission inside the prison was also found.

  2. 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

    Science.gov (United States)

    Kim, Hye Won; Kwon, Seong Ryul; Jung, Kyong-Hee; Kim, Seong-Kyu; Baek, Han Joo; Seo, Mi Ryung; Bang, So-Young; Lee, Hye-Soon; Suh, Chang-Hee; Jung, Ju Yang; Son, Chang-Nam; Shim, Seung Cheol; Lee, Sang-Hoon; Lee, Seung-Geun; Lee, Yeon-Ah; Lee, Eun Young; Kim, Tae-Hwan

    2016-01-01

    Backgrounds 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. Methods 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. Findings 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). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early

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

    Directory of Open Access Journals (Sweden)

    Lee Choon-Taek

    2010-10-01

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

  4. MicroRNA-223 Is Upregulated in Active Tuberculosis Patients and Inhibits Apoptosis of Macrophages by Targeting FOXO3.

    Science.gov (United States)

    Xi, Xiue; Zhang, Chunxiao; Han, Wei; Zhao, Huayang; Zhang, Huiqiang; Jiao, Junhua

    2015-12-01

    Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB). In this study, we aimed to investigate the role of microRNA-223 (miR-223) in macrophage apoptosis of TB. We analyzed apoptosis in peripheral blood macrophages of active TB patients, infected human macrophages (TDMs and MDMs) with the Mycobacterium tuberculosis (Mtb) strain H37Rv, and observed the expression of miR-223 to investigate the relationship between miR-223 and macrophage apoptosis induced by Mtb. The apoptosis rate of peripheral blood macrophages decreased in active TB patients compared with healthy controls, and miR-223 expression increased significantly in macrophages after H37Rv infection. Transfection of human macrophages (TDMs and MDMs) with miR-223 inhibited macrophage apoptosis. We also demonstrated that miR-223 directly suppressed forkhead box O3 (FOXO3), and FOXO3 played a critical role as a mediator of the biological effects of miR-223 in macrophage apoptosis. The overexpression of FOXO3 remarkably reversed the apoptosis inhibitory effect of miR-223. Our data provide new clues for the essential role of miR-223 in the regulation of anti-Mtb-directed immune responses, which relies on the regulation of FOXO3 expression.

  5. Differential expression of miRNAs and their relation to active tuberculosis.

    Science.gov (United States)

    Xu, Zhihong; Zhou, Aiping; Ni, Jinjing; Zhang, Qiufen; Wang, Ying; Lu, Jie; Wu, Wenjuan; Karakousis, Petros C; Lu, Shuihua; Yao, Yufeng

    2015-07-01

    The aim of this work was to screen miRNA signatures dysregulated in tuberculosis to improve our understanding of the biological role of miRNAs involved in the disease. Datasets deposited in publically available databases from microarray studies on infectious diseases and malignancies were retrieved, screened, and subjected to further analysis. Effect sizes were combined using the inverse-variance model and between-study heterogeneity was evaluated by the random effects model. 35 miRNAs were differentially expressed (12 up-regulated, 23 down-regulated; p tuberculosis and other infectious diseases. 15 miRNAs were found to be significantly differentially regulated (7 up-regulated, 8 down-regulated; p tuberculosis and malignancies. Most of the miRNA signatures identified in this study were found to be involved in immune responses and metabolism. Expression of these miRNA signatures in serum samples from TB subjects (n = 11) as well as healthy controls (n = 10) was examined by TaqMan miRNA array. Taken together, the results revealed differential expression of miRNAs in TB, but available datasets are limited and these miRNA signatures should be validated in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. [Penile Tuberculosis : A Case Report].

    Science.gov (United States)

    Imanaka, Takahiro; Nomura, Hironori; Tsujimura, Go; Ko, Yoko; Kinjyo, Takanori; Yoshioka, Iwao; Takada, Shingo; Yahata, Yoko; Mizutani, Tetsu

    2017-04-01

    A 66-year-old man presented with a chief complaint of glans penis pain, induration, and discharge of pus. He was prescribed a course of antibiotics, but the condition persisted despite treatment. Thus, we differrentially diagnosed the patient with penile tuberculosis and pyoderma gangrenosum, and performed a biopsy of the penis. The biopsy result was thickening of the horny layer epidermis with only a foreign body granuloma composed of inflammatory cells, and did not lead to a definitive diagnosis. Thoraca-abdominal computed tomography revealed axillary lymphadenopathy with necrosis. Suspecting tuberculosis lymphadenitis, we performed T-spot and QuantiFERONtests. The result was T-spot negative and QuantiFERONpositive, so we diagnosed the patient with penile tuberculosis, and started antituberculosis medication. In about half a year after the start of treatment the symptoms subsided, and lymphadenopathy showed reduction.

  7. The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA

    DEFF Research Database (Denmark)

    Greenaway, Christina; Pareek, Manish; Abou Chakra, Claire-Nour

    2018-01-01

    BACKGROUND: The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods: We conducted a systematic review to determine effectiveness (yield...... and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results: We identified six systematic reviews, one report and three individual...... studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110-2,340), migrant type (170-1,192), TB incidence in source...

  8. Diagnosis and treatment of spinal tuberculosis after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Peng-Cheng Gu; Rong-Huan Wu; Xiang-Jin Lin

    2009-01-01

    BACKGROUND: Spinal tuberculosis is a common disease in orthopedic clinical practice; however, it is seldom reported after organ transplantation. The aim of this study was to investigate the diagnosis and treatment of spinal tuberculosis after organ transplantation. METHOD: Two cases were diagnosed as spinal tuberculosis after liver transplantation and were treated with socarboxazide, rifampicin, streptomycin and ethambutol for more than one year. RESULTS: After treatment with anti-tuberculosis drugs for several months, the symptoms of both patients clearly improved. Back pain disappeared, and erythrocyte sedimentation and body temperature returned to normal. CONCLUSIONS: We should highly suspect spinal tuberculosis if notalgia and night sweats are present after organ transplantation. Anti-tuberculosis therapy is an effective treatment for spinal tuberculosis after organ transplantation.

  9. 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.

  10. Lateral Flow Urine Lipoarabinomannan Assay (LF-LAM) for Diagnosis of Active Tuberculosis in HIV-Infected Adults: a Prospective Cohort Study

    Science.gov (United States)

    Na Songkhla, Munjit; Tantipong, Hutsaya; Tongsai, Sasima; Angkasekwinai, Nasikarn

    2017-01-01

    Abstract Background Early diagnosis and treatment of active tuberculosis (TB) in HIV-positive patients is challenging. Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care tests for TB. However, limited data exists on their performance among HIV-TB co-infected patients from Southeast Asian countries. Methods We prospectively recruited HIV-positive adult patients with CD4 count less than or equal to 200/mm3 and symptoms suspected of active TB from two tertiary hospitals between December 2015 and March 2017. Freshly collected urine was applied to the Determine®-TB LAM Ag test strip (4 bands of graded intensity), using grade 1 cutoff. Diagnostic accuracy of urine LAM strip test were assessed against microbiological reference standard, defined as positive Mycobacterium tuberculosis cultured from one or more clinical specimens (definite TB) or composite reference standard including definite TB and probable TB, defined as those have symptoms consistent with TB and response to anti-TB treatment. Results A total of 280 patients were enrolled. Of whom, 72 (25.7%) and 65 (23.2%) had definite and probable TB. Amongst those with definite TB, LF-LAM test gave a sensitivity of 75.0% (95% CI 63.9–83.6), specificity of 86.0% (95% CI 79.4–90.8) and accuracy of 82.3% (95% CI 76.7–86.8). When compared with the composite reference standard, the test yielded a lower sensitivity (61.3%, 95% CI 53.0–69.1) and accuracy (73.9%, 95% CI 68.5–78.7), with equal specificity. The test showed the highest sensitivity (90.5%, 95% CI 77.9–96.2) and accuracy (85.9%, 95% CI 79.2–90.7) but lower specificity (84.0%, 95% CI 75.6–89.9) in HIV-infected patients with CD4 count less than 50/mm3. The sensitivity of the combined LF-LAM or sputum microscopy was higher than that of either test alone (86.1% vs. 75.0%, 61.1%, respectively). Mycobacterium avium complex (MAC) was cultured in 7 out of 20 with false positive

  11. Tuberculosis neonatal

    OpenAIRE

    Pastor Durán, Xavier

    1986-01-01

    PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..

  12. Validation of a homology model of Mycobacterium tuberculosis DXS: rationalization of observed activities of thiamine derivatives as potent inhibitors of two orthologues of DXS.

    Science.gov (United States)

    Masini, T; Lacy, B; Monjas, L; Hawksley, D; de Voogd, A R; Illarionov, B; Iqbal, A; Leeper, F J; Fischer, M; Kontoyianni, M; Hirsch, A K H

    2015-12-14

    The enzyme DXS catalyzes the first, rate-limiting step of the 2-C-methyl-d-erythritol-4-phosphate (MEP, 1) pathway using thiamine diphosphate (ThDP) as cofactor; the DXS-catalyzed reaction constitutes also the first step in vitamin B1 and B6 metabolism in bacteria. DXS is the least studied among the enzymes of this pathway in terms of crystallographic information, with only one complete crystal structure deposited in the Protein Data Bank (Deinococcus radiodurans DXS, PDB: ). We synthesized a series of thiamine and ThDP derivatives and tested them for their biochemical activity against two DXS orthologues, namely D. radiodurans DXS and Mycobacterium tuberculosis DXS. These experimental results, combined with advanced docking studies, led to the development and validation of a homology model of M. tuberculosis DXS, which, in turn, will guide medicinal chemists in rationally designing potential inhibitors for M. tuberculosis DXS.

  13. 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.

  14. Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection.

    Science.gov (United States)

    Santin, Miguel; García-García, José-María; Rigau, David; Altet, Neus; Anibarro, Luis; Casas, Irma; Díez, Nuria; García-Gasalla, Mercedes; Martínez-Lacasa, Xavier; Penas, Antón; Pérez-Escolano, Elvira; Sánchez, Francisca; Domínguez, José

    2016-09-01

    Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. The mass miniature chest radiography programme in Cape Town, South Africa, 1948-1994: The impact of active tuberculosis case finding

    NARCIS (Netherlands)

    Hermans, S. M.; Andrews, J. R.; Bekker, L.-G.; Wood, R.

    2016-01-01

    Tuberculosis (TB) control programmes rely mainly on passive detection of symptomatic individuals. The resurgence of TB has rekindled interest in active case finding. Cape Town (South Africa) had a mass miniature radiography (MMR) screening programme from 1948 to 1994. To evaluate screening coverage,

  16. 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...

  17. Mutation of katG in a clinical isolate of Mycobacterium tuberculosis: effects on catalase-peroxidase for isoniazid activation.

    Science.gov (United States)

    Purkan; Ihsanawati; Natalia, D; Syah, Y M; Retnoningrum, D S; Kusuma, H S

    2016-01-01

    Mutations in katG gene are often associated with isoniazid (INH) resistance in Mycobacterium tuberculosis strain. This research was perfomed to identify the katG mutation in clinical isolate (L8) that is resistant to INH at 1 μg/ml. In addition to characterize the catalase-peroxidase of KatG L8 and perform the ab initio structural study of the protein to get a more complete understanding in drug activation and the resistan­ce mechanism. The katG gene was cloned and expressed in Escherichia coli, then followed by characterization of catalase-peroxidase of KatG. The structure modelling was performed to know a basis of alterations in enzyme activity. A substitution of A713G that correspond to Asn238Ser replacement was found in the L8 katG. The Asn238Ser modification leads to a decline in the activity of catalase-peroxidase and INH oxidation of the L8 KatG protein. The catalytic efficiency (Kcat/KM) of mutant KatGAsn238Ser respectively decreases to 41 and 52% for catalase and peroxidase. The mutant KatGAsn238Ser also shows a decrease of 62% in INH oxidation if compared to a wild type KatG (KatGwt). The mutant Asn238Ser might cause instability in the substrate binding­ site of KatG, because of removal of a salt bridge connecting the amine group of Asn238 to the carbo­xyl group of Glu233, which presents in KatGwt. The lost of the salt bridge in the substrate binding site in mutant KatGAsn238Ser created changes unfavorable for enzyme activities, which in turn emerge as INH resistan­ce in the L8 isolate of M. tuberculosis.

  18. 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.

  19. Standardized radiographic interpretation of thoracic tuberculosis in children

    International Nuclear Information System (INIS)

    Concepcion, Nathan David P.; Laya, Bernard F.; Andronikou, Savvas; Daltro, Pedro A.N.; Sanchez, Marion O.; Uy, Jacqueline Austine U.; Lim, Timothy Reynold U.

    2017-01-01

    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.)

  20. 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.)

  1. Standardized radiographic interpretation of thoracic tuberculosis in children.

    Science.gov (United States)

    Concepcion, Nathan David P; Laya, Bernard F; Andronikou, Savvas; Daltro, Pedro A N; Sanchez, Marion O; Uy, Jacqueline Austine U; Lim, Timothy Reynold U

    2017-09-01

    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.

  2. Learn About Tuberculosis

    Science.gov (United States)

    ... Diseases > Lung Disease Lookup > Tuberculosis (TB) Learn About Tuberculosis Tuberculosis (TB) is an airborne bacterial infection caused by the organism Mycobacterium tuberculosis that primarily affects the lungs, although other organs ...

  3. Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model.

    Science.gov (United States)

    Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

    2016-01-01

    The evolution of a tuberculosis (TB) infection toward 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 fluctuations, 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 toward 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 progression of

  4. 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

  5. Anti-Tuberculosis Activity of Extract Ethyl Acetate Kenikir Leaves (Cosmos caudatus H.B.K and Sendok Leaves (Plantago Major L. By In Vitro Test

    Directory of Open Access Journals (Sweden)

    Tatang Irianti

    2018-04-01

    Full Text Available The increasing therapy problem including multidrug-resistant tuberculosis (TB has made it important to discover a new anti-TB drug candidate. The aim of this study was to acknowledge the activity of ethyl acetate extracts of kenikir (Cosmos caudatus H.B.K and sendok (Plantago major L. leaves against Mycobacterium tuberculosis (M. tuberculosis H37Rv. This research used Middlebrook (MB 7H9 media and observed the growth of M. tuberculosis using Lowenstein Jensen (LJ media. The concentration of extracts were 0.25 mg/ml, 0.50 mg/ml, and 1.00 mg/ml. The result of this study showed that ethyl acetate extracts exhibited anti-TB activity in 1000 µg/ml of both extracts. The active compound group was detected by thin layer chromatography (TLC and the separation of compounds was shown by retardation factor (Rf and the color of the spots. Based on TLC chromatograms, it is known that there are types of compounds, such as ortho-dihydroxy compounds, phenolic compounds, and compound leads to terpenoids for both extracts.

  6. 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.

  7. 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

  8. 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

  9. Gastrointestinal tuberculosis.

    Science.gov (United States)

    Galloway, D J; Scott, R N

    1986-10-01

    In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

  10. New indicators proposed to assess tuberculosis control and elimination in Cuba.

    Science.gov (United States)

    González, Edilberto R; Armas, Luisa

    2012-10-01

    Following 48 years of successful operation of the National Tuberculosis Control Program, Cuban health authorities have placed tuberculosis elimination on the agenda. To this end some tuberculosis control processes and their indicators need redesigned and new ones introduced, related to: number and proportion of suspected tuberculosis cases among vulnerable population groups; tuberculosis suspects with sputum microscopy and culture results useful for diagnosis (interpretable); and number of identified contacts of reported tuberculosis cases who were fully investigated. Such new indicators have been validated and successfully implemented in all provinces (2011-12) and are in the approval pipeline for generalized use in the National Tuberculosis Control Program. These indicators complement existing criteria for quality of case detection and support more comprehensive program performance assessment.

  11. Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning.

    Science.gov (United States)

    Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

    2013-02-02

    Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. The prioritization of appropriate target

  12. DIFFERENTIAL DIAGNOSTICS OF PROSTATE TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    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.

  13. Diagnostic utility of 99mTc-EDDA-tricine-HYNIC-Tyr3-octreotate SPECT for differentiation of active from inactive pulmonary tuberculosis.

    Science.gov (United States)

    Ahmadihosseini, Hossein; Abedi, Javad; Ghodsi Rad, Mohammad A; Zakavi, Seyed R; Knoll, Peter; Mirzaei, Siroos; Sadeghi, Ramin

    2014-12-01

    The current study was performed to evaluate the impact of Tc-EDDA-tricine-HYNIC-Tyr-octreotate in the differentiation of active from inactive pulmonary tuberculosis lesions. Ten consecutive patients (six male and four female, age range 24-83 years) with proven pulmonary tuberculosis (with a positive smear or culture) were enrolled in the study. At 120 min after injection of 740 MBq of Tc-EDDA-tricine-HYNIC-Tyr-octreotate, planar and single-photon emission computed tomography (SPECT) images of the thorax were taken. A semiquantitative evaluation of lesion and nonlesion areas was performed. The scan was repeated following the same protocol after standard treatment for tuberculosis after a negative sputum culture. Semiquantitative evaluation of the lesions showed a statistically significant higher uptake before treatment in both planar and SPECT images (P=0.005 and 0.007, respectively). Lesion-to-nonlesion ratios were also higher in the pretreatment sets on both planar and SPECT images (1.4±0.2 vs. 1.19±0.15, P=0.001, for planar images and 2.32±0.55 vs. 1.32±0.32, P=0.0001, for SPECT images). Tc-EDDA-tricine-HYNIC-Tyr-octreotate scintigraphy may help to differentiate between active and inactive pulmonary tuberculosis. SPECT imaging and semiquantitative evaluation are indispensable for increasing the diagnostic yield of this method. Larger studies are needed to corroborate our results.

  14. 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.

  15. [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

  16. 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

  17. Duodenal tuberculosis

    International Nuclear Information System (INIS)

    Mirza, M.R.; Sarwar, M.

    2004-01-01

    Tuberculosis is a world wide communicable disease caused by tubercle bacilli discovered by Robert Kock in 1882. In 1993 WHO declared TB as a global emergency due to its world wide resurgence. It can involve any organ of the body. Abdomen is the fourth commonest site of involvement in the extra pulmonary tuberculosis after the lymph-nodes, skeletal and Genito urinary variants. In the gastro intestinal tract tuberculosis can affect any part from the mouth to the anus but ileocaecal area is a favourite location. Duodenal involvement is uncommon and accounts for only 2.5% of tuberculous enteritis. Major pathogens are Mycobacterium Tuberculosis and bovis and the usual route of entry is by direct penetration of the intestinal mucosa by swallowed organisms. (author)

  18. 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

    . 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......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...... 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...

  19. A case of skeletal tuberculosis and psoas abscess: disease activity evaluated using (18) F-fluorodeoxyglucose positron emission tomography-computed tomography.

    Science.gov (United States)

    Kimizuka, Yoshifumi; Ishii, Makoto; Murakami, Koji; Ishioka, Kota; Yagi, Kazuma; Ishii, Ken; Watanabe, Kota; Soejima, Kenzo; Betsuyaku, Tomoko; Hasegawa, Naoki

    2013-11-14

    Psoas abscess complicating tuberculous spondylitis is a rare morbidity in extrapulmonary tuberculosis. There are no established guidelines for evaluating the clinical response of psoas abscess. Although several studies have shown that positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose can play a potential role in diagnosing multifocal tuberculosis and monitoring the clinical response of pulmonary tuberculosis, to our knowledge, this is the first report demonstrating that positron emission tomography-computed tomography is useful for evaluating local inflammation and disease activity of a tuberculous psoas abscess. We report a case of multifocal bone and lymph node tuberculosis with concomitant lumbar psoas abscess in a 77-year-old man, along with a literature review. An initial positron emission tomography-computed tomography scan showed intense 18 F-fluorodeoxyglucose accumulation in the sternum, ribs, vertebrae, and lymph nodes. The patient was successfully treated with antitubercular agents and computed tomography-guided drainage therapy. A follow-up positron emission tomography-computed tomography after abscess drainage and 9 months of antitubercular drug treatment revealed that the majority of lesions improved; however, protracted inflammation surrounding the psoas abscess was still observed. These results indicate that disease activity of psoas abscess can remain, even after successful drainage and antitubercular medication regime of appropriate duration. We have successfully followed up the extent of skeletal tuberculosis complicated with psoas abscess by positron emission tomography-computed tomography. In this patient, positron emission tomography-computed tomography is useful for evaluating the disease activity of tuberculous psoas abscess and for assessing the appropriate duration of antitubercular drug therapy in psoas abscess.

  20. A case of skeletal tuberculosis and psoas abscess: disease activity evaluated using 18 F-fluorodeoxyglucose positron emission tomography-computed tomography

    International Nuclear Information System (INIS)

    Kimizuka, Yoshifumi; Hasegawa, Naoki; Ishii, Makoto; Murakami, Koji; Ishioka, Kota; Yagi, Kazuma; Ishii, Ken; Watanabe, Kota; Soejima, Kenzo; Betsuyaku, Tomoko

    2013-01-01

    Psoas abscess complicating tuberculous spondylitis is a rare morbidity in extrapulmonary tuberculosis. There are no established guidelines for evaluating the clinical response of psoas abscess. Although several studies have shown that positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose can play a potential role in diagnosing multifocal tuberculosis and monitoring the clinical response of pulmonary tuberculosis, to our knowledge, this is the first report demonstrating that positron emission tomography-computed tomography is useful for evaluating local inflammation and disease activity of a tuberculous psoas abscess. We report a case of multifocal bone and lymph node tuberculosis with concomitant lumbar psoas abscess in a 77-year-old man, along with a literature review. An initial positron emission tomography-computed tomography scan showed intense 18 F-fluorodeoxyglucose accumulation in the sternum, ribs, vertebrae, and lymph nodes. The patient was successfully treated with antitubercular agents and computed tomography-guided drainage therapy. A follow-up positron emission tomography-computed tomography after abscess drainage and 9 months of antitubercular drug treatment revealed that the majority of lesions improved; however, protracted inflammation surrounding the psoas abscess was still observed. These results indicate that disease activity of psoas abscess can remain, even after successful drainage and antitubercular medication regime of appropriate duration. We have successfully followed up the extent of skeletal tuberculosis complicated with psoas abscess by positron emission tomography-computed tomography. In this patient, positron emission tomography-computed tomography is useful for evaluating the disease activity of tuberculous psoas abscess and for assessing the appropriate duration of antitubercular drug therapy in psoas abscess

  1. 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

  2. MiR-155 is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO3.

    Science.gov (United States)

    Huang, Jian; Jiao, Junhua; Xu, Weihua; Zhao, Huayang; Zhang, Chunxiao; Shi, Yan; Xiao, Zhijian

    2015-11-01

    The aim of the present study was to investigate the association between microRNA (miR)-155 and apoptosis of monocytes infected by Mycobacterium tuberculosis, to examine the effect of forkhead box O3 (FOXO3) on miR‑155. The present study analysed the apoptosis of CD14+ in the peripheral blood of patients with active tuberculosis, disposed the THP‑1 human monocytic cell line by BCG and examined the expression of miR‑155. Furthermore, the expression of FOXO3 in THP‑1 cells was determined, and wild- and mutant-type luciferase reporter plasmids containing FOXO3 3'‑untranslated regions (UTRs) were constructed to analyse the expression of luciferase. Finally, an over‑expression plasmid was constructed, and THP-1 cells were transfected with control miRNA, miR‑155 and the plasmid, which revealed that miR‑155 inhibited the apoptosis of THP‑1 cells. miR‑155 in the THP‑1 cells infected by BCG was upregulated and apoptosis also increased. However, the apoptosis declined when the cells were transfected with the control miRNA and miR‑155. Folllowing transfection with miR‑155, the expression of FOXO3 decreased. Transfection with miR‑155 and the FOXO3 3'-UTRs significantly reduced luciferase, and overexpression of FOXO3 reversed the inhibitory role of miR‑155. From these results, it was concluded that mycobacteria can improve the level of miR‑155, while BCG can induce apoptosis in THP‑1 cells. The results suggested FOXO3 is a downstream target gene of miR‑155, which combines 3'-UTRs to inhibit the expression of FOXO3.

  3. 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.

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

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    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

  5. Healthcare Worker Preferences for Active Tuberculosis Case Finding Programs in South Africa: A Best-Worst Scaling Choice Experiment.

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    Nathan N O'Hara

    Full Text Available Healthcare workers (HCWs in South Africa are at a high risk of developing active tuberculosis (TB due to their occupational exposures. This study aimed to systematically quantify and compare the preferred attributes of an active TB case finding program for HCWs in South Africa.A Best-Worst Scaling choice experiment estimated HCW's preferences using a random-effects conditional logit model. Latent class analysis (LCA was used to explore heterogeneity in preferences."No cost", "the assurance of confidentiality", "no wait" and testing at the occupational health unit at one's hospital were the most preferred attributes. LCA identified a four class model with consistent differences in preference strength. Sex, occupation, and the time since a previous TB test were statistically significant predictors of class membership.The findings support the strengthening of occupational health units in South Africa to offer free and confidential active TB case finding programs for HCWs with minimal wait times. There is considerable variation in active TB case finding preferences amongst HCWs of different gender, occupation, and testing history. Attention to heterogeneity in preferences should optimize screening utilization of target HCW populations.

  6. Evaluation of a tuberculosis active case finding project in peri-urban areas, Myanmar: 2014-2016.

    Science.gov (United States)

    Aye, Sandar; Majumdar, Suman S; Oo, Myo Minn; Tripathy, Jaya Prasad; Satyanarayana, S; Kyaw, Nang Thu Thu; Kyaw, Khine Wut Yee; Oo, Nay Lynn; Thein, Saw; Thu, Myat Kyaw; Soe, Kyaw Thu; Aung, Si Thu

    2018-05-01

    We assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). Cross-sectional analysis of project records, township TB registers and annual TB reports. In the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. The yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. Diagnosis and Healing In Veterans Suspected of Suffering from Post-Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and Reward Circuitry Natural Dopaminergic Activation

    OpenAIRE

    Blum, Kenneth; Giordano, John; Oscar-Berman, Marlene; Bowirrat, Abdalla; Simpatico, Thomas; Barh, Debmalya

    2012-01-01

    There is a need for understanding and treating post-traumatic stress disorder (PTSD), in soldiers returning to the United States of America after combat. Likewise, it would be beneficial to finding a way to reduce violence committed by soldiers, here and abroad, who are suspected of having post-traumatic stress disorder (PTSD). We hypothesize that even before combat, soldiers with a childhood background of violence (or with a familial susceptibility risk) would benefit from being genotyped fo...

  8. Radiological manifestations of intestinal tuberculosis

    International Nuclear Information System (INIS)

    Im, Jae Hoon

    1974-01-01

    Radiological findings of 87 cases of intestinal tuberculosis are analyzed and presented. The diagnosis was based on histopathology in 29 cases, and on clinical ground and radiological findings in 58 cases. The radio of male and female patients was 4:6, and peak incidence is between 10 and 30. Abdominal pain, diarrhea, weight loss, fever and general weakness are frequent symptoms, and tenderness of abdomen, ascites with abdominal distension, malnutrition and emaciation are frequent signs of the patients. Laboratory investigation reveal anemia, raised ESR, hypoalbuminaemia and positive occult blood reaction in the stool in most of the patients. Chest film show activity pulmonary tuberculosis in only 1/3 patients. There is no pathognomonic radiological findings in intestinal tuberculosis and their manifestations are protean, and differentiation from other inflammatory diseases and malignant tumors in gastrointestinal tract is very difficult on radiological ground alone. However, in patients with complaining vague abdominal symptoms and signs, the radiological diagnosis is most certain means in the decision of existence of organic lesion and suggestion of tuberculosis in the gastrointestinal tract and its extent as yet. Multiplicity of the lesion, involvement of adjacent organ such as peritoneum or mesenteric lymph nodes, typical nodularity or irregularity of mesenteric border and existence of active pulmonary tuberculosis are the suggestive findings of intestinal tuberculosis. In the diagnosis of inflammatory disease or malignant tumor of gastrointestinal tract, the possibility of tuberculosis should be borne in mind, and vice versa

  9. Radiological manifestations of intestinal tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Im, Jae Hoon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-10-15

    Radiological findings of 87 cases of intestinal tuberculosis are analyzed and presented. The diagnosis was based on histopathology in 29 cases, and on clinical ground and radiological findings in 58 cases. The radio of male and female patients was 4:6, and peak incidence is between 10 and 30. Abdominal pain, diarrhea, weight loss, fever and general weakness are frequent symptoms, and tenderness of abdomen, ascites with abdominal distension, malnutrition and emaciation are frequent signs of the patients. Laboratory investigation reveal anemia, raised ESR, hypoalbuminaemia and positive occult blood reaction in the stool in most of the patients. Chest film show activity pulmonary tuberculosis in only 1/3 patients. There is no pathognomonic radiological findings in intestinal tuberculosis and their manifestations are protean, and differentiation from other inflammatory diseases and malignant tumors in gastrointestinal tract is very difficult on radiological ground alone. However, in patients with complaining vague abdominal symptoms and signs, the radiological diagnosis is most certain means in the decision of existence of organic lesion and suggestion of tuberculosis in the gastrointestinal tract and its extent as yet. Multiplicity of the lesion, involvement of adjacent organ such as peritoneum or mesenteric lymph nodes, typical nodularity or irregularity of mesenteric border and existence of active pulmonary tuberculosis are the suggestive findings of intestinal tuberculosis. In the diagnosis of inflammatory disease or malignant tumor of gastrointestinal tract, the possibility of tuberculosis should be borne in mind, and vice versa.

  10. Antimycobacterial activity assessment of three ethnobotanical plants against Mycobacterium Tuberculosis: An In Vitro study.

    Science.gov (United States)

    Arjomandzadegan, Mohammad; Emami, Navid; Habibi, Ghasem; Farazi, Ali Asghar; Kahbazi, Manijeh; Sarmadian, Hossein; Jabbari, Mansooreh; Hosseini, Hossein; Ramezani, Mona

    2016-12-01

    Resistances to herbal medicines are still not defined and finding natural remedies against drug resistant Mycobacterium tuberculosis (MTB) has research priority. The antimycobacterial susceptibility method for herbal extracts is unclearly defined and there is no standard method for assessment of the materials against bacteria. In the present study, time kill of three medicinal plants was determined against MTB. The clinical isolate of MTB from a patient who harbored confirmed tuberculosis was used in the study. Aqueous extracts of Aloe vera leaves, mint, and Hypericum perforatum were prepared using reflux distillation. Disk diffusion methods were conducted in Petri dishes and McCartney bottles containing Löwenstein-Jensen medium to measure the sensitivity of plant extracts in serial concentrations of 0.25-8mg/mL. A pour plate method was performed by mixing 0.7mL of each concentration of extract in 5mL Löwenstein-Jensen medium followed by surface culturing of MTB fresh cells. The time kill method was conducted by bacterial suspension in equal amounts of the extract and viable evaluation in fresh culture at the beginning, and at 24-h, 48-h, 72-h, and 1-week intervals. All cultures were incubated at 37°C for 4weeks. Inoculum concentrations were considered as a variable. The zones of inhibition of A. vera, H. perforatum, and mint extracts in the disk diffusion method in McCartney bottles were 60mm, 41mm, and zero, respectively, but Petri dishes did not have repeatable results. In the pour plate method, an extract concentration up to 1mg/mL could inhibit cell growth. In mint extract, colony forming was four times more than the others at 0.5mg/mL. Time kill of 95% of cells occurred when exposed to extracts of A. vera and H. perforatum separately, but was 50% in 24 h and 20% in 10 min. The time kill for mint was 95% in 1week. The results give some scientific basis to the use of plant extracts for growth control of MTB cells. Clinical trials are recommended for

  11. Importance of Therapeutic Drug Monitoring in the Treatment of Active Tuberculosis - A Retrospective Study of 4 Cases

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    Sanaa HAMMI

    2016-06-01

    Full Text Available Background: In the treatment of active tuberculosis, therapeutic drug monitoring (TDM is used to optimize dosing that maximizes therapeutic benefit while minimizing toxicity. In Morocco, TDM is not routinely used, yet low levels of anti-TB drugs can be associated with poorer treatment outcomes.Methods: We retrospectively checked our archives for patients with active TB for whom TDM was performed during 2014. Medical records were reviewed to abstract demographic, clinical, radiographic and microbiological data including time until smear and culture conversion. Then, we looked for cases with delay of TB conversion.Results: In total, 24 patients were identified, for whom TDM was performed, they all had low serum drug levels. Among them, 4 patients showed delayed bacteriological conversion.Conclusions: Our study cases are showing the benefit of serum dosage in the follow-up of the patients showing a delay of sputum examination conversion, both direct and culture, during their evolutions. TDM is potentially useful for the treatment of active TB, but is currently underused in Morocco.

  12. Characteristics and outcomes of end-stage renal disease patients with active tuberculosis followed in intensive care units

    International Nuclear Information System (INIS)

    Ulasli, Sevinc Sarinc; Ulubay, Gaye; Arslan, Nevra Gullu; Akcay, Sule; Eyuboglu, Fusun Oner; Sezer, Siren; Haberal, Mehmet

    2009-01-01

    Tuberculosis (TB) remains a common problem in patients with chronic renal failure. In intensive care units, misdiagnosis or delayed diagnosis of TB is common. Therefore, a description of characteristics of active TB in patients with renal failure followed in intensive care units is important to reduce mortality and transmission of the disease. This study was performed to describe the characteristics of patients with renal failure admitted to the intensive care units and having active TB and evaluate predictive factors for in hospital mortality. The hospital records of 24 patients (11 women, 13 men) having ESRD and TB between 2001-2006 were reviewed. Clinical, radiological, and laboratory data on admission were recorded. Possible parameters contributing to in-hospital mortality were obtained from the medical records. In-hospital mortality rate was 66.6%. Factors associated with mortality were decreased partial pressure of oxygen and malnutrition. Fever was reported in 8 patients and hemoptysis was reported in 3 patients. Eight patients had consolidation on chest radiograph, while 4 had normal findings Seventeen patients had pulmonary involvement, and 11 had extra pulmonary involvement. The mortality rate in TB patients followed in intensive care units is high, with 3 factors contributing to in-hospital mortality. Clinicians should consider active TB in renal failure patients being followed in the intensive care unit, even when results of a chest radiograph are normal especially in patients with unexplained poor general health or respiratory failure. (author)

  13. 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.

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    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

  14. Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis

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    Valéria G. F. Pinheiro

    Full Text Available Low antimycobacterial drug concentrations have been observed in tuberculosis (TB patients under treatment. The lactulose/mannitol urinary excretion test (L/M, normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R and isoniazid (H were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL or H (3-6 mcg/mL in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.

  15. Collaborative activities and treatment outcomes in patients with HIV-associated tuberculosis in Viet Nam.

    Science.gov (United States)

    Huyen, T T T; Nhung, N V; Shewade, H D; Hoa, N B; Harries, A D

    2016-03-21

    The National Tuberculosis (TB) Programme in Viet Nam and Ho Chi Minh City (HCMC). To determine 1) at national level between 2011 and 2013, the relationship between human immunodeficiency virus (HIV) testing, uptake of TB-HIV interventions and adverse treatment outcomes among TB-HIV patients; and 2) in HCMC in 2013, patient characteristics associated with adverse outcomes. An ecological study reviewing aggregate nationwide data and a retrospective cohort review in HCMC. Nationwide, from 2011 to 2013, HIV testing increased in TB patients from 58% to 68% and antiretroviral therapy (ART) increased in TB-HIV patients from 54% to 63%. Adverse treatment outcomes in TB-HIV patients increased from 24% to 27%, largely due to transfer out (5-9% increase) and death. The Northern and Highland regions showed poor uptake of TB-HIV interventions. In HCMC, 303 (27%) of 1110 TB-HIV patients had adverse outcomes, with higher risks observed in those with previously treated TB, those diagnosed as HIV-positive before TB onset and those never placed on cotrimoxazole or ART. Despite improving HIV testing rates and TB-HIV interventions, adverse outcomes in TB-HIV patients remain at about 26%. Characteristics predicting higher risk of adverse outcomes must be addressed if Viet Nam wishes to end the TB epidemic by 2030.

  16. 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.

  17. 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.

  18. Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection

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    Lawrence Shih-Hsin Wu

    2014-01-01

    Full Text Available Tuberculosis (TB is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI, with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.

  19. Systematic expression profiling analysis identifies specific microRNA-gene interactions that may differentiate between active and latent tuberculosis infection.

    Science.gov (United States)

    Wu, Lawrence Shih-Hsin; Lee, Shih-Wei; Huang, Kai-Yao; Lee, Tzong-Yi; Hsu, Paul Wei-Che; Weng, Julia Tzu-Ya

    2014-01-01

    Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic--the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.

  20. 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 ...

  1. 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 ...

  2. 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.

  3. 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.

  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. Treatment of Latent Tuberculosis Infection

    OpenAIRE

    Tang, Patrick; Johnston, James

    2017-01-01

    Opinion statement The treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) elimination in regions that have a low incidence of TB. However, the decision to treat individuals with LTBI must consider the limitations of current diagnostic tests for LTBI, the risk of developing active TB disease, the potential adverse effects from chemoprophylactic therapy, and the importance of treatment adherence. When an individual has been diagnosed with LTBI and ac...

  6. Detection of lipoarabinomannan as a diagnostic test for tuberculosis.

    OpenAIRE

    Sada, E; Aguilar, D; Torres, M; Herrera, T

    1992-01-01

    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 favo...

  7. Influence of diabetes mellitus and risk factors in activating latent tuberculosis infection: a case for targeted screening in malaysia.

    Science.gov (United States)

    Swarna Nantha, Y

    2012-10-01

    A review of the epidemiology of tuberculosis, its contributing risk factors (excluding HIV) and the role of screening latent tuberculosis infection in Malaysia was done. Despite the global and domestic decrease in prevalence rates of tuberculosis in the past decade, there is an alarming increase in the trend of non communicable diseases in the country. High prevalence rates of major risk factors leading to reactivation of tuberculosis were seen within the population, with diabetes mellitus being in the forefront. The rising numbers in the ageing population of Malaysia poses a further threat of re-emergence of tuberculosis in the years to come. Economically, screening of diabetic patients with comorbidities for latent tuberculosis infection (LTBI) using two major techniques, namely tuberculin sensitivity (TST) and Interferon gamma release assay tests (IGRA) could be a viable option. The role of future research in the detection of LTBI in the Malaysian setting might be necessary to gauge the disease reservoir before implementing prophylactic measures for high risk groups involved.

  8. Evaluating Fluoroquinolone Use in Patients Admitted to the Tuberculosis Outpatient Clinic

    Directory of Open Access Journals (Sweden)

    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.

  9. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    OpenAIRE

    Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

    2012-01-01

    Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

  10. 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

  11. 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.

  12. Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

    NARCIS (Netherlands)

    Heuvelings, Charlotte C.; de Vries, Sophia G.; Greve, Patrick F.; Visser, Benjamin J.; Bélard, Sabine; Janssen, Saskia; Cremers, Anne L.; Spijker, René; Shaw, Beth; Hill, Ruaraidh A.; Zumla, Alimuddin; Sandgren, Andreas; van der Werf, Marieke J.; Grobusch, Martin P.

    2017-01-01

    Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a

  13. Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis.

    Science.gov (United States)

    Tasneen, Rokeya; Williams, Kathy; Amoabeng, Opokua; Minkowski, Austin; Mdluli, Khisimuzi E; Upton, Anna M; Nuermberger, Eric L

    2015-01-01

    New regimens based on two or more novel agents are sought in order to shorten or simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. PA-824 is a nitroimidazo-oxazine now in phase II trials and has shown significant early bactericidal activity alone and in combination with the newly approved agent bedaquiline or with pyrazinamide with or without moxifloxacin. While the development of PA-824 continues, a potential next-generation derivative, TBA-354, has been discovered to have in vitro potency superior to that of PA-824 and greater metabolic stability than that of the other nitroimidazole derivative in clinical development, delamanid. In the present study, we compared the activities of PA-824 and TBA-354 as monotherapies in murine models of the initial intensive and continuation phases of treatment, as well as in combination with bedaquiline plus pyrazinamide, sutezolid, and/or clofazimine. The monotherapy studies demonstrated that TBA-354 is 5 to 10 times more potent than PA-824, but selected mutants are cross-resistant to PA-824 and delamanid. The combination studies revealed that TBA-354 is 2 to 4 times more potent than PA-824 when combined with bedaquiline, and when administered at a dose equivalent to that of PA-824, TBA-354 demonstrated superior sterilizing efficacy. Perhaps most importantly, the addition of either nitroimidazole significantly improved the sterilizing activities of bedaquiline and sutezolid, with or without pyrazinamide, confirming the value of each agent in this potentially universally active short-course regimen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis.

    Science.gov (United States)

    De Groote, Mary A; Sterling, David G; Hraha, Thomas; Russell, Theresa M; Green, Louis S; Wall, Kirsten; Kraemer, Stephan; Ostroff, Rachel; Janjic, Nebojsa; Ochsner, Urs A

    2017-10-01

    New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant ( P CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform. Copyright © 2017 De Groote et al.

  15. Tuberculosis treatment outcome in a tertiary care setting

    International Nuclear Information System (INIS)

    Bukhary, Zakeya A.; Alrajhi, Abdulrahman A.

    2007-01-01

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

  16. Pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Juhl, J.H.

    1987-01-01

    Dissemination of the tubercle bacillus is of three types: bronchogenic, hematogenous, and lymphangitic. Bronchogenic dissemination occurs when exudate from a cavity or small area of caseation drains into a bronchus and is aspirated into previously uninfected areas either on the same or on the opposite side. This type of spreading occurs frequently after bleeding and when there is a cavity emptying into a bronchus. Hematogenous dissemination leads to miliary tuberculosis and to extrapulmonary lesions throughout the body. Acute massive hematogenous spread causes miliary tuberculosis, while chronic spread in smaller amounts usually results in the chronic extrapulmonary foci. Lymphangitic dissemination is common in primary infection. It is responsible for involvement with subsequent enlargement of hilar and mediastinal nodes that is often seen in children and in young black adults. The reaction to M. tuberculosis depends on the presence or absence of immunity to tuberculoprotein. In individuals having no tissue hypersensitivity or immunity, primary tuberculosis results. In those with immunity produced by previous infection or BCG vaccination, the reactivation (reinfection) disease may develop

  17. Tuberculosis Treatment

    African Journals Online (AJOL)

    Tuberculosis Treatment, Lusaka, Zambia. 1. 2. 2. 3. 3 ... TB treatment has contributed to the steady rise of TB incidence in ... respondents (89.4%) had positive attitude towards TB treatment ..... respondents described feelings of depression, anger and apathy .... Journal of Personality and Social Psychology,. 1979, 37:1-11.

  18. 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 ...

  19. Global Tuberculosis Report 2016

    Science.gov (United States)

    ... Alt+0 Navigation Alt+1 Content Alt+2 Tuberculosis (TB) Menu Tuberculosis Data and statistics Regional Framework Resources Meetings and events Global tuberculosis report 2017 WHO has published a global TB ...

  20. 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.

  1. Radiologic observation of renal tuberculosis

    International Nuclear Information System (INIS)

    Kim, S. W.; Ra, Y. W.; Kim, Y. J.

    1981-01-01

    Radiographic findings of thirty eight cases of renal tuberculosis treated at this hospital during last 4 years were analysed with following results. The cases examined were 24 male and 14 female patients. Age distribution was broad and evenly distributed ranging from 2nd decades to 5th decades. Main symptoms complained were urinary frequency, hematuria, dysuria and flank pain. Findings of physical examination revealed tenderness of costovertebral angle, palpable mass on flank area and epididymal indutration. The simple chest films showed pulmonary tuberculosis in 22 cases including 6 cases of active military type. Thirty one cases showed increased ESR, 8 cases showed AFB positive in urine and 12 cases showed bilateral renal tuberculosis. Through urographic findings nonvisualization, cyceopelviectasis, motheaten appearance of minor calyx, contracted bladder, delayed visualization, ureteral stricture and beading were observed in order of frequency. Five cases with miliary tuberculosis showed advanced renal lesion on urogram

  2. 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

  3. Active Site Loop Dynamics of a Class IIa Fructose 1,6-Bisphosphate Aldolase from Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Pegan, Scott D. [Univ. of Denver, CO (United States); Rukseree, Kamolchanok [National Center for Genetic Engineering and Biotechnology (BIOTEC), Tha Khlong (Thailand); Capodagli, Glenn C. [Univ. of Denver, CO (United States); Baker, Erica A. [Univ. of Denver, CO (United States); Krasnykh, Olga [Univ. of Illinois, Chicago, IL (United States); Franzblau, Scott G. [Univ. of Illinois, Chicago, IL (United States); Mesecar, Andrew D. [Purdue Univ., West Lafayette, IN (United States)

    2013-01-08

    The class II fructose 1,6-bisphosphate aldolases (FBAs, EC 4.1.2.13) comprises one of two families of aldolases. Instead of forming a Schiff base intermediate using an ε-amino group of a lysine side chain, class II FBAs utilize Zn(II) to stabilize a proposed hydroxyenolate intermediate (HEI) in the reversible cleavage of fructose 1,6-bisphosphate, forming glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). As class II FBAs have been shown to be essential in pathogenic bacteria, focus has been placed on these enzymes as potential antibacterial targets. Although structural studies of class II FBAs from Mycobacterium tuberculosis (MtFBA), other bacteria, and protozoa have been reported, the structure of the active site loop responsible for catalyzing the protonation–deprotonation steps of the reaction for class II FBAs has not yet been observed. We therefore utilized the potent class II FBA inhibitor phosphoglycolohydroxamate (PGH) as a mimic of the HEI- and DHAP-bound form of the enzyme and determined the X-ray structure of the MtFBA–PGH complex to 1.58 Å. Remarkably, we are able to observe well-defined electron density for the previously elusive active site loop of MtFBA trapped in a catalytically competent orientation. Utilization of this structural information and site-directed mutagenesis and kinetic studies conducted on a series of residues within the active site loop revealed that E169 facilitates a water-mediated deprotonation–protonation step of the MtFBA reaction mechanism. Furthermore, solvent isotope effects on MtFBA and catalytically relevant mutants were used to probe the effect of loop flexibility on catalytic efficiency. Additionally, we also reveal the structure of MtFBA in its holoenzyme form.

  4. 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

  5. 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...

  6. 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.

  7. Using giant African pouched rats to detect human tuberculosis

    African Journals Online (AJOL)

    ebutamanya

    2015-08-31

    Aug 31, 2015 ... Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. About one-third of Earth's population has latent TB, which means that they have been exposed to M. tuberculosis but not become ill. About 10% of people with latent TB develop active. TB, that is, they become ill with the disease, ...

  8. MDCT abnormalities of small- and medium-sized bronchus in active tuberculosis: a new angle on an old disease

    International Nuclear Information System (INIS)

    Oh, Jin Kyoung; Ahn, Myeong Im; Jung, Jung Im; Han, Dae Hee; Kim, Young Kyoon; Oh, Eun-Jee; Park, Yeon-Joon

    2011-01-01

    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

  9. 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

  10. Tuberculosis. Lung and extrapulmonary compromise (cutaneous and ganglionar)

    International Nuclear Information System (INIS)

    Paez Mildred; Neira, Myriam Consuelo; Latorre Pablo; Faisal, Michel

    2000-01-01

    We present the case or a male, 28 year old that consulted for fever, weight loss and axillary ulcer. Clinically had two skin lesions where cutaneous tuberculosis was proven (lupus vulgaris-scrofuloderma). The skin lesions led to the diagnosis of lung tuberculosis and tuberculous adenitis. In this case all the diagnostic criteria for cutaneous tuberculosis were completed: active presence of tuberculosis in another place, positive reaction to tuberculin test, physical signs and appropriate answer to the treatment

  11. Survey on medicinal plants traditionally used in Senegal for the treatment of tuberculosis (TB) and assessment of their antimycobacterial activity.

    Science.gov (United States)

    Diop, ElHadji Assane; Queiroz, Emerson Ferreira; Kicka, Sébastien; Rudaz, Serge; Diop, Tahir; Soldati, Thierry; Wolfender, Jean-Luc

    2018-04-24

    In West Africa, populations are used to taking traditional medicine as a first aid against common health problems. In this aspect, many plants are claimed to be effective in the treatment of Tuberculosis (TB), which according to the World Health Organization (WHO) remains one of the world's deadliest communicable diseases. The main aim of this study was to identify plants used to treat TB-symptoms by the population of Senegal and to evaluate their possible concomitant use with clinically approved TB-drugs. This approach allowed the selection of plants effectively used in traditional medicine. In order to verify if the usage of some of these plants can be rationalized, the activity of their traditional preparations was assessed with both an intracellular and extracellular antimycobacterial host-pathogen assays. An ethnopharmacological survey conducted on 117 TB-patients and 30 healers in Senegal from March to May 2014. The questionnaires were focused on the use of medicinal plants to treat common TB -symptoms (cough longer than 2 weeks, fever, night sweats, weight loss and bloody sputum). Local plant names, utilized organs (herbal drugs) and traditional formulations of the plants were recorded. Extracts were prepared by mimicking the traditional decoction in boiling water and screened for their antimycobacterial activity using Mycobacterium marinum, as a validated TB surrogate, and an Acanthamoeba castellanii - M. marinum whole-cell based host-pathogen assay, to detect anti-infective activities. By the end of the survey, nearly 30 plants were cited and the 12 most cited herbal drugs were collected and their usage documented by extensive literature search. Extracts of the chosen herbs were screened with the described assays; with a main focus on traditional formulas (mainly herbal decoctions). Two of the water extracts from Combretum aculeatum and Guiera senegalensis showed significant antimycobacterial activities when compared to the positive control drug (rifampin

  12. 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.

  13. Congenic tuberculosis. Presentation of clinical case

    International Nuclear Information System (INIS)

    David Calabria, Milena; Ojeda Leon, Paulina

    2004-01-01

    We are presenting the case of less than to 2 month old and premature infant, she had hyaline membrane disease and required mechanical ventilation during 6 days, at the first month. She presented a viral rhinopharyngitis symptomatology, perioral cyanosis with apnoea, and respiratory distress, the chest x-ray showed multiple bilateral hyperlucid images, mainly at the right side afterwards the patient presented intermittent fever of long evolution and initially received treatment for cavitary bronchopneumonia and sequel of mechanical ventilation, receiving multiple antimicrobial antibiotics, the mother had intermittent fevers since the sixth month of pregnancy and was hospitalized for suspected endometritis after delivery, she presented clinical impairment which evolved to sepsis and died in the ICU, the endometrial histopathology showed granulomas suggesting tuberculosis, due to long history of fevers in the baby and the genital tuberculosis in the mother a tuberculosis study was performed in the girl which resulted positive

  14. 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.

  15. Tuberculosis ocular

    OpenAIRE

    Infante Barrera, Francisco

    2011-01-01

    La evolución etiológica de la medicina la podemos dividir en dos grandes períodos: período de la sífilis y período de la tuberculosis. El período de la sífilis, gracias a las armas de combate de que hoy disponemos, ocupa un lugar secundario. El período de la tuberculosis y que no es sino el paralelo de la vida moderna, ocupa en vigencia el primer lugar. Es el período presente. Hasta hace poco tiempo el médico en general, iniciaba la exploración de su paciente con un interrogatorio, una inspec...

  16. Discriminating active from latent tuberculosis in patients presenting to community clinics.

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    Gurjinder Sandhu

    Full Text Available 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.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.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%.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.

  17. 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...

  18. 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

  19. Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

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    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.

  20. risk factors of active tuberculosis in people living with hiv/aids

    African Journals Online (AJOL)

    Abrham

    2011-07-02

    Jul 2, 2011 ... The objective of this study was to assess distal ... KEYWORDS: Active TB, HIV, risk factors, case control study, Southwest Ethiopia ... and Khat (stimulant plant from Chata Edulis), .... to live in a house made of a cement floor.

  1. 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.

  2. Tuberculosis among drug users and homeless persons: impact of voluntary X-ray investigation on active case finding.

    Science.gov (United States)

    Goetsch, U; Bellinger, O K; Buettel, K-L; Gottschalk, R

    2012-08-01

    Illicit drug use and homelessness are major contributors to the incidence of tuberculosis (TB) among inhabitants of major cities. The primary objective of this study was to establish a sustainable low-threshold chest X-ray screening programme for pulmonary TB among illicit drug users and homeless persons and to integrate this into the existing public health programme for active case finding. A secondary objective was to estimate the coverage of the programme, assess other risk factors and determine TB rates and treatment outcome in these two groups. Illicit drug users and homeless persons were asked to voluntarily participate in an X-ray screening programme. The coverage of the intervention, total number and characteristics of cases and the follow-up of treatment were assessed. A total of 4,529 chest radiographs were made from 3,477 persons, of whom 66% were homeless and 34% were illicit drug users, between May 2002 and April 2007. Coverage for screening once every 2 years ranged between 18 and 26%. Thirty-nine TB cases (14 drug users, 25 homeless persons) were identified, representing 8.7% of the total case load of 448 notified cases of pulmonary TB in Frankfurt during this period. Among the drug users, human immunodeficiency virus coinfection (10/14) seemed to play a key role in the development of TB. The case-finding rate of 861/100,000 radiographs (1,122/100,000 persons) is as high as that in routine contact investigations (1,078/100,000). Among all individuals with TB, 76% completed treatment. A novel targeted TB screening approach with voluntary radiographic examination of illicit drug users and homeless persons can be integrated into the existing public TB prevention programme and provides a high case-finding rate.

  3. Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease with 14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean Creutzfeldt-Jakob disease active surveillance program.

    Science.gov (United States)

    Lim, Jae-Sung; Kwon, Hyung-Min; Jang, Jae-Won; Ju, Young-Ran; Kim, SuYeon; Park, Young Ho; Park, So Young; Kim, SangYun

    2015-01-01

    Although Korea had a national surveillance system for Creutzfeldt-Jakob disease (CJD), it was mainly dependent on attending physician's reports. Thus, little prospective data about the epidemiology, characteristics, and final diagnoses of suspected patients were available. We have established a nationwide network for the active surveillance of patients with suspected CJD. When the requested cerebrospinal fluid (CSF) samples tested positive for 14-3-3 protein, we investigated the clinical characteristics of the corresponding patients and followed them until their final diagnoses were confirmed. A total of 218 samples were requested for CSF assays from May 2010 to August 2012, and 106 (48.6%) were positive for 14-3-3 protein. In 89 patients with complete clinical data, 38 (42.7%) were diagnosed with probable CJD and the estimated annual occurrence of CJD was 16.3 persons-per-year. The most common diagnoses of the remainder were central nervous system infection and any-cause encephalopathy. Non-CJD subjects showed worse initial consciousness levels than CJD patients. This preliminary study showed that the number of reported cases of CJD and the true positivity rates of CSF 14-3-3 protein assays were both low in Korea. An active surveillance system is urgently needed to provide the latest nationwide epidemiological data of CJD.

  4. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.

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    Grace Lui

    Full Text Available We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1 / Receptor-for-Advanced-Glycation-End-products (RAGE signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB.A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80; age-and-sex matched asymptomatic individuals (tested for latent TB were used for comparison (n = 45. Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan for cytokine induction ex vivo.In active PTB, plasma IL-8/CXCL8 [median(IQR, 6.0(3.6-15.1 vs 3.6(3.6-3.6 pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001, severity-score (rs +0.317, P = 0.004, and fever and hospitalization durations (rs +0.407, P<0.001. IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021 and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012 concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold. Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1 and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034. Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α when combined with lipoarabinomannan.In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important

  5. Tuberculosis ocular

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    Francisco Infante Barrera

    1950-01-01

    Full Text Available La evolución etiológica de la medicina la podemos dividir en dos grandes períodos: período de la sífilis y período de la tuberculosis. El período de la sífilis, gracias a las armas de combate de que hoy disponemos, ocupa un lugar secundario. El período de la tuberculosis y que no es sino el paralelo de la vida moderna, ocupa en vigencia el primer lugar. Es el período presente. Hasta hace poco tiempo el médico en general, iniciaba la exploración de su paciente con un interrogatorio, una inspección, un tacto y una serología con una obsesión sifilítica. En la época actual el médico y en especial el oftalmólogo debe tener una obsesión tuberculosa en la investigación etiológica. Cuántas veces en una afección ocular que de una manera lenta pero progresiva produce profundas alteraciones oculares, lleva el sello soterrado de una tuberculosis? Cuántos enfermos de una constitución en apariencia envidiable hacen precisamente por un exceso de sus defensas una alergia tuberculosa? Tan traicionera como la sífilis es la tuberculosis. La sífilis quema sus etapas y estalla con una hemorragia cerebral, una locura, una parálisis general, una ataxia locomotriz progresiva, una goma o una meningitis sifilítica. La tuberculosis hace su presentación con una afección ocular, una goma, una granulia, una artritis, una osteítis, o una meningitis óptico-quiasmática. Siendo esto así, es necesario, en la mayoría de las afecciones oculares, tratar de identificarla por los medios de diagnóstico de que hoy disponemos.

  6. [Analysis of the numbers and subsets of MTB-HAg specific TNF-α+ γδ T cells in peripheral blood of patients with active pulmonary tuberculosis].

    Science.gov (United States)

    Tang, Jie; Chen, Ce; Zha, Cheng; Wang, Zhaohua; Zhang, Chen; Zeng, Linli; Li, Baiqing

    2016-11-01

    Objective To investigate the differences of proportions of tumor necrosis factor α (TNF-α)-producing cells in peripheral blood γδ T cells stimulated with Mycobacterium tuberculosis heat resistant antigen (MTB-HAg) among patients with pulmonary tuberculosis (PTB), latent tuberculosis infection (LTBI) and healthy subjects (HC). Methods The peripheral blood specimens were collected from 15 normal adults, which were divided into HC group (n=9) and LTBI group (n=6), by enzyme-linked immunospot (ELISPOT) kit for diagnosis of Mycobacterium tuberculosis infection, and 12 patients with active PTB. The peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation and simulated with MTB-HAg for 20 hours. Then the cells were collected, and the proportions of TNF-α-producing cells in TCRαβ + T cells, TCRγδ + T cells, CD4 + αβ T cells, CD8 + αβ T cells, and TCR-Vδ2 + T cells were measured with flow cytometry. Results The proportion of TNF-α-producing cells in γδ T cells in patients with PTB was obviously lower than that in LTBI group and HC group; the proportion of TNF-α-producing cells in Vδ2 T cells in PTB patients was apparently lower than that in LTBI and HC; the proportion of Vδ2 T cells in TNF-α + γδ T cells in the peripheral blood of PTB patients was remarkably lower than that in LTBI and HC groups. The proportions of TNF-α-producing cells in peripheral αβ T cells, CD4 + and CD8 + αβ T cells were dramatically lower than those in γδ T cells of the three according groups. Moreover, there were no statistical differences in regard with the proportions of TNF-α-producing cells in αβ T cells, and CD4 + and CD8 + αβ T cells among the three groups. Conclusion The TNF-α production capacity of MTB-HAg specific γδ T cells and Vδ2 T cell subsets in patients with tuberculosis is obviously lower than that of LTBI and HC.

  7. An Evaluation of Passive and Active Approaches to Improve Tuberculosis Notifications in Afghanistan.

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    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

  8. An Evaluation of Passive and Active Approaches to Improve Tuberculosis Notifications in Afghanistan.

    Science.gov (United States)

    Sanaie, A; Mergenthaler, C; Nasrat, A; Seddiq, M K; Mahmoodi, S D; Stevens, R H; Creswell, J

    2016-01-01

    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 the Stop TB

  9. 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.

  10. miR-582-5p is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO1.

    Science.gov (United States)

    Liu, Yanhua; Jiang, Jing; Wang, Xinjing; Zhai, Fei; Cheng, Xiaoxing

    2013-01-01

    Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB). In this study, we found that percentage of apoptotic cells in peripheral blood monocytes from patients with active TB was lower than that from healthy controls (pmicroRNAs can modulate apoptosis of monocytes, we investigated differentially expressed microRNAs in patients with active TB. miR-582-5p was mainly expressed in monocytes and was upregulated in patients with active TB. The apoptotic percentage of THP-1 cells transfected with miR-582-5p mimics was significantly lower than those transfected with negative control of microRNA mimics (pmicroRNA mimics were transfected into THP-1 cells. RT-PCR and western blot analysis showed that the miR-582-5p could suppress both FOXO1 mRNA and protein expression. Co-transfection of miR-582-5p and FOXO1 3'UTR-luciferase reporter vector into cells demonstrated that significant decrease in luciferase activity was only found in reporter vector that contained a wild type sequence of FOXO1 3'UTR, suggesting that miR-582-5p could directly target FOXO1. In conclusion, miR-582-5p inhibited apoptosis of monocytes by down-regulating FOXO1 expression and might play an important role in regulating anti-M. tuberculosis directed immune responses.

  11. 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.

  12. Imaging in Tuberculosis abdominal

    International Nuclear Information System (INIS)

    Suarez, Tatiana; Garcia, Vanessa; Tamara, Estrada; Acosta, Federico

    2010-01-01

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

  13. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report.

    Science.gov (United States)

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem

    2015-09-01

    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  14. Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes

    DEFF Research Database (Denmark)

    Wang, Qiuzhen; Ma, Aiguo; Bygbjerg, Ib Christian

    2013-01-01

    The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients...

  15. Comparison of the in vivo and in vitro activities of adenylate cyclase from Mycobacterium tuberculosis H37Ra(NCTC 7417)

    International Nuclear Information System (INIS)

    Padh, Harish; Venkitsubramanian, T.A.

    1979-01-01

    The incorporation of [ 14 C] adenine into the adenosine 3', 5'-monophosphate (cyclic AMP) fraction by whole cells of Mycobacterium tuberculosis was taken as a measure of the in vivo activity of adenylate cyclase. The in vivo activity of adenylate cyclase was significantly inhibited by glucose, thus suggesting that the low level of cyclic AMP in the presence of glucose is due to the inhibited synthesis of cyclic AMP. In vitro activity of adenylate cyclase had optimum pH of 8.5 and Km of 1.33 mM for ATP. Glucose and other sugars did not show significant inhibition of in vitro activity. The results suggest that the adenylate cyclase activity becomes less sensitive to glucose when the bacterial cells are disrupted, an analogy with eukaryotic adenylate cyclase which loses sensitivity to hormones when the cells are disrupted. (auth.)

  16. 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.

  17. HIV and parasitic co-infections in tuberculosis patients

    DEFF Research Database (Denmark)

    Range, N.; Magnussen, Pascal; Mugomela, A.

    2007-01-01

    A cross-sectional study was conducted in Mwanza, Tanzania, to determine the burden of HIV and parasitic co-infections among patients who were confirmed or suspected cases of pulmonary tuberculosis (PTB). Of the 655 patients investigated, 532 (81.2%) had been confirmed as PTB cases, by microscopy...

  18. Integration of PET/CT in Current Diagnostic and Response Evaluation Methods in Patients with Tuberculosis

    International Nuclear Information System (INIS)

    Oezmen, Oelem; Goekcek, Atila; Tatci, Ebru; Biner, Inci; Akkalyoncu, Behiye

    2014-01-01

    Tuberculosis is a systemic disease that still affects many people. While pleural involvement is frequently observed in extrapulmonary tuberculosis, multiple skeletal system and articular involvements are quite rare. FDG PET imaging could be a promising diagnostic and treatment monitoring method, especially in complicated cases and if the other methods are inadequate. In this case study, we report a patient who was admitted with suspected malignancy and then diagnosed with tuberculosis pleuritis, lymphadenitis, spondylodiscitis, and sacroiliitis with specific symptoms; the response to anti-tuberculosis therapy was shown using FDG PET/CT

  19. Integration of PET/CT in Current Diagnostic and Response Evaluation Methods in Patients with Tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Oezmen, Oelem; Goekcek, Atila; Tatci, Ebru; Biner, Inci; Akkalyoncu, Behiye [Atatuerk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara (Turkmenistan)

    2014-03-15

    Tuberculosis is a systemic disease that still affects many people. While pleural involvement is frequently observed in extrapulmonary tuberculosis, multiple skeletal system and articular involvements are quite rare. FDG PET imaging could be a promising diagnostic and treatment monitoring method, especially in complicated cases and if the other methods are inadequate. In this case study, we report a patient who was admitted with suspected malignancy and then diagnosed with tuberculosis pleuritis, lymphadenitis, spondylodiscitis, and sacroiliitis with specific symptoms; the response to anti-tuberculosis therapy was shown using FDG PET/CT.

  20. 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.

  1. 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.

    Science.gov (United States)

    Kumar, Anuradha; Casey, Allen; Odingo, Joshua; Kesicki, Edward A; Abrahams, Garth; Vieth, Michal; Masquelin, Thierry; Mizrahi, Valerie; Hipskind, Philip A; Sherman, David R; Parish, Tanya

    2013-01-01

    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.

  2. Prime Suspect, Second Row Center

    Science.gov (United States)

    Laird, Ellen A.

    2011-01-01

    His father had been hacked to death in his own bed with an ax the previous November. His mother was similarly brutalized and left for dead with her husband but survived. On the last Monday of that August, after several months and many investigative twists, turns, and fumbles, there sat the son--the prime suspect--in Ellen Laird's literature class,…

  3. Active tuberculosis is associated with worse clinical outcomes in HIV-infected African patients on antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Abraham M Siika

    Full Text Available This cohort study utilized data from a large HIV treatment program in western Kenya to describe the impact of active tuberculosis (TB on clinical outcomes among African patients on antiretroviral therapy (ART.We included all patients initiating ART between March 2004 and November 2007. Clinical (signs and symptoms, radiological (chest radiographs and laboratory (mycobacterial smears, culture and tissue histology criteria were used to record the diagnosis of TB disease in the program's electronic medical record system.We assessed the impact of TB disease on mortality, loss to follow-up (LTFU and incident AIDS-defining events (ADEs through Cox models and CD4 cell and weight response to ART by non-linear mixed models.We studied 21,242 patients initiating ART-5,186 (24% with TB; 62% female; median age 37 years. There were proportionately more men in the active TB (46% than in the non-TB (35% group. Adjusting for baseline HIV-disease severity, TB patients were more likely to die (hazard ratio--HR = 1.32, 95% CI 1.18-1.47 or have incident ADEs (HR = 1.31, 95% CI: 1.19-1.45. They had lower median CD4 cell counts (77 versus 109, weight (52.5 versus 55.0 kg and higher ADE risk at baseline (CD4-adjusted odds ratio = 1.55, 95% CI: 1.31-1.85. ART adherence was similarly good in both groups. Adjusting for gender and baseline CD4 cell count, TB patients experienced virtually identical rise in CD4 counts after ART initiation as those without. However, the overall CD4 count at one year was lower among patients with TB (251 versus 269 cells/µl.Clinically detected TB disease is associated with greater mortality and morbidity despite salutary response to ART. Data suggest that identifying HIV patients co-infected with TB earlier in the HIV-disease trajectory may not fully address TB-related morbidity and mortality.

  4. Extended spectrum of antibiotic susceptibility for tuberculosis, Djibouti.

    Science.gov (United States)

    Bouzid, Fériel; Astier, Hélène; Osman, Djaltou Aboubaker; Javelle, Emilie; Hassan, Mohamed Osman; Simon, Fabrice; Garnotel, Eric; Drancourt, Michel

    2018-02-01

    In the Horn of Africa, there is a high prevalence of tuberculosis that is reported to be partly driven by multidrug-resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti, and their in vitro susceptibility to standard anti-tuberculous antibiotics in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M. tuberculosis, five Mycobacterium canettii, one 'Mycobacterium simulans' and one Mycobacterium kansasii were identified. Drug-susceptibility tests performed on the first 78 isolates yielded nine MDR M. tuberculosis isolates. All isolates were fully susceptible to clofazimine, minocycline and chloramphenicol, and 75 of 78 isolates were susceptible to sulfadiazine. In the Horn of Africa, patients with confirmed pulmonary tuberculosis caused by an in vitro susceptible strain may benefit from anti-leprosy drugs, sulfamides and phenicol antibiotics. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  5. Spinal tuberculosis.

    Science.gov (United States)

    Dunn, R N; Ben Husien, M

    2018-04-01

    Tuberculosis (TB) remains endemic in many parts of the developing world and is increasingly seen in the developed world due to migration. A total of 1.3 million people die annually from the disease. Spinal TB is the most common musculoskeletal manifestation, affecting about 1 to 2% of all cases of TB. The coexistence of HIV, which is endemic in some regions, adds to the burden and the complexity of management. This review discusses the epidemiology, clinical presentation, diagnosis, impact of HIV and both the medical and surgical options in the management of spinal TB. Cite this article: Bone Joint J 2018;100-B:425-31.

  6. 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 lobe anterior and posterior segments. Brucella melitensis was isolated in blood culture. Second bronchoscopy was performed with suspect of brucellosis pneumonia. Brucella tube agglutination test was positive at titer 1/320 in the bronchial lavage fluid and 1/640 in concurrent serum sample. In cases with chronic cough or pneumonia which is irresponsive to nonspecific antibiotherapy, respiratory brucellosis must be rememberred in endemic areas.

  7. Lung cancer, brucellosis and tuberculosis: remarkable togetherness

    Science.gov (United States)

    Akkoyunlu, Muhammed Emin; Akkoyunlu, Yasemin; Hakyemez, Ismail Necati; Erboy, Fatma; Arvas, Gulhan; Aslan, Turan

    2013-01-01

    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 lobe anterior and posterior segments. Brucella melitensis was isolated in blood culture. Second bronchoscopy was performed with suspect of brucellosis pneumonia. Brucella tube agglutination test was positive at titer 1/320 in the bronchial lavage fluid and 1/640 in concurrent serum sample. In cases with chronic cough or pneumonia which is irresponsive to nonspecific antibiotherapy, respiratory brucellosis must be rememberred in endemic areas.

  8. Mitigating Financial Burden of Tuberculosis through Active Case Finding Targeting Household and Neighbourhood Contacts in Cambodia.

    Science.gov (United States)

    Morishita, Fukushi; Yadav, Rajendra-Prasad; Eang, Mao Tan; Saint, Saly; Nishikiori, Nobuyuki

    2016-01-01

    Despite free TB services available in public health facilities, TB patients often face severe financial burden due to TB. WHO set a new global target that no TB-affected families experience catastrophic costs due to TB. To monitor the progress and strategize the optimal approach to achieve the target, there is a great need to assess baseline cost data, explore potential proxy indicators for catastrophic costs, and understand what intervention mitigates financial burden. In Cambodia, nationwide active case finding (ACF) targeting household and neighbourhood contacts was implemented alongside routine passive case finding (PCF). We analyzed household cost data from ACF and PCF to determine the financial benefit of ACF, update the baseline cost data, and explore whether any dissaving patterns can be a proxy for catastrophic costs in Cambodia. In this cross-sectional comparative study, structured interviews were carried out with 108 ACF patients and 100 PCF patients. Direct and indirect costs, costs before and during treatment, costs as percentage of annual household income and dissaving patterns were compared between the two groups. The median total costs were lower by 17% in ACF than in PCF ($240.7 [IQR 65.5-594.6] vs $290.5 [IQR 113.6-813.4], p = 0.104). The median costs before treatment were significantly lower in ACF than in PCF ($5.1 [IQR 1.5-25.8] vs $22.4 [IQR 4.4-70.8], pCambodia. ACF has the great potential to mitigate the costs incurred particularly before treatment. Social protection schemes that can replace lost income are critically needed to compensate for the most devastating costs in TB. An occurrence of selling household property can be a useful proxy for catastrophic cost in Cambodia.

  9. Estimation of pyrazinamidase activity using a cell-free In vitro synthesis of pnca and its association with pyrazinamide susceptibility in Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Daniel Rueda

    2018-01-01

    Full Text Available Background: The main mechanism of resistance to PZA in Mycobacterium tuberculosis relies on mutations on its pyrazinamidase/nicotinamidase. Recently, a rapid colorimetric test relying on the PCR-based in vitro-synthesized-PZase assay has been reported for PZase activity determination from clinical M. tuberculosis isolates but the assay has not been compared with other tests to evaluate PZA susceptibility in M. tuberculosis isolates. Methods: In this study, we have used the PCR-based in vitro-synthesized-PZase assay to analyze the specific pyrazinamidase (PZase activity of PncA mutants and have correlated the results to the PZA susceptibility phenotype determined by culture in acidic agar medium at pH 6.0. A set of 23 clinical isolates displaying mutated pncA genes (11 PZA-resistant and 12 PZA-susceptible and 55 PZA-susceptible clinical strains displaying a wild-type pncA gene were tested. Results: Among the 23 mutants tested, 4 corresponded to mutations not reported before (I5T, Y99S, T142R and P77L+V131G. Of the 11 PncA mutants expressed from PZA-resistant clinical isolates, 9 were expressed in vitro at yields > 50% relative to the wild type enzyme. Among them, 6 enzymes (T47P, H51P, H51R, H57D, L85R and T142R showed no detectable activity, while the relative activities for the 3 others, V9A (27%, G97D (10% and A146V (28% were low compared to the wild-type PZase. The remaining two mutants, I5T and V9G, presented very low relative expression (5% and relative activities values of 12 and 1%, respectively. Twelve mutants were expressed from PZA-susceptible isolates. Their expression was similar to the wild type enzyme and behaved as active pyrazinamidase with specific relative activities ranging from 34 to 314%. Finally, discrepant results were observed for two mutants, V7A and P62T. Conclusion: Thus, this study provides the proof of concept that the PCR-based in vitro-synthesized-PZase assay represents a promising rapid approach for the evaluation

  10. Estimation of pyrazinamidase activity using a cell-free In vitro synthesis of pnca and its association with pyrazinamide susceptibility in Mycobacterium tuberculosis.

    Science.gov (United States)

    Rueda, Daniel; Bernard, Christine; Gandy, Lucas; Capton, Estelle; Boudjelloul, Rachid; Brossier, Florence; Veziris, Nicolas; Zimic, Mirko; Sougakoff, Wladimir

    2018-01-01

    The main mechanism of resistance to PZA in Mycobacterium tuberculosis relies on mutations on its pyrazinamidase/nicotinamidase. Recently, a rapid colorimetric test relying on the PCR-based in vitro-synthesized-PZase assay has been reported for PZase activity determination from clinical M. tuberculosis isolates but the assay has not been compared with other tests to evaluate PZA susceptibility in M. tuberculosis isolates. In this study, we have used the PCR-based in vitro-synthesized-PZase assay to analyze the specific pyrazinamidase (PZase) activity of PncA mutants and have correlated the results to the PZA susceptibility phenotype determined by culture in acidic agar medium at pH 6.0. A set of 23 clinical isolates displaying mutated pncA genes (11 PZA-resistant and 12 PZA-susceptible) and 55 PZA-susceptible clinical strains displaying a wild-type pncA gene were tested. Among the 23 mutants tested, 4 corresponded to mutations not reported before (I5T, Y99S, T142R and P77L+V131G). Of the 11 PncA mutants expressed from PZA-resistant clinical isolates, 9 were expressed in vitro at yields > 50% relative to the wild type enzyme. Among them, 6 enzymes (T47P, H51P, H51R, H57D, L85R and T142R) showed no detectable activity, while the relative activities for the 3 others, V9A (27%), G97D (10%) and A146V (28%) were low compared to the wild-type PZase. The remaining two mutants, I5T and V9G, presented very low relative expression (5%) and relative activities values of 12 and 1%, respectively. Twelve mutants were expressed from PZA-susceptible isolates. Their expression was similar to the wild type enzyme and behaved as active pyrazinamidase with specific relative activities ranging from 34 to 314%. Finally, discrepant results were observed for two mutants, V7A and P62T. Thus, this study provides the proof of concept that the PCR-based in vitro-synthesized-PZase assay represents a promising rapid approach for the evaluation of PZA susceptibility based on the estimation of the

  11. Mathematical Models of Tuberculosis Reactivation and Relapse

    Directory of Open Access Journals (Sweden)

    Robert Steven Wallis

    2016-05-01

    Full Text Available The natural history of human infection with Mycobacterium tuberculosis (Mtb is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiology of tuberculosis in patients treated with tumor necrosis factor antagonists, and predict the risk of relapse in persons undergoing tuberculosis treatment. These examples illustrate the power of various types of mathematic models to increase knowledge and thereby inform interventions in the present global tuberculosis epidemic.

  12. Mitigating Financial Burden of Tuberculosis through Active Case Finding Targeting Household and Neighbourhood Contacts in Cambodia.

    Directory of Open Access Journals (Sweden)

    Fukushi Morishita

    Full Text Available Despite free TB services available in public health facilities, TB patients often face severe financial burden due to TB. WHO set a new global target that no TB-affected families experience catastrophic costs due to TB. To monitor the progress and strategize the optimal approach to achieve the target, there is a great need to assess baseline cost data, explore potential proxy indicators for catastrophic costs, and understand what intervention mitigates financial burden. In Cambodia, nationwide active case finding (ACF targeting household and neighbourhood contacts was implemented alongside routine passive case finding (PCF. We analyzed household cost data from ACF and PCF to determine the financial benefit of ACF, update the baseline cost data, and explore whether any dissaving patterns can be a proxy for catastrophic costs in Cambodia.In this cross-sectional comparative study, structured interviews were carried out with 108 ACF patients and 100 PCF patients. Direct and indirect costs, costs before and during treatment, costs as percentage of annual household income and dissaving patterns were compared between the two groups.The median total costs were lower by 17% in ACF than in PCF ($240.7 [IQR 65.5-594.6] vs $290.5 [IQR 113.6-813.4], p = 0.104. The median costs before treatment were significantly lower in ACF than in PCF ($5.1 [IQR 1.5-25.8] vs $22.4 [IQR 4.4-70.8], p<0.001. Indirect costs constituted the largest portion of total costs (72.3% in ACF and 61.5% in PCF. Total costs were equivalent to 11.3% and 18.6% of annual household income in ACF and PCF, respectively. ACF patients were less likely to dissave to afford TB-related expenses. Costs as percentage of annual household income were significantly associated with an occurrence of selling property (p = 0.02 for ACF, p = 0.005 for PCF.TB-affected households face severe financial hardship in Cambodia. ACF has the great potential to mitigate the costs incurred particularly before treatment

  13. Provider-initiated HIV testing and counselling for TB patients and suspects in Nairobi, Kenya.

    Science.gov (United States)

    Odhiambo, J; Kizito, W; Njoroge, A; Wambua, N; Nganga, L; Mburu, M; Mansoer, J; Marum, L; Phillips, E; Chakaya, J; De Cock, K M

    2008-03-01

    Integrated tuberculosis (TB) and human immunodeficiency virus (HIV) services in a resource-constrained setting. Pilot provider-initiated HIV testing and counselling (PITC) for TB patients and suspects. Through partnerships, resources were mobilised to establish and support services. After community sensitisation and staff training, PITC was introduced to TB patients and then to TB suspects from December 2003 to December 2005. Of 5457 TB suspects who received PITC, 89% underwent HIV testing. Although not statistically significant, TB suspects with TB disease had an HIV prevalence of 61% compared to 63% for those without. Of the 614 suspects who declined HIV testing, 402 (65%) had TB disease. Of 2283 patients referred for cotrimoxazole prophylaxis, 1951 (86%) were enrolled, and of 1727 patients assessed for antiretroviral treatment (ART), 1618 (94%) were eligible and 1441 (83%) started treatment. PITC represents a paradigm shift and is feasible and acceptable to TB patients and TB suspects. Clear directives are nevertheless required to change practice. When offered to TB suspects, PITC identifies large numbers of persons requiring HIV care. Community sensitisation, staff training, multitasking and access to HIV care contributed to a high acceptance of HIV testing. Kenya is using this experience to inform national response and advocate wide PITC implementation in settings faced with the TB-HIV epidemic.

  14. Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ignacio Boron

    2015-07-01

    Full Text Available Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •ŸNO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify Ÿ•NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, Ÿ•NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.

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

    Directory of Open Access Journals (Sweden)

    Eva Carolina del Portillo-Mustieles

    2013-01-01

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

  16. Phosphodiesterase-4 inhibition combined with isoniazid treatment of rabbits with pulmonary tuberculosis reduces macrophage activation and lung pathology.

    Science.gov (United States)

    Subbian, Selvakumar; Tsenova, Liana; O'Brien, Paul; Yang, Guibin; Koo, Mi-Sun; Peixoto, Blas; Fallows, Dorothy; Zeldis, Jerome B; Muller, George; Kaplan, Gilla

    2011-07-01

    Tuberculosis (TB) is responsible for significant morbidity and mortality worldwide. Even after successful microbiological cure of TB, many patients are left with residual pulmonary damage that can lead to chronic respiratory impairment and greater risk of additional TB episodes due to reinfection with Mycobacterium tuberculosis. Elevated levels of the proinflammatory cytokine tumor necrosis factor-α and several other markers of inflammation, together with expression of matrix metalloproteinases, have been associated with increased risk of pulmonary fibrosis, tissue damage, and poor treatment outcomes in TB patients. In this study, we used a rabbit model of pulmonary TB to evaluate the impact of adjunctive immune modulation, using a phosphodiesterase-4 inhibitor that dampens the innate immune response, on the outcome of treatment with the antibiotic isoniazid. Our data show that cotreatment of M. tuberculosis infected rabbits with the phosphodiesterase-4 inhibitor CC-3052 plus isoniazid significantly reduced the extent of immune pathogenesis, compared with antibiotic alone, as determined by histologic analysis of infected tissues and the expression of genes involved in inflammation, fibrosis, and wound healing in the lungs. Combined treatment with an antibiotic and CC-3052 not only lessened disease but also improved bacterial clearance from the lungs. These findings support the potential for adjunctive immune modulation to improve the treatment of pulmonary TB and reduce the risk of chronic respiratory impairment. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Extrathoracic manifestations of tuberculosis

    International Nuclear Information System (INIS)

    Kienzl-Palma, D.; Prosch, H.

    2016-01-01

    Besides the lungs, tuberculosis (TB) can affect any organ system. In most cases, extrathoracic TB occurs in immunosuppressed patients as part of a severe illness via hematogenous spread. Extrathoracic involvement most commonly involves abdominal organs, especially the urogenital tract and less commonly the central nervous system (CNS) and the musculoskeletal system. Most frequently, computed tomography (CT) is used for detecting extrathoracic TB manifestations, except for CNS and musculoskeletal manifestations, where contrast-enhanced magnetic resonance imaging (MRI) is the gold standard. Extrathoracic manifestations of TB may be indistinguishable from inflammatory or malignant causes. Due to unspecific symptoms the diagnosis is often delayed. This article summarizes and discusses the various radiological manifestations of extrathoracic manifestation of TB. Radiological modalities for screening extrathoracic TB are CT and MRI. Conventional X-radiographs do not play a role in the diagnosis of extrathoracic TB. The possibility of extrathoracic TB should be considered particularly in immunosuppressed patients, such as the homeless, alcoholics or drug addicts or in patients with an immigrant background from the endemic areas of TB. The most likely site of extrathoracic TB is the abdomen; however, infections of the CNS or musculoskeletal systems and multisystem infections can also occur. In patients with suspected extrathoracic TB, radiological modalities for screening are CT, especially for abdominal infections and lymphadenopathy and MRI with contrast media for the musculoskeletal system and the CNS. (orig.) [de

  18. 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.

  19. Tuberculosis verrucosa cutis

    Directory of Open Access Journals (Sweden)

    Krishnabharath S

    2017-08-01

    Full Text Available We report a case of 23-year-old male patient with tuberculosis verrucous cutis on the foot for a duration of six months without responding to routine treatment. Tuberculosis is a common disease worldwide. Extrapulmonary tuberculosis contributes to 10% of cases. Cutaneous tuberculosis occupies a small spectrum of extrapulmonary tuberculosis. Tuberculosis verrucosa cutis is an exogenous infection occurring in a previously sensitized patient by direct inoculation of the organism. It occurs in sensitized patients with a moderate to high immune response. The diagnosis in our patient was confirmed by history, clinical examination, histopathological examination and the patient’s response to anti-tuberculous therapy.

  20. Total-hip arthroplasty: Periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection

    International Nuclear Information System (INIS)

    Palestro, C.J.; Kim, C.K.; Swyer, A.J.; Capozzi, J.D.; Solomon, R.W.; Goldsmith, S.J.

    1990-01-01

    Indium-111-labeled leukocyte images of 92 cemented total-hip arthroplasties were correlated with final diagnoses. Prostheses were divided into four zones: head (including acetabulum), trochanter, shaft, and tip. The presence (or absence) and intensity of activity in each zone was noted, and compared to the corresponding contralateral zone. Though present in all 23 infected arthroplasties, periprosthetic activity was also present in 77% of uninfected arthroplasties, and was greater than the contralateral zone 51% of the time. When analyzed by zone, head zone activity was the best criterion for infection (87% sensitivity, 94% specificity, 92% accuracy). Fifty of the arthroplasties were studied with combined labeled leukocyte/sulfur colloid imaging. Using incongruence of images as the criterion for infection, the sensitivity, specificity, and accuracy of the study were 100%, 97%, and 98%, respectively. While variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection, the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure

  1. Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.

    Science.gov (United States)

    Graham, Stephen M; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E; Gale, Marianne; Gie, Robert P; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J; McNeeley, David F; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R; Swaminathan, Soumya; Wingfield, Claire

    2012-05-15

    There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

  2. Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

    Science.gov (United States)

    Graham, Stephen M.; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E.; Gale, Marianne; Gie, Robert P.; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C.; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J.; McNeeley, David F.; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R.; Swaminathan, Soumya; Wingfield, Claire

    2012-01-01

    There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis. PMID:22448023

  3. CT-Guided Transthoracic Core Biopsy for Pulmonary Tuberculosis: Diagnostic Value of the Histopathological Findings in the Specimen

    International Nuclear Information System (INIS)

    Fukuda, Hozumi; Ibukuro, Kenji; Tsukiyama, Toshitaka; Ishii, Rei

    2004-01-01

    We evaluated the value of CT-guided transthoracic core biopsy for the diagnosis of mycobacterial pulmonary nodules. The 30 subjects in this study had pulmonary nodules that had been either diagnosed histopathologically as tuberculosis or were suspected as tuberculosis based on a specimen obtained by CT-guided transthoracic core biopsy. The histopathological findings, the existence of acid-fast bacilli in the biopsy specimens, and the clinical course of the patients after the biopsy were reviewed retrospectively. Two of the three histological findings for tuberculosis that included epithelioid cells, multinucleated giant cells and caseous necrosis were observed in 21 of the nodules which were therefore diagnosed as histological tuberculosis. Six of these 21 nodules were positive for acid-fast bacilli, confirming the diagnosis of tuberculosis. Thirteen of the 21 nodules did not contain acid-fast bacilli but decreased in size in response to antituberculous treatment and were therefore diagnosed as clinical tuberculosis. Seven nodules with only caseous necrosis were diagnosed as suspected tuberculosis, with a final diagnosis of tuberculosis being made in 4 of the nodules and a diagnosis of old tuberculosis in 2 nodules. Two nodules with only multinucleated giant cells were diagnosed as suspected tuberculosis with 1 of these nodules being diagnosed finally as tuberculosis and the other nodule as a nonspecific granuloma. When any two of the three following histopathological findings - epithelioid cells, multinucleated giant cells or caseous necrosis - are observed in a specimen obtained by CT-guided transthoracic core biopsy, the diagnosis of tuberculosis can be established without the detection of acid-fast bacilli or Mycobacterium tuberculosis

  4. Clinical value of FDG dual-head tomography with coincidence imaging in suspected malignant pleural effusion or atelectasis

    International Nuclear Information System (INIS)

    Wang Huoqiang; Wu Jiyang; Pan Huizhong; Liu Jinjun; Shen Yi; Zhao Xianguo

    2004-01-01

    tuberculosis, 21 with inflammation and 1 with blood vessel malformation). FDG DHTC found the positive primary lung lesions in 37 of 38 patients with lung cancer, and was negative in 1 squamous cell carcinoma patient who had a atelectasis whose lesion size was 12 mm in diameter. FDG DHTC found false positive in 16 of 72 patients with benign diseases (14 with tuberculosis and 2 with inflammation). The sensitivity, specificity and accuracy of FDG DHTC in detecting lung cancer in patients with suspected malignant pleural effusion or malignant atelectasis were 97%, 78% and 85%, respectively. 30 patients with lung cancer and a pleural effusion, FDG DHTC correctly detected the presence of malignant pleural effusion and malignant pleural involvement in 18 of 21 patients and excluded malignant pleural effusion or pleural metastatic involvement in 8 of 9 patients (sensitivity, specificity and accuracy of 86%, 89% and 87% respectively). The mediastinal lymph node metastasis was found in 6 of these 21 patients with malignant pleural effusions. Conclusions: FDG DHTC imaging is a highly accurate and reliable noninvasive test in finding primary lung malignant lesions in patients with pleural effusion or atelectasis on CT scanning. Active tuberculosis or tuberculo-pleurisy is the main reason of false positivity on FDG DHTC imaging. FDG DHTC is also useful to differentiate malignant from benign pleural effusion in patients with lung cancer. (authors)

  5. Impact of fluoroquinolone treatment on delay of tuberculosis diagnosis: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Catherine A Hogan

    2017-01-01

    Full Text Available Background: Fluoroquinolones are among the most commonly used antibiotics for the treatment of respiratory infections. Because fluoroquinolones show bactericidal activity against Mycobacterium tuberculosis, there is concern that their use can delay the diagnosis of tuberculosis. We conducted a systematic review and meta-analysis to assess whether empiric treatment with fluoroquinolones delays the diagnosis and treatment of tuberculosis in patients with respiratory tract infections. Objectives: The primary objective was to assess the delay in days in the diagnosis and treatment of tuberculosis, among patients who received quinolones, compared to those who received non-fluoroquinolone antibiotics. Methods: We included studies of adult patients treated with fluoroquinolones prior to a confirmed diagnosis of tuberculosis. We performed a literature search of 7 databases (including PubMed, Embase and Cochrane Library with no language restrictions. We calculated an unweighted mean of estimate of difference in delay across all studies. For the studies for which the estimate was available as a mean with standard deviation, a weighted average using a random effects meta-analysis model was estimated. Results: A total of 3983 citations were identified from the literature search; of these, 17 articles were selected for full-text review. A total of 10 studies were retained for the synthesis. These included 7 retrospective cohort studies and 3 case-control studies. Only one of these studies was from a high TB burden country, South Africa. The most commonly used fluoroquinolones were levofloxacin, gemifloxacin and moxifloxacin. The unweighted average of difference in delay between the fluoroquinolone group and non-fluoroquinolone group was 12.9 days (95% CI 6.1–19.7. When these differences were pooled using a random effects model, the weighted estimate was 10.9 days (95% CI 4.2–17.6. When stratified by acid-fast smear status, the delay was

  6. Global fund financing of tuberculosis services delivery in prisons.

    Science.gov (United States)

    Lee, Donna; Lal, S S; Komatsu, Ryuichi; Zumla, Alimuddin; Atun, Rifat

    2012-05-15

    Despite concerted efforts to scale up tuberculosis control with large amounts of international financing in the last 2 decades, tuberculosis continues to be a social issue affecting the world's most marginalized and disadvantaged communities. This includes prisoners, estimated at about 10 million globally, for whom tuberculosis is a leading cause of mortality and morbidity. The Global Fund to Fight AIDS, Tuberculosis and Malaria has emerged as the single largest international donor for tuberculosis control, including funding support in delivering tuberculosis treatment for the confined population. The Global Fund grants database, with an aggregate approved investment of $21.7 billion in 150 countries by the end of 2010, was reviewed to identify tuberculosis and human immunodeficiency virus/tuberculosis grants and activities that monitored the delivery of tuberculosis treatment and support activities in penitentiary settings. The distribution and trend of number of countries with tuberculosis prison support was mapped by year, geographic region, tuberculosis or multidrug-resistant tuberculosis burden, and prison population rate. We examined the types of grant recipients managing program delivery, their performance, and the nature and range of services provided. Fifty-three of the 105 countries (50%) with Global Fund-supported tuberculosis programs delivered services within prison settings. Thirty-two percent (73 of 228) of tuberculosis grants, representing $558 million of all disbursements of Global Fund tuberculosis support by the end of 2010, included output indicators related to tuberculosis services delivered in prisons. Nearly two-thirds (64%) of these grants were implemented by governments, with the remaining by civil society and other partners. In terms of services, half (36 of 73) of grants provided diagnosis and treatment and an additional 27% provided screening and monitoring of tuberculosis for prisoners. The range of services tracked was limited in scope

  7. Prevalence of smear positive pulmonary tuberculosis among prisoners in North Gondar Zone Prison, northwest Ethiopia.

    Science.gov (United States)

    Moges, Beyene; Amare, Bemnet; Asfaw, Fanaye; Tesfaye, Wogahta; Tiruneh, Moges; Belyhun, Yeshambel; Mulu, Andargachew; Kassu, Afework

    2012-12-15

    People concentrated in congregated systems, such as prisons, are important but often neglected reservoirs for TB transmission, and threaten those in the outside community. Therefore, this study was conducted to determine the prevalence of tuberculosis in a prison system of North Gondar Zone. An active case-finding survey in North Gondar Prison was carried out from March to May 2011. All prison inmates who had history of cough for at least a week were included in the study. Three morning sputum samples were collected from suspected inmates and examined through fluorescence microscopy. Fine needle aspiration cytology was done for those having significant lymphadenopathy. Pre and post HIV test counseling was provided after written consent. Binary logistic and multivariable analysis was performed using SPSS version 16. A total of 250 prisoners were included in the survey. Among these, 26 (10.4%) prisoners were found to have TB giving a point prevalence of 1482.3 per 100,000 populations of smear positive TB among the TB suspects. All the inmates who participated in the study volunteered for HIV testing and a total of 19(7.6%) inmates were found to be reactive for the HIV antibody test amongst of which 9(47.4%) had TB co-infection. The prevalence of HIV infection in the TB infected inmates was found to be 34.6% (9/26). From the 26 TB cases identified 12 (46.2%) were having under nutrition (BMI Prison with possible active transmission of TB within the prison. There was a high prevalence of HIV among the TB suspects. Strong cooperation between prison authorities and the national tuberculosis control programmes is urgently required to develop locally appropriate interventions to reduce transmission. The determinants for poor nutrition in the prison need also further investigation.

  8. A prospective audit of the use of diagnostic laparoscopy to establish the diagnosis of abdominal tuberculosis.

    Science.gov (United States)

    Islam, J; Clarke, D; Thomson, S R; Wilson, D; Dawood, H

    2014-06-01

    The incidence of abdominal tuberculosis is much higher in an HIV-positive cohort. The use of laparoscopy in the diagnostic work-up of suspected abdominal tuberculosis is underutilized and its use and efficacy in the context of HIV co-infection has never been examined. A prospective clinical audit of the use of diagnostic laparoscopy was conducted in patients with clinically suspected abdominal tuberculosis but histologically or microbiologically unconfirmed tuberculosis at any site. From January 2008 to June 2010, 81 patients underwent diagnostic laparoscopy; 34 were male and 47 were female, with a mean age of 33 years, and 77 % were HIV-positive. Fifty-five patients (68 %) had positive histology or culture for tuberculosis. In 15 patients (19 %), histology revealed non-specific inflammation, no pathology was found in one patient, and no specimen was taken from one patient. Eighty percent of peritoneal deposits and 77 % of lymph nodes were positive for tuberculosis, whereas 35 % of ascitic fluid cultures were positive. In nine patients (11 %) an alternative diagnosis was found; nine patients (11 %) had conversion to laparotomy. There was no procedure-related death. Nine patients (11 %) died during the 2-month follow-up period. Diagnostic laparoscopy avoids the morbidity and mortality of laparotomy in chronically ill patients, and reduces the rate of misdiagnosis of other abdominal conditions and unnecessary long-term therapy. Diagnostic laparoscopy and tissue sampling is a viable and reliable strategy in patients with suspected abdominal tuberculosis.

  9. Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition.

    Science.gov (United States)

    Wolf, Nina M; Gutka, Hiten J; Movahedzadeh, Farahnaz; Abad-Zapatero, Celerino

    2018-04-01

    The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus. This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and is probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis (MtFBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of MtFBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of MtFBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.

  10. HIV status and tuberculosis

    African Journals Online (AJOL)

    User

    Failure to perform mycobacterium culture bacterial blood culture and results of other causes of .... for Identification of Highly Infectious Tuberculosis in People Living with HIV in Southeast Asia. ... Indian Journal of Tuberculosis 58, 108-112.

  11. Tuberculosis Lymphoedema Cutis

    Directory of Open Access Journals (Sweden)

    Gangopadhyay Asok Kumar

    2001-01-01

    Full Text Available Lymphoedema following cutaneous tuberculosis is a rare occurrence. A case of elephantiasis of leg following lupus vulgaris is presented. It can still be seen in rural India in untreated advanced cutaneous tuberculosis.

  12. Tuberculosis Treatment and Pregnancy

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  13. Play the Tuberculosis Game

    Science.gov (United States)

    ... Questionnaire Tuberculosis Play Tuberculosis Experiments & Discoveries About the game Discover and experience some of the classic methods ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  14. The imaging feature of multidrug-resistant tuberculosis

    International Nuclear Information System (INIS)

    Yang Jun; Zhou Xinhua; Li Xi; Fu Yuhong; Zheng Suhua; Lv Pingxin; Ma Daqing

    2004-01-01

    Objective: To evaluate the imaging features of multidrug-resistant tuberculosis by collecting multidrug-resistant tuberculosis verified by test of drug-sensitivity, which defined as resistance to three anti-tuberculosis drugs. Methods:Fifty-one cases of multidrug-resistant tuberculosis were categorized as group of observed, and 46 cases of drug sensitive tuberculosis were categorized as control. Cultures were positive for Mycobacterium tuberculosis in all cases with no other illness such as diabetes mellitus. All patients had chest radiographs available for review, while 64 cases had tomography and 30 cases had CT during the same time. All images were analyzed by three of the radiologists, disagreement among them was discussed and a consensus was reached. Results: There was no difference in the distribution of lesions between the multidrug-resistant tuberculosis group and control group. However, the radiological findings in the multidrug-resistant tuberculosis group were significantly more common than in control group, such as multiple nodules (10 cases), disseminated foci (23 cases), cavity (9 cases), and complications (10 cases). Comparing the dynamic cases, deteriorating cases were more commonly seen in observed group than in control group, while improved cases were less in observed group than in control group. Conclusion: Multidrug-resistant tuberculosis is the most serious tuberculosis, which is characterized with significant activity, more disseminated foci, cavity, and complications. The lesion deteriorated while correct anti-tuberculosis treatment is applied. (authors)

  15. Tuberculosis as occupational disease

    OpenAIRE

    Mendoza-Ticona, Alberto; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia. Lima, Perú. Médico infectólogo tropicalista magister en Epidemiología Clínica.

    2014-01-01

    There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupationa...

  16. Tuberculosis-Diagnostic Expert System: an architecture for translating patients information from the web for use in tuberculosis diagnosis.

    Science.gov (United States)

    Osamor, Victor C; Azeta, Ambrose A; Ajulo, Oluseyi O

    2014-12-01

    Over 1.5-2 million tuberculosis deaths occur annually. Medical professionals are faced with a lot of challenges in delivering good health-care with unassisted automation in hospitals where there are several patients who need the doctor's attention. To automate the pre-laboratory screening process against tuberculosis infection to aid diagnosis and make it fast and accessible to the public via the Internet. The expert system we have built is designed to also take care of people who do not have access to medical experts, but would want to check their medical status. A rule-based approach has been used, and unified modeling language and the client-server architecture technique were applied to model the system and to develop it as a web-based expert system for tuberculosis diagnosis. Algorithmic rules in the Tuberculosis-Diagnosis Expert System necessitate decision coverage where tuberculosis is either suspected or not suspected. The architecture consists of a rule base, knowledge base, and patient database. These units interact with the inference engine, which receives patient' data through the Internet via a user interface. We present the architecture of the Tuberculosis-Diagnosis Expert System and its implementation. We evaluated it for usability to determine the level of effectiveness, efficiency and user satisfaction. The result of the usability evaluation reveals that the system has a usability of 4.08 out of a scale of 5. This is an indication of a more-than-average system performance. Several existing expert systems have been developed for the purpose of supporting different medical diagnoses, but none is designed to translate tuberculosis patients' symptomatic data for online pre-laboratory screening. Our Tuberculosis-Diagnosis Expert System is an effective solution for the implementation of the needed web-based expert system diagnosis. © The Author(s) 2013.

  17. Mycobacterium tuberculosis UvrB Is a Robust DNA-Stimulated ATPase That Also Possesses Structure-Specific ATP-Dependent DNA Helicase Activity.

    Science.gov (United States)

    Thakur, Manoj; Kumar, Mohan B J; Muniyappa, K

    2016-10-18

    Much is known about the Escherichia coli nucleotide excision repair (NER) pathway; however, very little is understood about the proteins involved and the molecular mechanism of NER in mycobacteria. In this study, we show that Mycobacterium tuberculosis UvrB (MtUvrB), which exists in solution as a monomer, binds to DNA in a structure-dependent manner. A systematic examination of MtUvrB substrate specificity reveals that it associates preferentially with single-stranded DNA, duplexes with 3' or 5' overhangs, and linear duplex DNA with splayed arms. Whereas E. coli UvrB (EcUvrB) binds weakly to undamaged DNA and has no ATPase activity, MtUvrB possesses intrinsic ATPase activity that is greatly stimulated by both single- and double-stranded DNA. Strikingly, we found that MtUvrB, but not EcUvrB, possesses the DNA unwinding activity characteristic of an ATP-dependent DNA helicase. The helicase activity of MtUvrB proceeds in the 3' to 5' direction and is strongly modulated by a nontranslocating 5' single-stranded tail, indicating that in addition to the translocating strand it also interacts with the 5' end of the substrate. The fraction of DNA unwound by MtUvrB decreases significantly as the length of the duplex increases: it fails to unwind duplexes longer than 70 bp. These results, on one hand, reveal significant mechanistic differences between MtUvrB and EcUvrB and, on the other, support an alternative role for UvrB in the processing of key DNA replication intermediates. Altogether, our findings provide insights into the catalytic functions of UvrB and lay the foundation for further understanding of the NER pathway in M. tuberculosis.

  18. Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation

    Directory of Open Access Journals (Sweden)

    David Pires

    2017-12-01

    Full Text Available The success of tuberculosis (TB bacillus, Mycobacterium tuberculosis (Mtb, relies on the ability to survive in host cells and escape to immune surveillance and activation. We recently demonstrated that Mtb manipulation of host lysosomal cathepsins in macrophages leads to decreased enzymatic activity and pathogen survival. In addition, while searching for microRNAs (miRNAs involved in posttranscriptional gene regulation during mycobacteria infection of human macrophages, we found that selected miRNAs such as miR-106b-5p were specifically upregulated by pathogenic mycobacteria. Here, we show that miR-106b-5p is actively manipulated by Mtb to ensure its survival in macrophages. Using an in silico prediction approach, we identified miR-106b-5p with a potential binding to the 3′-untranslated region of cathepsin S (CtsS mRNA. We demonstrated by luminescence-based methods that miR-106b-5p indeed targets CTSS mRNA resulting in protein translation silencing. Moreover, miR-106b-5p gain-of-function experiments lead to a decreased CtsS expression favoring Mtb intracellular survival. By contrast, miR-106b-5p loss-of-function in infected cells was concomitant with increased CtsS expression, with significant intracellular killing of Mtb and T-cell activation. Modulation of miR-106b-5p did not impact necrosis, apoptosis or autophagy arguing that miR-106b-5p directly targeted CtsS expression as a way for Mtb to avoid exposure to degradative enzymes in the endocytic pathway. Altogether, our data suggest that manipulation of miR-106b-5p as a potential target for host-directed therapy for Mtb infection.

  19. Cutaneous tuberculosis, tuberculosis verrucosa cutis

    Directory of Open Access Journals (Sweden)

    Nilamani Mohanty

    2014-01-01

    Full Text Available Cutaneous tuberculosis because of its variability in presentation, wider differential diagnosis, and difficulty in obtaining microbiological confirmation continues to be the most challenging to diagnose for dermatologists in developing countries. Despite the evolution of sophisticated techniques such as polymerase chain reaction (PCR and enzyme-linked-immunosorbent serologic assay (ELISA, the sensitivity of new methods are not better than the isolation of Mycobacterium tuberculosum in culture. Even in the 21 st century, we rely on methods as old as the intradermal reaction purified protein derivative standard test and therapeutic trials, as diagnostic tools. We describe a case which has been diagnosed and treated as eczema by renowned physicians for 2 years. Incisional biopsy showed the presence of well-defined granulomas and ZN staining of the biopsy specimen showed the presence of acid fast bacilli; a trial of ATT (antitubercular therapy for 6 months lead to permanent cure of the lesion.

  20. Abdominal tuberculosis in children

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2001-06-01

    supported the diagnosis. There was no positive results of acid fast bacilli and culture done for Mycobacterium tuberculosis in gastric aspirate as well as ascitic fuid. Peritonitis tuberculosis was most commonly diagnosed (80.0%, followed by mesenterial/nodal tuberculosis (20.0%. All of the children followed (60.0% responded well to the drugs therapy.

  1. pulmonary tuberculosis, jimma hospital

    African Journals Online (AJOL)

    and National Tuberculosis and Leprosy Control Program manual. RESULTS: A total of 112 extra pulmonary ... Key words: Clinical audit; extra pulmonary Tuberculosis; National Tuberculosis and. Leprosy Control manual. "Addis Ababa ..... intern influence drug regimen selection. Compliance to the 1997 NTLCP inanual is.

  2. Citoquinas en tuberculosis Cytokines in tuberculosis

    Directory of Open Access Journals (Sweden)

    Jaime I. Rodríguez

    1997-04-01

    specific antigens of Iymphocytes from tuberculin positive healthy subjects induces a type I cytokine pattern (1'IL.2, 1'IFN.y, -VIL.4, -VIL.5 whereas Iymphocytes from tuberculous patients do not exhibit it. Type I cytokines activate macrophages able to inhibit mycobacteria intracellular growth. In mice, nitric oxide produced by activated macrophages is responsible for such effect; however, the productJon of nitric oxide by human macrophages has not been conclusively demonstrated. Recent reports have shown that infection with M. tuberculosis induces apoptosis in infected macrophages. Apoptosis in such conditions is Tumor Necrosis Factor.a and nitric oxide dependent. Paradoxically, mannosylated liparabinomann (ManLAM, a structural component of the rñycobacterial cell wall, inhibits apoptosis of infected macrophages. These results demonstrate a new aspect of the mycobacteria.macrophage relatJonship that must be finely regulated by both the microorganism and the host.

  3. Mycobacterium tuberculosis Latent Antigen Rv2029c from the Multistage DNA Vaccine A39 Drives TH1 Responses via TLR-mediated Macrophage Activation

    Directory of Open Access Journals (Sweden)

    Haibo Su

    2017-11-01

    Full Text Available Targeting of Mycobacterium tuberculosis (MTB latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB vaccine(s that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population. Subsequently, we investigated the effect of Rv2029c on innate immunity and characterized the molecular details of the interaction of this protein with the host via iTRAQ proteomic and biochemical assay analyses. Rv2029c activated macrophages, triggered the production of pro-inflammatory cytokines, and promoted toll-like receptor/mitogen-activated protein kinase (TLR/MAPK-dependent macrophage apoptosis. Furthermore, Rv2029c treatment enhanced the ability of Mycobacterium bovis Bacillus Calmette-Guérin (BCG-infected macrophages to present antigens to CD4+ T cells in vitro, which correlated with an increase in MHC-II expression. Lastly, Rv2029c-treated macrophages activated T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and specifically expanded a population of CD44highCD62LlowCD4+/CD8+ effector/memory cells, indicating that Rv2029c, as a specific recall antigen, contributes to Th1 polarization in T cell immunity. These results suggest that Rv2029c and A39 comprise promising targets for the development of next-generation clinical TB therapeutic vaccines.

  4. Drug-resistant spinal tuberculosis

    Directory of Open Access Journals (Sweden)

    Anil K Jain

    2018-01-01

    Full Text Available Drug-resistant spinal tuberculosis (TB is an emerging health problem in both developing and developed countries. In this review article, we aim to define management protocols for suspicion, diagnosis, and treatment of such patients. Spinal TB is a deep-seated paucibacillary lesion, and the demonstration of acid-fast bacilli on Ziehl-Neelsen staining is possible only in 10%–30% of cases. Drug resistance is suspected in patients showing the failure of clinicoradiological improvement or appearance of a fresh lesion of osteoarticular TB while on anti tubercular therapy (ATT for a minimum period of 5 months. The conventional culture of Mycobacterium tuberculosis remains the gold standard for both bacteriological diagnosis and drug sensitivity testing (DST; however, the high turn around time of 2–6 weeks for detection with added 3 weeks for DST is a major limitation. To overcome this problem, rapid culture methods and molecular methods have been introduced. From a public health perspective, reducing the period between diagnosis and treatment initiation has direct benefits for both the patient and the community. For all patients of drug-resistant spinal TB, a complete Drug-O-Gram should be prepared which includes details of all drugs, their doses, and duration. Patients with confirmed multidrug-resistant TB strains should receive a regimen with at least five effective drugs, including pyrazinamide and one injectable. Patients with resistance to additional antitubercular drugs should receive individualized ATT as per their DST results.

  5. The Association between active and passive smoking and latent tuberculosis infection in adults and children in the united states: results from NHANES.

    Directory of Open Access Journals (Sweden)

    Ryan P Lindsay

    Full Text Available Few studies assessing the relationship between active and passive smoking and tuberculosis have used biomarkers to measure smoke exposure. We sought to determine the association between active and passive smoking and LTBI in a representative sample of US adults and children.We used the 1999-2000 US National Health and Nutrition Examination Survey (NHANES dataset with tuberculin skin test (TST data to assess the association between cotinine-confirmed smoke exposure and latent tuberculosis infection (LTBI among adults ages ≥20 years (n = 3598 and children 3-19 years (n = 2943 and estimate the prevalence of smoke exposure among those with LTBI. Weighted multivariate logistic regression was used to measure the associations between active and passive smoking and LTBI.LTBI prevalence in 1999-2000 among cotinine-confirmed active, passive, and non-smoking adults and children was 6.0%, 5.2%, 3.3% and 0.3%, 1.0%, 1.5%, respectively. This corresponds to approximately 3,556,000 active and 3,379,000 passive smoking adults with LTBI in the US civilian non-institutionalized population in 1999-2000. Controlling for age, gender, socioeconomic status, race, birthplace (US vs. foreign-born, household size, and having ever lived with someone with TB, adult active smokers were significantly more likely to have LTBI than non-smoking adults (AOR = 2.31 95% CI 1.17-4.55. Adult passive smokers also had a greater odds of LTBI compared with non-smokers, but this association did not achieve statistical significance (AOR = 2.00 95% CI 0.87-4.60. Neither active or passive smoking was associated with LTBI among children. Among only the foreign-born adults, both active (AOR = 2.56 (95% CI 1.20-5.45 and passive smoking (AOR = 2.27 95% CI 1.09-4.72 were significantly associated with LTBI.Active adult smokers and both foreign-born active and passive smokers in the United States are at elevated risk for LTBI. Targeted smoking prevention and cessation

  6. Rv3634c from Mycobacterium tuberculosis H37Rv encodes an enzyme with UDP-Gal/Glc and UDP-GalNAc 4-epimerase activities.

    Directory of Open Access Journals (Sweden)

    Peehu Pardeshi

    Full Text Available A bioinformatics study revealed that Mycobacterium tuberculosis H37Rv (Mtb contains sequence homologs of Campylobacter jejuni protein glycosylation enzymes. The ORF Rv3634c from Mtb was identified as a sequence homolog of C. jejuni UDP-Gal/GalNAc 4-epimerase. This study reports the cloning of Rv3634c and its expression as an N-terminal His-tagged protein. The recombinant protein was shown to have UDP-Gal/Glc 4-epimerase activity by GOD-POD assay and by reverse phase HPLC. This enzyme was shown to have UDP-GalNAc 4-epimerase activity also. Residues Ser121, Tyr146 and Lys150 were shown by site-directed mutagenesis to be important for enzyme activity. Mutation of Ser121 and Tyr146 to Ala and Phe, respectively, led to complete loss of activity whereas mutation of Lys150 to Arg led to partial loss of activity. There were no gross changes in the secondary structures of any of these three mutants. These results suggest that Ser121 and Tyr146 are essential for epimerase activity of Rv3634c. UDP-Gal/Glc 4-epimerases from other organisms also have a catalytic triad consisting of Ser, Tyr and Lys. The triad carries out proton transfer from nucleotide sugar to NAD+ and back, thus effecting the epimerization of the substrate. Addition of NAD+ to Lys150 significantly abrogates the loss of activity, suggesting that, as in other epimerases, NAD+ is associated with Rv3634c.

  7. Diagnosis of sputum-scarce HIV-associated pulmonary tuberculosis in Lima, Peru

    Science.gov (United States)

    Vargas, Daniel; García, Luis; Gilman, Robert H; Evans, Carlton; Ticona, Eduardo; Ñavincopa, Marcos; Luo, Robert F; Caviedes, Luz; Hong, Clemens; Escombe, Rod; Moore, David A J

    2010-01-01

    Sputum induction, bronchoalveolar lavage, or gastric aspiration are often needed to produce adequate diagnostic respiratory samples from people with HIV in whom tuberculosis is suspected. Since these procedures are rarely appropriate in less-developed countries, we compared the performances of a simple string test and the gold-standard sputum induction. 160 HIV-positive adults under investigation for tuberculosis, and 52 asymptomatic HIV-positive control patients underwent the string test followed by sputum induction. The string test detected tuberculosis in 14 patients in whom this disease was suspected; sputum induction detected only eight of them (McNemar's test, p=0·03). These preliminary data suggest that the string test is safe and effective for retrieval of useful clinical specimens for diagnosis of pulmonary tuberculosis, and is at least as sensitive as sputum induction. PMID:15639297

  8. Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

    2014-10-02

    Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

  9. Symptom-based screening tool in ruling out active tuberculosis among HIV-infected patients eligible for isoniazid preventive therapy in Tanzania.

    Science.gov (United States)

    Shayo, Grace A; Minja, Lilian T; Egwaga, Said; Bakari, Muhammad; Mugusi, Ferdinand M

    2014-06-01

    We assessed the usefulness of the National TB and Leprosy Control Program (NTLP) symptom-based tuberculosis (TB) screening tool in identifying HIV-infected patients eligible for isoniazid preventive therapy in Muhimbili National Hospital, Dar es Salaam Tanzania. Descriptive cross-sectional study. Data collected included socio-demographic and clinical data. Chest X-ray, sputum for acid-fast bacilli (AFB) microscopy, mycobacterial culture, CD4 + count and complete blood count were performed. Patients were considered not having active TB if they presented with no symptom in the screening tool, which comprised these symptoms: cough, fever and excessive night sweats for ≥2 weeks; weight loss of ≥3 kg in 4 weeks and haemoptysis of any duration. The reference standard was a negative culture for Mycobacterium tuberculosis. We enroled 373 patients, of whom 72.1% were females. Active pulmonary TB was found in 4.1% (14/338) of the participants as defined by a positive culture. The sensitivity and specificity of the NTLP screening tool were 71.4% (10/14) and 75.9% (246/324), respectively. False-negative rate was 28.6% (4/10). Cough, fever for ≥2 weeks and weight loss were independent predictors of NTLP-defined TB. Cough ≥2 weeks predicted TB when a positive culture was used to define TB. The screening tool had fairly good sensitivity and specificity for TB screening; however, there is a possibility that about 29% of the screened population will be given IPT while they are supposed to receive a full course of TB treatment. © 2014 John Wiley & Sons Ltd.

  10. Validation of a model for predicting smear-positive active pulmonary tuberculosis in patients with initial acid-fast bacilli smear-negative sputum

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Jun-Jun [Department of Chest Medicine, Section of Thoracic Imaging, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City (China); Chia Nan University of Pharmacy and Science, Tainan (China); Meiho University, Pingtung (China); Pingtung Christian Hospital, Pingtung (China); Heng Chun Christian Hospital, Pingtung (China)

    2018-01-15

    The objective of this study was to develop a predictive model for final smear-positive (SP) active pulmonary tuberculosis (aPTB) in patients with initial negative acid fast bacilli (AFB) sputum smears (iSN-SP-aPTB) based on high-resolution computed tomography (HRCT). Eighty (126, 21) patients of iSN-SP-aPTB and 402 (459, 876) patients of non-initial positive acid fast bacilli (non-iSP) pulmonary disease without iSN-SP-aPTB were included in a derivation (validation, prospective) cohort. HRCT characteristics were analysed, and multivariable regression and receiver operating characteristic (ROC) curve analysis was performed to develop a score predictive of iSN-SP-aPTB. The derivation cohort showed clusters of nodules/mass of the right upper lobe or left upper lobe were independent predictors of iSN-SP-aPTB, while bronchiectasis in the right middle lobe or left lingual lobe were negatively associated with iSN-SP-aPTB. A predictive score for iSN-SP-aPTB based on these findings was tested in the validation and prospective cohorts. With an ideal cut-off score = 1, the sensitivity, specificity, positive predictive value, and negative predictive value of the prediction model were 87.5% (90%, 90.5%), 99% (97.1%, 98.4%), 94.6% (81.3%, 57.5%), and 97.6% (97%, 99.8%) in the derivation (validation, prospective) cohorts, respectively. The model may help identify iSN-SP-aPTB among patients with non-iSP pulmonary diseases. circle Smear-positive active pulmonary tuberculosis that is initial smear-negative (iSN-SP-aPTB) is infectious. (orig.)

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

    Science.gov (United States)

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

    2012-05-15

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

  12. Drug development against tuberculosis: Impact of alkaloids.

    Science.gov (United States)

    Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K

    2017-09-08

    Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Principles of order in the course of tuberculosis

    International Nuclear Information System (INIS)

    Wolfart, W.; Wenz, W.

    1981-01-01

    Presentation of different kinds in the course of tuberculosis of the lung. Comparison of pathologic-anatomical findings and radiology of an active, exudative, cavernous, cirrhotic, and miliary tuberculosis. Discussion of the concept of activity from different points of views: clinical, radioligical, and histological. (orig.) [de

  14. The mechanisms of substrates interaction with the active site of Mycobacterium tuberculosis tyrosyl-tRNA synthetase studied by molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Mykuliak V. V.

    2014-03-01

    Full Text Available Aim. To study the mechanisms of substrates interaction with the active site of Mycobacterium tuberculosis tyrosyl-tRNA synthetase (MtTyrRS. Methods. Complexes of MtTyrRS with tyrosine, ATP and tyrosyl adenylate were constructed by superposition of the MtTyrRS structure and crystallographic structures of bacterial TyrRS. All complexes of MtTyrRS with substrates were investigated by molecular dynamics (MD simulations in solution. Results. It was shown the formation of network of hydrogen bonds between substrates and the MtTyrRS active center, which were stable in the course of MD simulations. ATP binds in the active site both by hydrogen bonds and via electrostatic interactions with Lys231 and Lys234 of catalytic KFGKS motif. Conclusions. The L-tyrosine binding site in the enzyme active site is negatively charged, whereas the ATP binding site contains positive Lys231 and Lys234 residues of catalytic KFGKS motif. The occupancy of H-bonds between substrates and the enzyme evidences a significant conformational mobility of the active site.

  15. The use of combined heart rate response and accelerometry to assess the level and predictors of physical activity in tuberculosis patients in Tanzania

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Maria; Faurholt-Jepsen, Daniel; Range, N

    2014-01-01

    , HIV and physical activity estimates were assessed in multivariable linear regression models adjusted for age, sex, haemoglobin and alpha-1-acid glycoprotein (AGP). Sputum-positive [eB 0·43, 95% confidence interval (CI) 0·29-0·64] and sputum-negative (eB 0·67, 95% CI 0·47-0·94) TB as well as HIV......SUMMARY: We assessed the role of tuberculosis (TB) disease and HIV infection on the level of physical activity. A combined heart rate and movement sensor was used to assess habitual physical activity in TB patients and non-TB controls. The association between sputum-negative TB, sputum-positive TB...... infection (eB 0·59, 95% CI 0·46-0·75) were associated with reduced activity compared to controls. Anaemia accounted for a substantial part of the effects of HIV, while elevated AGP primarily mediated the TB effect. The level of physical activity is highly influenced by TB and HIV, and mainly mediated...

  16. Tuberculosis in the lung (image)

    Science.gov (United States)

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

  17. Tuberculosis Facts - Exposure to TB

    Science.gov (United States)

    Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  18. Tuberculosis Facts - Testing for TB

    Science.gov (United States)

    Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  19. Drivers of Tuberculosis Transmission.

    Science.gov (United States)

    Mathema, Barun; Andrews, Jason R; Cohen, Ted; Borgdorff, Martien W; Behr, Marcel; Glynn, Judith R; Rustomjee, Roxana; Silk, Benjamin J; Wood, Robin

    2017-11-03

    Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  20. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

    Science.gov (United States)

    Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

    2012-01-01

    To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. Virulence factors of the Mycobacterium tuberculosis complex

    Science.gov (United States)

    Forrellad, Marina A.; Klepp, Laura I.; Gioffré, Andrea; Sabio y García, Julia; Morbidoni, Hector R.; Santangelo, María de la Paz; Cataldi, Angel A.; Bigi, Fabiana

    2013-01-01

    The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world. PMID:23076359

  2. Risk assessment of tuberculosis in immunocompromised patients

    DEFF Research Database (Denmark)

    Sester, Martina; van Leth, Frank; Bruchfeld, Judith

    2014-01-01

    RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES: This study compared the performance...... of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation......, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS: Frequencies of positive...

  3. A high-resolution computed tomography-based scoring system to differentiate the most infectious active pulmonary tuberculosis from community-acquired pneumonia in elderly and non-elderly patients

    International Nuclear Information System (INIS)

    Yeh, Jun-Jun; Chen, Solomon Chih-Cheng; Chen, Cheng-Ren; Yeh, Ting-Chun; Lin, Hsin-Kai; Hong, Jia-Bin; Wu, Bing-Tsang; Wu, Ming-Ting

    2014-01-01

    The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. (orig.)

  4. A high-resolution computed tomography-based scoring system to differentiate the most infectious active pulmonary tuberculosis from community-acquired pneumonia in elderly and non-elderly patients

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Jun-Jun [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Section of Thoracic Imaging, Department of Chest Medicine and Family Medicine, Chiayi City (China); Chia Nan University of Pharmacy and Science, Tainan (China); Meiho University, Pingtung (China); Pingtung Christian Hospital, Pingtung (China); Chen, Solomon Chih-Cheng; Chen, Cheng-Ren [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Department of Medical Research, Chiayi City (China); Yeh, Ting-Chun; Lin, Hsin-Kai; Hong, Jia-Bin; Wu, Bing-Tsang [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Department of Family Medicine, Chiayi City (China); Wu, Ming-Ting [Department of Radiology, Kaohsiung Veterans General Hospital, Section of Thoracic and Circulation Imaging, Kaohsiung (China); School of Medicine, National Yang Ming University, Faculty of Medicine, Taipei (China)

    2014-10-15

    The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. (orig.)

  5. Revisiting the natural history of tuberculosis. The inclusion of constant reinfection, host tolerance, and damage-response frameworks leads to a better understanding of latent infection and its evolution towards active disease.

    Science.gov (United States)

    Cardona, Pere-Joan

    2010-02-01

    Once Mycobacterium tuberculosis infects a person it can persist for a long time in a process called latent tuberculosis infection (LTBI). LTBI has traditionally been considered to involve the bacilli remaining in a non-replicating state (dormant) in old lesions but still retaining their ability to induce reactivation and cause active tuberculosis (TB) once a disruption of the immune response takes place. The present review aims to challenge these concepts by including recent experimental data supporting LTBI as a constant endogenous reinfection process as well as the recently introduced concepts of damage-response and tolerance frameworks to explain TB induction. These frameworks highlight the key role of an exaggerated and intolerant host response against M. tuberculosis bacilli which induces the classical TB cavity in immunocompetent adults once the constant endogenous reinfection process has resulted in the presence of bacilli in the upper lobes, where they can grow faster and the immune response is delayed. This essay intends to provide new clues to understanding the induction of TB in non-immunosuppressed patients.

  6. Endocrine dysfunction among adult patients with tuberculosis: An African experience

    Directory of Open Access Journals (Sweden)

    Davis Kibirige

    2014-01-01

    Full Text Available A broad spectrum of endocrine conditions has been reported among adult patients with tuberculosis in Africa. This review aims to describe the magnitude and pathogenesis of the following endocrinopathies among patients with tuberculosis in Africa: adrenal insufficiency, diabetes mellitus, disorders of calcium and vitamin D metabolism, thyroid dysfunction and hypogonadism. PubMed database and Google scholar were used to search for the relevant published English language studies and case reports relating to endocrine abnormalities and tuberculosis in Africa up to July 2013. The search terms used were endocrine dysfunction, endocrine abnormalities, adrenal insufficiency, diabetes mellitus, thyroid dysfunction, hypogonadism, disorders of calcium and vitamin D metabolism, tuberculosis, Africa. Reference lists of the identified articles were further used to identify other studies. Adrenal insufficiency, diabetes mellitus and calcium-vitamin D abnormalities were the most prevalent and frequently reported endocrine disorders among adult patients with tuberculosis in Africa. A meticulous endocrine evaluation among tuberculosis patients with suspected endocrine abnormalities should be encouraged in Africa and other high TB endemic regions. Treatment of these endocrine disorders has generally been shown to improve quality of life and reduce mortality.

  7. Clinics of ocular tuberculosis.

    Science.gov (United States)

    Gupta, Vishali; Shoughy, Samir S; Mahajan, Sarakshi; Khairallah, Moncef; Rosenbaum, James T; Curi, Andre; Tabbara, Khalid F

    2015-02-01

    Ocular tuberculosis is an extrapulmonary tuberculous condition and has variable manifestations. The purpose of this review is to describe the clinical manifestations of ocular tuberculosis affecting the anterior and posterior segments of the eye in both immunocompetent and immunocompromised patients. Review of literature using Pubmed database. Mycobacterium tuberculosis may lead to formation of conjunctival granuloma, nodular scleritis, and interstitial keratitis. Lacrimal gland and orbital caseating granulomas are rare but may occur. The intraocular structures are also a target of insult by M. tuberculosis and may cause anterior granulomatous uveitis, anterior and posterior synechiae, secondary glaucoma, and cataract. The bacillus may involve the ciliary body, resulting in the formation of a localized caseating granuloma. Posterior segment manifestations include vitritis, retinal vasculitis, optic neuritis, serpiginous-like choroiditis, choroidal tubercules, subretinal neovascularization, and, rarely, endophthalmitis. The recognition of clinical signs of ocular tuberculosis is of utmost importance as it can provide clinical pathway toward tailored investigations and decision making for initiating anti-tuberculosis therapy.

  8. Childhood tuberculosis and malnutrition.

    Science.gov (United States)

    Jaganath, Devan; Mupere, Ezekiel

    2012-12-15

    Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease.

  9. Miliary Tuberculosis with Concurrent Brain and Spinal Cord Involvement: A Case Report

    International Nuclear Information System (INIS)

    Sung, Chang Keun; Na, Hyoung Il; Yu, Hyeon; Byun, Jun Soo; Youn, Young Chul; Seo, Jae Seung; Kim, Gi Hyeon

    2008-01-01

    Central nervous system involvement by tuberculosis is rare, and intramedullary involvement is even more rare. A patient that developed intermittent amnesia during anti-tuberculous therapy underwent brain CT and MRI and spine MRI. The latter showed multiple small enhancing nodules in the brain and spinal cord. The patient was treated with anti-tuberculous medication and steroids under the suspected diagnosis of miliary tuberculosis. Follow-up CT showed decreased nodule size and number. We report a case of miliary tuberculosis in the brain and spinal cord and present a review of the literature related to similar cases

  10. Miliary Tuberculosis with Concurrent Brain and Spinal Cord Involvement: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Chang Keun; Na, Hyoung Il; Yu, Hyeon; Byun, Jun Soo; Youn, Young Chul; Seo, Jae Seung; Kim, Gi Hyeon [Chung-Ang University, Seoul (Korea, Republic of)

    2008-11-15

    Central nervous system involvement by tuberculosis is rare, and intramedullary involvement is even more rare. A patient that developed intermittent amnesia during anti-tuberculous therapy underwent brain CT and MRI and spine MRI. The latter showed multiple small enhancing nodules in the brain and spinal cord. The patient was treated with anti-tuberculous medication and steroids under the suspected diagnosis of miliary tuberculosis. Follow-up CT showed decreased nodule size and number. We report a case of miliary tuberculosis in the brain and spinal cord and present a review of the literature related to similar cases.

  11. HIV INFECTION AS A RISK FACTOR OF TUBERCULOSIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    E. P. Eremenko

    2017-01-01

    Full Text Available The article presents the results of three year follow-up over 96 HIV positive children registered in the AIDS Center. During 3 year follow up the infection with tuberculous mycobacteria was diagnosed in 27.3% (n = 23 of HIV positive children from the followed up group. The leading risk factor of tuberculosis is family exposure to a tuberculosis patient – 22.6% (n = 19. Compliance to follow-up and treatment, timely prescribed preventive anti-tuberculosis chemotherapy and highly active antiretroviral therapy enhanced prevention of development of local forms of tuberculosis in the followed up group of children.

  12. Analysis of peculiarities of identification, diagnostics and course of tuberculosis in patients with tuberculosis/HIV co-infection

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    V. P. Melnyk

    2017-10-01

    Full Text Available Objective – to analyse dynamics of detection of tuberculosis and HIV/AIDS in tuberculosis/HIV co-infection, to identify the main clinical forms of tuberculosis, the type of tuberculosis process and the structure of incidence of tuberculosis, to analyse dependence of a clinical form of tuberculosis on quantity of CD4 cells. Materials and methods. 155 patients with tuberculosis/HIV co-infection and 155 patients with tuberculosis without HIV infection were examined. All patients underwent general clinical examination, laboratory tests, X-ray, microbiological, histological studies (with extrapulmonary tuberculosis. Results. In all patients, co-infection was detected mainly by respiratory tuberculosis (in 73 % of HIV-positive and 89 % of HIV-negative patients. In HIV-positive patients, tuberculosis was more often detected by the passive way (81 %, and in HIV-negative patients – by the active way (78 %. 66.5 % of patients had HIV infection first, 21.3 % had the first tuberculosis, and 12.2 % had HIV infection and tuberculosis at the same time. In clinical forms in patients with HIV-infection, infiltrative and disseminated tuberculosis prevailed. Pulmonary tuberculosis was diagnosed in 70.3 % of patients, extrapulmonary – in 11 %, pulmonary and extrapulmonary tuberculosis – in 18.7 %. In 28.4 % of patients, immunodeficiency was detected with CD4 cells less than 100 in 1mm3, in 22.6 % of patients – 101–200 CD4 cells in 1 mm3, in 10.3 % in 201–300 CD4 in 1 mm3, in 14.8 % of patients – 301–500 CD4 in 1 mm3 and in 23.9 % ≥ 500 CD4 in 1 mm3. In 56.1 % of patients, first diagnosed tuberculosis was detected, 28.4 % had the relapse of tuberculosis, 7.7 % had tuberculosis after a previous ineffective treatment, 7.7 % had tuberculosis with treatment after the break. Bacterial excretion (by the scopic method was detected in 42.6 % of patients, by the bacteriological method – in 73.9 %, by the molecular-genetic method – in 93.2 %, typical

  13. Routine examination for tuberculosis is still indicated during bronchoscopy for pulmonary infiltrates

    DEFF Research Database (Denmark)

    Laub, Rasmus Rude; Sivapalan, Pradeesh; Wilcke, Torgny

    2015-01-01

    INTRODUCTION: Tuberculosis (TB) can present in numerous ways and can be radiological indistinguishable from cancer. In several guidelines for bronchoscopy (FOB) in low-incidence areas, a Mycobacterium tuberculosis test is only recommended when TB is clinically suspected. Due to the expenses...... associated with M. tuberculosis cultures, we did an analysis of tests obtained by FOB and other invasive procedures (endoscopic ultrasound (EUS)-guided needle biopsy via the oesophagus or trachea and percutaneous needle lung biopsy (PNLB)). METHODS: All patients tested positive for M. tuberculosis by culture...... and with samples obtained by FOB, EUS or PNLB in the 2008-2012 period were identified retrospectively in two centres in a low-incidence area (Copenhagen, Denmark). Patient records and radiological reports were reviewed. RESULTS: A total of 57 (1.2%) patients out of the 4,680 tested were M. tuberculosis culture...

  14. Pictorial essay: Orbital tuberculosis

    International Nuclear Information System (INIS)

    Narula, Mahender K; Chaudhary, Vikas; Baruah, Dhiraj; Kathuria, Manoj; Anand, Rama

    2010-01-01

    Tuberculosis of the orbit is rare, even in places where tuberculosis is endemic. The disease may involve soft tissue, the lacrimal gland, or the periosteum or bones of the orbital wall. Intracranial extension, in the form of extradural abscess, and infratemporal fossa extension has been described. This pictorial essay illustrates the imaging findings of nine histopathologically confirmed cases of orbital tuberculosis. All these patients responded to antituberculous treatment

  15. Updates on antibody functions in Mycobacterium tuberculosis infection and their relevance for developing a vaccine against tuberculosis.

    Science.gov (United States)

    Achkar, Jacqueline M; Prados-Rosales, Rafael

    2018-04-12

    A more effective vaccine to control tuberculosis (TB), a major global public health problem, is urgently needed. Current vaccine candidates focus predominantly on eliciting cell-mediated immunity but other arms of the immune system also contribute to protection against TB. We review here recent studies that enhance our current knowledge of antibody-mediated functions against Mycobacterium tuberculosis. These findings, which contribute to the increasing evidence that antibodies have a protective role against TB, include demonstrations that firstly distinct human antibody Fc glycosylation patterns, found in latent M. tuberculosis infection but not in active TB, influence the efficacy of the host to control M. tuberculosis infection, secondly antibody isotype influences human antibody functions, and thirdly that antibodies targeting M. tuberculosis surface antigens are protective. We discuss these findings in the context of TB vaccine development and highlight the need for further research on antibody-mediated immunity in M. tuberculosis infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. miR-582-5p is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO1.

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    Yanhua Liu

    Full Text Available Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB. In this study, we found that percentage of apoptotic cells in peripheral blood monocytes from patients with active TB was lower than that from healthy controls (p<0.001. To understand whether microRNAs can modulate apoptosis of monocytes, we investigated differentially expressed microRNAs in patients with active TB. miR-582-5p was mainly expressed in monocytes and was upregulated in patients with active TB. The apoptotic percentage of THP-1 cells transfected with miR-582-5p mimics was significantly lower than those transfected with negative control of microRNA mimics (p<0.001, suggesting that miR-582-5p could inhibit apoptosis of monocytes. To our knowledge, the role of miR-582-5p in regulating apoptosis of monocytes has not been reported so far. Systematic bioinformatics analysis indicated that FOXO1 might be a target gene for miR-582-5p and its 3'UTR contains potential binding sites for miR-582-5p. To determine whether miR-582-5p could influence FOXO1 expression, miR-582-5p mimics or negative control of microRNA mimics were transfected into THP-1 cells. RT-PCR and western blot analysis showed that the miR-582-5p could suppress both FOXO1 mRNA and protein expression. Co-transfection of miR-582-5p and FOXO1 3'UTR-luciferase reporter vector into cells demonstrated that significant decrease in luciferase activity was only found in reporter vector that contained a wild type sequence of FOXO1 3'UTR, suggesting that miR-582-5p could directly target FOXO1. In conclusion, miR-582-5p inhibited apoptosis of monocytes by down-regulating FOXO1 expression and might play an important role in regulating anti-M. tuberculosis directed immune responses.

  17. The outcome of tuberculosis treatment in subjects with chronic kidney disease in Brazil: a multinomial analysis

    Directory of Open Access Journals (Sweden)

    Barbara Reis-Santos

    2013-09-01

    Full Text Available OBJECTIVE: To analyze the association between clinical/epidemiological characteristics and outcomes of tuberculosis treatment in patients with concomitant tuberculosis and chronic kidney disease (CKD in Brazil. METHODS: We used the Brazilian Ministry of Health National Case Registry Database to identify patients with tuberculosis and CKD, treated between 2007 and 2011. The tuberculosis treatment outcomes were compared with epidemiological and clinical characteristics of the subjects using a hierarchical multinomial logistic regression model, in which cure was the reference outcome. RESULTS: The prevalence of CKD among patients with tuberculosis was 0.4% (95% CI: 0.37-0.42%. The sample comprised 1,077 subjects. The outcomes were cure, in 58%; treatment abandonment, in 7%; death from tuberculosis, in 13%; and death from other causes, in 22%. The characteristics that differentiated the ORs for treatment abandonment or death were age; alcoholism; AIDS; previous noncompliance with treatment; transfer to another facility; suspected tuberculosis on chest X-ray; positive results in the first smear microscopy; and indications for/use of directly observed treatment, short-course strategy. CONCLUSIONS: Our data indicate the importance of sociodemographic characteristics for the diagnosis of tuberculosis in patients with CKD and underscore the need for tuberculosis control strategies targeting patients with chronic noncommunicable diseases, such as CKD.

  18. "Impact of and response to increased tuberculosis prevalence among Syrian refugees compared with Jordanian tuberculosis prevalence: case study of a tuberculosis public health strategy".

    Science.gov (United States)

    Cookson, Susan T; Abaza, Hiba; Clarke, Kevin R; Burton, Ann; Sabrah, Nadia A; Rumman, Khaled A; Odeh, Nedal; Naoum, Marwan

    2015-01-01

    By the summer of 2014, the Syrian crisis resulted in a regional humanitarian emergency with 2.9 million refugees, including 608,000 in Jordan. These refugees access United Nations High Commissioner for Refugees (UNHCR)-sponsored clinics or Jordan Ministry of Health clinics, including tuberculosis diagnosis and treatment. Tuberculosis care in Syria has deteriorated with destroyed health infrastructure and drug supply chain. Syrian refugees may have undiagnosed tuberculosis; therefore, the UNHCR, the International Organization for Migration (IOM), the National Tuberculosis Program (NTP), and the Centers for Disease Control and Prevention developed the Public Health Strategy for Tuberculosis among Syrian Refugees in Jordan. This case study presents that strategy, its impact, and recommendations for other neighboring countries. UNHCR determined that World Health Organization (WHO) criteria for implementing a tuberculosis program in an emergency were met for the Syrian refugees in Jordan. Jordan NTP assessed their tuberculosis program and found that access to Syrian refugees was the one component of their program missing. Therefore, a strategy for tuberculosis control among Syrian refugees was developed. Since that development through work with IOM, UNHCR, and NTP, tuberculosis case detection among Syrian refugees is almost 40 % greater (74 cases/12 months or 1.01/100,000 monthly through June 2014 vs. 56 cases/16 months or 0.73/100,000 monthly through June 2013) using estimated population figures; more than two fold the 2012 Jordan tuberculosis incidence. Additionally, the WHO objective of curing ≥85 % of newly identified infectious tuberculosis cases was met among Syrian refugees. Tuberculosis (TB) rates among displaced persons are high, but increased detection is possible. High TB rates were found among Syrian refugees through active screening and will probably persist as the Syrian crisis continues. Active screening can detect tuberculosis early and reduce risk

  19. Presentation of suspected pediatric uveitis.

    Science.gov (United States)

    Saeed, Muhammad Usman; Raza, Syed Hamid; Goyal, Sudeshna; Cleary, Gavin; Newman, William David; Chandna, Arvind

    2014-01-01

    Presentation of suspected pediatric uveitis: Pediatric uveitis is usually managed in specialized ophthalmic centers in the UK. Meaningful data acquisition in these clinics may be helpful in clinical governance, and healthcare planning in a specialty that is gradually changing due to changes in treatment choices. Retrospective analysis of prospectively acquired data in the Liverpool pediatric uveitis database was performed. Analysis of our data, based on 147 patients, with a mean age of 10 years, indicated a female to male ratio of 2:1. 99% of patients were Caucasian. Our data indicates 86% of all patients attending the uveitis clinic were diagnosed with juvenile idiopathic arthritis, followed by intermediate uveitis 5% and idiopathic uveitis 4%. 46% of patients required treatment. Systemic treatment included methotrexate (34%), prednisolone (14%), etanercept (6%), ciclosporin (6%), mycophenolate (3%), and infliximab (1%). Severe visual loss (defined by counting fingers or below vision) was seen in 10 eyes despite appropriately treated chronic uveitis. Our data shows uveitis-related ocular morbidity in a predominantly pediatric Caucasian population. Patients with severe and chronic uveitis may experience significant uveitis-related complications and subsequent visual loss despite aggressive treatment.

  20. Tuberculosis treatment among smear positive tuberculosis patients

    International Nuclear Information System (INIS)

    Munir, M.K.; Iqbal, R.; Shabbir, I.; Chaudhry, K

    2012-01-01

    Tuberculosis is a major health problem in many parts of the world. Delay in initiation