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Sample records for active tb infection

  1. Difference Between Latent TB Infection and Active TB Disease

    MedlinePlus

    ... person with infectious TB coughs or sneezes, droplet nuclei containing M. tuberculosis are expelled into the air. If another person inhales air containing these droplet nuclei, he or she may become infected. However, not ...

  2. Testing for TB Infection

    MedlinePlus

    ... Search The CDC 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 ...

  3. CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between individuals with latent and active TB infection.

    PubMed

    Canaday, David H; Sridaran, Sankar; Van Epps, Puja; Aung, Htin; Burant, Christopher J; Nsereko, Mary; Mayanja-Kizza, Harriet; Betts, Michael R; Toossi, Zahra

    2015-07-01

    CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher than with other opportunistic infections suggesting that progression to PTB is not merely due to T cell depletion but also dysfunction. There are limited data examining T cell functional signatures in human HIV-TB co-infection particularly in PTB which accounts for about 80% of active TB disease overall. We examined a cohort of HIV-infected anti-retroviral naïve individuals in Kampala, Uganda, a TB endemic area using multiparametric flow cytometry analysis to determine IFN-γ, IL-2, IL-17, and TNF-α production in CD4+ memory T cell subsets. The cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a smoldering state of persistent MTB replication rather than dormant infection. This may be a contributory mechanism to the significantly increased risk of progression to PTB in this population.

  4. Functional profile of CD4+ and CD8+ T cells in latently infected individuals and patients with active TB.

    PubMed

    Marín, Nancy D; París, Sara C; Rojas, Mauricio; García, Luis F

    2013-03-01

    Tuberculosis (TB) is one of the most important infectious diseases around the world. Several studies have focused on the identification of correlates of protection against TB. Most of them have concentrated on the study of IFN-γ due to its robust association with protection against TB. However, given the complexity of the immune response elicited after Mtb infection, other cytokines should also be considered. In the present study, we evaluated Th1 and Th17 responses and their association with the protection or development of active disease. Therefore, non infected individuals (nonTBi), latently infected individuals (LTBi) and patients with active TB (ATB) were studied. The evaluation of the number of cytokine producing cells by ELISPOT showed a higher number of IFN-γ-producing cells in ATB patients, but no differences were found regarding the number of IL-17 producing cells among studied groups. The evaluation of IFN-γ, IL-2, TNF-α and IL-17 producing CD4+ and CD8+ T cells at 1 day and 6 days of stimulation with mycobacterial antigens suggests the presence of functional signatures associated with latency or active TB. The results presented herein suggest the possible use of the evaluation of Th1-type cytokines, such as IFN-γ and/or TNF-α, as a correlate of protection against TB; however, these results need to be validated for other groups.

  5. Immune Activation at Sites of HIV/TB Co-Infection Contributes to the Pathogenesis of HIV-1 Disease

    PubMed Central

    Meng, Qinglai; Sayin, Ismail; Canaday, David H.; Mayanja-Kizza, Harriet; Baseke, Joy; Toossi, Zahra

    2016-01-01

    Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed. The T cell phenotype and activation status of HIV-1 p24 + T cells in PFMC and PBMC from HIV/TB patients were determined. We found that T cell and macrophage-specific and non-specific soluble markers of immune activation, sCD27, sCD163, IL1Ra, and sCD14, were higher in pleural fluid as compared to plasma from HIV/TB co-infected subjects, and higher as compared to pleural fluid from TB mono-infected subjects. Intestinal fatty acid-binding protein, a marker of intestinal tract damage, in plasma from HIV/TB co-infected patients was not different than that in HIV+ subjects. Expression of HLADR and CD38 double positive (HLADR/CD38) on CD4 T cells, and CD69+ on CD8 T cells correlated with pleural fluid viral load, and inversely with blood CD4 T cell count. Higher expression of HLADR/CD38 and CCR5 on CD4 T cells, and HLADR/CD38 and CD69 on CD8 T cells in PFMC were limited to effector memory populations. HIV-1 p24+ CD8 negative (includes CD4 + and double negative T cells) effector memory T cells in PFMC had higher expression of HLADR/CD38, Ki67, and CCR5 compared to HIV-1 p24- CD8 negative PFMC. Cumulatively, these data indicate that sites of HIV/TB co-infection are the source of intense immune activation. PMID:27870882

  6. Treatment: Latent TB Infection (LTBI) and TB Disease

    MedlinePlus

    ... Search The CDC 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 ...

  7. First Outcome of MDR-TB among Co-Infected HIV/TB Patients from South-West Iran

    PubMed Central

    Motamedifar, Mohammad; Abadi, Ali Reza Hassan; Moghadam, Mahboube Nakhzari

    2015-01-01

    Background Tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV) patients and the majority of them occur in developing countries. The aims of the present study were to determine the frequency of HIV/TB co-infection and other probable associated factors. Methods This 10 year retrospective study was conducted on 824 HIV patients in the south-west of Iran. HIV infection was diagnosed by the enzyme linked immunosorbent assay and confirmed by Western blot. TB diagnosis was based on consistency of the clinical manifestations, chest X-ray, and microscopic examination. Drug susceptibility testing was done by the proportional method on Löwenstein-Jensen media. Results Of 824 HIV patients, 59 (7.2%) were identified as TB co-infected and the majority (86.4%) of them were male. Of the overall TB infected patients, 6 cases (10.2%) showed multidrug-resistant with the mean CD4+ lymphocyte count of 163±166 cells/mm3. The main clinical forms of TB were pulmonary (73%). There was a significant (p<0.05) correlation between TB infection and CD4+ lymphocyte counts ≤200 cells/mm3, gender, prison history, addiction history, and highly active anti-retroviral therapy. Conclusion We reported novel information on frequency of HIV/TB co-infection and multidrug resistant-TB outcome among co-infected patients that could facilitate better management of such infections on a global scale. PMID:26175780

  8. Serial T-SPOT.TB and quantiFERON-TB-Gold In-Tube assays to monitor response to antitubercular treatment in Italian children with active or latent tuberculosis infection.

    PubMed

    Chiappini, Elena; Bonsignori, Francesca; Mangone, Giusi; Galli, Luisa; Mazzantini, Rachele; Sollai, Sara; Azzari, Chiara; de Martino, Maurizio

    2012-09-01

    We performed a prospective study to investigate T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-G-IT) dynamics during antitubercular treatment in active tuberculosis (TB) or latent TB. Eighteen children with latent TB and 26 with TB were enrolled. At 6 months of follow-up reversion rate was 5.88% (95% CI:0-13.79) for QFT-G-IT; 9.09% (95% CI:0.59-17.58) for T-SPOT.TB (P=0.921) in TB cases. Significant decline in quantitative response was observed exclusively in TB cases. Our results suggest that serial IGRA have limited use in children receiving antitubercular treatment.

  9. Relevance of latent TB infection in areas of high TB prevalence.

    PubMed

    Sharma, Surendra K; Mohanan, Sandeep; Sharma, Abhishek

    2012-09-01

    About one-third of the world population has latent TB infection (LTBI), the majority of which is distributed in 22 high-burden countries. Early diagnosis and treatment of active TB remains the top priority in resource-poor countries with high TB prevalence. Notwithstanding, because LTBI contributes significantly to the pool of active TB cases later on, its diagnosis and treatment is essential, especially in high-risk groups. The lack of a gold standard and several limitations of currently available tools, namely the tuberculin skin test and interferon-γ release assays, are major constraints for LTBI diagnosis. In areas with high TB prevalence, interferon-γ release assays have not shown superiority over the conventional tuberculin skin test and are yet to be systematically studied. Decisions regarding LTBI treatment with isoniazid preventive therapy should be made, keeping in mind the high prevalence of isoniazid resistance in these settings. Although efforts to shorten the LTBI treatment duration are encouraging, most trials have focused on adherence and toxicity. Future trials on short-duration regimens in high-burden settings should address drug efficacy issues as well. LTBI management, therefore, should comprise a targeted screening approach and individualization of LTBI treatment protocols. In addition, efforts should focus on airborne infection control measures in high-burden countries. A high prevalence of drug-resistant TB, the HIV epidemic, and delays in the diagnosis of active TB cases are other major concerns in areas of high TB prevalence. There is ample space for further research in these countries, whose outcomes may strengthen future national guidelines.

  10. Pyrido[1,2-a]benzimidazole-based agents active against tuberculosis (TB), multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB.

    PubMed

    Pieroni, Marco; Tipparaju, Suresh K; Lun, Shichun; Song, Yang; Sturm, A Willem; Bishai, William R; Kozikowski, Alan P

    2011-02-07

    The struggle against tuberculosis (TB) is still far from over. TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. Co-infection with human immunodeficiency virus (HIV) and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. Herein, we report the discovery of 2-(4-chlorobenzyl)-3-methyl-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitrile as an effective antitubercular agent and the structural modifications of this molecule that have led to analogues with improved potency and lower toxicity. A number of these derivatives were also active at sub-micromolar concentrations against resistant TB strains and devoid of apparent toxicity to Vero cells, thereby underscoring their value as novel scaffolds for the development of new anti-TB drugs.

  11. Donor-derived tuberculosis (TB): isoniazid-resistant TB transmitted from a lung transplant donor with inadequately treated latent infection.

    PubMed

    Jensen, T O; Darley, D R; Goeman, E E; Shaw, K; Marriott, D J; Glanville, A R

    2016-10-01

    Donor-derived tuberculosis (TB) is an increasingly recognized complication of solid organ transplantation. We report a case of isoniazid-resistant pulmonary TB in a lung transplant recipient. The patient acquired the infection from the lung donor who was previously empirically treated with isoniazid for latent TB. The case highlights the caveat that, while adequate treatment of latent TB with isoniazid is presumed, meticulous screening of donors is required.

  12. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection.

    PubMed

    Hoff, Soren T; Peter, Jonathan G; Theron, Grant; Pascoe, Mellissa; Tingskov, Pernille N; Aggerbeck, Henrik; Kolbus, Daniel; Ruhwald, Morten; Andersen, Peter; Dheda, Keertan

    2016-03-01

    C-Tb, a novel Mycobacterium tuberculosis and 6-kDa early secretory antigenic target/10-kDa culture filtrate protein (ESAT-6/CFP-10)-specific skin test, has high specificity in bacille Calmette-Guerin-vaccinated healthy controls. However, the sensitivity of C-Tb has hitherto not been determined. The objective was to determine the sensitivity of C-Tb in patients with active tuberculosis (TB) in comparison with the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT).C-Tb and TST were randomly administered in a double-blinded fashion to one or the other forearm in 253 patients with active TB with or without HIV co-infection. QFT-GIT testing was performed prior to skin testing.Using a receiver operating characteristic curve-derived cut-point of 5 mm, C-Tb sensitivity was similar to QFT-GIT (73.9 (95% CI 67.8-79.3) versus 75.1 (95% CI 69.3-80.2)), and similar in HIV-infected and HIV-uninfected patients (76.7 (95% CI 69.0-83.3) versus 69.5 (95% CI 59.2-78.5)). However, sensitivity was significantly diminished in HIV-infected patients with CD4 counts <100 cells·mm(-3). C-Tb and QFT-GIT combined had significantly higher sensitivity than C-Tb alone (p<0.0001). C-Tb was safe with no significant adverse events. The 5 mm cut-point corresponded to that found in the previously published specificity study (TESEC-04).C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection. Sensitivity was reduced only in HIV-infected patients with severe immunosuppression. Further studies in different settings are required to validate the proposed 5 mm cut-point.

  13. Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

    PubMed Central

    Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

    2014-01-01

    Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

  14. The Characteristics of TB Epidemic and TB/HIV Co-Infection Epidemic: A 2007–2013 Retrospective Study in Urumqi, Xinjiang Province, China

    PubMed Central

    Wei, Wang; Wei-Sheng, Zhang; Ahan, Alayi; Ci, Yan; Wei-Wen, Zhang; Ming-Qin, Cao

    2016-01-01

    Objective This study was aimed to find out epidemiologic characteristic of tuberculosis (TB) cases, and Human Immunodeficiency Virus (HIV) positive cases among TB patients (TB/HIV co-infection) through demographic, temporal, and spatial study in Urumqi. Methods Descriptive statistics and multivariate logistic regression were applied to identify the epidemiologic characteristics and risk factors of TB epidemic and TB/HIV co-infection epidemic. All addresses of each TB case, TB/HIV co-infection case, and administrative street were transformed into geographical coordinate. Subsequently, the geocoded address for 82 streets was transformed into a dot map used as the basis of spatial datasets. In addition, the paper also used quantile map and the spatial scan statistic in order to identify the spatial distribution and spatial clusters of TB epidemic and TB/HIV co-infection epidemic. Result There was a declining trend of the notification rates of TB epidemic from 2007 to 2009, as well as a rising trend from 2010 to 2013. However, the notification rates of TB/HIV co-infection epidemic showed a rising trend from 2007 to 2010, and a declining trend from 2011 to 2013. Moreover, a significant share of TB epidemic and TB/HIV co-infection epidemic happened between the age of 15 to 45 years old, indicating an increase in risk of TB and TB/HIV infection. It is worth noting that the risk of HIV infection for male TB patients was 2.947 times (95% CI [2.178, 3.988]) than that of female patients. Han ethnicity and Uygur ethnicity in urban region accounted for a large proportion of total TB and TB/HIV co-infection cases. Most of the TB cases of minorities in Urumqi showed a statistically significant increase in risk of HIV infection than Han ethnicity in Urumqi. In addition, the spatial distribution of TB epidemic and TB/HIV co-infection epidemic was highly skewed. Most of the local clusters were located in urban area and rural-urban continuum where showed an increase in risk of TB and

  15. Prevalence of latent TB infection and TB disease among adolescents in high TB burden countries in Africa: a systematic review protocol

    PubMed Central

    Bunyasi, Erick Wekesa; Schmidt, Bey-Marrie; Abdullahi, Leila Hussein; Mulenga, Humphrey; Tameris, Michele; Luabeya, Angelique; Shenje, Justin; Scriba, Thomas; Geldenhuys, Hennie; Wood, Robin; Hatherill, Mark

    2017-01-01

    Introduction Almost a third of the world population has latent tuberculosis (TB) infection (LTBI), ∼10 million of whom develop TB disease annually, despite existence of effective, but lengthy, preventive and curative drug regimens. Although adolescents appear to have a very high force of LTBI, their reported incidence of TB disease is less than that of their corresponding general population. The few available studies on adolescent TB infection and disease prevalence are not sufficient to address the apparent discordance between rates of infection and disease in high TB burden countries in Africa. Therefore, we aim to perform a systematic review to examine the relationship between adolescent LTBI and TB disease, benchmarked against national TB disease burden data. Methods and analysis A comprehensive literature search will be performed for cross-sectional studies and screening data in cohort studies to determine the prevalence of LTBI and TB disease among adolescents in high TB burden countries in Africa in the following databases: PubMed, Scopus, Cochrane library, Web of Science, Africa Wide, CINAHL and the Africa Index Medicus. This will be supplemented by a search of reference lists of selected articles for potentially relevant articles. We will restrict our search to articles published in the English language between 1990 and 2016 among adolescents in order to obtain estimates reflective of the mature HIV epidemic in most high TB burden countries in Africa that occurred over this critical period. Primary end points are: prevalence of LTBI and TB disease. We will use the random-effects or fixed-effects modelling for our meta-analysis based on heterogeneity estimates. Ethics and dissemination No ethics approval is required given that this is a systematic review. Findings will be disseminated in a peer-reviewed journal in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Trial registration number CRD42015023495. PMID

  16. Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.

    PubMed

    Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi

    2013-01-01

    High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.

  17. Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting

    PubMed Central

    Sharma, Surendra K.; Vashishtha, Richa; Chauhan, L. S.; Sreenivas, V.; Seth, Divya

    2017-01-01

    Background There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings. Methods 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases. Results Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72–1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97–2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients. Conclusion Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings. PMID:28060926

  18. Diagnostic accuracy of chest radiography for the diagnosis of tuberculosis (TB) and its role in the detection of latent TB infection: a systematic review.

    PubMed

    Piccazzo, Riccardo; Paparo, Francesco; Garlaschi, Giacomo

    2014-05-01

    In this systematic review we evaluate the role of chest radiography (CXR) in the diagnostic flow chart for tuberculosis (TB) infection, focusing on latent TB infection (LTBI) in patients requiring medical treatment with biological drugs. In recent findings, patients scheduled for immunomodulatory therapy with biologic drugs are a group at risk of TB reactivation and, in such patients, detection of LTBI is of great importance. CXR for diagnosis of pulmonary TB has good sensitivity, but poor specificity. Radiographic diagnosis of active disease can only be reliably made on the basis of temporal evolution of pulmonary lesions. In vivo tuberculin skin test and ex vivo interferon-γ release assays are designed to identify development of an adaptive immune response, but not necessarily LTBI. Computed tomography (CT) is able to distinguish active from inactive disease. CT is considered a complementary imaging modality to CXR in the screening procedure to detect past and LTBI infection in specific subgroups of patients who have increased risk for TB reactivation, including those scheduled for medical treatment with biological drugs.

  19. Targeted screening and treatment for latent tuberculosis infection using QuantiFERON®-TB Gold is cost-effective in Mexico

    PubMed Central

    Burgos, J. L.; Kahn, J. G.; Strathdee, S. A.; Valencia-Mendoza, A.; Bautista-Arredondo, S.; Laniado-Laborin, R.; Castañeda, R.; Deiss, R.; Garfein, R. S.

    2009-01-01

    SUMMARY OBJECTIVE To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. PMID:19723375

  20. Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study.

    PubMed

    Rakotosamimanana, Niaina; Richard, Vincent; Raharimanga, Vaomalala; Gicquel, Brigitte; Doherty, T Mark; Zumla, Alimuddin; Rasolofo Razanamparany, Voahangy

    2015-10-01

    Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ≥14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ≥14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, 95% CI 1.74-41.22; p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB.

  1. Spatial Alterations between CD4+ TFH, B and CD8+T cells during SIV infection: T/B cell homeostasis, activation and potential mechanism for viral escape

    PubMed Central

    Hong, Jung Joo; Amancha, Praveen K; Rogers, Kenneth; Ansari, Aftab A; Villinger, Francois

    2012-01-01

    HIV/SIV infections induce chronic immune activation with remodeling of lymphoid architecture and hypergammaglobulinemia, although the mechanisms leading to such symptoms remain to be fully elucidated. Moreover, lymph nodes have been highlighted as a predilection site for SIV escape in vivo. Following 20 rhesus macaques infected with SIVmac239, as they progress from pre to acute and chronic infection, we document for the first time the local dynamics T follicular helper (TFH) cells and B cells in situ. Progression of SIV infection was accompanied with increased numbers of well delineated follicles containing germinal centers (GCs) and TFH cells with a progressive increase in the density of PD-1 expression in lymph nodes. The rise in PD-1+ TFH cells was followed by a substantial accumulation of Ki67+ B cells within GCs. However, unlike in blood, major increases in the frequency of CD27+ memory B cells were observed in lymph nodes, indicating increased turnover of these cells, correlated with increases in total and SIV specific antibody levels. Of importance, compared to T cell zones, GCs seemed to exclude CD8+ T cells while harboring increasing numbers of CD4+ T cells, many of which are positive for SIVgag, providing an environment particularly beneficial for virus replication and reservoirs. Our data highlight for the first time important spatial interactions of GC cell subsets during SIV infection, the capacity of lymphoid tissues to maintain stable relative levels of circulating B cell subsets and a potential mechanism for viral reservoirs within GCs during SIV infection. PMID:22387550

  2. Comparison of tuberculin skin testing and T-SPOT.TB for diagnosis of latent and active tuberculosis.

    PubMed

    Simsek, Hulya; Alpar, Sibel; Ucar, Nazire; Aksu, Funda; Ceyhan, Ismail; Gözalan, Aysegul; Cesur, Salih; Ertek, Mustafa

    2010-03-01

    The T-SPOT.TB test does not cross-react with Bacille Calmette-Guérin or most non-tuberculosis mycobacterium species, and is based on IFN-gamma responses to Mycobacterium tuberculosis-specific antigens. The objective of this study was to compare tuberculin skin test (TST) with T-SPOT.TB results used in the diagnosis of active tuberculosis (TB) as well as latent tuberculosis infection (LTBI). A total of 136 subjects participated in three different groups (47 patients with active pulmonary TB, 47 healthy persons without M. tuberculosis exposure, and 42 hospital members with a history of close contact with active TB patients). The T-SPOT.TB sensitivity (83.0%) and the negative predictive value (NPV) (82.6%) in the diagnosis of active TB were significantly higher than those of TST. The sensitivity and NPV of the TST were 38.3 and 60.8%, respectively. The T-SPOT.TB specificity (80.9%) and positive predictive value (81.3%) were lower than those of TST (95.7 and 90.0%, respectively). The performance of T-SPOT.TB and TST for diagnosing LTBI was the same (54.8%). T-SPOT.TB was superior in terms of sensitivity (83.0%); TST detected only 18, whereas T-SPOT.TB test detected 39 out of 47 patients with active TB. T-SPOT.TB is thought to have better performance than TST due to false-negative results in diagnosing active TB. However, it is considered that large prospective longitudinal studies are needed for diagnosing LTBI.

  3. Aerosol immunisation for TB: matching route of vaccination to route of infection.

    PubMed

    Manjaly Thomas, Zita-Rose; McShane, Helen

    2015-03-01

    TB remains a very significant global health burden. There is an urgent need for better tools for TB control, which include an effective vaccine. Bacillus Calmette-Guérin (BCG), the currently licensed vaccine, confers highly variable protection against pulmonary TB, the main source of TB transmission. Replacing BCG completely or boosting BCG with another vaccine are the two current strategies for TB vaccine development. Delivering a vaccine by aerosol represents a way to match the route of vaccination to the route of infection. This route of immunisation offers not only the scientific advantage of delivering the vaccine directly to the respiratory mucosa, but also practical and logistical advantages. This review summarises the state of current TB vaccine candidates in the pipeline, reviews current progress in aerosol administration of vaccines in general and evaluates the potential for TB vaccine candidates to be administered by the aerosol route.

  4. Interferon Gamma Release Assays for the Diagnosis of Latent TB Infection in HIV-Infected Individuals in a Low TB Burden Country

    PubMed Central

    Ní Cheallaigh, Clíona; Fitzgerald, Ian; Grace, Jacinta; Jagjit Singh, Gurmit; El-Eraki, Nahla; Gibbons, Noel; Keane, Joseph; Rogers, Thomas R.; Clarke, Susan; Bergin, Colm

    2013-01-01

    Background Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting. Methodology/Principal Findings T-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar’s test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1–1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02). Conclusions/Significance In low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts. PMID:23382842

  5. staffTRAK-TB: software for surveillance of tuberculosis infection in healthcare workers.

    PubMed

    Burwen, D R; Seawright, M F

    1999-11-01

    The Centers for Disease Control and Prevention (CDC) recommends periodic tuberculin skin testing of healthcare workers with potential exposure to Mycobacterium tuberculosis. However, many healthcare facilities have neither a system to identify workers due for their skin test nor a means of analyzing aggregate data. To illustrate some of the complexities involved in tuberculin skin test (TST) tracking and analysis, and how these might be addressed, this report describes a software package called staffTRAK-TB, developed by the CDC to facilitate surveillance of tuberculosis infection in healthcare workers. staffTRAK-TB records data for each healthcare worker, including demographic information, occupation, work location, multiple TST results, and results of evaluations to determine if clinically active tuberculosis is present. Programmed reports include lists of workers due and overdue for skin tests, and skin test conversion rates by occupation or worksite. Standardization of types of occupations and locations allows data from multiple facilities to be aggregated and compared. Data transfer to the CDC can be performed via floppy diskettes. staffTRAK-TB illustrates important issues in software structure, standardization of occupation and work-location information, relevant data items, and reports and analyses that would be useful in practice. Developing software that adequately addresses the epidemiological issues is complex, and the lessons learned may serve as a model for hospital epidemiologists, infection control personnel, occupational health personnel, and computer programmers considering software development in this area or trying to optimize their facility's TST surveillance.

  6. TB infection prevention and control experiences of South African nurses - a phenomenological study

    PubMed Central

    2011-01-01

    Background The tuberculosis (TB) epidemic in South Africa is characterised by one of the highest levels of TB/HIV co-infection and growing multidrug-resistant TB worldwide. Hospitals play a central role in the management of TB. We investigated nurses' experiences of factors influencing TB infection prevention and control (IPC) practices to identify risks associated with potential nosocomial transmission. Methods The qualitative study employed a phenomenological approach, using semi-structured interviews with a quota sample of 20 nurses in a large tertiary academic hospital in Cape Town, South Africa. The data was subjected to thematic analysis. Results Nurses expressed concerns about the possible risk of TB transmission to both patients and staff. Factors influencing TB-IPC, and increasing the potential risk of nosocomial transmission, emerged in interconnected overarching themes. Influences related to the healthcare system included suboptimal IPC provision such as the lack of isolation facilities and personal protective equipment, and the lack of a TB-IPC policy. Further influences included inadequate TB training for staff and patients, communication barriers owing to cultural and linguistic differences between staff and patients, the excessive workload of nurses, and a sense of duty of care. Influences related to wider contextual conditions included TB concerns and stigma, and the role of traditional healers. Influences related to patient behaviour included late uptake of hospital care owing to poverty and the use of traditional medicine, and poor adherence to IPC measures by patients, family members and carers. Conclusions Several interconnected influences related to the healthcare system, wider contextual conditions and patient behavior could increase the potential risk of nosocomial TB transmission at hospital level. There is an urgent need for the implementation and evaluation of a comprehensive contextually appropriate TB IPC policy with the setting and

  7. HIV/TB Co-Infection in Mainland China: A Meta-Analysis

    PubMed Central

    Gao, Lei; Zhou, Feng; Li, XiangWei; Jin, Qi

    2010-01-01

    Background TB and HIV co-epidemic is a major public health problem in many parts of the world, particularly in developing counties. We aimed to summarize the prevalence of TB and HIV co-infection in mainland China, using meta-analysis based on systematic review of published articles. Methods We systematically reviewed published studies, from the MEDLINE and Chinese BioMedical Literature Databases, on the prevalence of HIV infection among TB patients and on the prevalence of TB among HIV/AIDS population until 15 April 2010, and quantitatively summarized the estimates using meta-analysis. Results In total, 29 studies were included in this review, with consistently homogeneous results. TB patients, for whom the summary prevalence of HIV infection was 0.9% (0.6%–1.4%) in mainland China, were found to be a potential target population for HIV screening. The prevalence of TB among HIV/AIDS population was 7.2% (4.2%–12.3%), but this was much higher when the analyses were restricted to AIDS patients (22.8%). Significantly higher prevalence was observed for males and hospital-based studies. Conclusions Our analyses indicated that the prevalence of HIV/TB co-infection in China deserves special attention, screening of TB among HIV/AIDS populations should be attached more importance, which would be much more helpful for treatment of both diseases. PMID:20505769

  8. Performance of the WHO 2011 TB Symptom Screening Algorithm for Pulmonary TB Diagnosis among HIV-Infected Patients in Gondar University Referral Hospital, Ethiopia

    PubMed Central

    2016-01-01

    The new WHO 2011 guidelines on TB screening among HIV-infected individuals recommend screening using four TB symptoms (current cough, fever, weight loss, and night sweats). This study aimed to assess the performance of WHO 2011 TB symptom screening algorithm for diagnosing pulmonary TB in HIV patients and identify possible risk factors for TB. Institutional based cross-sectional study was conducted from February 2012 to November 2012. A total of 250 HIV-infected patients aged ≥18 years visiting the University of Gondar Hospital, ART clinic, were enrolled. Information about WHO TB clinical symptoms and other known risk factors for TB was collected using structured questionnaire. Spot-morning-spot sputum samples were collected and direct AFB microscopy, sputum culture, and RD9 molecular typing were performed. Statistical data analysis was performed using SPSS Version 20.0 software. Of 250 study participants, fever was reported in 169 (67.6%), whereas cough and night sweats were reported in 167 (66.8%) and 152 (60.8%), respectively. A total of 11 (4.4%) TB cases were identified. Of these, 82% (9/11) TB patients reported cough, so that the negative predictive value was 98%. In addition, 66% (158/239) TB negative patients reported cough, so that positive predictive value of cough was 5%. According to the new WHOTB symptom screening algorithm, out of 250 HIV-infected persons, 83% (5/6) have been investigated by TB symptom screening and AFB smear microscopy. Therefore, the 2011 WHO TB symptom screening tool for the diagnosis of pulmonary TB is likely to reduce the diagnostic delay and lower TB morbidity and mortality rate particularly in HIV prevalent settings. PMID:28058048

  9. Major challenges in clinical management of TB/HIV co-infected patients in Eastern Europe compared with Western Europe and Latin America

    PubMed Central

    Efsen, Anne Marie; Schultze, Anna; Post, Frank; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert; Skrahin, Aliaksandr; Losso, Marcelo H; Toibaro, Javier; Girardi, Enrico; Miro, José; Bruyand, Mathias; Obel, Niels; Caylá, Joan; Podlekareva, Daria; Lundgren, Jens; Mocroft, Amanda; Kirk, Ole

    2014-01-01

    Introduction Rates of both TB/HIV co-infection and multi-drug-resistant (MDR) TB are increasing in Eastern Europe (EE). Data on the clinical management of TB/HIV co-infected patients are scarce. Our aim was to study the clinical characteristics of TB/HIV patients in Europe and Latin America (LA) at TB diagnosis, identify factors associated with MDR-TB and assess the activity of initial TB treatment regimens given the results of drug-susceptibility tests (DST). Material and Methods We enrolled 1413 TB/HIV patients from 62 clinics in 19 countries in EE, Western Europe (WE), Southern Europe (SE) and LA from January 2011 to December 2013. Among patients who completed DST within the first month of TB therapy, we linked initial TB treatment regimens to the DST results and calculated the distribution of patients receiving 0, 1, 2, 3 and ≥4 active drugs in each region. Risk factors for MDR-TB were identified in logistic regression models. Results Significant differences were observed between EE (n=844), WE (n=152), SE (n=164) and LA (n=253) for use of combination antiretroviral therapy (cART) at TB diagnosis (17%, 40%, 44% and 35%, p<0.0001), a definite TB diagnosis (culture and/or PCR positive for Mycobacterium tuberculosis; 47%, 71%, 72% and 40%, p<0.0001) and MDR-TB prevalence (34%, 3%, 3% and 11%, p <0.0001 among those with DST results). The history of injecting drug use [adjusted OR (aOR) = 2.03, (95% CI 1.00–4.09)], prior TB treatment (aOR = 3.42, 95% CI 1.88–6.22) and living in EE (aOR = 7.19, 95% CI 3.28–15.78) were associated with MDR-TB. For 569 patients with available DST, the initial TB treatment contained ≥3 active drugs in 64% of patients in EE compared with 90–94% of patients in other regions (Figure 1a). Had the patients received initial therapy with standard therapy [Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RHZE)], the corresponding proportions would have been 64% vs. 86–97%, respectively (Figure 1b). Conclusions In EE, TB

  10. Dotting the Three I's for collaborative TB-HIV activities: evaluation of a pilot programme in Kathmandu, Nepal.

    PubMed

    Sah, S K; Sahu, S K; Lamichhane, B; Bhatta, G K; Bhandari, K B; Owiti, P; Majumdar, S S

    2016-09-01

    Setting: The three government tertiary care hospitals providing care for people living with the human immunodeficiency virus (PLHIV) in Kathmandu, Nepal. Objectives: To assess 1) the screening cascades for intensified case finding for tuberculosis (TB), 2) isoniazid preventive therapy (IPT), including demographic and clinical factors associated with treatment interruption, and 3) TB infection control (IC) in the health facilities. Design: A cross-sectional study of new PLHIV enrolled from January 2012 to December 2014. Results: Among 572 registered PLHIV, 91% were on antiretroviral therapy. Of those registered, 561 (98%) were screened for TB and 73 (13%) were diagnosed with TB (17 [25%] sputum smear-positive, 17 [25%] smear-negative and 35 [51%] extra-pulmonary). Among the 488 (87%) PLHIV without active TB, 157 (32%) were initiated on IPT, of whom 136 (87%) completed treatment and 17 (11%) interrupted treatment. Those who experienced adverse events were 12 times more likely to interrupt IPT. TB IC showed gaps in personal control measures and supporting structures and policies. Conclusion: The implementation of the Three I's for collaborative TB-HIV activities in pilot sites in Nepal was successful and should be scaled up.

  11. Immigrant screening for TB: a missed opportunity to improve TB control in the United Kingdom.

    PubMed

    Lalvani, Ajit; Pareek, Manish

    2012-03-01

    Tuberculosis in the United Kingdom and other high-income countries is primarily a disease of the foreign-born arising from the synergy of migration from high TB burden regions and the reactivation of remotely acquired latent TB infection. UK immigrant screening policy primarily aims to identify active, rather than latent, TB although mounting evidence indicates that implementing latent TB screening for new entrants from intermediate and high incidence countries could cost-effectively reduce TB incidence in the UK.

  12. Common mental disorders in TB/HIV co-infected patients in Ethiopia

    PubMed Central

    2010-01-01

    Background- The relationship between TB/HIV co-infection and common mental disorders (CMD) has been scarcely investigated. In this study, we compared the occurrence of CMD in TB/HIV co-infected and non-co-infected HIV patients in Ethiopia. Methods- We conducted a cross sectional study in three hospitals in Ethiopia from February to April, 2009. The study population consisted of 155 TB/HIV co-infected and 465 non-co-infected HIV patients. CMD was assessed through face to face interviews by trained clinical nurses using the Kessler 10 scale. Several risk factors for CMD were assessed using a structured questionnaire. Results- TB/HIV co-infected patients had significantly (p = 0.001) greater risk of CMD (63.7%) than the non-co-infected patients (46.7%). When adjusted for the effect of potential confounding variables, the odds of having CMD for TB/HIV co-infected individuals was 1.7 times the odds for non-co-infected patients [OR = 1.7, (95%CI: 1.0, 2.9)]. Individuals who had no source of income [OR = 1.7, (95%CI: 1.1, 2.8)], and day labourers [OR = 2.4, 95%CI: 1.2, 5.1)] were more likely to have CMD as compared to individuals who had a source of income and government employees respectively. Patients who perceived stigma [OR = 2.2, 95%CI: 1.5, 3.2)] and who rate their general health as "poor" [OR = 10.0, 95%CI: 2.8, 35.1)] had significantly greater risk of CMD than individual who did not perceive stigma or who perceived their general health to be "good". Conclusion- TB/HIV control programs should develop guidelines to screen and treat CMD among TB/HIV co-infected patients. Screening programs should focus on individuals with no source of income, jobless people and day labourers. PMID:20618942

  13. Recent advances in testing for latent TB.

    PubMed

    Schluger, Neil W; Burzynski, Joseph

    2010-12-01

    After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of interferon γ release assays (IGRAs). These tests are generally associated with higher sensitivity and specificity for diagnosis of latent TB infection. This article reviews the indications for testing and treatment of latent TB infection in the overall context of a TB control program and describes how IGRAs might be used in specific clinical settings and populations, including people having close contact with an active case of TB, the foreign born, and health-care workers.

  14. Solitary Endobronchial Papilloma with Malignant Transformation and Concomitant TB Infection: Case Report and Literature Review

    PubMed Central

    2017-01-01

    We are reporting a case of solitary endobronchial papilloma located in posterior segment of the left upper lobe of the lung with malignant transformation and negative human papilloma virus (HPV) strains in a 40-year-old Saudi nonsmoker man. The patient had a concomitant tuberculosis (TB) infection. The patient received appropriate treatment in the form of anti-TB medication and surgical resection of the squamous cell carcinoma followed by chemotherapy. There was no evidence of tumor recurrence, resulting in a complete cure. We are reporting the case as well as a literature review related to the topic. PMID:28270942

  15. Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253

    PubMed Central

    Shiboski, C. H.; Chen, H.; Ghannoum, M. A.; Komarow, L.; Evans, S.; Mukherjee, P. K.; Isham, N.; Katzenstein, D.; Asmelash, A.; Omozoarhe, A. E.; Gengiah, S.; Allen, R.; Tripathy, S.; Swindells, S.

    2014-01-01

    SUMMARY OBJECTIVE To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. METHODS Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. RESULTS Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm3. Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2–4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22–48) and the specificity 85% (95%CI 81–88). CONCLUSION We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding. PMID:24903939

  16. Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

    PubMed Central

    Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

    2012-01-01

    Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

  17. Microscopic observation drug susceptibility assay for the diagnosis of TB and MDR-TB in HIV-infected patients: a systematic review and meta-analysis.

    PubMed

    Wikman-Jorgensen, Philip; Llenas-García, Jara; Hobbins, Michael; Ehmer, Jochen; Abellana, Rosa; Gonçalves, Alessandra Queiroga; Pérez-Porcuna, Tomàs Maria; Ascaso, Carlos

    2014-10-01

    The objective of the present study was to assess the diagnostic accuracy of the microscopic observation drug susceptibility (MODS) assay for tuberculosis (TB) diagnosis in HIV-infected patients. MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, African Index Medicus, ResearchGate, SciELO, and the abstracts of the main conferences on infectious diseases and tropical medicine were searched, and other sources investigated. Only studies including HIV-infected patients evaluating MODS for the diagnosis of TB and using culture-based diagnostic tests as a gold standard were analysed. Summary sensitivity and specificity were calculated with a bivariate model. 3259 citations were found, 29 were selected for full-text review and 10 studies including 3075 samples were finally analysed. Overall diagnostic accuracy of MODS for the diagnosis of TB was a sensitivity of 88.3% (95% CI 86.18-90.2%) and specificity 98.2% (95% CI 97.75-98.55%). For multidrug-resistant (MDR)-TB, sensitivity was 89% (95% CI 66.07-97%) and specificity was 100% (95 CI 94.81-100%). For smear-negative pulmonary TB, a sensitivity of 88.2% (95% CI 86.1-89.9%) and specificity of 98.2% (95% CI 96.8-98.9%) were found. Costs varied between USD 0.72 and 7.31 per sample. Mean time to positivity was 8.24 days. MODS was found to have a good accuracy for the diagnosis of TB and MDR-TB in HIV-infected patients with low cost and fast results.

  18. PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection.

    PubMed

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

    2016-01-01

    HIV co-infection is an important risk factor for tuberculosis (TB) providing a powerful model in which to dissect out defective, protective and dysfunctional Mycobacterium tuberculosis (MTB)-specific immune responses. To identify the changes induced by HIV co-infection we compared MTB-specific CD4+ responses in subjects with active TB and latent TB infection (LTBI), with and without HIV co-infection. CD4+ T-cell subsets producing interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α) and expressing CD279 (PD-1) were measured using polychromatic flow-cytometry. HIV-TB co-infection was consistently and independently associated with a reduced frequency of CD4+ IFN-γ and IL-2-dual secreting T-cells and the proportion correlated inversely with HIV viral load (VL). The impact of HIV co-infection on this key MTB-specific T-cell subset identifies them as a potential correlate of mycobacterial immune containment. The percentage of MTB-specific IFN-γ-secreting T-cell subsets that expressed PD-1 was increased in active TB with HIV co-infection and correlated with VL. This identifies a novel correlate of dysregulated immunity to MTB, which may in part explain the paucity of inflammatory response in the face of mycobacterial dissemination that characterizes active TB with HIV co-infection.

  19. Cytokine Patterns in Tuberculosis Infection; IL-1ra, IL-2 and IP-10 Differentiate Borderline QuantiFERON-TB Samples from Uninfected Controls

    PubMed Central

    Wergeland, Ida; Assmus, Jörg; Dyrhol-Riise, Anne Ma

    2016-01-01

    Background Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values. Methods 27 soluble biomarkers were analysed in QFT supernatants from patients with active TB (n = 18), individuals with LTBI (n = 48) and from QFT negative controls (n = 16) by the Multiplex bead assay. The LTBI group was classified into two groups according to QFT IFN-γ levels; QFT borderline (0.35–0.70 IU/mL, n = 11) or QFT high (>0.70 IU/mL, n = 36). Results The levels of IL-1ra, IL-2, IL-13, IL-15, IFN-γ, IP-10 and MCP-1 in background corrected TB antigen stimulated supernatants (TBAg-Nil) significantly distinguished both active TB and LTBI QFT high groups from the QFT negative controls (p≤0.004). In addition, IL-1ra, IL-2 and IP-10 significantly differentiated the QFT borderline group from the controls (p≤0.001). Still, in the QFT borderline group the IL-1ra and IP-10 levels were not significant different from neither the QFT high nor the active TB group, whereas the IL-2 levels were lower (p≤0.003). The level of IP-10 showed the best separation between the QFT borderline group and the QFT negative controls (AUC 0.92) and offered 100% sensitivity for active TB. Conclusion IL-1ra, IL-2 and IP-10 differentiate QFT borderline samples from uninfected controls and the majority of QFT borderline subjects were classified as LTBI by these markers. Still, inconsistency was seen, and further studies are needed to examine the performance of alternative markers before concluded if they could be used as diagnostics tools. PMID:27685462

  20. ERK activation by thymosin-beta-4 (TB4) overexpression induces paclitaxel-resistance.

    PubMed

    Oh, Su-Young; Song, Ji-Hee; Gil, Jung-Eun; Kim, Jeong-Hee; Yeom, Young-Il; Moon, Eun-Yi

    2006-05-15

    The development of paclitaxel-resistance in tumors is one of the most significant obstacles to successful therapy. Thymosin-beta-4 (TB4) has been known as actin-sequestering protein and functions in tumor metastasis. Here, we overexpressed TB4 in HeLa cells (TB4-HeLa) and examined the effect of TB4 in paclitaxel-induced cell death. TB4-HeLa cells showed a higher growth rate and a lower percentage of basal apoptosis than HeLa cells. TB4-HeLa cells were more resistant to paclitaxel-induced cell death than HeLa cells. TB4 transcript expression with paclitaxel treatment was dose-dependently increased in HeLa cells but that was not in TB4-HeLa cells. Small interfering RNA (siRNA) of TB4 inhibited HeLa cell growth and enhanced paclitaxel-induced cell death. Basal ERK phosphorylation was elevated and basal p38 kinase phosphorylation was reduced in paclitaxel non-treated TB4-HeLa cells. When treated with paclitaxel, cell death and resistance-induction were independent of ERK and p38 kinase activation. Paclitaxel-resistance of TB4-HeLa cells was overcome by the inhibition of basal ERK activity with PD98059 pre-treatment. The inhibition of basal p38 kinase activity with SB203580 pre-treatment attenuated the paclitaxel-induced HeLa cell death. In conclusion, TB4 induced paclitaxel-resistance through the elevation of basal level of ERK phosphorylation. Therefore, TB4 could be a novel target to regulate paclitaxel-resistance.

  1. Circulating B-lymphocytes as potential biomarkers of tuberculosis infection activity.

    PubMed

    Sebina, Ismail; Biraro, Irene A; Dockrell, Hazel M; Elliott, Alison M; Cose, Stephen

    2014-01-01

    Accurate biomarkers of Mycobacterium tuberculosis infection activity would significantly improve early diagnosis, treatment and management of M. tuberculosis infection. We hypothesised that circulating B-lymphocytes may be useful biomarkers of tuberculosis (TB) infection status in highly TB-endemic settings. Ex-vivo and in-vitro mycobacteria-specific B-cell ELISPOT assays were used to examine the plasmablast (PB) and memory B-cell (MBC) responses in the peripheral blood of adult, healthy, community controls (n = 151) and of active TB patients (n = 48) living in Uganda. Frequencies of mycobacteria-specific PBs were markedly higher in active TB patients compared to healthy controls, and, conversely, MBCs were markedly higher in the healthy controls compared to active TB patients. In addition, the community controls with evidence of latent TB infection had higher peripheral blood PB and MBC responses than those without evidence of TB infection. These data demonstrate that peripheral blood B-cell responses are differentially modulated during latent and active M. tuberculosis infection, and suggest that the PB to MBC ratio may be a useful biomarker of TB infection activity.

  2. Spatial alterations between CD4(+) T follicular helper, B, and CD8(+) T cells during simian immunodeficiency virus infection: T/B cell homeostasis, activation, and potential mechanism for viral escape.

    PubMed

    Hong, Jung Joo; Amancha, Praveen K; Rogers, Kenneth; Ansari, Aftab A; Villinger, Francois

    2012-04-01

    HIV/SIV infections induce chronic immune activation with remodeling of lymphoid architecture and hypergammaglobulinemia, although the mechanisms leading to such symptoms remain to be fully elucidated. Moreover, lymph nodes have been highlighted as a predilection site for SIV escape in vivo. Following 20 rhesus macaques infected with SIVmac239 as they progress from pre-infection to acute and chronic infection, we document for the first time, to our knowledge, the local dynamics of T follicular helper (T(FH)) cells and B cells in situ. Progression of SIV infection was accompanied by increased numbers of well-delineated follicles containing germinal centers (GCs) and T(FH) cells with a progressive increase in the density of programmed death-1 (PD-1) expression in lymph nodes. The rise in PD-1(+) T(FH) cells was followed by a substantial accumulation of Ki67(+) B cells within GCs. However, unlike in blood, major increases in the frequency of CD27(+) memory B cells were observed in lymph nodes, indicating increased turnover of these cells, correlated with increases in total and SIV specific Ab levels. Of importance, compared with T cell zones, GCs seemed to exclude CD8(+) T cells while harboring increasing numbers of CD4(+) T cells, many of which are positive for SIVgag, providing an environment particularly beneficial for virus replication and reservoirs. Our data highlight for the first time, to our knowledge, important spatial interactions of GC cell subsets during SIV infection, the capacity of lymphoid tissues to maintain stable relative levels of circulating B cell subsets, and a potential mechanism for viral reservoirs within GCs during SIV infection.

  3. Increased mortality associated with treated active tuberculosis in HIV-infected adults in Tanzania.

    PubMed

    Kabali, Conrad; Mtei, Lillian; Brooks, Daniel R; Waddell, Richard; Bakari, Muhammad; Matee, Mecky; Arbeit, Robert D; Pallangyo, Kisali; von Reyn, C Fordham; Horsburgh, C Robert

    2013-07-01

    Active tuberculosis (TB) among HIV-infected patients, even when successfully treated, may be associated with excess mortality. We conducted a prospective cohort study nested in a randomized TB vaccine trial to compare mortality between HIV-infected patients diagnosed and treated for TB (TB, n = 77) and HIV-infected patients within the same CD4 range, who were not diagnosed with or treated for active TB (non-TB, n = 308) in the period 2001-2008. Only twenty four subjects (6%) were on antiretroviral therapy at the beginning of this study. After accounting for covariate effects including use of antiretroviral therapy, isoniazid preventive therapy, and receipt of vaccine, we found a four-fold increase in mortality in TB patients compared with non-TB patients (adjusted Hazard Ratio 4.61; 95% Confidence Interval (CI): 1.63, 13.05). These findings suggest that treatment for TB alone is not sufficient to avert the excess mortality associated with HIV-related TB and that prevention of TB may provide a mortality benefit.

  4. Assessment of latent tuberculosis infection in Takayasu arteritis with tuberculin skin test and Quantiferon-TB Gold test.

    PubMed

    Karadag, Omer; Aksu, Kenan; Sahin, Abdurrahman; Zihni, Figen Yargucu; Sener, Burcin; Inanc, Nevsun; Kalyoncu, Umut; Aydin, Sibel Zehra; Ascioglu, Sibel; Ocakci, Pinar Talu; Bilgen, Sule Apras; Keser, Gokhan; Inal, Vedat; Direskeneli, Haner; Calguneri, Meral; Ertenli, Ihsan; Kiraz, Sedat

    2010-09-01

    A possible relationship between Takayasu arteritis (TA) and tuberculosis (TB) has been suggested. An increased frequency of tuberculin skin test (TST) was observed in TA patients. Quantiferon-TB Gold test (QFT) is a new in vitro assay measuring interferon-gamma response to M. tuberculosis antigens and helpful in diagnosing latent TB infection. The aim of this study was to investigate latent TB infection among TA patients by the use of both TST and QFT Gold test. Ninety-four (male/female: 7/87) TA patients fulfilling ACR 1990 TA criteria from three different university hospitals in Turkey and 107 control subjects without inflammatory diseases were included in the study. Data about medical history (TA and TB) were collected for both groups. TST and QFT were performed. TST values > or =5 mm for TA patients and > or =15 mm for controls was accepted as TST positivity. Even though TA group was older (40 +/- 12 vs. 32 +/- 8, P < 0.001), there was no significant difference between TA patients and controls regarding demographic characteristics. Six TA patients and one control had a history of previous TB infection (P = 0.054). Although TST positivity was higher in TA group [55 patients (62.5%) vs. 24 controls (41.4%), P = 0.008], QFT positivity was similar between two groups [21 patients (22.3%) vs. 24 controls (22.4%), P > 0.05]. QFT was negative in two of six TA patients with previous TB history. Rate of latent TB infection in TA patients measured with QFT is no more than controls. QFT seems to be a good and favorable test compared with TST in detecting LTBI in TA.

  5. Association of autophagy-related IRGM polymorphisms with latent versus active tuberculosis infection in a Chinese population.

    PubMed

    Lu, Yanjun; Li, Qian; Peng, Jing; Zhu, Yaowu; Wang, Feng; Wang, Chunyu; Wang, Xiong

    2016-03-01

    The autophagy-related immunity-related GTPase family M protein, IRGM, plays an important role in the defense against tuberculosis (TB) infection. IRGM polymorphisms are associated with TB infection susceptibility, and recent studies demonstrate host genetic differences between active and latent TB. Here, we investigated the association between IRGM polymorphisms and TB infection type in a Chinese population. We recruited 268 and 321 patients with confirmed or latent TB, respectively, and 475 TB-free healthy controls. Three single nucleotide polymorphisms, rs10065172, rs10051924, and rs13361189 within IRGM were genotyped using TaqMan-based assays. Interferon-gamma release levels were tested by T-SPOT. rs10065172 (P = 0.024, OR 0.67 (95% CI 0.48-0.95)), rs10051924 (P = 0.01, OR 0.64 (95% CI 0.46-0.90)), and rs13361189 (P = 0.055, OR 0.72 (95% CI 0.51-1.01)) were associated with a protective role against latent TB progression. Haplotype analysis showed that TCC was protective for latent TB (P = 0.022, OR 0.74 (95% CI 0.57-0.96)) whereas TTC conferred a higher risk of active TB. Additionally, patients with the rs10065172 TT genotype had a higher response to TB specific antigens. Thus, IRGM polymorphism differences between latent and active TB suggests that genetic differences in autophagy might partly affect host TB infection status.

  6. Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection

    PubMed Central

    Wong, Emily B.; Akilimali, Ngomu Akeem; Govender, Pamla; Sullivan, Zuri A.; Cosgrove, Cormac; Pillay, Mona; Lewinsohn, David M.; Bishai, William R.; Walker, Bruce D.; Ndung'u, Thumbi; Klenerman, Paul; Kasprowicz, Victoria O.

    2013-01-01

    Background High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting. Methods A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 13), latent MTB infection (LTBI) only (n = 14), pulmonary tuberculosis (TB) only (n = 9), HIV only (n = 16), HIV and LTBI co-infection (n = 13) and HIV and TB co-infection (n = 15). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients. Results CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection. Conclusions The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB

  7. Anti-TB activity of Evodia elleryana bark extract

    PubMed Central

    Barrows, Louis R.; Powan, Emma; Pond, Christopher D.; Matainaho, Teatulohi

    2009-01-01

    An ethyl acetate extract of bark from Evodia elleryana produced significant growth inhibition of Mycobacterium tuberculosis at concentrations only minimally inhibitory to human T cells. The crude extract yielded 95% inhibition of TB at 50 μg/ml. The crude extract yielded 29 % growth inhibition of human T-cells in culture at that concentration. PMID:17350179

  8. Analysis of Host Responses to Mycobacterium tuberculosis Antigens in a Multi-Site Study of Subjects with Different TB and HIV Infection States in Sub-Saharan Africa

    PubMed Central

    Sutherland, Jayne S.; Lalor, Maeve K.; Black, Gillian F.; Ambrose, Lyn R.; Loxton, Andre G.; Chegou, Novel N.; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P.; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R.; Parida, Shreemanta K.; Boom, W. Henry; Thiel, Bonnie A.; Crampin, Amelia C.; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Kaufmann, Stefan H. E.

    2013-01-01

    Background Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. Methods We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. Results There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST- and TST+ contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST+ contacts (LTBI) compared to TB and TST- contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Conclusions Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may

  9. Mortality, TB/HIV co-infection, and treatment dropout: predictors of tuberculosis prognosis in Recife, Pernambuco State, Brazil.

    PubMed

    Domingos, Mirian Pereira; Caiaffa, Waleska Teixeira; Colosimo, Enrico Antônio

    2008-04-01

    This non-concurrent cohort study aims to identify predictors of tuberculosis mortality in a large population database in Brazil. Tuberculosis, death, and TB/HIV cases were validated respectively from the tuberculosis surveillance (SINAN/TB), mortality (SIM), and SINAN/AIDS databases for a five-year period. Analysis included proportional hazard models with relative risk estimates. Out of 5,451 individuals reported with tuberculosis, 320 (5.9%) died (incidence and mortality rates of 98.6 and 12.2/100 thousand inhabitants, respectively). After adjustment, relative risk of dying from tuberculosis was 9.8 for individuals>50 years of age; 9.0 for TB/HIV co-infection; 3.0 for mixed TB clinical presentation; and 2.0 for treatment dropout. In the multivariate model, using cases with HIV/AIDS, all adjusted predictors lost significance except mixed clinical presentation (RR 1.9; 1.1-3.1). TB/HIV co-infection is an important predictor of TB mortality. However, among individuals without HIV/AIDS, mortality is still highly associated with older age, mixed clinical forms, and treatment dropout.

  10. Recent tuberculosis diagnosis toward the end TB strategy.

    PubMed

    Cheon, Seon Ah; Cho, Hyun Hee; Kim, Jeonghyo; Lee, Jaebeom; Kim, Hwa-Jung; Park, Tae Jung

    2016-04-01

    Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis. Despite global TB eradication efforts, it is still a global public health concern, especially in low- and middle-income countries. Most of the active TB infections are curable with early diagnosis and appropriate treatment, but drug-resistant TB is difficult and expensive to treat in immunocompetent as well as immunocompromised individuals. Thus, rapid, economic, and accurate point-of care tools for TB diagnosis are required urgently. This review describes the history of M. tuberculosis detection methods up to date and the recent advances using nanotechnology for point-of-care testing of TB diagnosis.

  11. HIV and Tuberculosis (TB)

    MedlinePlus

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Tuberculosis (TB) (Last updated 9/1/2016; last reviewed ... depends on a person’s individual circumstances. What is tuberculosis? Tuberculosis (TB) is a contagious disease that can ...

  12. Comparison of two interferon-gamma release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB) in testing for latent tuberculosis infection among HIV-infected adults.

    PubMed

    Sultan, B; Benn, P; Mahungu, T; Young, M; Mercey, D; Morris-Jones, S; Miller, R F

    2013-10-01

    There is currently no 'gold standard' for diagnosis of latent tuberculosis infection (LTBI), and both the tuberculin skin test and interferon-gamma release assays (IGRAs) are used for diagnosis; the latter have a higher sensitivity than tuberculin skin tests for diagnosis of LTBI in HIV-infected individuals with lower CD4 counts. No evidence base exists for selection of IGRA methodology to identify LTBI among human immunodeficiency virus-infected patients in the UK. We prospectively evaluated two commercially available IGRA methods (QuantiFERON-TB Gold In Tube [QFG] and T-SPOT.TB) for testing LTBI among HIV-infected patients potentially nosocomially exposed to an HIV-infected patient with 'smear-positive' pulmonary tuberculosis. Among the exposed patients median CD4 count was 550 cells/µL; 105 (90%) of 117 were receiving antiretroviral therapy, of who 104 (99%) had an undetectable plasma HIV load. IGRAs were positive in 12 patients (10.3%); QFG positive in 11 (9.4%) and T-SPOT.TB positive in six (5.1%); both IGRAs were positive in five patients (4.3%). There was one indeterminate QFG and one borderline T-SPOT.TB result. Concordance between the two IGRAs was moderate (κ = 0.56, 95% confidence interval = 0.27-0.85). IGRAs were positive in only 4 (29%) of 14 patients with previous culture-proven tuberculosis. No patient developed tuberculosis during 20 months of follow-up.

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

    PubMed Central

    Belay, Mulugeta; Bjune, Gunnar; Abebe, Fekadu

    2015-01-01

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

  14. Clinical Predictors and Accuracy of Empiric Tuberculosis Treatment among Sputum Smear-Negative HIV-Infected Adult TB Suspects in Uganda

    PubMed Central

    Nakiyingi, Lydia; Bwanika, John Mark; Kirenga, Bruce; Nakanjako, Damalie; Katabira, Catherine; Lubega, Gloria; Sempa, Joseph; Nyesiga, Barnabas; Albert, Heidi; Manabe, Yukari C.

    2013-01-01

    Introduction The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard. Setting Out-patient HIV-TB integrated urban clinic in Kampala, Uganda. Methods HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation. Results Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31–44) years, with a median CD4 cell count of 291 IQR (150–482) cells/mm3. Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001). Abnormal chest X-ray [aOR 10.18, 95% CI (3.14–33.00), p<0.001] and advanced HIV clinical stage [aOR 3.92, 95% CI (1.20–12.85), p = 0.024] were significantly associated with empiric TB treatment initiation. The sensitivity and specificity of empiric TB treatment initiation in the diagnosis of TB in HIV-infected patients after negative smear microscopy was 62.5% and 73.7% respectively. Conclusion In resource-limited settings, clinically advanced HIV and abnormal chest X-ray significantly predict a clinical decision to empirically initiate TB treatment in smear-negative HIV-infected

  15. Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

    PubMed

    Igari, Hidetoshi; Watanabe, Akira; Ichimura, Yasunori; Sakurai, Takayuki; Taniguchi, Toshibumi; Ishiwada, Naruhiko

    2017-04-01

    QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube.

  16. Tuberculosis Infection and Latent Tuberculosis

    PubMed Central

    2016-01-01

    Active tuberculosis (TB) has a greater burden of TB bacilli than latent TB and acts as an infection source for contacts. Latent tuberculosis infection (LTBI) is the state in which humans are infected with Mycobacterium tuberculosis without any clinical symptoms, radiological abnormality, or microbiological evidence. TB is transmissible by respiratory droplet nucleus of 1–5 µm in diameter, containing 1–10 TB bacilli. TB transmission is affected by the strength of the infectious source, infectiousness of TB bacilli, immunoresistance of the host, environmental stresses, and biosocial factors. Infection controls to reduce TB transmission consist of managerial activities, administrative control, engineering control, environmental control, and personal protective equipment provision. However, diagnosis and treatment for LTBI as a national TB control program is an important strategy on the precondition that active TB is not missed. Therefore, more concrete evidences for LTBI management based on clinical and public perspectives are needed. PMID:27790271

  17. Contribution of Interferon gamma release assays testing to the diagnosis of latent tuberculosis infection in HIV-infected patients: A comparison of QuantiFERON-TB Gold In Tube, T-SPOT.TB and tuberculin skin test

    PubMed Central

    2012-01-01

    Background Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERON-tuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients. Methods A prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAs and TST were performed simultaneously. TST induration ≥ 5 mm was considered positive. Results QFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/μl with a median nadir of 150/μl. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p < 0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%–16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/μl and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.8; 95% CI, 1.4 – 9.9; and aOR: 3.3; 95% CI, 1.3 – 8.3, respectively). Conclusions IGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIV-infected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this

  18. Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

    ERIC Educational Resources Information Center

    Migrant Clinicians Network, Inc., Austin, TX.

    A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…

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

    PubMed

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

    2014-04-01

    Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with <7 days of TB treatment had 1 sputum specimen tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical identification of mycobacterial species, and culture-based drug-susceptibility testing (DST). Of 639 participants, 59.3% were MGIT M. tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

  20. [Abandonment of tuberculosis treatment among patients co-infected with TB/HIV].

    PubMed

    Rodrigues, Ivaneide Leal Ataide; Monteiro, Larissa Lima; Pacheco, Régia Hevelline Barros; da Silva, Sílvio Eder Dias

    2010-06-01

    This study aimed at analyzing the reasons that patients co-infected with tuberculosis and HIV leave the treatment of tuberculosis and to know the conduct of the health team toward that abandonment. The study, using a qualitative approach, performed semi-structured interviews on 45 professionals working at a referral health center in Pará state. Two units emerged based on the thematic analysis: patient-associated factors that make TB treatment adherence difficult; and service-associated factors that contribute to treatment abandonment. It was found that, in terms of the patients, that their low socioeconomic condition was the most common factor that led to abandonment. Other factors that led to this outcome included the adverse drug effects, the use of illegal drugs, and poor personal motivation. Regarding the service, issues related to the physical structure, working process organization and accessibility were also relevant to their non-adherence. Results show there is a need to change the practices performed at the health care services.

  1. TB Terms

    MedlinePlus

    ... Search The CDC 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 ...

  2. Augmented photocatalytic activity and luminescence response of Tb³⁺ doped nanoscale titania systems

    SciTech Connect

    Paul, Nibedita; Deka, Amrita; Mohanta, Dambarudhar

    2014-10-14

    The present work reports on the effect of Tb³⁺ doping on the luminescence and photocatalytic performance of nano-structured titania derived through a sol-gel route. X-ray diffraction patterns have revealed the existence of anatase phase with and without Tb³⁺ doping and with an improved orientation factor along (004) and (200) planes. Transmission electron microscopy and selective area electron diffraction studies, while exhibiting ample poly-crystallinity feature, have predicted an average particle size of ~9 nm and ~6 nm for the un-doped and 5% Tb³⁺ doped nano-titania samples; respectively. Apart from emissions accompanied by different types of defects, Tb³⁺ related transitions, such as, ⁵D₃ → ⁷F₅, ⁵D₃ → ⁷F₄, and ⁵D₄ → ⁷F₆ were identified in the photoluminescence spectra. Brunauer-Emmett-Teller surface area analysis, as carried out on a Tb³⁺ doped nano-titania system, has demonstrated a more-open hysteretic loop owing to significant difference of N₂ adsorption/desorption rates. The photocatalytic activity of nano-titania, as evaluated from the nature of degradation of methyl orange under UV illumination, exhibited the highest efficiency for a Tb³⁺ doping level of 2.5%. The augmented photocatalytic degradation has also been discussed in the light of a model based on pseudo first-order kinetics.

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

    PubMed Central

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

    2015-01-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  4. Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.

    PubMed

    Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V; Mondal, Debasis; Nair, Madhavan

    2015-01-01

    Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

  5. Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections

    PubMed Central

    Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V.; Mondal, Debasis; Nair, Madhavan

    2015-01-01

    Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters. PMID:26441882

  6. Antigen-Specific IFN-γ Responses Correlate with the Activity of M. tuberculosis Infection but Are Not Associated with the Severity of Tuberculosis Disease

    PubMed Central

    Nikitina, Irina Yu.; Panteleev, Alexander V.; Karpina, Natalya L.; Bagdasarian, Tatef R.; Burmistrova, Irina A.; Andreevskaya, Sofia N.; Chernousova, Larisa N.; Vasilyeva, Irina A.

    2016-01-01

    IFN-γ is a key cytokine in antituberculosis (TB) defense. However, how the levels of its secretion affect M. tuberculosis (Mtb) infection is not clear. We have analyzed associations between IFN-γ responses measured in QuantiFERON®-TB Gold In-tube (QFT) assay, TB disease severity, and Mtb infection activity. TB severity was evaluated based on the results of radiological, microbiological, and clinical examinations. Antigen-driven IFN-γ secretion did not correlate with TB severity. Mitogen-induced IFN-γ secretion correlated inversely with the form of pulmonary pathology and the area of affected pulmonary tissue; the levels of spontaneous IFN-γ secretion correlated with patients' age (r = 0.395, p = 0.001). Mtb infection activity was evaluated based on radiological data of lung tissue infiltration, destruction, dissemination or calcification, and condensation. The rate of positive QFT results and the levels of antigen-driven IFN-γ secretion increased in a row: patients with residual TB lesions < patients with low TB activity < patients with high TB activity. Thus, antigen-driven IFN-γ secretion and QFT results did not associate with TB severity but associated with the infection activity. The results suggest that quantitative parameters of IFN-γ secretion play a minor role in determining the course of TB disease but mirror the activity of the infectious process. PMID:28042583

  7. Antigen-Specific IFN-γ Responses Correlate with the Activity of M. tuberculosis Infection but Are Not Associated with the Severity of Tuberculosis Disease.

    PubMed

    Nikitina, Irina Yu; Panteleev, Alexander V; Sosunova, Ekaterina V; Karpina, Natalya L; Bagdasarian, Tatef R; Burmistrova, Irina A; Andreevskaya, Sofia N; Chernousova, Larisa N; Vasilyeva, Irina A; Lyadova, Irina V

    2016-01-01

    IFN-γ is a key cytokine in antituberculosis (TB) defense. However, how the levels of its secretion affect M. tuberculosis (Mtb) infection is not clear. We have analyzed associations between IFN-γ responses measured in QuantiFERON®-TB Gold In-tube (QFT) assay, TB disease severity, and Mtb infection activity. TB severity was evaluated based on the results of radiological, microbiological, and clinical examinations. Antigen-driven IFN-γ secretion did not correlate with TB severity. Mitogen-induced IFN-γ secretion correlated inversely with the form of pulmonary pathology and the area of affected pulmonary tissue; the levels of spontaneous IFN-γ secretion correlated with patients' age (r = 0.395, p = 0.001). Mtb infection activity was evaluated based on radiological data of lung tissue infiltration, destruction, dissemination or calcification, and condensation. The rate of positive QFT results and the levels of antigen-driven IFN-γ secretion increased in a row: patients with residual TB lesions < patients with low TB activity < patients with high TB activity. Thus, antigen-driven IFN-γ secretion and QFT results did not associate with TB severity but associated with the infection activity. The results suggest that quantitative parameters of IFN-γ secretion play a minor role in determining the course of TB disease but mirror the activity of the infectious process.

  8. Comparison of the tuberculin skin test and Quanti-FERON-TB Gold In-Tube (QFT-G) test for the diagnosis of latent tuberculosis infection in dialysis patients.

    PubMed

    Al Jahdali, Hamdan; Ahmed, Anwar E; Balkhy, Hanan H; Baharoon, Salim; Al Hejaili, Fayez F; Hajeer, Ali; Memish, Ziad; Binsalih, Salih; Al Sayyari, Abdullah A

    2013-06-01

    Dialysis patients are more likely than the general population to develop active tuberculosis (TB). In these patients, the availability of a highly sensitive and specific test to diagnose latent TB will ensure earlier treatment and decreased progression to active disease. In the current study, the Quanti-FERON-TB Gold In-Tube (QFT-G) test was compared with the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) among 200 hemodialysis patients and 15 confirmed TB disease cases in a tertiary care center in Saudi Arabia. Among the LTBI cases, 26 (13%) were TST positive, and 65 (32.5%) were positive by the QTF-G test, with an overall agreement between the 2 tests of 75.5% (k=0.34) being observed. Among the confirmed tuberculosis disease cases, none were positive by TST, and 10 (66.7%) were positive by the QTF-G test, resulting in an overall agreement of 33.3% (k=0). A comparison between the TST and the QTF-G test was performed based on the sensitivity, specificity, and area under the curve (AUC) obtained for the tests. The QTF-G test was more sensitive and less specific than the TST in predicting the confirmed TB disease cases. When we tested the correspondence of the AUC values between the 2 diagnostic modalities, the obtained p-value was 0.0003. In conclusion, the AUCs of the examined diagnostic modalities are significantly different in predicting LTBI and tuberculosis.

  9. Comparison of Interferon gamma inducible protein-10 and Interferon gamma based QuantiFERON TB Gold assays with tuberculin skin test in HIV infected subjects

    PubMed Central

    Basirudeen, S; Rajasekaran, S; Alamelu, R

    2011-01-01

    We aimed to compare the positivity of the QuantiFERON TB gold in-tube (QFT-IT antigens) specific Interferon gamma (IFN-γ/QFT-IT) and IFN-γ nducible protein-10 (IP-10/QFT-IT) assays with tuberculin skin test (TST) among human immunodeficiency virus (HIV) infected individuals in a TB endemic setting. A total of 180 HIV infected subjects, with no evidence of active TB were recruited. IFN-γ nd IP-10 levels specific to QFT-IT antigens were measured in plasma from QFT-IT tubes. The overall positivity of TST at 5mm cut-off point (19%) was significantly lower when compared to IFN-γ/QFT-IT (38%) and IP-10/QFT-IT (45%) assays. The positivity of IP-10/QFT-IT was significantly higher than IFN-γ/QFT-IT (p=0.038). Indeterminate results for IFN-γ/QFT-IT and IP-10/QFT-IT were more frequent in subjects with CD4 count <100 cells/µl, than those with >100 cells/µl. IFN-γ/QFT-IT (9%) yielded significantly higher number of indeterminate results than IP-10/QFT-IT (5%). The frequency of these responses is higher than the proportion of individuals with positive TST results. However, 6 IFN-γ/QFT-IT or IP-10/QFT-IT negative subjects were positive for TST at 5mm cut-off point. Prospective and prognostic studies are required to clarify the significance of these data. PMID:21996360

  10. TAIMA (Stop) TB: The Impact of a Multifaceted TB Awareness and Door-to-Door Campaign in Residential Areas of High Risk for TB in Iqaluit, Nunavut

    PubMed Central

    Alvarez, Gonzalo G.; VanDyk, Deborah D.; Aaron, Shawn D.; Cameron, D. William; Davies, Naomi; Stephen, Natasha; Mallick, Ranjeeta; Momoli, Franco; Moreau, Katherine; Obed, Natan; Baikie, Maureen; Osborne, Geraldine

    2014-01-01

    Background The incidence rate of active tuberculosis (TB) disease in the Canadian Territory of Nunavut has shown a rising trend over the past 10 years. In 2010 it was 60 times greater than the national incidence rate. The objective of the Taima (translates to “stop” in Inuktitut) TB study was to implement and evaluate a public health campaign to enhance existing TB prevention efforts in Nunavut. Methods A TB awareness campaign followed by a door-to-door screening campaign was carried out in Iqaluit, Nunavut. The aim of the campaign was to raise awareness about TB, and to provide in-home screening and treatment for people living in residential areas at high risk for TB. Screening was based on geographic location rather than on individual risk factors. Results During the general awareness campaign an increase in the number of people who requested TB testing at the local public health clinic was observed. However, this increase was not sustained following cessation of the awareness campaign. Targeted TB screening in high risk residential areas in Iqaluit resulted in 224 individuals having TSTs read, and detection of 42 previously unidentified cases of latent TB, (overall yield of 18.8% or number needed to screen = 5.3). These cases of latent TB infection (LTBI) were extra cases that had not been picked up by traditional screening practices (34% relative increase within the community). This resulted in a 33% relative increase in the completion of LTBI treatment within the community. The program directly and indirectly identified 5/17 new cases of active TB disease in Iqaluit during the study period (29.5% of all incident cases). Conclusions While contact tracing investigations remain a cornerstone of TB prevention, additional awareness, screening, and treatment programs like Taima TB may contribute to the successful control of TB in Aboriginal communities. PMID:25033320

  11. Tuberculosis (TB)

    MedlinePlus

    ... with facebook share with twitter share with linkedin Tuberculosis (TB) Tuberculosis (TB) is a contagious and often ... are drug resistant. Why Is the Study of Tuberculosis (TB) a Priority for NIAID? Tuberculosis is one ...

  12. TB Is Back.

    ERIC Educational Resources Information Center

    Natale, Jo Anna

    1992-01-01

    The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…

  13. Evaluation of QuantiFERON-TB Gold Plus for Detection of Mycobacterium tuberculosis infection in Japan

    PubMed Central

    Yi, Lina; Sasaki, Yuka; Nagai, Hideaki; Ishikawa, Satoru; Takamori, Mikio; Sakashita, Kentaro; Saito, Takefumi; Fukushima, Kiyoyasu; Igarashi, Yuriko; Aono, Akio; Chikamatsu, Kinuyo; Yamada, Hiroyuki; Takaki, Akiko; Mori, Toru; Mitarai, Satoshi

    2016-01-01

    Performance of interferon-γ (IFN-γ) release assays still needs to be improved. The data on the performance of QuantiFERON-TB Gold Plus (QFT-Plus), a new-generation of QFT assay are limited. This study evaluated the diagnostic performance of QFT-Plus, and compared to that of QuantiFERON-TB Gold In-Tube (QFT-GIT). Blood samples were collected from 162 bacteriologically confirmed tuberculosis (TB) patients and 212 Mycobacterium tuberculosis-uninfected volunteers; these samples were then tested with QFT-GIT and QFT-Plus. The IFN-γ concentration of QFT-Plus was lower than that of QFT-GIT in TB patients (p < 0.001). Receiver operating characteristic curves were compared between QFT-GIT and QFT-Plus. Both assays showed area under the curve values over 0.99 without significant difference. Using the conventional cut-off (0.35 IU/mL) for QFT-GIT, QFT-Plus had a lower sensitivity of 91.1% compared to 96.2% (p = 0.008) at its optimum cut-off (0.168 IU/mL) with the same specificity. Moreover, IFN-γ values were significantly reduced with age in QFT-GIT (p = 0.035) but not in QFT-Plus. The diagnostic performance of QFT-Plus was as accurate as that of QFT-GIT despite a lack of TB7.7 antigen and despite the decrease in quantitative values. However, the cut-off value for QFT-Plus should be considered independently from that of QFT-GIT to obtain the best sensitivity without compromising specificity. PMID:27470684

  14. Evaluation of QuantiFERON-TB Gold Plus for Detection of Mycobacterium tuberculosis infection in Japan.

    PubMed

    Yi, Lina; Sasaki, Yuka; Nagai, Hideaki; Ishikawa, Satoru; Takamori, Mikio; Sakashita, Kentaro; Saito, Takefumi; Fukushima, Kiyoyasu; Igarashi, Yuriko; Aono, Akio; Chikamatsu, Kinuyo; Yamada, Hiroyuki; Takaki, Akiko; Mori, Toru; Mitarai, Satoshi

    2016-07-29

    Performance of interferon-γ (IFN-γ) release assays still needs to be improved. The data on the performance of QuantiFERON-TB Gold Plus (QFT-Plus), a new-generation of QFT assay are limited. This study evaluated the diagnostic performance of QFT-Plus, and compared to that of QuantiFERON-TB Gold In-Tube (QFT-GIT). Blood samples were collected from 162 bacteriologically confirmed tuberculosis (TB) patients and 212 Mycobacterium tuberculosis-uninfected volunteers; these samples were then tested with QFT-GIT and QFT-Plus. The IFN-γ concentration of QFT-Plus was lower than that of QFT-GIT in TB patients (p < 0.001). Receiver operating characteristic curves were compared between QFT-GIT and QFT-Plus. Both assays showed area under the curve values over 0.99 without significant difference. Using the conventional cut-off (0.35 IU/mL) for QFT-GIT, QFT-Plus had a lower sensitivity of 91.1% compared to 96.2% (p = 0.008) at its optimum cut-off (0.168 IU/mL) with the same specificity. Moreover, IFN-γ values were significantly reduced with age in QFT-GIT (p = 0.035) but not in QFT-Plus. The diagnostic performance of QFT-Plus was as accurate as that of QFT-GIT despite a lack of TB7.7 antigen and despite the decrease in quantitative values. However, the cut-off value for QFT-Plus should be considered independently from that of QFT-GIT to obtain the best sensitivity without compromising specificity.

  15. Low implementation of Xpert MTB/RIF among HIV/TB co-infected adults in the International epidemiologic Databases to Evaluate AIDS (IeDEA) program

    PubMed Central

    Blevins, Meridith; Lindegren, Mary Lou; Yotebieng, Marcel; Nguyen, Dung Thi; Omondi, Alfred; Michael, Denna; Zannou, Djimon Marcel; Carriquiry, Gabriela; Pettit, April

    2017-01-01

    Objective Xpert MTB/RIF is recommended by the World Health Organization (WHO) as the initial tuberculosis (TB) diagnostic test in individuals suspected of HIV-associated TB. We sought to evaluate field implementation of Xpert among a cohort of HIV/TB co-infected individuals, including availability, utilization and outcomes. Design Observational cohort study (patient-level data) and cross-sectional study (site-level Xpert availability data). Methods Data were collected at 30 participating International epidemiologic Databases to Evaluate AIDS (IeDEA) sites in 18 countries from January 2012-January 2016. All patients were HIV-infected and diagnosed with TB, either bacteriologically or clinically, and followed until a determination of TB treatment outcome. We used multivariable modified Poisson regression to estimate adjusted relative risk (RR) and 95% confidence intervals for unfavorable TB treatment outcomes. Results Most sites (63%) had access to Xpert, either in the clinic (13%), in the same facility (20%) or offsite (30%). Among 2722 HIV/TB patients included, median age was 35.4 years and 41% were female; BMI and CD4 count were low. Overall, most patients (76%) received at least one TB test; 45% were positive. Only 4% of all patients were tested using Xpert: 64% were Xpert-positive, 13% showed rifampicin (RIF) resistance and 30% were extrapulmonary (EPTB) or both pulmonary-EPTB. Treatment outcomes were mostly favorable (77%) and we found little association between Xpert use and an unfavorable TB treatment outcome (RR 1.25, 95%CI: 0.83, 1.90). Conclusions In this cohort, Xpert utilization was low even though the majority of sites had access to the test. Our findings show the need for expanded implementation and further research exploring barriers to use in low-resource settings. PMID:28182705

  16. Long lasting phosphorescence and photostimulated luminescence in Tb-ion-activated reduced calcium aluminate glasses

    NASA Astrophysics Data System (ADS)

    Kinoshita, Takeru; Yamazaki, Masaaki; Kawazoe, Hiroshi; Hosono, Hideo

    1999-10-01

    Long lasting phosphorescence (LLP) and photostimulated luminescence (PSL) were found in reduced calcium aluminate glasses activated with Tb3+ ions. The LLP from Tb3+ was observed by illuminating the Tb3+ 4f→5d charge transfer band with ultraviolet (UV) 254 nm light, while the PSL was seen by stimulating the UV-illuminated glasses with 633 nm light. The decay curve of the LLP was fitted with a second-order kinetic for the initial period (030 min). An electron paramagnetic resonance (EPR) signal, which is attributed to an F+-like center associated with Ca2+ ions, was induced by illumination with UV light and its intensity decay was fitted with a first-order kinetic similarly to the later stage of the LLP. The appearance of the PSL by illumination is accompanied by a distinct intensity reduction of the EPR signal due to the F+-like center. The thermoluminescence spectra of the specimen illuminated with UV light at 77 K consist of two components peaking at ˜240 and ˜390 K. The low temperature component and the high temperature component were attributed to an F-like center and an F+-like center, respectively. These results lead to a conclusion that electrons of the F-like center and the F+-like center contribute predominantly to the emergence of the LLP and the PSL, respectively.

  17. Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age

    PubMed Central

    Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

    2016-01-01

    Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30–49 years, 86.5% and 94.7%; 50–69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age. PMID:27258377

  18. Rapid detection of serum antibody by dual-path platform VetTB assay in white-tailed deer infected with Mycobacterium bovis.

    PubMed

    Lyashchenko, Konstantin P; Greenwald, Rena; Esfandiari, Javan; O'Brien, Daniel J; Schmitt, Stephen M; Palmer, Mitchell V; Waters, W Ray

    2013-06-01

    Bovine tuberculosis (TB) in cervids remains a significant problem affecting farmed herds and wild populations. Traditional skin testing has serious limitations in certain species, whereas emerging serological assays showed promising diagnostic performance. The recently developed immunochromatographic dual-path platform (DPP) VetTB assay has two antigen bands, T1 (MPB83 protein) and T2 (CFP10/ESAT-6 fusion protein), for antibody detection. We evaluated the diagnostic accuracy of this test by using serum samples collected from groups of white-tailed deer experimentally inoculated with Mycobacterium bovis, M. avium subsp. paratuberculosis, or M. bovis BCG Pasteur. In addition, we used serum samples from farmed white-tailed deer in herds with no history of TB, as well as from free-ranging white-tailed deer culled during field surveillance studies performed in Michigan known to have bovine TB in the wild deer population. The DPP VetTB assay detected antibody responses in 58.1% of experimentally infected animals within 8 to 16 weeks postinoculation and in 71.9% of naturally infected deer, resulting in an estimated test sensitivity of 65.1% and a specificity of 97.8%. The higher seroreactivity found in deer with naturally acquired M. bovis infection was associated with an increased frequency of antibody responses to the ESAT-6 and CFP10 proteins, resulting in a greater contribution of these antigens, in addition to MPB83, to the detection of seropositive animals, compared with experimental M. bovis infection. Deer experimentally inoculated with either M. avium subsp. paratuberculosis or M. bovis BCG Pasteur did not produce cross-reactive antibodies that could be detected by the DPP VetTB assay. The present findings demonstrate the relatively high diagnostic accuracy of the DPP VetTB test for white-tailed deer, especially in the detection of naturally infected animals.

  19. Evaluation of heat shock proteins for discriminating between latent tuberculosis infection and active tuberculosis: A preliminary report.

    PubMed

    Shekhawat, Seema D; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

    2016-01-01

    The diagnosis of a latent tuberculosis infection (LTBI) is of the utmost concern. The available tests, the tuberculin skin test (TST) and the Quantiferon-TB Gold test (QFT-G) cannot discriminate between active TB and LTBI. Therefore, the aim of the study is to identify new biomarkers that can discriminate between active TB and LTBI and can also assess the risk of the individual developing active TB. In total, 55 blood samples were collected, of which 10 samples were from the active TB infection group, 10 were from the high-risk exposure group, 23 were from the low-risk exposure group, and 12 were from healthy controls living in a non-TB endemic area. A panel of heat shock proteins (Hsps), including host Hsp25, Hsp60, Hsp70, and Hsp90 and Mycobacterium tuberculosis (MTB) Hsp16, were evaluated in all of the collected samples using ELISA. The levels of the host Hsp(s) (Hsp25, Hsp60, Hsp70 and Hsp90) and MTB Hsp16 were significantly (p<0.05) elevated in the active TB group compared to the high-risk exposure group, the low-risk exposure group and the control group. Notably, the levels of the same panel of Hsp(s) were elevated in the high-risk exposure group compared to the low-risk exposure group. On follow-up, out of the 10 high-risk exposure participants, 3 converted into active TB, indicating that this group has the highest risk of developing TB. Thus, the evaluated panel of Hsp(s) can discriminate between LTBI and active TB. They can also identify individuals who are at the highest risk of developing active TB. Because they can be rapidly detected, Hsp(s) have an edge over the existing diagnostic tools for LTBI. The evaluation of these proteins will be useful in designing better diagnostic methods for LTBI.

  20. Characterization of hepatitis C infection in tuberculosis patients in an urban city in the USA.

    PubMed

    Campo, M; Shrestha, A; Oren, E; Thiede, H; Duchin, J; Narita, M; Crothers, K

    2014-07-01

    The impact of hepatitis C virus infection (HCI), the most common bloodborne virus infection in the USA, on outcome of active tuberculosis (TB) treatment is largely unknown. We aimed to describe characteristics of TB patients with hepatitis C virus infection (TB-HCI) in King County, Washington, including TB treatment duration and outcome. We reviewed 1510 records of patients treated for active TB at the Public Health - Seattle & King County Tuberculosis Control Program between 2000 and 2010, and identified 53 with HCI. Advanced age, being born in the USA, HIV infection, homelessness and injection drug use were independently associated with HCI in TB cases. Independent factors associated with increased treatment duration included HIV infection, excess alcohol use, extrapulmonary TB, and any drug-resistant TB disease. Our findings suggest that TB-HCI patients can be successfully treated for active TB without extending treatment duration.

  1. Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: a brief report.

    PubMed

    Tabarsi, Payam; Yousefzadeh, Amir; Najafizadeh, Katayoun; Droudinia, Atousa; Bayati, Rouzbeh; Marjani, Majid; Shafaghi, Shadi; Farokhzad, Banafsheh; Javanmard, Pedram; Velayati, Ali Akbar

    2014-11-01

    With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G) test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber-culosis and Lung Diseases (NRITLD) in Iran, from January to March 2013. A total of 38 conse-cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi-cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA). The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9%) turned out to be positive, negative for 24 donors (63.1%), and indeterminate for 11 cases (28.9%). Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.

  2. TB & HIV: the deadly intersection.

    PubMed

    MacDougall, D S

    1999-05-01

    About 2 billion people worldwide are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is the leading cause of premature death in less industrialized countries, and 8 million more people become infected every year. The World Health Organization (WHO) declared TB a global emergency in 1993 and launched a series of prevention and vaccination programs. In spite of effective drug therapy and a vaccine, tuberculosis remains a major public health problem. The TB and HIV epidemics are closely intertwined, and the risk of TB disease progression is 100 times greater in HIV-positive individuals. TB is the leading cause of death among HIV-infected people worldwide, and virologic evidence suggests that the host immune response to TB may enhance HIV replication and accelerate the progression of HIV infection. The interaction between the two diseases was the subject of a conference called TB & HIV: Applying Advances to the Clinic, Public Health, and the World. Charts and tables show reported TB cases in the U.S., trends in TB cases among foreign-born persons in the U.S., and the country of origin for foreign-born persons with TB in the U.S. Several poster sessions from the conference are summarized. Strategies for dealing with the TB epidemic are outlined.

  3. Bovine TB infection status in cattle in Great Britain in 2015.

    PubMed

    Harris, K A; Brunton, L; Brouwer, A; Garcia, M P Romero; Gibbens, J C; Smith, N H; Upton, P A

    2017-02-18

    This report, provided by the APHA, presents the key descriptive epidemiological parameters of bovine TB in cattle in Great Britain from January 1 to December 31, 2015, providing summary information on the epidemic, including key statistics and epidemiological parameters as presented in the annual surveillance report for Great Britain, with supporting detail from specific reports for England and Wales. It updates the previous annual summaries for 2012 to 2014, also published in Veterinary Record.

  4. TB Screening Tests

    MedlinePlus

    ... known as: Purified Protein Derivative; PPD; Mantoux; Latent Tuberculosis Infection Test; Interferon-gamma Release Assays; IGRA; T- ... else I should know? How is it used? Tuberculosis (TB) screening tests are not used as general ...

  5. Infection control in home-based care for people living with HIV/AIDS/TB in South Africa: an exploratory study.

    PubMed

    Akintola, Olagoke; Hangulu, Lydia

    2014-01-01

    The majority of HIV and AIDS patients in sub-Saharan African countries receive health care services at home. Yet research on infection control in home-based care settings is virtually non-existent. This study explored infection control practices in home-based care in a South African province with a high HIV/TB prevalence. We conducted interviews with 10 managers of home-based care organizations and 10 focus group discussions with 80 volunteer caregivers working in high HIV/TB prevalent communities in South Africa. Findings show that volunteers had insufficient training on infection control. Materials necessary for the maintenance of hygiene and protective equipment were in short supply and the protective equipment supplied was of poor quality. Home-based care patients lived in crowded and poor conditions, and family members were negatively disposed to the use of protective devices. Together, these factors put volunteers and family caregivers at risk of infection with HIV and TB. Health policy should address the training of volunteer caregivers and the regular supply of good quality materials to ensure effective infection control. It is also important to educate families on infection control. Finally, there is a need to integrate HIV and TB control at the community level.

  6. HIV-Associated TB: Facts 2013

    MedlinePlus

    ... HIV worldwide are infected with latent TB. Persons co-infected with TB and HIV are 29.6 ... 5 million in 2011).  Antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) should be given to ...

  7. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    PubMed Central

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  8. Active Referral: An Innovative Approach to Engaging Traditional Healthcare Providers in TB Control in Burkina Faso

    PubMed Central

    Kaboru, Berthollet Bwira

    2013-01-01

    Background and objective: The involvement of traditional healthcare providers (THPs) has been suggested among strategies to increase tuberculosis case detection. Burkina Faso has embarked on such an attempt. This study is a preliminary assessment of that model. Methods: Qualitative data were collected using unstructured key informant interviews with policy makers, group interviews with THPs and health workers, and field visits to THPs. Quantitative data were collected from program reports and the national tuberculosis (TB) control database. Results and analysis: The distribution of tasks among THPs, intermediary organizations and clinicians is appealing, especially the focus on active referral. THPs are offered incentives based on numbers of suspected cases confirmed by health workers at the clinic, based on microscopy results or clinical assessment. The positivity rate was 23% and 9% for 2006 and 2007, respectively. The contribution of the program to national case detection was estimated at 2% for 2006. Because it relied totally on donor funding, the program suffered from irregular disbursements, resulting in periodic decreases in activities and outcomes. Conclusions: The study shows that single interventions require a broader positive policy environment to be sustainable. Even if the active referral approach seems effective in enhancing TB case detection, more complex policy work and direction, domestic financial contribution and additional evidence for cost-effectiveness are needed before the approach can be established as a national policy. PMID:24359717

  9. Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants.

    PubMed

    Liu, Xueting; Chen, Caixia; He, Wenni; Huang, Pei; Liu, Miaomiao; Wang, Qian; Guo, Hui; Bolla, Krishna; Lu, Yan; Song, Fuhang; Dai, Huanqin; Liu, Mei; Zhang, Lixin

    2012-10-01

    Multidrug-resistant tuberculosis (MDR-TB) and TB-HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40 years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.

  10. Accuracy of QuantiFERON-TB Gold Test for Tuberculosis Diagnosis in Children

    PubMed Central

    Sali, Michela; Buonsenso, Danilo; Goletti, Delia; D’Alfonso, Pamela; Zumbo, Antonella; Fadda, Giovanni; Sanguinetti, Maurizio; Delogu, Giovanni; Valentini, Piero

    2015-01-01

    Objectives To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in children with suspected active or latent TB infection (LTBI). Methods A retrospective study was conducted on 621 children (0–14 years old) evaluated for TB infection or disease. Following clinical assessment, children were tested with the QFT-IT assay. Results Among the 140 active TB suspects, we identified 19 cases of active disease. The overall sensitivity for active TB was 87.5%, ranging from 62.5% in children 25–36 months old to 100% in children older than 49 months. The overall specificity for active TB was 93.6%. Among the 481 children tested for LTBI screening, 38 scored positive and all but 2 had at least one risk factor for TB infection. Among the 26 children with indeterminate results, bacterial, viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB related extra-pulmonary infections in 12 (46.1%). Conclusions Our results indicate that the children's response to QFT-IT associates to active TB and risk factors for LTBI. Moreover, we show that mitogen response is also found in children of 1 year of age, providing support for QFT-IT use also in young children. PMID:26439935

  11. Wind-Driven Roof Turbines: A Novel Way to Improve Ventilation for TB Infection Control in Health Facilities

    PubMed Central

    Cox, Helen; Escombe, Rod; McDermid, Cheryl; Mtshemla, Yolanda; Spelman, Tim; Azevedo, Virginia; London, Leslie

    2012-01-01

    Objective Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa. Methods Room ventilation was assessed (CO2 gas tracer technique) in 4 rooms where roof turbines and air-intake grates were installed, across three scenarios: turbine, grate and window closed, only window open, and only turbine and grate open, with concurrent wind speed measurement. 332 measurements were conducted over 24 months. Findings For all 4 rooms combined, median air changes per hour (ACH) increased with wind speed quartiles across all scenarios. Higher median ACH were recorded with open roof turbines and grates, compared to open windows across all wind speed quartiles. Ventilation with open turbine and grate exceeded WHO-recommended levels (60 Litres/second/patient) for 95% or more of measurements in 3 of the 4 rooms; 47% in the remaining room, where wind speeds were lower and a smaller diameter turbine was installed. Conclusion High room ventilation rates, meeting recommended thresholds, may be achieved using wind-driven roof turbines and grates, even at low wind speeds. Roof turbines and air-intake grates are not easily closed by staff, allowing continued ventilation through colder periods. This simple, low-cost technology represents an important addition to our tools for TB infection control. PMID:22253742

  12. MDR-TB Antibody Response (Western Blot) to Fractions of Isoniazid and Rifampicin Resistant Antigens of Mycobacterium tuberculosis.

    PubMed

    Hadizadeh Tasbiti, Alireza; Yari, Shamsi; Ghanei, Mostafa; Shokrgozar, Mohammad Ali; Bahrmand, Ahmadreza

    2015-12-01

    Drug-resistant TB poses a major threat to control of TB worldwide. Despite progress in the detection of Multidrug-resistant TB (MDR-TB) cases, a major diagnostic gap remains: 55% of reported TB patients estimated to have MDR-TB were not detected in 2013. MDR-TB antigens were conjugated to CNBr-activated Sepharose 4B. Specific polyclonal antibodies against MDR-TB Ags were prepared in rabbits using two boosted injections of the MDR-TB antigen. The antibodies were purified and treated with susceptible TB to remove any non-specific and cross-reactive antibodies. In the present study, comparative analysis of electrophoretic pattern of different antigens of INH/RIF-resistant TB were studied for identifying protein profiles. A RIF-resistant TB antigen was shown here to have different protein profiles from INH-resistant TB isolate. The results of Western blotting analysis showed that in the RIF- and INH-resistant antigenic fractions some bands of 14.4 and 45 kDa as immunogenic were common. Moreover, four bands of RIF-resistant TB antigen fractions (16, 19, 21, and 45 KDa) and one band of INH-resistant TB (about 26 KDa) were detected as diagnostic antigens. This study suggests that the Western blot is an accurate test to survey INH- and RIF-resistant TB antigens of M. tuberculosis infection. These findings indicate that MDR-TB diagnosis (based on Ag detection) could be useful in the identification of disease stages that precede symptomatic and microbiologically positive TB, such as subclinical and incipient TB.

  13. Solgel-hydrothermal synthesis of Tb/Tourmaline/TiO2 nano tubes and enhanced photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Huang, Fengping; Guo, Yuyu; Wang, Shuai; Zhang, Shuang; Cui, Mengli

    2017-02-01

    In this study, we synthesized Tb/Tourmaline/TiO2 nano tubes (NTs) through a solgel-hydrothermal method. The as-prepared samples were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectromicroscope, scanning electron microscopy, transmission electron microscopy and UV-vis diffuse reflectance spectroscopy. The resulting Tb/Tourmaline/TiO2 NTs exhibited higher photocatalytic activity than pure TiO2 and TiO2 nano particles (NPs) in the degradation of menthyl orange under UV-light. Results revealed that doping rare earth element Tb could narrow the wide band gap of TiO2 and tourmaline could trap the photogenerated electron of TiO2 to inhibit the recombination of photogenerated electron-hole pairs.

  14. Rate of tuberculosis infection in children and adolescents with household contact with adults with active pulmonary tuberculosis as assessed by tuberculin skin test and interferon-gamma release assays.

    PubMed

    Ferrarini, M A G; Spina, F G; Weckx, L Y; Lederman, H M; De Moraes-Pinto, M I

    2016-03-01

    Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT.TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69·5% and 9·5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57·6% by T-SPOT.TB, and 59·3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83·1% and 92·8% in the exposed and control groups, respectively. In the exposed group, T-SPOT.TB added four TB diagnoses [16%, 95% confidence interval (CI) 1·6-30·4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24·7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6·9; >60 days: OR 27·0] and sleeping in the same room as an adult with active TB (OR 5·2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI.

  15. Screening for tuberculosis infection among newly arrived asylum seekers: Comparison of QuantiFERON®TB Gold with tuberculin skin test

    PubMed Central

    Winje, Brita Askeland; Oftung, Fredrik; Korsvold, Gro Ellen; Mannsåker, Turid; Jeppesen, Anette Skistad; Harstad, Ingunn; Heier, Berit Tafjord; Heldal, Einar

    2008-01-01

    Background QuantiFERON®TB Gold (QFT) is a promising blood test for tuberculosis infection but with few data so far from immigrant screening. The aim of this study was to compare results of QFT and tuberculin skin test (TST) among newly arrived asylum seekers in Norway and to assess the role of QFT in routine diagnostic screening for latent tuberculosis infection. Methods The 1000 asylum seekers (age ≥ 18 years) enrolled in the study were voluntarily recruited from 2813 consecutive asylum seekers arriving at the national reception centre from September 2005 to June 2006. Participation included a QFT test and a questionnaire in addition to the mandatory TST and chest X-ray. Results Among 912 asylum seekers with valid test results, 29% (264) had a positive QFT test whereas 50% (460) tested positive with TST (indurations ≥ 6 mm), indicating a high proportion of latent infection within this group. Among the TST positive participants 50% were QFT negative, whereas 7% of the TST negative participants were QFT positive. There was a significant association between increase in size of TST result and the likelihood of being QFT positive. Agreement between the tests was 71–79% depending on the chosen TST cut-off and it was higher for non-vaccinated individuals. Conclusion By using QFT in routine screening, further follow-up could be avoided in 43% of the asylum seekers who would have been referred if based only on a positive TST (≥ 6 mm). The proportion of individuals referred will be the same whether QFT replaces TST or is used as a supplement to confirm a positive TST, but the number tested will vary greatly. All three screening approaches would identify the same proportion (88–89%) of asylum seekers with a positive QFT and/or a TST ≥ 15 mm, but different groups will be missed. PMID:18479508

  16. Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis.

    PubMed

    Williams, Ann; Hatch, Graham J; Clark, Simon O; Gooch, Karen E; Hatch, Kim A; Hall, Graham A; Huygen, Kris; Ottenhoff, Tom H M; Franken, Kees L M C; Andersen, Peter; Doherty, T Mark; Kaufmann, Stefan H E; Grode, Leander; Seiler, Peter; Martin, Carlos; Gicquel, Brigitte; Cole, Stewart T; Brodin, Priscille; Pym, Alexander S; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian; Parish, Tanya; Smith, Debbie; Stoker, Neil G; Lowrie, Douglas B; Källenius, Gunilla; Svenson, Stefan; Pawlowski, Andrzej; Blake, Karen; Marsh, Philip D

    2005-01-01

    The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.

  17. Usefulness and limitations of QuantiFERON-TB Gold in Japanese rheumatoid arthritis patients: proposal to decrease the lower cutoff level for assessing latent tuberculosis infection.

    PubMed

    Maeda, Tomoyo; Banno, Shogo; Maeda, Shinji; Naniwa, Taio; Hayami, Yoshihito; Watanabe, Maiko; Itoh, Rei; Sato, Shigeki; Ueda, Ryuzo

    2010-02-01

    We aimed to determine the sensitivity and specificity of QuantiFERON-TB Gold (QFT-G) in Japanese rheumatoid arthritis (RA) patients with a past history of tuberculosis (TB). We assessed whether it is possible to decrease the cutoff using receiver operating characteristic (ROC) analysis. We evaluated chest computed tomography (CT) findings, prior history of treatment, and contact with active TB in 370 RA patients. Forty-nine patients before initiation of treatment with tumor necrosis factor (TNF) inhibitors were divided into two groups: 22 with a past history of TB and 27 without. We estimated the efficacy of QFT-G compared with the tuberculin skin test and antituberculosis (anti-TB) glycolipid antigen antibody. QFT-G was positive (>or=0.35 IU/ml) in 13.6% with a past history of TB, increasing to 27.3% at the intermediate range cutoff of 0.1 IU/ml. The sensitivity and specificity of QFT-G was 0.27 and 1.00, respectively, at 0.1 IU/ml. Using ROC analysis, the area under the curve (AUC) of QFT-G but not for the other two tests was significantly large. QFT-G is a useful diagnostic method due to its superior specificity, but the use of a cutoff value of 0.35 IU/ml will likely result in an underestimate. We propose that a lower interferon-gamma (IFN-gamma) titer of 0.1 IU/ml be adopted when deciding to administer anti-TB drugs before initiation of TNF inhibitors.

  18. Changes in CD4+ T-cells and HIV RNA resulting from combination of anti-TB therapy with Dzherelo in TB/HIV dually infected patients

    PubMed Central

    Nikolaeva, Lyudmila G; Maystat, Tatyana V; Masyuk, Lilia A; Pylypchuk, Volodymyr S; Volyanskii, Yuri L; Kutsyna, Galyna A

    2008-01-01

    The open-label, phase II clinical trial of antituberculosis therapy (ATT) with or without oral immunomodulator Dzherelo (Immunoxel) was conducted in TB/HIV coinfected, antiretroviral therapy naïve patients to evaluate the effect on CD4 T-lymphocyte counts and viral load. The arm A (n = 20) received isoniazid (H); rimfapicin (R); pyrazinamide (Z); streptomycin (S); and ethambutol (E), and arm B (n = 20) received 50 drops of Dzherelo twice per day in addition to HRZSE. After 2 months in 90% of Dzherelo patients the population of absolute CD4 T-cells expanded by an average of 71.2% (from 174 to 283 cells/μl; P = 0.00003), but declined in ATT-alone patients (182 to 174; P = 0.34). The ratio between CD4/CD8 cells deteriorated in 80% of individuals in arm A (1.213 > 0.943; P = 0.002), but improved in the same proportion of patients in arm B (1.244 > 1.536; P = 0.007). The number of total CD3+ lymphocytes rose from 728 to 921 cells in arm B (P = 0.025) whereas it fell from 650 to 585 cells in arm A (P = 0.25). The viral load, as measured by plasma RNA-PCR, decreased in 70% of Dzherelo recipients (2.174 > 1.558 copies/ml; P = 0.002), but increased in 70% of HRZSE only receivers (1.907 > 2.076 copies/ml; P = 0.03). Dzherelo has a favorable effect on the immune status and viral burden in TB/HIV patients when given as an immunomodulating adjunct to ATT. PMID:19920896

  19. Electrocatalysis of carbon black- or poly(diallyldimethylammonium chloride)-functionalized activated carbon nanotubes-supported Pd-Tb towards methanol oxidation in alkaline media

    NASA Astrophysics Data System (ADS)

    Wang, Li; Wang, Yi; Li, An; Yang, Yunshang; Tang, Qinghu; Cao, Hongbin; Qi, Tao; Li, Changming

    2014-07-01

    The Pd-Tb/C catalysts with different Pd/Tb ratios were synthesized by a simple simultaneous reduction reaction with sodium borohydride in aqueous solution. The structure and morphology of those catalysts had been characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The electrocatalytic performance of those catalysts for methanol oxidation in alkaline media was investigated using cyclic voltammetry (CV), linear sweep voltammetry (LSV) and CO stripping experiments. It is found that the 20%Pd-1%Tb/C catalyst has a higher catalytic activity than the 20%Pd/C catalyst, but the effect of Tb cannot be explained by a bi-functional mechanism. According to the X-Ray photoelectron spectroscopy (XPS) analyses, it is suggested that the higher content of metallic Pd caused by the addition of Tb contributes to the better catalytic activity of 20%Pd-1%Tb/C. Based on the good electrocatalytic performance of 20%Pd-1%Tb/C, the 20%Pd-1%Tb catalyst supported on poly(diallyldimethylammonium chloride) (PDDA)-functionalized activated carbon nanotubes was prepared, and it exhibits a better catalytic activity. The improvement mainly results from the further increase of metallic Pd due to the presence of PDDA.

  20. Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals.

    PubMed

    Bai, Xue-juan; Liang, Yan; Yang, You-rong; Feng, Jin-dong; Luo, Zhan-peng; Zhang, Jun-Xian; Wu, Xue-qiong

    2016-02-01

    Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-γ in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals.

  1. Analysis of latent tuberculosis infection treatment adherence among refugees and other patient groups referred to the Baltimore City Health Department TB clinic, February 2009-March 2011.

    PubMed

    Nuzzo, Jennifer B; Golub, Jonathan E; Chaulk, Patrick; Shah, Maunank

    2015-02-01

    We sought to determine the proportion of refugee patients at the Baltimore City Health Department Tuberculosis program (BCHD-TB) successfully completing latent tuberculosis infection (LTBI) treatment, as compared to other referral groups, and to identify factors associated with treatment completion. We completed a retrospective cohort analysis of individuals referred to BCHD-TB program for LTBI care between February 1, 2009 and March 31, 2011. Among 841 patients evaluated by BCHD-TB and diagnosed with LTBI, 81% of refugees, 50% of non-refugee foreign-born, and 35% of US-born patients completed LTBI treatment. In multivariate analysis, refugees had greater odds of LTBI treatment completion (Adjusted Odds Ratio 7.2; 95% CI 4.2-12.4, p < 0.001) compared to US-born individuals adjusting for age, gender, and treatment regimen. Overall, LTBI treatment completion remains suboptimal. At BCHD-TB, LTBI treatment completion was significantly higher among refugees than other referral groups. Additional efforts are needed to optimize LTBI care, and future efforts may need to be tailored for different risk groups.

  2. On the saturation of Tb phosphors under cathode-ray excitation. I. Excited-state absorption in Tb-activated phosphor powders

    NASA Astrophysics Data System (ADS)

    Nieuwesteeg, K. J. B. M.; Raue, R.; Busselt, W.

    1990-12-01

    Optical transitions between the 5D4 excited state of the Tb3+ (4f)8 configuration and the crystal-field split components of the (4f)7(5d) configuration are observed using high-resolution laser excitation of Tb-doped powder samples at room temperature. Excited-state absorption spectra of Tb3+ in YAG, YAGaG, Y2SiO5, and LaOBr are presented. Superimposed on the broadband excitation spectrum of these transitions we find the relatively narrow 4f→4f lines. We present a theoretical model for interpreting the 4f→5d transitions, which predicts a strict proportionality between the (4f)8 5D4→(4f)7(5d) and the (4f)8 7F6→(4f)7(5d) transitions. This model is used to estimate the optical-absorption cross section for the former transitions. Although the terminating 4f levels lie at the same energy as the 5d bands, the 4f→4f transitions can be interpreted on the basis of the Judd-Ofelt theory. We derived a method for calibration of the Tb3+ 4f→5d fluorescence-excitation spectra from powder samples. For YAG:Tb, the resulting optical cross sections were confirmed by direct-absorption measurements on a Tb3+ -doped epitaxial YAG layer. To our knowledge, this is the first time that the probabilities for excited-state absorption to highly excited 5d and 4f states in Tb3+ have been obtained theoretically and experimentally from Tb-doped powder materials.

  3. A model dynamic for effect latent population to co-epidemic of HIV-TB

    NASA Astrophysics Data System (ADS)

    Jafaruddin, Sutimin, Ariyanto

    2014-02-01

    Threat of co-epidemic HIV-TB is a major problem that must be faced by countries around the world. In 2011, approximately about one-third of the 34 million people living with HIV worldwide is infected with latent TB. Persons co-infected with TB and HIV are 21-34 times more likely to develop active TB disease than persons without HIV. In this paper, we develop a simple co-epidemic model of HIV-TB. We calculate the basic reproduction ratio at the disease-free equilibrium, and the quasi-disease-free equilibrium, which we define as the existence of one disease along with the complete eradication of the other disease, and the co-infection equilibrium for specific conditions. Using this model, we study co-epidemic HIV-TB in Indonesia based on demography data in 2009 to explore the effects of hypothetical prevention and treatment scenarios. Our simple model of co-epidemic HIV-TB describes the importance of including the effects of HIV on TB and vice versa on the transmission and progression of the HIV and TB epidemic.

  4. Declining tuberculosis notification trend associated with strengthened TB and expanded HIV care in Swaziland.

    PubMed

    Haumba, S; Dlamini, T; Calnan, M; Ghazaryan, V; Smith-Arthur, A E; Preko, P; Ehrenkranz, P

    2015-06-21

    This retrospective observational review documents the efforts of the Swaziland National Tuberculosis (TB) Control Programme between 2004 and 2014. The objective is to describe the disparity between actual declines in case notification and increases in estimated incidence. The review of policies and practices shows the most influential factors associated with the decrease in TB case notification to be an increase in access to antiretroviral therapy for co-infected TB patients, the general success of TB and human immunodeficiency virus service integration in the country and improvements in implementation of all components of directly observed treatment, active case finding, and rapid diagnosis using new technologies.

  5. Optimal Control for TB disease with vaccination assuming endogeneous reactivation and exogeneous reinfection

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.

    2016-06-01

    Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.

  6. Voices of decision makers on evidence-based policy: A case of evolving TB/HIV co-infection policy in India.

    PubMed

    Reddy, K Srikanth; Sahay, Seema

    2016-01-01

    This study explores decision makers' perspectives on evidence-based policy (EBP) development using the case of TB/HIV co-infection in India. Twelve in-depth interviews were conducted with purposively selected key national and international policy decision makers in India. Verbatim transcripts were processed and analysed thematically using QSR (NUD*IST 6). The decision makers were unequivocal in recognizing the TB/HIV co-infection as an important public health issue in India and stated the problem to be different than Africa. The need of having a "third programme" for co-infection was not felt. According to them, the public health management of this co-infection must be within the realm of these two programmes. The study also emphasized on decision makers' perspectives on evidence and the process of utilization of evidence for decision-making for co-infection. Study findings showed global evidence was not always accepted by the decision makers and study shows several examples of decision makers demanding local evidence for policy decisions. Decision makers did make interim policies based on global evidence but most of the time their mandate was to get local evidence. Thus, operations research/implementation science especially multi-centric studies emerge as important strategy for EBP development. Researcher-policy maker interface was a gap where role of researcher as aggressive communicator of research findings was expected.

  7. A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults.

    PubMed

    Minassian, Angela M; Rowland, Rosalind; Beveridge, Natalie E R; Poulton, Ian D; Satti, Iman; Harris, Stephanie; Poyntz, Hazel; Hamill, Matthew; Griffiths, Kristin; Sander, Clare R; Ambrozak, David R; Price, David A; Hill, Brenna J; Casazza, Joseph P; Douek, Daniel C; Koup, Richard A; Roederer, Mario; Winston, Alan; Ross, Jonathan; Sherrard, Jackie; Rooney, Guy; Williams, Nicola; Lawrie, Alison M; Fletcher, Helen A; Pathan, Ansar A; McShane, Helen

    2011-01-01

    Objectives Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis. Results MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited.

  8. Tuberculosis infection control in health facilities in Lithuania: lessons learnt from a capacity support project.

    PubMed

    Turusbekova, N; Ljungqvist, I; Davidavičiene, E; Mikaityte, J; van der Werf, M J

    2016-03-21

    Tuberculosis (TB) infection control (IC) is key in controlling TB transmission in health facilities in Lithuania. This article presents a project that aimed at supporting health care facilities in Lithuania in implementing TB-IC. The project consisted of 1) facility TB-IC assessments, 2) development of facility TB-IC plans, 3) TB-IC training and 4) site visits. We assessed the impact of these activities through a self-assessment questionnaire. The project resulted in limited improvements. Most progress was seen in administrative and managerial activities. Possible reasons for the limited improvements are challenges with funding and the lack of supportive legislation and a national TB-IC plan.

  9. DNA-Launched Alphavirus Replicons Encoding a Fusion of Mycobacterial Antigens Acr and Ag85B Are Immunogenic and Protective in a Murine Model of TB Infection.

    PubMed

    Dalmia, Neha; Klimstra, William B; Mason, Carol; Ramsay, Alistair J

    2015-01-01

    There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb) infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis (TB). Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines. Novel formulations and delivery strategies to improve the immunogenicity of DNA-based vaccines have recently been evaluated, and have shown varying degrees of success. In the present study, we evaluated DNA-launched Venezuelan equine encephalitis replicons (Vrep) encoding a novel fusion of the mycobacterial antigens α-crystallin (Acr) and antigen 85B (Ag85B), termed Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T cell responses that persisted for at least 10 wk post-immunization. Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell responses in the lung tissues, the primary site of infection, and inhibited bacterial growth in both the lungs and spleens following aerosol challenge with Mtb. DNA-launched Vrep may, therefore, represent an effective approach to the development of gene-based vaccines against TB, particularly as components of heterologous prime-boost strategies or as BCG boosters.

  10. HIV-TB co-infection in children: associated factors and access to HIV services in Lagos, Nigeria.

    PubMed

    Daniel, O J; Adejumo, O A; Gidado, M; Abdur-Razzaq, H A; Jaiyesimi, E O

    2015-09-21

    Contexte : Le virus de l'immunodéficience humaine (VIH) et la tuberculose (TB) sont les causes majeures de décès dû à une maladie infectieuse dans le monde. L'Organisation Mondiale de la Santé estime que la prévalence du VIH parmi les enfants atteints de TB dans des pays à prévalence modérée à élevée va de 10% à 60%. Cette étude a eu pour but de déterminer l'accès aux services VIH pour les enfants coinfectés par TB-VIH.Méthodes : Une revue rétrospective des données d'enfants ayant eu un diagnostic de TB dans l'état de Lagos au Nigeria entre le 1(e) janvier 2012 et le 31 décembre 2013.Résultats : Un total de 1199 enfants âgés de 0 à 14 ans ont eu un diagnostic de TB. Parmi eux, 1095 (91,3%) ont eu un test VIH, dont 320 (29,2%) ont été positifs. Le ratio garçon/fille de coinfection TB-VIH a été de 1:0,9. Sur les 320 enfants coinfectés TB-VIH, 57 (17,8%), 86 (26,9%) et 186 (58,1%) respectivement avaient <1 an, 1–4 ans et 5–14 ans. Sur les 320 enfants coinfectés TB-VIH, 186 (58,1%) ont débuté le cotrimoxazole (CPT) tandis que 151 (47,2%) étaient sous traitement antirétroviral (ART). La mise sous ART n'a pas été significativement plus élevée dans les structures où les services TB-VIH se trouvaient au même endroit (P > 0,05).Conclusion : La mise sous CPT et ART a été faible. Il est nécessaire d'intensifier les efforts d'amélioration de l'accès aux services VIH à Lagos, Nigeria.

  11. Cidofovir Activity against Poxvirus Infections

    PubMed Central

    Andrei, Graciela; Snoeck, Robert

    2010-01-01

    Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Cidofovir (CDV) has broad-spectrum activity against DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among poxviruses, cidofovir has shown in vitro activity against orthopox [vaccinia, variola (smallpox), cowpox, monkeypox, camelpox, ectromelia], molluscipox [molluscum contagiosum] and parapox [orf] viruses. The anti-poxvirus activity of cidofovir in vivo has been shown in different models of infection when the compound was administered either intraperitoneal, intranasal (aerosolized) or topically. In humans, cidofovir has been successfully used for the treatment of recalcitrant molluscum contagiosum virus and orf virus in immunocompromised patients. CDV remains a reference compound against poxviruses and holds potential for the therapy and short-term prophylaxis of not only orthopox- but also parapox- and molluscipoxvirus infections. PMID:21994641

  12. Cidofovir Activity against Poxvirus Infections.

    PubMed

    Andrei, Graciela; Snoeck, Robert

    2010-12-01

    Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Cidofovir (CDV) has broad-spectrum activity against DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among poxviruses, cidofovir has shown in vitro activity against orthopox [vaccinia, variola (smallpox), cowpox, monkeypox, camelpox, ectromelia], molluscipox [molluscum contagiosum] and parapox [orf] viruses. The anti-poxvirus activity of cidofovir in vivo has been shown in different models of infection when the compound was administered either intraperitoneal, intranasal (aerosolized) or topically. In humans, cidofovir has been successfully used for the treatment of recalcitrant molluscum contagiosum virus and orf virus in immunocompromised patients. CDV remains a reference compound against poxviruses and holds potential for the therapy and short-term prophylaxis of not only orthopox- but also parapox- and molluscipoxvirus infections.

  13. Predictors and Timing of ATT Initiation among HIV-TB Patients at ART Centers of Karnataka, India: Two Year Follow-Up

    PubMed Central

    Shastri, Suresh; Nagaraja, Sharath Burugina; Tripathy, Jaya Prasad; Satyanarayana, Srinath; Rewari, Bharat Bhushan

    2015-01-01

    Background In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states. Objectives To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients. Methods Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011. Results A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome. Conclusions The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment. PMID:26394397

  14. HIV-infected presumptive tuberculosis patients without tuberculosis: How many are eligible for antiretroviral therapy in Karnataka, India?

    PubMed

    Kumar, Ajay M V; Singarajipura, Anil; Naik, Balaji; Guddemane, Deepak K; Patel, Yogesh; Shastri, Suresh; Kumar, Sunil; Deshmukh, Rajesh; Rewari, B B; Harries, Anthony David

    2017-03-01

    For certain subgroups within people living with the human immunodeficiency virus (HIV) [active tuberculosis (TB), pregnant women, children <5years old, and serodiscordant couples], the World Health Organization recommends antiretroviral therapy (ART) irrespective of CD4 count. Another subgroup which has received increased attention is "HIV-infected presumptive TB patients without TB". In this study, we assess the proportion of HIV-infected presumptive TB patients eligible for ART in Karnataka State (population 60million), India. This was a cross-sectional analysis of data of HIV-infected presumptive TB patients diagnosed in May 2015 abstracted from national TB and HIV program records. Of 42,585 presumptive TB patients, 28,964 (68%) were tested for HIV and 2262 (8%) were HIV positive. Of the latter, 377 (17%) had active TB. Of 1885 "presumptive TB patients without active TB", 1100 (58%) were already receiving ART. Of the remaining 785 who were not receiving ART, 617 (79%) were assessed for ART eligibility and of those, 548 (89%) were eligible for ART. About 90% of "HIV-infected presumptive TB patients without TB" were eligible for ART. This evidence supports a public health approach of starting all "HIV-infected presumptive TB patients without TB" on ART irrespective of CD4 count in line with global thinking about 'test and treat'.

  15. Modulation of pro- and anti-inflammatory cytokines in active and latent tuberculosis by coexistent Strongyloides stercoralis infection.

    PubMed

    George, Parakkal Jovvian; Pavan Kumar, Nathella; Jaganathan, Jeeva; Dolla, Chandrakumar; Kumaran, Paul; Nair, Dina; Banurekha, Vaithilingam V; Shen, Kui; Nutman, Thomas B; Babu, Subash

    2015-12-01

    Helminth infections are known to induce modulation of both innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating systemic cytokine responses in active and latent tuberculosis (LTB) is not known. To define the systemic cytokine levels in helminth-TB coinfection, we measured the circulating plasma levels of Type 1, Type 2, Type 17, other pro-inflammatory and regulatory cytokines in individuals with active TB (ATB) with or without coexistent Strongyloides stercoralis (Ss) infection by multiplex ELISA. Similarly, we also measured the same cytokine levels in individuals with LTB with or without concomitant Ss infection in a cross-sectional study. Our data reveal that individuals with ATB or LTB and coexistent Ss infection have significantly lower levels of Type 1 (IFNγ, TNFα and IL-2) and Type 17 (IL-17A and IL-17F) cytokines compared to those without Ss infection. In contrast, those with ATB and LTB with Ss infection have significantly higher levels of the regulatory cytokines (IL-10 and TGFβ), and those with LTB and Ss infection also have significantly higher levels of Type 2 cytokines (IL-4, IL-5 and IL-13) as well. Finally, those with LTB (but not ATB) exhibit significantly lower levels of other pro-inflammatory cytokines (IFNα, IFNβ, IL-6, IL-12 and GM-CSF). Our data therefore reveal a profound effect of Ss infection on the systemic cytokine responses in ATB and LTB and indicate that coincident helminth infections might influence pathogenesis of TB infection and disease.

  16. Tuberculosis incidence in developing countries with high prevalence of HIV infection.

    PubMed

    Bermejo, A; Veeken, H; Berra, A

    1992-10-01

    95% of tuberculosis (TB) cases in the world live in developing countries. HIV infection greatly increases the risk of developing active TB among those with latent Mycobacterium tuberculosis infection. Thus researchers have used data from existing research to develop a mathematical model to gauge the increase in TB incidence in developing countries while considering rising HIV prevalence among adults. They look at 2 groups with sizable differences in risk of acquiring TB: adults with both HIV and M. tuberculosis infections and all other adults. The researchers plot the expected increase in TB incidence and percentage of TB cases that also have HIV infection against HIV prevalence. According to the model, when the prevalence of HIV infection hits 13% of adults in developing countries, the number of new TB cases doubles. Most of this increase will occur in areas that already lack diagnostic services, drugs, hospital beds, and other needed supplies. TB chemoprophylaxis treatment of HIV-positive people could result in a lower increase in TB incidence, however. WHO has set a goal of 50% reduction in TB incidence by 2002. Public health officials could use this model to plan TB control programs to bring about a reduction in the increase. Even though TB control programs can help stem the projected increase, it will be very difficult for developing countries with high HIV prevalence to hold back the projected rise in TB incidence. Developing countries must take considerable appropriate action soon to prevent doubling of TB incidence as HIV prevalence nears 13% of adults.

  17. Decreasing cost effectiveness of testing for latent TB in HIV in a low TB incidence area.

    PubMed

    Capocci, Santino; Smith, Colette; Morris, Stephen; Bhagani, Sanjay; Cropley, Ian; Abubakar, Ibrahim; Johnson, Margaret; Lipman, Marc

    2015-07-01

    Testing for latent tuberculosis infection (LTBI) in HIV-infected persons in low tuberculosis (TB) incidence areas is often recommended. Using contemporary, clinical data, we report the yield and cost-effectiveness of testing all HIV attendees, two current UK strategies and no LTBI testing. Economic modelling was performed utilising 10-year follow up data from a large HIV clinical cohort. Outcomes were numbers of cases of active TB and incremental cost per quality-adjusted life year (QALY) gained. Between 2000 and 2010, 256 people were treated for TB/HIV co-infection. 72 (28%) occurred ≥3 months after HIV diagnosis and may have been prevented by LTBI testing. Between 2000 and 2005, the incremental cost per QALY gained for the British HIV Association (BHIVA) and UK National Institute of Care Excellence (NICE) strategies, and testing all clinic attendees was €6270, €6998 and €33,473, respectively. These rose to €9332, €32,564 and €74,067, respectively, between 2005 and 2010. Probabilistic sensitivity analysis suggested that at a threshold of €24,000 per additional QALY, the most cost-effective strategies would be NICE or testing all in 2000-2005 and BHIVA during 2005-2010. Both UK testing regimens missed cases but are cost-effective compared with no testing. Using recent data, they all became more expensive, suggesting that alternative or more targeted TB testing strategies must be considered.

  18. New tests will improve detection of latent TB.

    PubMed

    Chapman, Ann L N

    2011-11-01

    In the UK cases of active TB have risen substantially over the past 20 years. This increase has occurred almost exclusively in individuals born outside the UK, who now constitute more than two-thirds of cases. Only around one in ten people who are infected will develop active disease. The remaining 90% are presumed to have latent TB infection (LTBI) where viable mycobacteria are thought to persist for decades, and may reactivate if the host's immune system is weakened. In a country such as the UK with a low incidence of TB, a high proportion of cases result from reactivation of latent TB, rather than transmission by infectious cases. In the past 10 years a novel type of diagnostic test for LTBI has been developed: the interferon-gamma release assays (IGRA). Their major advantage over the tuberculin skin test is that they are not affected by prior BCG vaccination and they have a specificity of well over 90%. These tests are unable to distinguish between active and latent TB infection: this distinction must be performed purely on clinical grounds. Patients with a positive test should be assessed by a clinician with expertise in TB to ensure an appropriate management plan for each patient. The role of IGRAs in diagnosis of active TB is limited since in a patient with suspected active TB a positive result may indicate LTBI in combination with an alternative diagnosis. At a population level screening and chemoprophylaxis contributes usefully to TB control. However, only those under 35 with LTBI should receive prophylaxis. After this age the increasing risks of hepatotoxicity begin to outweigh the diminishing benefits of prophylaxis. The exceptions are healthcare workers, where the benefits are not just to the individual but also extend to their patients, and immunocompromised patients. The IGRAs represent a major development in the diagnosis of LTBI. While currently most of their use is through established TB screening services, it is likely in future that they will

  19. Risk factors associated with Tuberculosis (TB) among people living with HIV/AIDS: A pair-matched case-control study in Guangxi, China

    PubMed Central

    Cui, Zhezhe; Lin, Mei; Nie, Shaofa; Lan, Rushu

    2017-01-01

    Background As one of the poorest provinces in China, Guangxi has a high HIV and TB prevalence, with the annual number of TB/HIV cases reported by health department among the highest in the country. However, studies on the burden of TB-HIV co-infection and risk factors for active TB among HIV-infected persons in Guangxi have rarely been reported. Objective To investigate the risk factors for active TB among people living with HIV/AIDS in Guangxi Zhuang autonomous region, China. Methods A surveillance survey was conducted of 1 019 HIV-infected patients receiving care at three AIDS prevention and control departments between 2013 and 2015. We investigated the cumulative prevalence of TB during 2 years. To analyze risk factors associated with active TB, we conducted a 1:1 pair-matched case-control study of newly reported active TB/HIV co-infected patients. Controls were patients with HIV without active TB, latent TB infection or other lung disease, who were matched with the case group based on sex and age (± 3 years). Results A total of 1 019 subjects were evaluated. 160 subjects (15.70%) were diagnosed with active TB, including 85 clinically diagnosed cases and 75 confirmed cases. We performed a 1:1 matched case-control study, with 82 TB/HIV patients and 82 people living with HIV/AIDS based on surveillance site, sex and age (±3) years. According to multivariate analysis, smoking (OR = 2.996, 0.992–9.053), lower CD 4+ T-cell count (OR = 3.288, 1.161–9.311), long duration of HIV-infection (OR = 5.946, 2.221–15.915) and non-use of ART (OR = 7.775, 2.618–23.094) were independent risk factors for TB in people living with HIV/AIDS. Conclusion The prevalence of active TB among people living with HIV/AIDS in Guangxi was 173 times higher than general population in Guangxi. It is necessary for government to integrate control planning and resources for the two diseases. Medical and public health workers should strengthen health education for TB/HIV prevention and

  20. Gene expression profiles of bronchoalveolar cells in Pulmonary TB

    PubMed Central

    Raju, Bindu; Hoshino, Yoshihiko; Belitskaya-Lévy, Ilana; Dawson, Rod; Ress, Stanley; Gold, Jeffrey A.; Condos, Rany; Pine, Richard; Brown, Stuart; Nolan, Anna; Rom, William N.; Weiden, Michael D.

    2008-01-01

    The host response to Mycobacterium tuberculosis includes macrophage activation, inflammation with increased immune effector cells, tissue necrosis and cavity formation, and fibrosis, distortion, and bronchiectasis. To evaluate the molecular basis of the immune response in the lungs of patients with active pulmonary tuberculosis (TB), we used bronchoalveolar lavage to obtain cells at the site of infection. Affymetrix Genechip micro-arrays and cDNA nylon filter microarrays interrogated gene expression in BAL cells from 11 healthy controls and 17 patients with active pulmonary TB. We found altered gene expression for 69 genes in TB versus normal controls that included cell surface markers, cytokines, chemokines, receptors, transcription factors, and complement components. In addition, TB BAL cell gene expression patternssegregated into 2 groups: one suggestive of a T helper type 1 (Th1) cellular immune response with increased STAT-4, IFN-γ receptor, and MIG expression with increased IFN-γ protein levels in BAL fluid; the other group displayed characteristics of Th2 immunity with increased STAT-6, CD81, and IL-10 receptor expression. We were able to demonstrate that a Th2 presentation could change to a Th1 pattern after anti-tuberculous treatment in one TB patient studied serially. These gene expression data support the conclusion that pulmonary TB produces a global change in the BAL cell transcriptome with manifestations of either Th1 or Th2 immunity. PMID:17921069

  1. Measurement of the MACS of 159Tb(n, γ) at kT = 30 keV by Activation

    NASA Astrophysics Data System (ADS)

    Praena, J.; Mastinu, P. F.; Pignatari, M.; Quesada, J. M.; Capote, R.; Morilla, Y.

    2014-06-01

    The measurement of the Maxwellian-Averaged Cross-Section (MACS) of the 159Tb(n, γ) reaction at kT = 30 keV by the activation technique is presented. An innovative method for the generation of Maxwellian neutron spectra at kT = 30 keV is used. An experimental value of 2166 ± 181 mb agrees well with the MACS value derived from the ENDF/B-VII.1 evaluation, but is higher than KADoNiS recommended value of 1580 ± 150 mb. Astrophysical implications are studied.

  2. Impact of mycobacterial culture among HIV-infected adults with presumed TB in Uganda: a prospective cohort study.

    PubMed

    Semitala, F C; Chaisson, L H; den Boon, S; Walter, N; Cattamanchi, A; Awor, M; Katende, J; Huang, L; Joloba, M; Albert, H; Kamya, M R; Davis, J L

    2015-06-21

    Contexte : La mise en œuvre de nouvelles stratégies de diagnostic de la tuberculose (TB) dans les contextes de ressources limitées constitue un défi. Nous avons mesuré l'impact des cultures mycobactériennes en milieu solide et liquide sur les pratiques de traitement des patients ayant une évaluation de la TB à Kampala, Ouganda.Méthodes : Nous avons enrôlé des patients adultes consécutifs à frottis négatif, positifs pour le virus de l'immunodéficience humaine avec toux de ⩾2 semaines, de septembre 2009 à avril 2010. Les techniciens de laboratoire ont réalisé des cultures mycobactériennes en milieu solide et liquide. Nous avons comparé les décisions de traitement empirique aux cultures en milieu solide et liquide en termes de rendement diagnostique et de délai d'obtention des résultats et nous avons évalué l'impact sur la gestion des patients.Résultats : Des 200 patients enrôlés, 26 (13%) avaient une TB confirmée par culture, 22 (85%) par culture en milieu solide seule, 2 (8%) par culture en milieu liquide seul et 2 (8%) par culture à la fois en milieu solide et liquide. Trente-quatre patients ont reçu un traitement de TB empirique, mais seulement 10 (29%) ont eu une TB à culture positive. Le délai médian d'obtention d'un résultat de culture positive en milieu solide a été de 92 jours (IQR 69–148). Le délai médian d'obtention d'un résultat de culture positive en milieu liquide a été de 106 jours (IQR 66–157). Aucun patient n'a commencé un traitement à la suite d'un résultat de culture positive en milieu liquide.Conclusion : L'introduction de la culture mycobactérienne n'a pas influencé les soins aux patients bénéficiant d'une évaluation de TB à Kampala, Ouganda. Il est nécessaire d'être attentif aux facteurs contextuels entourant la mise en œuvre afin d'assurer une introduction effective de nouvelles stratégies de tests dans les pays à faible revenu.

  3. Modification of the QuantiFERON-TB Gold (In-Tube) assay for the diagnosis of Mycobacterium bovis infection in African buffaloes (Syncerus caffer).

    PubMed

    Parsons, Sven D C; Cooper, David; McCall, Alicia J; McCall, Warren A; Streicher, Elizabeth M; le Maitre, Nicholas C; Müller, Annélle; Gey van Pittius, Nicolaas C; Warren, Robin M; van Helden, Paul D

    2011-07-15

    African buffaloes (Syncerus caffer) are the most significant wildlife maintenance hosts of Mycobacterium bovis, the causative organism of bovine tuberculosis (BTB). Current diagnostic tests for the detection of M. bovis infection in free-ranging buffaloes have numerous limitations and we wished to evaluate a modification to a human TB assay, the QuantiFERON-TB Gold (In-Tube) assay (QFT), as a practical diagnostic test for BTB in buffaloes. One hundred and seventy-five buffaloes were tested using the single intradermal comparative tuberculin test (SICTT) and a modified QFT (mQFT). An appropriate cut-off point for the mQFT was derived from SICTT results using receiver operator characteristic curve analysis. Twenty-six SICTT-positive buffaloes were killed and subjected to necropsy, and selected tissues were processed for mycobacterial culture and speciation. An optimal cut-off point for the mQFT was calculated as 66pg/ml. The assay correctly detected 39/40 SICTT-positive buffaloes and 129/134 TST-negative buffaloes and M. bovis was cultured from 21/26 slaughtered SICTT/mQFT-positive animals. The mQFT shows promise as a practical test for M. bovis infection in buffaloes and shows a sensitivity and specificity at least similar to that of the TST.

  4. Comparison of the QuantiFERON-TB Gold In-Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation.

    PubMed

    Moon, S M; Lee, S-O; Choi, S-H; Kim, Y S; Woo, J H; Yoon, D H; Suh, C; Kim, D-Y; Lee, J-H; Lee, Je-H; Lee, K-H; Kim, S-H

    2013-02-01

    A total of 244 patients including 100 (41%) autologous hematopoietic stem cell transplant (HCT) recipients and 144 (59%) allogeneic HCT recipients were enrolled over a 28-month period. During the study period, no prophylaxis for latent tuberculosis (TB) infection was administrated. Of these, 201 (82%) had Bacillus Calmette-Guérin (BCG) scars or prior histories of BCG vaccination. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed simultaneously in all 244 patients. TST indurations were ≥ 5 mm in 39 of these patients (15%), and in 25 (10%) indurations were ≥ 10 mm. In addition, 40 (16%) had positive QFT-GIT outcomes, and 34 (14%) indeterminate outcomes. If the 34 patients with indeterminate QFT-GIT results were excluded from the overall agreement analysis, the agreement between the TST results (induration size ≥ 5 mm) and the QFT-GIT results in the 210 patients with clear QFT results was poor (κ = 0.08, 95% confidence interval [CI] -0.06 to 0.24), as it was for the patients with indurations ≥ 10 mm (κ = 0.15, 95% CI -0.004 to 0.31). During follow up, 2 patients developed TB after HCT. The incidence of TB in the patients with positive QFT-GIT outcomes was 2.80 per 100 person-years (95% CI 0.07-15.81), whereas among those with positive TST (≥ 5 mm) results, it was 0 per 100 person-years (95% CI 0-8.00). However, this finding should be cautiously interpreted because of the relatively short follow up and the fact that the sample size of the study cohort did not have adequate power. In conclusion, our data show that, although the frequencies of positive outcomes in the 2 TB screening tests were similar, the overall agreement between the TST and the QFT-GIT test was poor, regardless of BCG vaccination history.

  5. Staying on Track with TB Medicine

    MedlinePlus

    ... if you have other health problems like HIV infection or diabetes. • You will need treatment, whether you have TB ... disease along with other health problems, like HIV infection or diabetes, you may need to have blood, phlegm, or ...

  6. Screening for latent tuberculosis infection in psoriasis and psoriatic arthritis patients in a tuberculosis-endemic country: a comparison of the QuantiFERON®-TB Gold In-Tube test and tuberculin skin test.

    PubMed

    Duman, Nilay; Ersoy-Evans, Sibel; Karadağ, Omer; Aşçıoğlu, Sibel; Sener, Burçin; Kiraz, Sedat; Sahin, Sedef

    2014-10-01

    Since the introduction of biologic therapies for tuberculosis (TB), screening for latent TB infection has increased in importance, especially in countries in which TB is endemic. The aim of this study was to evaluate the effect of psoriasis on tuberculin skin test (TST) results and to compare two TB screening tests, the TST and QuantiFERON(®)-TB Gold In-Tube (QFT-GIT) test, in psoriasis and psoriatic arthritis (PA) patients living in a TB-endemic country (Turkey). This prospective study included 61 psoriasis and 40 PA patients, and 58 healthy controls. Demographic data, medical history, human immunodeficiency virus (HIV) status, level of education, smoking status, exposure to TB, personal and family histories of TB, and bacillus Calmette-Guérin (BCG) vaccination status were recorded for all participants. The TST and QFT-GIT were performed in all participants. The mean ± standard deviation TST indurations in the patient and control groups were 12.6 ± 6.4 mm and 10.2 ± 6.5 mm, respectively (P = 0.051). The TST positivity rate was higher in patients than in controls (86.1% vs. 37.9%; P < 0.001), whereas QFT-GIT positivity did not differ significantly (patients: 20.8%; controls: 17.2%; P = 0.737). False positive results can lead to unnecessary prophylactic TB treatment; therefore, the cut-off point for TST positivity in psoriasis and PA patients should be re-evaluated, or other tests, such as the QFT-GIT, should be used.

  7. Barriers to managing TB in emergency departments.

    PubMed

    Morton, Rachel

    Improved management of tuberculosis is a key priority for Public Health England due to unacceptably high rates of the disease in the UK, particularly in London and other major cities. A survey of 20 staff in the acute medical unit at Queen Alexandra Hospital, Portsmouth, explored potential barriers to early TB detection and infection control in busy emergency departments. Low awareness and little familiarity with TB among many emergency admissions staff increased the likelihood of transmission from undiagnosed patients in crowded waiting areas. The study suggested regular updates on TB so staff could refresh their knowledge and awareness, and help improve TB detection and infection control.

  8. Snapshot of Quantiferon TB gold testing in Northern Mexico.

    PubMed

    González-Salazar, F; Vargas-Villarreal, J; Garcialuna-Martínez, F J; Rivera, G; Moreno-Treviño, M G; Montfort-Gardeazabal, J M; Garcialuna-Martínez, E

    2011-12-01

    Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection.

  9. Antiretroviral Treatment Scale-Up and Tuberculosis Mortality in High TB/HIV Burden Countries: An Econometric Analysis

    PubMed Central

    Yan, Isabel; Bendavid, Eran; Korenromp, Eline L.

    2016-01-01

    Introduction Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries. Methods We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects. Results Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (p<0.001), and 31% fewer deaths in 2011. TB mortality was higher at higher HIV prevalence (p<0.001), but not related to coverage of isoniazid preventive therapy, cotrimoxazole preventive therapy, or other covariates. Conclusion This econometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data. PMID:27536864

  10. Mass spectrometry imaging of levofloxacin distribution in TB-infected pulmonary lesions by MALDI-MSI and continuous liquid microjunction surface sampling.

    PubMed

    Prideaux, Brendan; ElNaggar, Mariam S; Zimmerman, Matthew; Wiseman, Justin M; Li, Xiaohua; Dartois, Véronique

    2015-02-01

    A multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and a commercial liquid microjunction surface sampling technology (LMJ-SSP), or flowprobe, have been used to both spatially profile and image drug distributions in lung tissue sections from TB-infected rabbits following oral administration of a single human-equivalent dose. Levofloxacin levels were highest at 6 h post-dose in normal lung, cellular granuloma, and necrotic caseum compartments. The drug accumulated in the cellular granuloma regions with lower amounts partitioning into central caseous compartments. Flowprobe imaging at 630 μm (limited by the probe tip diameter) enabled visualization of drug distribution into lesion compartments, including limited differentiation of relative drug abundance in cellular versus caseous regions of the lesions. MALDI-MSI analysis at 75 μm provided more detailed drug distribution, which clearly accumulated in the cellular region immediately surrounding the central caseum core. Imaging and profiling data acquired by flowprobe and MALDI-MSI were validated by quantitative LC/MS/MS analysis of lung and granuloma homogenates taken from the same animals. The results of the investigation show flowprobe imaging and sampling as a rapid and sensitive alternative to MALDI-MSI for profiling drug distributions into tissues when spatial resolution of data below the threshold of the probe diameter is not required.

  11. The management for tuberculosis control in Greater London in comparison with that in Osaka City: lessons for improvement of TB control management in Osaka City urban setting.

    PubMed

    Ohkado, Akihiro; Williams, Gini; Ishikawa, Nobukatsu; Shimouchi, Akira; Simon, Carter

    2005-07-01

    The tuberculosis (TB) notification in Osaka City has been persistently high compared with other urban areas in Japan. Although the TB notification in Greater London has kept much lower level compared with that in Osaka City, it has been also persistently high compared with other urban areas in the UK. Nonetheless, the contexts of the two cities relating TB control programme as well as the epidemiological situation greatly vary; there must be some lessons to be learnt from each other to improve each TB control programme to tackle against TB more effectively. Comparing the epidemiological situation of TB in both cities, it is obvious that Osaka City suffers TB more than Greater London in terms of the TB notification rate. Concerning the context of the TB control programme, Osaka City has centralised approach with strong local government commitment; Greater London, on the other hand, has an approach that is greatly fragmented but coordinated through voluntary TB Networks. This paper aims to draw some constructive and practical lessons from Greater London TB control management for further improvement of Osaka City TB control management through literature review and interview to health professionals. TB epidemiology in Greater London shows distinct features in the extent of TB in new entrants and TB co-infected with HIV in comparison with those in Osaka City. TB epidemiology in Osaka City is to a great extent specifically related to homeless people whereas in Greater London, this relationship occurs to a lesser extent. Both areas have relatively high TB-notification rates compared with national figures, and they have "TB hot spots" where remarkably high TB-notification rates exist. TB control in Greater London is characterised with decentralised and devolved services to local government health authorities supplemented with co-ordinating bodies across sectors as well as across Greater London. Sector-wide TB Network as well as London TB Group (LTBG) and London TB Nurses

  12. Sensitivity of the Quantiferon-Gold In-Tube Assay in Sputum Smear Positive TB Cases in Indonesia

    PubMed Central

    Rutherford, Merrin; Alisjahbana, Bachti; Maharani, Winni; Sampurno, Hedy; van Crevel, Reinout; Hill, Philip C.

    2010-01-01

    Background As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection. Methods and Findings We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results. Conclusions The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests. PMID:20711257

  13. Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERON-TB Gold IGRA alone is more cost-effective for immigrants from high burden countries.

    PubMed

    Hardy, A B; Varma, R; Collyns, T; Moffitt, S J; Mullarkey, C; Watson, J P

    2010-02-01

    NICE (National Institute for Health and Clinical Excellence) guidelines for new entrant tuberculosis (TB) screening recommend chest x ray (CXR) for immigrants from countries with TB incidence >40/10(5), and tuberculin skin test (TST) for people with normal CXR from very high TB prevalence countries. A revised screening policy using first-line QuantiFERON-TB Gold (QFT) in high risk immigrants was piloted in 2007. Initially, TST was offered to immigrants from countries with TB incidence 200-339/10(5), and QFT to those from countries with incidence >340/10(5). When increased resources became available, all immigrants from countries with TB incidence >200/10(5) had QFT. Those with positive QFT were invited for CXR. 1336 immigrant were invited for screening, with a 32% attendance rate. 280 patients had QFT, of which 38% were positive, with <2% being indeterminate. Using the NICE approach, the cost of screening these 280 immigrants would be pound 13,346.75 ( pound 47.67 per immigrant) and would identify 83 cases of latent TB infection (LTBI). Using first-line QFT followed by CXR the cost was pound 9781.82 ( pound 34.94 per immigrant) and identified 105 cases of LTBI. The cost to identify one case of LTBI following NICE guidelines would be pound 160.81 and using the present protocol was pound 93.16. For immigrants from high risk countries QFT blood testing followed by CXR is feasible for TB screening, cheaper than screening using the NICE guideline and identifies more cases of LTBI.

  14. A two-strain TB model with multiple latent stages.

    PubMed

    Jabbari, Azizeh; Castillo-Chavez, Carlos; Nazari, Fereshteh; Song, Baojun; Kheiri, Hossein

    2016-08-01

    A two-strain tuberculosis (TB) transmission model incorporating antibiotic-generated TB resistant strains and long and variable waiting periods within the latently infected class is introduced. The mathematical analysis is carried out when the waiting periods are modeled via parametrically friendly gamma distributions, a reasonable alternative to the use of exponential distributed waiting periods or to integral equations involving ``arbitrary'' distributions. The model supports a globally-asymptotically stable disease-free equilibrium when the reproduction number is less than one and an endemic equilibriums, shown to be locally asymptotically stable, or l.a.s., whenever the basic reproduction number is greater than one. Conditions for the existence and maintenance of TB resistant strains are discussed. The possibility of exogenous re-infection is added and shown to be capable of supporting multiple equilibria; a situation that increases the challenges faced by public health experts. We show that exogenous re-infection may help established resilient communities of actively-TB infected individuals that cannot be eliminated using approaches based exclusively on the ability to bring the control reproductive number just below 1.

  15. Performance of QuantiFERON-TB Gold In-Tube test and Tuberculin Skin Test for diagnosis of latent tuberculosis infection in BCG vaccinated health care workers

    PubMed Central

    Babayigit, Cenk; Ozer, Burcin; Inandi, Tacettin; Ozer, Cahit; Duran, Nizami; Gocmen, Orhan

    2014-01-01

    Background Tuberculin skin test (TST) has been used for years as an aid in diagnosing latent tuberculosis infection (LTBI) but it suffers from a number of well-documented performance and logistic problems. Quantiferon-TB Gold In Tube test (QFT-GIT) has been reported to have better sensitivity and specifity than TST. In this study, it was aimed to compare the performance of a commercial IFN-γ release assay (QFT-GIT) with TST in the diagnosis of HCWs at risk for latent TB infection in BCG vaccinated population. Material/Methods Hundred healthy volunteer health care workers were enrolled. All were subjected to TST and QFT-GIT. Results were compared among Health Care Workers (HCWs) groups in terms of profession, workplace, working duration. Results TST is affected by previous BCG vaccinations and number of cases with QFT-GIT positivity is increased in accordance with the TST induration diameter range. QFT-GIT result was negative in 17 of 32 TST positive (≥15 mm) cases and positive in 4 of 61 cases whose TST diameters are between 6–14 mm, that is attritutable to previous BCG vaccination(s). It was negative in all cases with TST diameters between 0–5 mm. HCWs with positive QFT-GIT results were significantly older than the ones with negative results. Furthermore duration of work was significantly longer in QFT-GIT positive than in negative HCWs. Conclusions There was a moderate concordance between QFT-GIT and TST, when TST result was defined as positive with a ≥15 mm diameter of induration. We suggest that QFT-GIT can be used as an alternative to TST for detection of LTBI, especially in groups with high risk of LTBI and in population with routine BCG vaccination program. PMID:24681806

  16. Suppression of Protective Responses upon Activation of L-Type Voltage Gated Calcium Channel in Macrophages during Mycobacterium bovis BCG Infection

    PubMed Central

    Sharma, Deepika; Tiwari, Brijendra Kumar; Mehto, Subhash; Antony, Cecil; Kak, Gunjan; Singh, Yogendra; Natarajan, Krishnamurthy

    2016-01-01

    The prevalence of Mycobacterium tuberculosis (M. tb) strains eliciting drug resistance has necessitated the need for understanding the complexities of host pathogen interactions. The regulation of calcium homeostasis by Voltage Gated Calcium Channel (VGCCs) upon M. tb infection has recently assumed importance in this area. We previously showed a suppressor role of VGCC during M. tb infections and recently reported the mechanisms of its regulation by M. tb. Here in this report, we further characterize the role of VGCC in mediating defence responses of macrophages during mycobacterial infection. We report that activation of VGCC during infection synergistically downmodulates the generation of oxidative burst (ROS) by macrophages. This attenuation of ROS is regulated in a manner which is dependent on Toll like Receptor (TLR) and also on the route of calcium influx, Protein Kinase C (PKC) and by Mitogen Activation Protein Kinase (MAPK) pathways. VGCC activation during infection increases cell survival and downmodulates autophagy. Concomitantly, pro-inflammatory responses such as IL-12 and IFN-γ secretion and the levels of their receptors on cell surface are inhibited. Finally, the ability of phagosomes to fuse with lysosomes in M. bovis BCG and M. tb H37Rv infected macrophages is also compromised when VGCC activation occurs during infection. The results point towards a well-orchestrated strategy adopted by mycobacteria to supress protective responses mounted by the host. This begins with the increase in the surface levels of VGCCs by mycobacteria and their antigens by well-controlled and regulated mechanisms. Subsequent activation of the upregulated VGCC following tweaking of calcium levels by molecular sensors in turn mediates suppressor responses and prepare the macrophages for long term persistent infection. PMID:27723836

  17. Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity

    PubMed Central

    Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina

    2017-01-01

    Background Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Methods Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. Results All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. Conclusion This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB. PMID:28182700

  18. Health professionals as stigmatisers of tuberculosis: insights from community members and patients with TB in an urban district in Ghana.

    PubMed

    Dodor, Emmanuel Atsu; Kelly, Shona; Neal, Keith

    2009-05-01

    Health professionals are in a power category within any social setting so when they identify and label diseases with negative attributes, it can be recognised by society with discriminatory consequences for individuals affected in the community. This article reports how activities of health professionals, as perceived and construed by community members can be a basis of stigmatisation of patients with tuberculosis (TB) in society. One hundred individual interviews and 22 focus groups were held with community members and patients with TB, and the generated data analysed using the grounded theory techniques and procedures. Through examination of the words and statements of the participants, five inter-related ways by which activities of health professionals may expose patients with TB to stigmatisation in the community were identified: isolation and exclusionary practices; behaviours of health professionals towards patients with TB; public health discourse; food safety and hygiene practices and prohibition of full burial rites to those who died from TB. These activities are mirrored in the attitudes and behaviours of community members, and often become the basis of stigmatisation of individuals affected by TB in society. This may considerably contribute to diagnostic delay and low case finding in Ghana. Because, for fear of stigmatisation, community members who may be experiencing symptoms suggestive of TB may fail to go to the hospital. The stigma attached to TB in society may also contribute to the poor adherence to treatment seen among patients with TB in Ghana. To help to improve case finding and defaulter rate, the TB control programme should organise regular refresher courses in TB control and management for health professionals, and address the fear of infection by developing a national guidelines on how to prevent transmission of TB to health professionals within the hospital setting.

  19. Diabetes Mellitus as Hub for Tuberculosis Infection: A Snapshot

    PubMed Central

    Pal, Rahul; Ansari, Moiz A.

    2016-01-01

    Tuberculosis (TB) still remains the thorn in the flesh of efficient therapeutics affecting one-third of global population annually. There are several factors that enhance the susceptibility to TB infections including malnutrition, smoking, and immunocompromised conditions such as AIDS. In the recent years, growing body of evidence has gained considerable prominence which suggests that Diabetes Mellitus (DM) is individual risk factor leading to complicated TB infections. In this article the authors have attempted to summarize the link of type 2 DM with TB, the mechanistic action of how DM sensitizes for developing the active TB infection from the latent infection, and problems faced during treatment followed by possible preventive measures. We have tried to give account of the alterations that occurred in DM making a person more prone to develop TB. PMID:27819024

  20. Diabetes Mellitus as Hub for Tuberculosis Infection: A Snapshot.

    PubMed

    Pal, Rahul; Ansari, Moiz A; Hameed, Saif; Fatima, Zeeshan

    2016-01-01

    Tuberculosis (TB) still remains the thorn in the flesh of efficient therapeutics affecting one-third of global population annually. There are several factors that enhance the susceptibility to TB infections including malnutrition, smoking, and immunocompromised conditions such as AIDS. In the recent years, growing body of evidence has gained considerable prominence which suggests that Diabetes Mellitus (DM) is individual risk factor leading to complicated TB infections. In this article the authors have attempted to summarize the link of type 2 DM with TB, the mechanistic action of how DM sensitizes for developing the active TB infection from the latent infection, and problems faced during treatment followed by possible preventive measures. We have tried to give account of the alterations that occurred in DM making a person more prone to develop TB.

  1. Guidance from WHO on the prevention and control of TB during air travel.

    PubMed

    Martinez, Lindsay; Thomas, Kathrin; Figueroa, José

    2010-03-01

    Although tuberculosis (TB) is not highly transmissible, there is a risk of transmission of infection when close contact occurs between a person with active pulmonary TB and other passengers for prolonged periods during air travel. The World Health Organization first published Tuberculosis and air travel: guidelines for prevention and control in 1998, in response to several incidents involving TB in air travellers, with a second edition in 2006. A further revision was undertaken to address issues arising from the emergence of extensively resistant TB (XDR-TB), the occurrence of several international incidents involving TB and air travel, and the entry into force of the revised International Health Regulations (IHR) in 2007. This article describes the process followed in preparing the third edition, the special issues considered and the conclusions reached, with recommendations for travellers, physicians, public health authorities, and airline companies. New material includes: (i) additional guidance on the assessment of infectiousness, and on procedures, roles and responsibilities involved in the prevention of transmission of infection on board and for dealing with incidents; (ii) information on basic provisions of the IHR and measures relevant to incidents involving TB among air travellers; and (iii) a proposed procedure for carrying out contact investigations.

  2. The assessment of cytokines in Quantiferon supernatants for the diagnosis of latent TB infection in a tribal population of Melghat, India.

    PubMed

    Bapat, Prachi R; Husain, Aliabbas A; Daginawala, Hatim F; Agrawal, Neha P; Panchbhai, Milind S; Satav, Ashish R; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    The tuberculin skin test (TST) and interferon-gamma release assays (IGRA), namely, the QuantiFERON-TB Gold test (QFT), remain the standard immunological diagnostic tools for latent tuberculosis (TB) infection (LTBI). However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma (IFN-γ) as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: (i) QFT+/TST+ (n = 26), (ii) QFT+/TST- (n = 12), (iii) QFT-/TST- (n = 35) and (iv) QFT-/TST+ (n = 1) groups. A panel of cytokines (IL-6, IL-10, TNF-α and IL-2R) was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT-/TST- group. Correlation analysis identified a positive correlation between IL-6 and the QFT response (r = 0.6723, P < 0.0001), while a negative correlation was seen between QFT and IL-10 expression (r = -0.3271, P = 0.0044). Similarly, IL-6 was positively correlated with TST levels (r = 0.6631, P <0 .0001), and conversely, a negative correlation was found between TST and IL-10 expression (r = -0.5698, P < 0.0001). The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and/or TST could markedly improve the detection

  3. Elevated serum 25-hydroxy (OH) vitamin D levels are associated with risk of TB progression in Gambian adults

    PubMed Central

    Owolabi, Olumuyiwa; Agbla, Schadrac; Owiafe, Patrick; Donkor, Simon; Togun, Toyin; Sillah, Abdou K.; Ota, Martin O.C.; Sutherland, Jayne S.

    2016-01-01

    Summary Background Vitamin D is essential in the host defence against tuberculosis (TB) as an immune modulator. The aim of this study was to determine the level of 25-hydroxyvitamin D (25 (OH) D) from adult TB index cases before and after treatment and their exposed household contacts (HHC) in The Gambia. Methods Serum from adult index TB cases and their TB-exposed household contacts (HHC) was analysed for 25(OH) D and Vitamin D binding protein (VDBP) concentrations. Tuberculin skin test (TST) status was used as a measure of Mycobacterium tuberculosis (Mtb) infectivity in the HHC. In addition, HHC who later progressed to active TB (incident cases) were assessed alongside non-progressors to determine the influence of 25 (OH) D levels on TB risk. Results Eighty-three TB cases, 46 TST+ and 52 TST− HHC were analysed. Generally levels of 25(OH) D were considered insufficient in all subjects. However, median levels of 25(OH) D and VDBP were significantly higher in TB cases compared to both TST+ and TST− HHC at recruitment and were significantly reduced after TB therapy (p < 0.0001 for all). In addition, levels of serum 25(OH) D at recruitment were significantly higher in TB progressors compared to non-progressors (median (IQR): 25.0(20.8–29.2) in progressors and 20.3 (16.3–24.6) ng/ml in non-progressors; p = 0.007). Conclusion In The Gambia, an equatorial country, 25(OH) D levels are higher in serum of TB progressors and those with active disease compared to latently infected and uninfected subjects. These results contrast to findings in non-equatorial countries. PMID:27156622

  4. Tuberculosis Facts - Testing for TB

    MedlinePlus

    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

  5. Tuberculosis Facts - Exposure to TB

    MedlinePlus

    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

  6. Fc gamma receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection.

    PubMed

    Maglione, Paul J; Xu, Jiayong; Casadevall, Arturo; Chan, John

    2008-03-01

    The critical role of cellular immunity during tuberculosis (TB) has been extensively studied, but the impact of Abs upon this infection remains poorly defined. Previously, we demonstrated that B cells are required for optimal protection in Mycobacterium tuberculosis-infected mice. FcgammaR modulate immunity by engaging Igs produced by B cells. We report that C57BL/6 mice deficient in inhibitory FcgammaRIIB (RIIB-/-) manifested enhanced mycobacterial containment and diminished immunopathology compared with wild-type controls. These findings corresponded with enhanced pulmonary Th1 responses, evidenced by increased IFN-gamma-producing CD4+ T cells, and elevated expression of MHC class II and costimulatory molecules B7-1 and B7-2 in the lungs. Upon M. tuberculosis infection and immune complex engagement, RIIB-/- macrophages produced more of the p40 component of the Th1-promoting cytokine IL-12. These data strongly suggest that FcgammaRIIB engagement can dampen the TB Th1 response by attenuating IL-12p40 production or activation of APCs. Conversely, C57BL/6 mice lacking the gamma-chain shared by activating FcgammaR had enhanced susceptibility and exacerbated immunopathology upon M. tuberculosis challenge, associated with increased production of the immunosuppressive cytokine IL-10. Thus, engagement of distinct FcgammaR can divergently affect cytokine production and susceptibility during M. tuberculosis infection.

  7. Hydrothermal fabrication of multi-functional Eu3+ and Tb3+ co-doped BiPO4: Photocatalytic activity and tunable luminescence properties

    NASA Astrophysics Data System (ADS)

    Wang, Yao; Huang, Hongwei; Quan, Chaoming; Tian, Na; Zhang, Yihe

    2016-01-01

    We demonstrated for first time the tunable photoluminescence (PL) properties and photocatalytic activity of the Tb3+ and Eu3+ co-doped BiPO4 assemblies. They are fabricated via a facile hydrothermal approach. Through co-doping of Eu3+ and Tb3+ ions and changing the doping ratio, the emission color of the co-doped BiPO4 phosphors can be tuned precisely from green to yellow and red. Meanwhile, a very efficient energy transfer from Tb3+ to Eu3+ can be observed. Fascinatingly, a warmwhite color has been realized in the co-doped sample by tuning the ratio of Tb3+/Eu3+ to a certain value as displayed in the CIE chromaticity diagram. The doped BiPO4 samples also exhibit significantly enhanced photocatalytic activity compared to the pristine BiPO4 pertaining to Rhodamine (RhB) degradation under UV light. This enhancement should be attributed to the trapping electron effect induced by ion doping that endows BiPO4 with high separation of photoinduced electron-hole pairs, thereby greatly promoting the photocatalytic reactivity. It was corroborated by the electrochemical impedance spectra (EIS). Moreover, the crystal structure, microstructure and optical properties of as-prepared samples were investigated in details.

  8. PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis

    PubMed Central

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

    2016-01-01

    The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN-γ-secreting T-cell proportion. CD4+ T-cell proliferation and macrophage functions were investigated in the presence or absence of PD-1/PD-L pathway blockade. Proportions of both PD-1+CD4+ and PD-L1+CD4+ T cells in ATB patients were more significantly increased than in the HC group (P = 0.0112 and P = 0.0141, respectively). The expressions of PD-1, PD-L1, and PD-L2 on CD14+ monocytes in ATB patients were much higher than those in the HC group (P = 0.0016, P = 0.0001, and P = 0.0088, respectively). Blockade of PD-1 could significantly enhance CD4+ T-cell proliferation (P = 0.0433). Phagocytosis and intracellular killing activity of macrophages increased significantly with PD-1/PD-L pathway blockade. In conclusion, the PD-1/PD-L pathway inhibits not only M.tb-specific CD4+ T-cell-mediated immunity but also innate immunity. PMID:27924827

  9. Multidrug-Resistant Tuberculosis (MDR TB)

    MedlinePlus

    ... prisons, or homeless shelters. If you work in hospitals or health-care settings where TB patients are likely to be seen, you should consult infection control or occupational health experts. Ask about administrative and ...

  10. Extensively Drug-Resistant Tuberculosis (XDR TB)

    MedlinePlus

    ... Correctional and Detention Facilities Guidelines for Preventing the Transmission of M. TB in Health care Settings Investigation ... infection control measures in place. Documented places where transmission has occurred include crowded hospitals, prisons, homeless shelters, ...

  11. VUV spectroscopic properties of rare-earth (RE3+ = Sm3+, Eu3+, Tb3+, Dy3+) -activated layered borate Ba6Gd9B79O138

    NASA Astrophysics Data System (ADS)

    Zhang, Zhi-Jun; Zhang, Shao-Lin; Zhang, Wei-Bin; Yang, Woochul

    2017-02-01

    Vacuum ultraviolet (VUV) spectroscopic properties of rare-earth RE3+- activated (RE3+ = Sm3+, Eu3+, Tb3+ and Dy3+) Ba6Gd9B79O138 borates (BGBO) are investigated. The strong absorption bands in the VUV range of un-doped and RE3+-activated BGBO were observed. The band range from 140 to 200 nm with a peak at about 173 nm results from the host lattice absorption. For Sm3+-activated BGBO, the charge transfer transition from O2- to Sm3+ was observed at 202 nm. In addition, it exhibits bright red emission originating from the Sm3+f-f transitions of 4G5/2 → 6HJ (J = 5/2, 7/2 and 9/2). The O2--Eu3+ charge transfer (CT) at 249 nm is observed in the excitation spectrum for Eu3+-doped BGBO. For Tb3+-activated BGBO, the broad bands around 208 and 230 nm are due to the spin-allowed and spin-forbidden f-d transitions of Tb3+, respectively. In addition, the absence of the f-d transitions of Sm3+ and Dy3+ in the excitation spectra probably due to the photo-ionization effect. It is demonstrated that there are energy transfers from the BGBO host lattice to the luminescent activators depending on the activators.

  12. Anti-Inflammatory and Antimicrobial Actions of Vitamin D in Combating TB/HIV

    PubMed Central

    Coussens, Anna K.; Martineau, Adrian R.; Wilkinson, Robert J.

    2014-01-01

    Tuberculosis (TB) disease activation is now believed to arise due to a lack of inflammatory homeostatic control at either end of the spectrum of inflammation: either due to immunosuppression (decreased antimicrobial activity) or due to immune activation (excess/aberrant inflammation). Vitamin D metabolites can increase antimicrobial activity in innate immune cells, which, in the context of HIV-1 coinfection, have insufficient T cell-mediated help to combat Mycobacterium tuberculosis (MTB) infection. Moreover, maintaining vitamin D sufficiency prior to MTB infection enhances the innate antimicrobial response to T cell-mediated interferon-γ. Conversely, vitamin D can act to inhibit expression and secretion of a broad range of inflammatory mediators and matrix degrading enzymes driving immunopathology during active TB and antiretroviral- (ARV-) mediated immune reconstitution inflammatory syndrome (IRIS). Adjunct vitamin D therapy during treatment of active TB may therefore reduce lung pathology and TB morbidity, accelerate resolution of cavitation and thereby decrease the chance of transmission, improve lung function following therapy, prevent relapse, and prevent IRIS in those initiating ARVs. Future clinical trials of vitamin D for TB prevention and treatment must be designed to detect the most appropriate primary endpoint, which in some cases should be anti-inflammatory and not antimicrobial. PMID:25101194

  13. A "turn-on" and label-free fluorescent assay for the rapid detection of exonuclease III activity based on Tb(3+)-induced G-quadruplex conjugates.

    PubMed

    Yang, WeiJuan; Ruan, YaJuan; Wu, WeiHua; Chen, PingPing; Xu, LiangJun; Fu, FengFu

    2014-07-01

    A "turn-on" and label-free fluorescent assay for the specific, rapid, and sensitive detection of 3' → 5' exonuclease III activity is reported in this study. The assay is based on the Tb(3+)-promoted G-quadruplex, which lead to the enhancement of Tb(3+) fluorescence due to the energy transfer from guanines. The proposed assay is highly simple, rapid, and cost-effective, and does not require sophisticated experimental techniques such as gel-based equipment or radioactive labels. It can be used for the rapid detection of exonuclease III activity with a detection limit of 0.8 U and a RSD (n = 6) <5 %. Notably, no dye was covalently conjugated to the DNA strands, which offers the advantages of low-cost and being interference-free.

  14. Immunity to TB and targets for immunotherapy.

    PubMed

    Gonzalez-Juarrero, Mercedes

    2012-02-01

    For centuries the treatment of TB has presented an enormous challenge to global health. In the 20th century, the treatment of TB patients with long-term multidrug therapy gave hope that TB could be controlled and cured; however, contrary to these expectations and coinciding with the emergence of AIDS, the world has witnessed a rampant increase in hard-to-treat cases of TB, along with the emergence of highly virulent and multidrug-resistant Mycobacterium tuberculosis strains. Unfortunately, these bacteria are now circulating around the world, and there are few effective drugs to treat them. As a result, the prospects for improved treatment and control of TB in the 21st century have worsened and we urgently need to identify new therapies that deal with this problem. The potential use of immunotherapy for TB is now of greater consideration than ever before, as immunotherapy could potentially overcome the problem of drug resistance. TB immunotherapy targets the already existing host anti-TB immune response and aims to enhance killing of the bacilli. For this purpose, several approaches have been used: the use of anti-Mycobacteria antibodies; enhancing the Th1 protective responses by using mycobacterial antigens or increasing Th1 cytokines; interfering with the inflammatory process and targeting of immunosuppressive pathways and targeting the cell activation/proliferation pathways. This article reviews our current understanding of TB immunity and targets for immunotherapy that could be used in combination with current TB chemotherapy.

  15. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

    PubMed

    Bapat, Prachi R; Satav, Ashish R; Husain, Aliabbas A; Shekhawat, Seema D; Kawle, Anuja P; Chu, Justin J; Purohit, Hemant J; Daginawala, Hatim F; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

  16. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India

    PubMed Central

    Bapat, Prachi R.; Satav, Ashish R.; Husain, Aliabbas A.; Shekhawat, Seema D.; Kawle, Anuja P.; Chu, Justin J.; Purohit, Hemant J.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S.

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis. PMID:26241963

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

    PubMed Central

    Krauss, Margot R; Harris, D Robert; Abreu, Thalita; Ferreira, Fabiana G; Ruz, Noris Pavia; Worrell, Carol; Hazra, Rohan

    2016-01-01

    Objective To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis (TB) in a cohort of HIV-infected infants, children and adolescents from Latin America. Methods A retrospective analysis of children with TB and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. Results Of 1114 HIV-infected infants, children, and adolescents followed from 2002-2011, 69 that could be classified as having confirmed or presumed TB were included in this case series; 52.2% (95% CI: 39.8-64.4%) had laboratory-confirmed TB, 15.9% (95% CI: 8.2-26.7%) had clinically-confirmed disease and 31.9% (95% CI: 21.2-44.2%) had presumed TB. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult TB case; however information on exposure to active TB was missing for 17 participants. At the time of TB diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. Conclusions Our study emphasizes the need for adequate contact tracing of adult TB cases and screening for HIV or TB in Latin American children diagnosed with either condition. Preventive strategies in TB-exposed, HIV-infected children should be optimized. PMID:25307683

  18. Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.

    PubMed

    Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Nagase, Hiroyuki; Nakamura, Hiroyuki; Matsui, Hirotoshi; Hebisawa, Akira; Ohta, Ken

    2016-01-01

    The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.

  19. Tuberculosis (TB): Treatment

    MedlinePlus

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

  20. Questions and Answers about TB

    MedlinePlus

    ... Search The CDC 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 ...

  1. Dy(3)(+) -, Sm(3)(+) -, Ce(3)(+) - and Tb(3)(+) -activated optical properties of microcrystalline BaMgP2 O7 phosphors.

    PubMed

    Wani, J A; Dhoble, N S; Kokode, N S; Singh, Vijay; Dhoble, S J

    2017-03-01

    Photoluminescence (PL) and thermoluminescence (TL) properties of rare earth (RE) ion (RE = Dy(3)(+) , Sm(3)(+) , Ce(3)(+) , Tb(3)(+) ) activated microcrystalline BaMgP2 O7 phosphors are presented in this work. Non-doped and doped samples of BaMgP2 O7 were prepared using a solid state diffusion method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), PL and TL. The XRD measurement confirmed the phase purity of the BaMgP2 O7 host matrix. The average particle size was found through SEM measurement to be around 2 μm. All activators using the PL technique displayed characteristic excitation and emission spectra that corresponded to their typical f → f and f → d transitions respectively. Thermoluminescence measurements showed that BaMgP2 O7 :RE (RE = Dy(3)(+) , Sm(3)(+) , Tb(3)(+) , Ce(3)(+) ) and co-doped BaMgP2 O7 :Ce(3)(+) ,Tb(3)(+) phosphors have also TL behaviour.

  2. Multidrug and extensively drug-resistant TB (M/XDR-TB): problems and solutions.

    PubMed

    Prasad, Rajendra

    2010-10-01

    Multi Drug Resistant Tuberculosis (MDR-TB) and Extensively Drug Resistant Tuberculosis (XDR-TB) are posing a threat to the control of tuberculosis. The first WHO-IUATLD antituberculosis drug resistance surveillance carried out in 1994 in 35 countries reported the median prevalence of primary and acquired multi drug resistance as 1.4% and 13% respectively. Subsequently, second, third and fourth WHO-IUATLD global drug resistance surveillances were carried out in 1996-99, 1999-2002 and 2002-2007 respectively. Based on drug resistance information from 114 countries, the proportion of MDR-TB among all cases was estimated for countries with no survey information. It was estimated that 4,89,139 cases of MDR-TB emerged in 2006. China and India carry approximately 50% of the global burden. 35 countries and two Special Administrative Regions (SARs) reported data on XDR-TB for the first time in 2006. Multidrug and extensively drug-resistant TB 2010 Global report on Surveillance and response estimated that 4,40,000 cases of MDR-TB emerged globally in 2008 and caused an estimated 1,50,000 deaths. 5.4% of MDR-TB cases were found to have XDR-TB. To date, a cumulative total of 58 countries have confirmed at least one case of XDR-TB. M/XDR-TB is a man-made problem and its emergence can be prevented by prompt diagnosis and effective use of first line drugs in every new patient. The DOTS Plus proposed by WHO highlights the comprehensive management strategy to control MDR-TB. Laboratory services for adequate and timely diagnosis of M/XDR-TB must be strengthened and programmatic management of M/XDR-TB must be scaled up as per target set by global plan. Proper use of second-line drugs must be ensured to cure existing MDR-TB, to reduce its transmission and to prevent XDR-TB. Sound infection control measures to avoid further transmission of M/XDR-TB and research towards development of new diagnostics, drugs and vaccines should be promoted to control M/XDR-TB.

  3. A world of cities and the end of TB.

    PubMed

    Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

    2016-03-01

    The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB.

  4. A world of cities and the end of TB

    PubMed Central

    Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

    2016-01-01

    The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID:26884491

  5. Combining PMTCT with active case finding for tuberculosis.

    PubMed

    Kali, Paula B N; Gray, Glenda E; Violari, Avy; Chaisson, Richard E; McIntyre, James A; Martinson, Neil A

    2006-07-01

    Tuberculosis (TB) is the preeminent manifestation of HIV infection and has become a leading cause of maternal mortality and morbidity in high HIV-prevalence settings. Active TB in pregnant women has potentially serious consequences for fetuses and newborns. In Soweto, South Africa, there is a more than 90% uptake of voluntary counseling and HIV testing during routine antenatal care, and almost one third of pregnant women are HIV-infected. The posttest counseling session of the prevention of mother-to-child transmission program provides an opportunity to screen HIV-infected pregnant women for TB. In this study, 370 HIV-infected pregnant women were screened for symptoms of active TB by lay counselors at the posttest counseling session. If symptomatic, they were referred to nurses who investigated them further. Eight women were found to have previously undiagnosed, smear-negative, culture-confirmed TB (2160/100,000). The mean CD4 count in those with active TB compared to those without TB was 276 x 10(6) cells per liter vs 447 x 10(6) cells per liter (P = 0.051). Symptoms most associated with active TB were hemoptysis and fever. We conclude that rates of TB in HIV-infected pregnant women are high, and screening for TB during routine antenatal care should be implemented in high HIV-prevalence settings.

  6. Incremental Yield of Serial Sputum Cultures for Diagnosis of Tuberculosis among HIV Infected Smear Negative Pulmonary TB Suspects in Kampala, Uganda

    PubMed Central

    Ssengooba, Willy; Kiwanuka, Noah; Kateete, David P.; Katamba, Achilles; Joloba, Moses L.

    2012-01-01

    Background Sputum culture is the gold standard for diagnosis of pulmonary tuberculosis (PTB). Although mostly used for research, culture is recommended by the World Health Organization for TB diagnosis among HIV infected smear negative PTB suspects. Even then, the number of sputum samples required remains unspecified. Here, we determined the Incremental Yield (IY) and number of samples required to diagnose an additional PTB case upon second and third serial sputum culture. Methods/Findings This was a cross sectional study done between January and March 2011. Serial sputum samples were provided by participants within two days and cultured using Lowenstein Jensen (LJ) and Mycobacteria Growth Indicator Tube (MGIT) methods. A PTB case was defined as a positive culture on either one or both methods. The IY from the second and third serial cultures was determined and the reciprocal of the product of the fractions of IY provided the number of samples required for an additional PTB case. Of the 170 smear negative PTB suspects, 62 (36.5%) met the case definition. The IY of the second sample culture was 12.7%, 23.6% and 12.6% and for the third sample culture was 6.8%, 7.5% and 7.3% with LJ, MGIT and LJ or MGIT, respectively. The number of samples required for an additional PTB case and 95% CI upon the second sample culture were 29.9 (16.6, 156.5), 11.3 (7.6, 21.9) and 20.8 (12.5, 62.7); while for the third sample culture were 55.6 (26.4, 500.4), 35.7 (19.0, 313.8) and 36.1 (19.1, 330.9) by LJ, MGIT and LJ or MGIT respectively. Conclusions/Significance Among HIV infected smear negative PTB suspects in Kampala, 93% of PTB cases are diagnosed upon the second serial sputum culture. The number of cultures needed to diagnose an additional PTB case, ranges from 11–30 and 35–56 by the second and third sputum samples, respectively. PMID:22629439

  7. Effect of prolonged incubation time on results of the QuantiFERON TB gold in-tube assay for diagnosis of latent tuberculosis infection.

    PubMed

    Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo; Yim, Jae-Joon

    2013-09-01

    Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.

  8. Use of the QuantiFERON-TB Gold In-Tube Test in the Diagnosis and Monitoring of Treatment Efficacy in Active Pulmonary Tuberculosis

    PubMed Central

    Chang, Ping-Chin; Wang, Pin-Hui; Chen, Kow-Tong

    2017-01-01

    The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment. PMID:28264462

  9. Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study

    PubMed Central

    Vincenti, D; Carrara, S; Butera, O; Bizzoni, F; Casetti, R; Girardi, E; Goletti, D

    2007-01-01

    Tuberculosis is the most frequent co-infection in human immunodeficiency virus (HIV)-infected individuals, and which still presents diagnostic difficulties. Recently we set up an assay based on interferon (IFN)-γ response to region of difference 1 (RD1) peptides selected by computational analysis which is associated with active Mycobacterium tuberculosis replication. The objective of this study was to investigate the response to RD1 selected peptides in HIV-1-infected individuals in a clinical setting. The mechanisms of this immune response and comparison with other immune assays were also investigated. A total of 111 HIV-infected individuals with symptoms and signs consistent with active tuberculosis were enrolled prospectively. Interferon (IFN)-γ responses to RD1 selected peptides and recall antigens were evaluated by enzyme-linked immunospot assay. Results were correlated with CD4− T cell counts, individuals' characteristics, tuberculin skin test, QuantiFERON-TB Gold and T-SPOT.TB. Results from 21 (19%) individuals were indeterminate due to in vitro cell anergy. Among ‘non-anergic’ individuals, sensitivity for active tuberculosis of the assay based on RD1 selected peptides was 67% (24 of 36), specificity was 94% (three of 54). The assay also resulted positive in cases of extra-pulmonary and smear-negative pulmonary active tuberculosis. The response was mediated by CD4− effector/memory T cells and correlated with CD4− T cell counts, but not with plasma HIV-RNA load. Moreover, the RD1 selected peptides assay had the highest diagnostic odds ratio for active tuberculosis compared to tuberculin skin test (TST), QuantiFERON-TB Gold and T-SPOT.TB. RD1 selected peptides assay is associated with M. tuberculosis replication in HIV-infected individuals, although T cell anergy remains an important obstacle to be overcome before the test can be proposed as a diagnostic tool. PMID:17680823

  10. Potential Role for Mycobacterium tuberculosis Specific IL-2 and IFN-γ Responses in Discriminating between Latent Infection and Active Disease after Long-Term Stimulation

    PubMed Central

    Sun, Qin; Wei, Wei; Sha, Wei

    2016-01-01

    Interferon gamma release assays (IGRAs) could accurately diagnose Mycobacterium tuberculosis (M.tuberculosis) infection. However, these assays do not discriminate between latent tuberculosis infection (LTBI) and active tuberculosis disease (ATB). Here, a total of 177 subjects, including 65 patients with ATB, 43 subjects with LTBI, and 69 TB-uninfected controls (CON group) were enrolled. The concentration of IFN-γ, IP-10, and IL-2 was determined in peripheral blood mononuclear cells (PBMCs) after short-term (24h) or long-term (72h) stimulation with TB antigens including ESAT-6/CFP-10 (EC) and purified protein derivative (PPD).EC-stimulated IL-2 and gamma interferon-inducible protein 10 (IP-10) release (24h and 72h) showed a good diagnostic performance in distinguishing between TB-infected and TB-uninfected individuals, but failed to discriminate between ATB and LTBI. After 72h of incubation, the release of IL-2 was higher in LTBI patients after stimulation with EC and PPD. The PPD-stimulated IL-2/IFN-γ ratio after 72h incubation had the diagnostic potential to discriminate between ATB and LTBI, with a sensitivity of 90.8% and a specificity of 97.7%. In addition, these new biomarkers, combined with T-SPOT test in a two-step strategy, were validated with high levels of accuracy in a prospective clinical-based cohort. Collectively, the PPD-stimulated IL-2/IFN-γ ratio after long-term incubation may be an alternative diagnostic biomarker in distinguishing between active TB patients and subjects with latent infection. PMID:28033330

  11. Activity of andrographolide against chikungunya virus infection

    PubMed Central

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R.

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  12. Rapid identification of tuberculosis epididymo-orchitis by INNO-LiPA Rif TB and QuantiFERON-TB Gold In Tube tests: case report.

    PubMed

    Paluch-Oleś, Jolanta; Magryś, Agnieszka; Kot, Ewa; Kozioł-Montewka, Maria

    2010-03-01

    Diagnosis of extrapulmonary tuberculosis (TB) is often missed or delayed because of nonspecific clinical and laboratory findings. Novel detection methods, such as polymerase chain reaction and QuantiFERON-TB Gold In Tube, can aid in the diagnosis of active extrapulmonary TB. Here, we demonstrate a case of epididymo-orchitis as the sole presentation of TB in a 32-year-old man.

  13. Human papillomavirus infections in nonsexually active perinatally HIV infected children.

    PubMed

    Moscicki, Anna-Barbara; Puga, Ana; Farhat, Sepideh; Ma, Yifei

    2014-02-01

    Although human papillomavirus (HPV) infections are common in HIV-infected adults, little is known about children. Our objective was to examine the prevalence of and risks for HPV of the oral mucosal and external genital areas in nonsexually active (NSA) perinatally (P) HIV+ children and compare with HIV-exposed but uninfected (HEU) children. A convenience sample attending a pediatric clinic were enrolled. Samples for HPV were obtained from the oral and anogenital areas and tested for one of 37 HPV types. The mean age of the 48 PHIV+ children was 14.3±3.9 years vs. 6.2±4.8 for the 52 HEU (p<0.001). Of the 23 PHIV+ girls, 30.4% had anogenital and 17% had oral HPV, and of the 27 HEU girls, 2 (7.4%) anogenital and 0 had oral HPV. Of the boys, 4/23 (17.4%) and 1/25 (4%) PHIV+ had anogenital and oral HPV, respectively, and 3/24 (12.5%) and 1/25 (4%) HEU had anogenital and oral HPV, respectively. Rates of HPV did not differ by age among the PHIV+, whereas older HEU were more likely to have HPV than younger HEU (p=0.07). This large age gap precluded statistical comparison by HIV status. The presence of HPV in NSA PHIV+ children may have implications regarding HPV vaccination efficacy.

  14. Measurement of Phenotype and Absolute Number of Circulating Heparin-Binding Hemagglutinin, ESAT-6 and CFP-10, and Purified Protein Derivative Antigen-Specific CD4 T Cells Can Discriminate Active from Latent Tuberculosis Infection

    PubMed Central

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

    2014-01-01

    The tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are used as adjunctive tests for the evaluation of suspected cases of active tuberculosis (TB). However, a positive test does not differentiate latent from active TB. We investigated whether flow cytometric measurement of novel combinations of intracellular cytokines and surface makers on CD4 T cells could differentiate between active and latent TB after stimulation with Mycobacterium tuberculosis-specific proteins. Blood samples from 60 patients referred to the Singapore Tuberculosis Control Unit for evaluation for active TB or as TB contacts were stimulated with purified protein derivative (PPD), ESAT-6 and CFP-10, or heparin-binding hemagglutinin (HBHA). The CD4 T cell cytokine response (IFN-γ, interleukin-2 [IL-2], interleukin-17A [IL-17A], interleukin-22 [IL-22], granulocyte-macrophage colony-stimulating factor [GM-CSF], and tumor necrosis factor alpha [TNF-α]) and surface marker expression (CD27, CXCR3, and CD154) were then measured. We found that the proportion of PPD-specific CD4 T cells, defined as CD154+ TNF-α+ cells that were negative for CD27 and positive for GM-CSF, gave the strongest discrimination between subjects with latent and those with active TB (area under the receiver operator characteristic [ROC] curve of 0.9277; P < 0.0001). Also, the proportions and absolute numbers of HBHA-specific CD4 T cells were significantly higher in those with latent TB infection, particularly CD154+ TNF-α+ IFN-γ+ IL-2+ and CD154+ TNF-α+ CXCR3+. Finally, we found that the ratio of ESAT-6- and CFP-10-responding to HBHA-responding CD4 T cells was significantly different between the two study populations. In conclusion, we found novel markers of M. tuberculosis-specific CD4 cells which differentiate between active and latent TB. PMID:25520147

  15. Passive transfer of interferon-γ over-expressing macrophages enhances resistance of SCID mice to Mycobacterium tuberculosis infection.

    PubMed

    Pasula, Rajamouli; Martin, William J; Kesavalu, Banu Rekha; Abdalla, Maher Y; Britigan, Bradley E

    2017-02-23

    Infection with Mycobacterium tuberculosis (M.tb) is associated with increased deaths worldwide. Alveolar macrophages (AMs) play a critical role in host defense against infection with this pathogen. In this work we tested the hypothesis that passive transfer of normal AMs, IFN-γ activated AMs, or macrophages transduced to over-express IFN-γ into the lungs of immunosuppressed SCID mice, where resident macrophages are present but not functional, would enhance alveolar immunity and increase clearance of pulmonary M.tb infection. Accordingly, SCID mice were infected with M.tb intratracheally (I.T.), following which they received either control macrophages or macrophages overexpressing IFN-γ (J774A.1). The extent of M.tb infection was assessed at 30days post-M.tb infection. SCID mice administered macrophages over-expressing IFN-γ showed a significant decrease in M.tb burden and increased survival compared to J774A.1 control macrophages or untreated mice. This was further associated with a significant increase in IFN-γ and TNF-α mRNA and protein expression, as well as NF-κB (p65) mRNA, in the lungs. The increase in IFN-γ and TNF-α lung levels was inversely proportional to the number of M.tb organisms recovered. These results provide evidence that administration of macrophages overexpressing IFN-γ inhibit M.tb growth in vivo and may enhance host defense against M.tb infection.

  16. Management of tuberculosis and latent tuberculosis infection in human immunodeficiency virus-infected persons.

    PubMed

    Lee, Shui Shan; Meintjes, Graeme; Kamarulzaman, Adeeba; Leung, Chi Chiu

    2013-08-01

    The syndemic of human immunodeficiency virus (HIV)/tuberculosis (TB) co-infection has grown as a result of the considerable sociogeographic overlaps between the two epidemics. The situation is particularly worrisome in countries with high or intermediate TB burden against the background of a variable HIV epidemic state. Early diagnosis of TB disease in an HIV-infected person is paramount but suffers from lack of sensitive and specific diagnostic tools. Enhanced symptom screening is currently advocated, and the wide application of affordable molecular diagnostics is urgently needed. Treatment of TB/HIV co-infection involves the concurrent use of standard antiretrovirals and antimycobacterials during which harmful drug interaction may occur. The pharmacokinetic interaction between rifamycin and antiretrovirals is a case in point, requiring dosage adjustment and preferential use of rifabutin, if available. Early initiation of antiretroviral therapy is indicated, preferably at 2 weeks after starting TB treatment for patients with a CD4 of <50 cells/μL. Development of TB-immune reconstitution inflammatory syndrome (TB-IRIS) is however more frequent with early antiretroviral therapy. The diagnosis of TB-IRIS is another clinical challenge, and cautious use of corticosteroids is suggested to improve clinical outcome. As a preventive measure against active TB disease, the screening for latent TB infection should be widely practiced, followed by at least 6-9 months of isoniazid treatment. To date tuberculin skin test remains the only diagnostic tool in high TB burden countries. The role of alternative tests, for example, interferon-γ release assay, would need to be better defined for clinical application.

  17. Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

    PubMed Central

    Scordo, Julia M.; Arcos, Jesús; Kelley, Holden V.; Diangelo, Lauren; Sasindran, Smitha J.; Youngmin, Ellie; Wewers, Mark D.; Wang, Shu-Hua; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B.

    2017-01-01

    In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis (M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site. PMID:28373877

  18. Rapid detection of serum antibody by dual-path platform VetTB assay in white-tailed deer infected with Mycobacterium bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine tuberculosis (TB) in various cervid species remains a significant problem affecting both farmed herds and free-ranging populations. Traditional skin testing was demonstrated to have serious limitations in certain deer species, whereas emerging serological assays showed promising diagnostic pe...

  19. Tuberculosis and the risk of infection with other intracellular bacteria: a population-based study.

    PubMed

    Huaman, M A; Fiske, C T; Jones, T F; Warkentin, J; Shepherd, B E; Ingram, L A; Maruri, F; Sterling, T R

    2015-04-01

    SUMMARY Persons who develop tuberculosis (TB) may have subtle immune defects that could predispose to other intracellular bacterial infections (ICBIs). We obtained data on TB and five ICBIs (Chlamydia trachomatis, Salmonella spp., Shigella spp., Yersinia spp., Listeria monocytogenes) reported to the Tennessee Department of Health, USA, 2000-2011. Incidence rate ratios (IRRs) comparing ICBIs in persons who developed TB and ICBIs in the Tennessee population, adjusted for age, sex, race and ethnicity were estimated. IRRs were not significantly elevated for all ICBIs combined [IRR 0.87, 95% confidence interval (CI) 0.71-1.06]. C. trachomatis rate was lowest in the year post-TB diagnosis (IRR 0.17, 95% CI 0.04-0.70). More Salmonella infections occurred in extrapulmonary TB compared to pulmonary TB patients (IRR 14.3, 95% CI 1.67-122); however, this appeared to be related to HIV co-infection. TB was not associated with an increased risk of other ICBIs. In fact, fewer C. trachomatis infections occurred after recent TB diagnosis. Reasons for this association, including reduced exposure, protection conferred by anti-TB drugs or macrophage activation by Mycobacterium tuberculosis infection warrant further investigation.

  20. TB and MDR/XDR-TB in European Union and European Economic Area countries: managed or mismanaged?

    PubMed

    Migliori, G B; Sotgiu, G; D'Ambrosio, L; Centis, R; Lange, C; Bothamley, G; Cirillo, D M; De Lorenzo, S; Guenther, G; Kliiman, K; Muetterlein, R; Spinu, V; Villar, M; Zellweger, J P; Sandgren, A; Huitric, E; Manissero, D

    2012-03-01

    In spite of the growing awareness of emerging drug-resistant Mycobacterium tuberculosis, the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/European Economic Area countries, with special focus on multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool. National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards. Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms. Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance.

  1. Stimulus Response of Au-NPs@GMP-Tb Core-Shell Nanoparticles: Toward Colorimetric and Fluorescent Dual-Mode Sensing of Alkaline Phosphatase Activity in Algal Blooms of a Freshwater Lake.

    PubMed

    Zhang, Xiaolei; Deng, Jingjing; Xue, Yumeng; Shi, Guoyue; Zhou, Tianshu

    2016-01-19

    In this study, we demonstrate a colorimetric and fluorescent dual-mode method for alkaline phosphatase activity (APA) sensing in freshwater lake with stimuli-responsive gold nanoparticles@terbium-guanosine monophosphate (Au-NPs@GMP-Tb) core-shell nanoparticles. Initially, the core-shell nanoparticles were fabricated based on Au-NPs decorated with a fluorescent GMP-Tb shell. Upon being excited at 290 nm, the as-formed Au-NPs@GMP-Tb core-shell nanoparticles emit green fluorescence, and the decorated GMP-Tb shell causes the aggregation of Au-NPs. However, the addition of ALP destroys GMP-Tb shell, resulting in the release of Au-NPs from the shell into the solvent. As a consequence, the aggregated Au-NPs solubilizes with the changes in the UV-vis spectrum of the dispersion, and in the meantime, the fluorescence of GMP-Tb shell turns off, which constitutes a new mechanism for colorimetric and fluorescent dual-mode sensing of APA. With the method developed here, we could monitor the dynamic change of APA during an algal bloom of a freshwater lake, both by the naked eye and further confirmed by fluorometric determination. This study not only offers a new method for on-site visible detection of APA but also provides a strategy for dual-mode sensing mechanisms by the rational design of the excellent optical properties of Au-NPs and the adaptive inclusion properties of the luminescent infinite coordination polymers.

  2. Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients.

    PubMed

    Kobashi, Y; Mouri, K; Obase, Y; Fukuda, M; Miyashita, N; Oka, M

    2007-11-01

    The usefulness of the tuberculin skin test (TST) and the QuantiFERON TB-2G (QFT-TB) test were compared in immunocompromised patients. The subjects consisted of 252 immunocompromised patients who were clinically suspected of tuberculosis (TB) infection between April 2005 and December 2006. Regarding the underlying diseases, 74 subjects had malignant diseases, 72 were undergoing immunosuppressive treatment, 52 had diabetes mellitus, 50 had chronic renal failure and four had HIV infection. While the positive rate of the QFT-TB test for the diagnosis of TB infection (TB disease or latent TB infection) was 78.1%, that of TST for TB infection was 50.0%. The QFT-TB test was significantly better than TST. However, 32 (13%) patients had an indeterminate QFT-TB result. Indeterminate findings were significantly more frequent in patients receiving immunosuppressive treatment (28%), especially with lymphocytopaenia in the peripheral blood, than in those who had other underlying diseases. While TST-positive and QFT-TB test-negative results were recognised in immunocompromised patients with bacille Calmette-Guérin vaccination or nontuberculous mycobacterial disease, TST-negative and QFT-TB test-positive results were recognised in immunocompromised patients with a past history of TB infection. It was concluded that the QuantiFERON TB-2G test is a more useful diagnostic method for tuberculosis infection than tuberculin skin test for immunocompromised patients suspected of tuberculosis disease. However, because the results of the QuantiFERON TB-2G test show an indeterminate response for patients receiving immunosuppressive treatment, especially for those with lymphocytopaenia due to severe underlying diseases, care must be taken in the interpretation of the QuantiFERON TB-2G test for these patients.

  3. Drug-resistant TB: deadly, costly and in need of a vaccine.

    PubMed

    Manjelievskaia, Janna; Erck, Dara; Piracha, Samina; Schrager, Lewis

    2016-03-01

    TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9-25 times higher than treating drug-susceptible TB. Developing new drugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be 'resistant' to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035.

  4. Drug-resistant TB: deadly, costly and in need of a vaccine

    PubMed Central

    Manjelievskaia, Janna; Erck, Dara; Piracha, Samina; Schrager, Lewis

    2016-01-01

    TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9–25 times higher than treating drug-susceptible TB. Developing new drugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be ‘resistant’ to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035. PMID:26884499

  5. Renal allograft tuberculosis with infected lymphocele transmitted from the donor.

    PubMed

    Al-Nesf, Maryam Ali; Al-Ani, Omar Isam; Al-Ani, Ahmed Abdul-Rahman; Rashed, Awad Hamed

    2014-03-01

    Transmission of tuberculosis (TB) from a donor through renal transplantation is a rare incident. We are reporting a 53-year-old Qatari woman diagnosed with renal allograft TB infection. The disease was confirmed by isolation of Mycobacterium tuberculosis from fluid from the lymphocele and demonstration of caseating granuloma in graft biopsy with acid-fast bacilli seen on Ziehl-Neelsen staining. The diagnosis was made quite early post-transplantation. The presence of the granuloma, which is unusual with patients on intensive immunosuppressant medications, suggests that transmission of the infection occurred from the donor rather than from the activation of latent infection. In reviewing the literature, we found ten case reports of TB in transplanted kidney with transmission of TB infection from the donor. The presence of TB in lymphocele in association with the infected transplant by TB, to the best of our knowledge, was reported only once in the literature. Our case had unfavorable outcome and ended by renal allograft nephrectomy and hemodialysis. We are presenting this case of TB infection of renal allograft and lymphocele diagnosed early post-transplantation transmitted from the donor and pertinent review from the literature.

  6. Cell Death and Autophagy in TB

    PubMed Central

    Moraco, Andrew H.; Kornfeld, Hardy

    2014-01-01

    Mycobacterium tuberculosis has succeeded in infecting one third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease. PMID:25453227

  7. A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis

    PubMed Central

    Schnippel, Kathryn; Sharp, Alana

    2016-01-01

    Objective Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. Methods We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Findings Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low

  8. Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania

    PubMed Central

    Hella, Jerry; Said, Khadija; Kamwela, Lujeko; Sasamalo, Mohamed; Maroa, Thomas; Chiryamkubi, Magreth; Mhalu, Grace; Schindler, Christian; Reither, Klaus; Knopp, Stefanie; Utzinger, Jürg; Gagneux, Sébastien; Fenner, Lukas

    2017-01-01

    Background Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania. Methodology Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB. Principal findings A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI): 0.88–1.80, p = 0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03–4.45, p = 0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38–5.26, p = 0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12–1.16, p = 0.088). Conclusions/Significance S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB

  9. Tuberculosis Facts - TB and HIV/AIDS

    MedlinePlus

    Tuberculosis (TB) Facts TB and HIV/AIDS 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

  10. Tuberculosis of the bladder without previous renal infection.

    PubMed

    Pommerville, Peter John; Zakus, Paul; van der Westhuizen, Nicholas; Kibsey, Pamela Catherine

    2006-04-01

    Tuberculous (TB) infections are usually limited to the pulmonary system but the hematogenous spread of TB can result in secondary infections in any part of the body. Genitourinary TB is uncommon and follows hematogenous spread from a primary pulmonary infection to the kidneys. A rare case of a TB infection of the bladder without renal involvement is described.

  11. IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection.

    PubMed

    Prabhavathi, Maddineni; Pathakumari, Balaji; Raja, Alamelu

    2015-08-01

    The enormous reservoir of latent TB infection (LTBI) poses a major hurdle for global TB control. The existing Tuberculin skin test (TST) and IFN-γ release assays (IGRAs) are found to be suboptimal for LTBI diagnosis. Previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by LTBI. In a cohort of 40 pulmonary TB patients (PTB) and 35 healthy household contacts (HHC), IFN-γ and TNF-α response were measured against 16 antigens by using 1:10 diluted whole blood assay. Among all the antigens, IFN-γ response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-γ response to combination of Rv2626c + Rv3716c has demonstrated 100% positivity in HHC and 17.5% positivity in PTB respectively. Compared to individual cytokines (i.e. IFN-γ and TNF-α), ratio of IFN-γ/TNF-α has shown promising results for diagnosis of LTBI. IFN-γ/TNF-α ratio against Rv3716c and TrxC has exhibited a positivity of 94.29% in HHC and 5% in PTB group. Accession of Rv2626c and Rv3716c may improve the diagnostic performance of existing QFT-GIT. Independent of QFT-GIT assay, ratio of IFN-γ/TNF-α in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI.

  12. Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar

    PubMed Central

    Shewade, H. D.; Kyaw, N. T. T.; Oo, M. M.; Aung, T. K.; Aung, S. T.; Oo, H. N.; Win, T.; Harries, A. D.

    2016-01-01

    Setting: Integrated HIV Care programme, Mandalay, Myanmar. Objectives: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. Design: Retrospective cohort study. Results: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm3 had a four times higher risk of an unsuccessful outcome. Conclusions: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV. PMID:27358804

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

    PubMed

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

    2016-08-01

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

  14. Implementation and evaluation of an isoniazid preventive therapy pilot program among HIV-infected patients in Vietnam, 2008–2010

    PubMed Central

    Trinh, Thuy T.; Han, Dien T.; Bloss, Emily; Le, Thai H.; Vu, Tung T.; Mai, Anh H.; Nguyen, Nhung V.; Nguyen, Long T.; Dinh, Sy N.; Whitehead, Sara

    2016-01-01

    Background WHO recommends screening for TB and evaluation for isoniazid preventive therapy (IPT) based on evidence that they reduce TB-related morbidity and mortality among HIV-infected persons. In Vietnam, an IPT pilot was implemented in two provinces; TB screening, treatment and outcomes were evaluated to inform the adoption and scale-up of IPT. Methods During April 2008 to March 2010, eligible HIV-infected persons aged >15 years, with no previous or current TB treatment, alcohol abuse or liver disease were screened for TB. If TB disease was ruled out based on symptoms, chest x-rays and sputum smears, isoniazid was administered for 9 months. Results Among 1281 HIV-infected persons who received initial eligibility screening, 520 were referred to and evaluated at district TB clinics for TB disease or IPT eligibility. Active TB was diagnosed in 17 patients and all were started on treatment. Of 520 patients evaluated, 416 (80.0%) initiated IPT: 382 (91.8%) completed IPT, 17 (4.1%) stopped treatment, 8 (1.9%) died, 3 (0.7%) developed TB during IPT and 6 (1.4%) had unknown outcomes. No severe adverse events were reported. Conclusions IPT treatment completion was high; no serious complications occurred. Improving and expanding intensified case-finding and IPT should be considered in Vietnam. PMID:26385936

  15. Working towards TB elimination the WHO Regional Strategic Plan (2006-2015).

    PubMed

    Nair, Nani; Cooreman, Erwin

    2006-03-01

    DOTS has expanded rapidly in the South-East Asia Region over the period of the Partnership's first Global Plan (2001-2005), with almost 100% geographical coverage achieved in 2005. All countries have made impressive progress in improving coverage and quality. This progress has been made possible through strong political commitment and large investments in TB control for improved infrastructure, reliable drug supply, increased staffing, improved laboratory services, and intensified training and supervision. Accomplishing the objectives outlined in this document will require sustaining the progress in all countries and particularly in the five high burden countries for achieving major regional and global impact. National TB programmes will need to be supported to maintain or surpass the 70% case detection and 85% treatment success rates. The achievement of the TB-related targets linked to the MDGs will also depend on how effectively initiatives such as DOTS-Plus, PPM DOTS and interventions for TB/ HIV among others, are implemented. National governments and development partners must fulfill their commitments to mobilizing and sustaining adequate resources to support the full range of activities envisaged. The benefits of full and effective implementation of all the planned interventions would be substantial. These will result in 20 to 25 million TB cases being treated in DOTS program mes and more than 150 000 drug-resistant cases receiving treatment through DOTS-Plus during the period 2006-2015. In addition, at least 250 000 HIV-infected TB patients may also receive anti-retroviral therapy. As a consequence, the prevalence of TB is expected to fall below 175/100 000 and the number of TB deaths is expected to fall to between 100 000 and 150 000 per year. There would also be substantial economic benefits given that TB disproportionately affects adults in their most productive years. Considering these aspects, it is expected that the TB incidence will decline

  16. Prevalence of latent tuberculosis infection among tuberculosis laboratory workers in Iran

    PubMed Central

    2017-01-01

    OBJECTIVES The risk of transmission of Mycobacterium tuberculosis from patients to health care workers (HCWs) is a neglected problem in many countries, including Iran. The aim of this study was to estimate the prevalence of latent tuberculosis (TB) infection (LTBI) among TB laboratory staff in Iran, and to elucidate the risk factors associated with LTBI. METHODS All TB laboratory staff (689 individuals) employed in the TB laboratories of 50 Iranian universities of medical sciences and a random sample consisting of 317 low-risk HCWs were included in this cross-sectional study. Participants with tuberculin skin test indurations of 10 mm or more were considered to have an LTBI. RESULTS The prevalence of LTBI among TB laboratory staff and low-risk HCWs was 24.83% (95% confidence interval [CI], 21.31 to 27.74%) and 14.82% (95% CI, 11.31 to 19.20%), respectively. No active TB cases were found in either group. After adjusting for potential confounders, TB laboratory staff were more likely to have an LTBI than low-risk HCWs (prevalence odds ratio, 2.06; 95% CI, 1.35 to 3.17). CONCLUSIONS This study showed that LTBI are an occupational health problem among TB laboratory staff in Iran. This study reinforces the need to design and implement simple, effective, and affordable TB infection control programs in TB laboratories in Iran. PMID:28092930

  17. Alternatively activated macrophages in infection and autoimmunity

    PubMed Central

    Fairweather, DeLisa; Cihakova, Daniela

    2009-01-01

    Macrophages are innate immune cells that play an important role in activation of the immune response and wound healing. Pathogens that require T helper-type 2 (Th2) responses for effective clearance, such as parasitic worms, are strong inducers of alternatively activated or M2 macrophages. However, infections such as bacteria and viruses that require Th1-type responses may induce M2 as a strategy to evade the immune system. M2 are particularly efficient at scavenging self tissues following injury through receptors like the mannose receptor and scavenger receptor-A. Thus, M2 may increase autoimmune disease by presenting self tissue to T cells. M2 may also exacerbate immune complex (IC)-mediated pathology and fibrosis, a hallmark of autoimmune disease in women, due to the release of profibrotic factors such as interleukin (IL)-1β, transforming growth factor-β, fibronectin and matrix metalloproteinases. We have found that M2 comprise anywhere from 30% to 70% of the infiltrate during acute viral or experimental autoimmune myocarditis, and shifts in M2 populations correlate with increased IC-deposition, fibrosis and chronic autoimmune pathology. Thus, women may be at an increased risk of M2-mediated autoimmunity due to estrogen’s ability to increase Th2 responses. PMID:19819674

  18. Decrease of U(VI) Immobilization Capability of the Facultative Anaerobic Strain Paenibacillus sp. JG-TB8 under Anoxic Conditions Due to Strongly Reduced Phosphatase Activity

    PubMed Central

    Reitz, Thomas; Rossberg, Andre; Barkleit, Astrid; Selenska-Pobell, Sonja; Merroun, Mohamed L.

    2014-01-01

    Interactions of a facultative anaerobic bacterial isolate named Paenibacillus sp. JG-TB8 with U(VI) were studied under oxic and anoxic conditions in order to assess the influence of the oxygen-dependent cell metabolism on microbial uranium mobilization and immobilization. We demonstrated that aerobically and anaerobically grown cells of Paenibacillus sp. JG-TB8 accumulate uranium from aqueous solutions under acidic conditions (pH 2 to 6), under oxic and anoxic conditions. A combination of spectroscopic and microscopic methods revealed that the speciation of U(VI) associated with the cells of the strain depend on the pH as well as on the aeration conditions. At pH 2 and pH 3, uranium was exclusively bound by organic phosphate groups provided by cellular components, independently on the aeration conditions. At higher pH values, a part (pH 4.5) or the total amount (pH 6) of the dissolved uranium was precipitated under oxic conditions in a meta-autunite-like uranyl phosphate mineral phase without supplying an additional organic phosphate substrate. In contrast to that, under anoxic conditions no mineral formation was observed at pH 4.5 and pH 6, which was clearly assigned to decreased orthophosphate release by the cells. This in turn was caused by a suppression of the indigenous phosphatase activity of the strain. The results demonstrate that changes in the metabolism of facultative anaerobic microorganisms caused by the presence or absence of oxygen can decisively influence U(VI) biomineralization. PMID:25157416

  19. Integrating patients’ perspectives into integrated TB/HIV healthcare

    PubMed Central

    Daftary, Amrita; Padayatchi, Nesri

    2013-01-01

    Background Escalating rates of TB/HIV coinfection call for improved coordination of TB and HIV healthcare services in high-burden countries such as South Africa. Patient perspectives, however, are poorly understood in the context of current integration efforts. Method Under a qualitative research framework, we interviewed 40 HIV-positive adult TB patients and 8 key-informant healthcare workers across 3 clinics in KwaZulu-Natal province to explore non-clinical and non-operational aspects of TB/HIV healthcare. Findings Qualitative analysis highlighted critical social and ethical considerations for the concurrent delivery of TB and HIV care. Coinfected patients navigating between TB and HIV programs are exposed to missed opportunities for TB and HIV service integration, fragmented or vertical care for their dual infections, and contrasting experiences within TB and HIV clinics. These intersecting issues appear to affect patients’ health-related decisions, particularly HIV nondisclosure to non-HIV healthcare workers, and their preferences for integrated healthcare. Conclusion Our study highlights the imperative to address service fragmentation, HIV medical confidentiality and provider mistrust within the healthcare system, and the cultural differences associated with TB and HIV disease control. PMID:23407149

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

    PubMed Central

    Dobler, Claudia Caroline

    2016-01-01

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

  1. Tuberculosis Facts - You Can Prevent TB

    MedlinePlus

    Tuberculosis (TB) Facts You Can Prevent 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 TB Facts: You Can Prevent TB What ...

  2. Tuberculosis Facts - TB Can Be Treated

    MedlinePlus

    Tuberculosis (TB) Facts TB Can Be Treated 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 Page 1 of 2 TB Facts: TB ...

  3. IL-37 Confers Protection against Mycobacterial Infection Involving Suppressing Inflammation and Modulating T Cell Activation

    PubMed Central

    Yang, Hua; He, Xin; Ji, Qun; Bai, Wenjuan; Chen, Hao; Chen, Jianxia; Peng, Wenxia; Liu, Siyu; Liu, Zhonghua; Ge, Baoxue

    2017-01-01

    Interleukin-37 (IL-37), a novel member of the IL-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (TB) has not been clearly elucidated. In this study, single nucleotide polymorphism (SNP) analysis demonstrated an association of the genetic variant rs3811047 of IL-37 with TB susceptibility. In line with previous report, a significant elevated IL-37 abundance in the sera and increased expression of IL-37 protein in the peripheral blood mononuclear cells (PBMC) were observed in TB patients in comparison to healthy controls. Moreover, release of IL-37 were detected in either macrophages infected with Mycobacterium tuberculosis (Mtb) or the lung of BCG-infected mice, concurrent with reduced production of proinflammatory cytokines including IL-6 and TNF-α. Furthermore, in contrast to wild-type mice, BCG-infected IL-37-Tg mice manifested with reduced mycobacterial burden and tissue damage in the lung, accompanied by higher frequency of Th1 cell and less frequencies of regulatory T cells and Th17 cells in the spleen. Taken together, our findings demonstrated that IL-37 conferred resistance to Mtb infection possibly involving suppressing detrimental inflammation and modulating T cell responses. These findings implicated that IL-37 may be employed as a new molecular target for the therapy and diagnosis of TB. PMID:28076390

  4. Supporting clinical management of the difficult-to-treat TB cases: the ERS-WHO TB Consilium.

    PubMed

    D'Ambrosio, Lia; Tadolini, Marina; Centis, Rosella; Duarte, Raquel; Sotgiu, Giovanni; Aliberti, Stefano; Dara, Masoud; Migliori, Giovanni Battista

    2015-03-01

    Multi-drug and extensively drug-resistant tuberculosis (MDR/XDR-TB) are considered a serious threat for TB control and elimination. The outcome of these patients is still largely unsatisfactory as of today, with treatment success rates being consistently below 50% at global level. The World Health Organization (WHO) recommends that management of MDR-TB cases is supported by a specialized team, including complementary medical professionals able to cover several perspectives (clinical, both for adults and children; surgical; radiological; public health; psychological; nursing, among others). Implementation of such a body (known as Consilium in most of the former Soviet Union countries) is often a pre-requisite to apply for international TB control funding and concessionally priced medicines to treat M/XDR-TB cases. The primary objective of the ERS/WHO TB Consilium is to provide clinical consultation for drug-resistant TB and other difficult-to-treat TB cases, including co-infection with HIV and paediatric cases. Through technical guidance to clinicians managing complex TB cases, the main contribution and outcome of the initiative will be a public health response aimed at achieving correct treatment of affected patients and preventing further development of drug resistance. The Consilum's secondary objective is to ensure monitoring and evaluation of clinical practices on the ground (diagnosis, treatment and prevention).

  5. Health systems in the Republic of Congo: challenges and opportunities for implementing tuberculosis and HIV collaborative service, research, and training activities.

    PubMed

    Linguissi, Laure Stella Ghoma; Gwom, Luc Christian; Nkenfou, Celine Nguefeu; Bates, Matthew; Petersen, Eskild; Zumla, Alimuddin; Ntoumi, Francine

    2017-03-01

    The Republic of Congo is on the World Health Organization (WHO) list of 'high burden' countries for tuberculosis (TB) and HIV. TB is the leading cause of death among HIV-infected patients in the Republic of Congo. In this viewpoint, the available data on TB and HIV in the Republic of Congo are reviewed, and the gaps and bottlenecks that the National TB Control Program (NTCP) faces are discussed. Furthermore, priority requirements for developing and implementing TB and HIV collaborative service activities are identified. HIV and TB control programs operate as distinct entities with separate case management plans. The implementation of collaborative TB/HIV activities to evaluate and monitor the management of TB/HIV co-infected individuals remains inefficient in most regions, and these activities are sometimes non-existent. This reveals major challenges that require definition in order to improve the delivery of healthcare. The NTCP lacks adequate resources for optimal implementation of control measures of TB and HIV compliance and outcomes. The importance of aligning and integrating TB and HIV treatment services (including follow-up) and adherence support services through coordinated and collaborative efforts between individual TB and HIV programs is discussed. Aligning and integrating TB and HIV treatment services through coordinated and collaborative efforts between individual TB and HIV programs is required. However, the WHO recommendations are generic, and health services in the Republic of Congo need to tailor their TB and HIV programs according to the availability of resources and operational feasibility. This will also open opportunities for synergizing collaborative TB/HIV research and training activities, which should be prioritized by the donors supporting the TB/HIV programs.

  6. Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South Africa

    PubMed Central

    Gilbert, Jennifer A.; Shenoi, Sheela V.; Moll, Anthony P.; Friedland, Gerald H.; Paltiel, A. David; Galvani, Alison P.

    2016-01-01

    South Africa has one of the highest burdens of TB worldwide, driven by the country’s widespread prevalence of HIV, and further complicated by drug resistance. Active case finding within the community, particularly in rural areas where healthcare access is limited, can significantly improve diagnosis and treatment coverage in high-incidence settings. We evaluated the potential health and economic consequences of implementing community-based TB/HIV screening and linkage to care. Using a dynamic model of TB and HIV transmission over a time horizon of 10 years, we compared status quo TB/HIV control to community-based TB/HIV screening at frequencies of once every two years, one year, and six months. We also considered the impact of extending IPT from 36 months for TST positive and 12 months for TST negative or unknown patients (36/12) to lifetime use for all HIV-infected patients. We conducted a probabilistic sensitivity analysis to assess the effect of parameter uncertainty on the cost-effectiveness results. We identified four strategies that saved the most life years for a given outlay: status quo TB/HIV control with 36/12 months of IPT and TB/HIV screening strategies at frequencies of once every two years, one year, and six months with lifetime IPT. All of these strategies were very cost-effective at a threshold of $6,618 per life year saved (the per capita GDP of South Africa). Community-based TB/HIV screening with linkage to care is therefore very cost-effective in rural South Africa. PMID:27906986

  7. Linkage and association analysis of candidate genes for TB and TNFalpha cytokine expression: evidence for association with IFNGR1, IL-10, and TNF receptor 1 genes.

    PubMed

    Stein, Catherine M; Zalwango, Sarah; Chiunda, Allan B; Millard, Christopher; Leontiev, Dmitry V; Horvath, Amanda L; Cartier, Kevin C; Chervenak, Keith; Boom, W Henry; Elston, Robert C; Mugerwa, Roy D; Whalen, Christopher C; Iyengar, Sudha K

    2007-07-01

    Tuberculosis (TB) is a growing public health threat globally and several studies suggest a role of host genetic susceptibility in increased TB risk. As part of a household contact study in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB by developing an intermediate phenotype model for TB susceptibility, analyzing levels of tumor necrosis factor-alpha (TNFalpha) in response to culture filtrate as the phenotype. In the present study, we analyzed candidate genes related to TNFalpha regulation and found that interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFalpha receptor 1 (TNFR1) genes were linked and associated to both TB and TNFalpha. We also show that these associations are with progression to active disease and not susceptibility to latent infection. This is the first report of an association between TB and TNFR1 in a human population and our findings for IL-10 and IFNGR1 replicate previous findings. By observing pleiotropic effects on both phenotypes, we show construct validity of our intermediate phenotype model, which enables the characterization of the role of these genetic polymorphisms on TB pathogenesis. This study further illustrates the utility of such a model for disentangling complex traits.

  8. Luminescence, Energy Transfer and Tunable Color of Ce3+- and Tb3+-Activated Na3Gd(BO3)2 Phosphors

    NASA Astrophysics Data System (ADS)

    Zhang, Xinguo; Pan, Jialiang; Mo, Fuwang

    2017-02-01

    A series of blue Na3Gd(BO3)2:Ce3+ and blue-to-green color-tunable Na3Gd (BO3)2:Ce3+,Tb3+ phosphors were synthesized by the solid-state method. The luminescence, concentration quenching and energy transfer (ET) process of Na3Gd(BO3)2:Ce3+,Tb3+ were investigated. Both Ce3+ and Tb3+ occupy the Gd3+ site in the Na3Gd(BO3)2 host. Na3Gd(BO3)2:Ce3+ exhibits strong ultraviolet absorption and broadband blue emission. The Ce3+ sensitization effect on Tb3+ has been verified by the variation of PL/PLE spectra, the Ce3+ decay lifetimes and the energy transfer efficiency of Na3Gd(BO3)2:Ce3+,Tb3+ phosphors. The maximum Ce3+-Tb3+ ET efficiency has been calculated to be 95%. The emitting color of the obtained phosphors can be modulated from blue (0.179, 0.204) through bluish-green (0.271, 0.391) to green (0.349, 0.551) by properly changing the ratio of Ce3+/Tb3+.

  9. TB in Vulnerable Populations

    PubMed Central

    Ugarte-Gil, César; Caro, Godofredo; Aylas, Rula; Castro, César; Lema, Claudia

    2016-01-01

    Abstract This article analyzes the factors associated with vulnerability of the Ashaninka, the most populous indigenous Peruvian Amazonian people, to tuberculosis (TB). By applying a human rights-based analytical framework that assesses public policy against human rights standards and principles, and by offering a step-by-step framework for a full assessment of compliance, it provides evidence of the relationship between the incidence of TB among the Ashaninka and Peru’s poor level of compliance with its human rights obligations. The article argues that one of the main reasons for the historical vulnerability of the Ashaninka to diseases such as TB is a lack of political will on the part of the national government to increase public health spending, ensure that resources reach the most vulnerable population, and adopt and invest in a culturally appropriate health system. PMID:27780999

  10. Photoluminescence properties of rare earths (Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+}) activated NaInW{sub 2}O{sub 8} wolframite host lattice

    SciTech Connect

    Asiri Naidu, S.; Boudin, S.; Varadaraju, U.V.; Raveau, B.

    2012-01-15

    The photoluminescence (PL) studies on NaIn{sub 1-x}RE{sub x}W{sub 2}O{sub 8}, with RE=Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+} phases have shown that the relative contribution of the host lattice and of the intra-f-f emission of the activators to the PL varies with the nature of the rare earth cation. In the case of Dy{sup 3+} and Tm{sup 3+} activators, with yellow and blue emission, respectively, the energy transfer from host to the activator plays a major role. In contrast for Eu{sup 3+}, with intense red emission, the host absorption is less pronounced and the intra-f-f transitions of the Eu{sup 3+} ions play a major role, whereas for Tb{sup 3+} intra-f-f transitions are only observed, giving rise to green emission. - Graphical abstract: NaInW{sub 2}O{sub 8} double tungstate doped with Eu{sup 3+}, Dy{sup 3+}, Tb{sup 3+}and Tm{sup 3+} shows characteristic emission of intense red for Eu{sup 3+}, yellow for Dy{sup 3+}, green for Tb{sup 3+} and blue for Tm{sup 3+}. Highlights: Black-Right-Pointing-Pointer Characteristic emissions of rare earths (Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+}) are observed NaInW{sub 2}O{sub 8} wolframite. Black-Right-Pointing-Pointer Energy transfer from host to the activators (Eu{sup 3+} Dy{sup 3+} Tm{sup 3+} is observed. Black-Right-Pointing-Pointer PL properties of rare earth ions depend on minor structural variations in the host lattice.

  11. Evaluation of a domestic interferon-gamma release assay for detecting Mycobacterium tuberculosis infection in China.

    PubMed

    Liu, Yongliang; Ou, Mingzhan; He, Shuizhen; Li, Xiaofei; Lin, Yanyan; Xiong, Junhui; Zhang, Jun; Ge, Shengxiang

    2015-07-01

    Interferon-gamma release assays (IGRAs) have been demonstrated to be useful in the diagnosis of Mycobacterium tuberculosis (MTB) infection. However, IGRAs have not been recommended for clinical usage in most low-income countries due to the shortage of clinical data available resulting from their high test cost. Recently, a cheaper domestic TB-IGRA was approved in China. In this study, we compared TB-IGRA with QuantiFERON-TB Gold In-Tube (QFT-GIT) for MTB infection diagnosis in 253 active TB patients, 48 non-TB lung disease patients, 115 healthcare workers and 216 healthy individuals. The proportion of positive TB-IGRA results in active TB patients, patients with non-TB lung disease, healthcare workers and healthy individuals was 88.3%, 27.1%, 40.9% and 17.6%, respectively, which was similar to the results of QFT-GIT, with an overall agreement of 95% (κ = 0.89) and a high correlation between their responses (r = 0.85, p < 0.001) being observed. In conclusion, the TB-IGRA has comparable clinical performance with QFT-GIT.

  12. Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease.

    PubMed

    Guggino, Giuliana; Orlando, Valentina; Cutrera, Stella; La Manna, Marco P; Di Liberto, Diana; Vanini, Valentina; Petruccioli, Elisa; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia

    2015-08-01

    Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals.

  13. Relationship between disease activity and infection in patients with spondyloarthropathies

    PubMed Central

    Martinez, A; Pacheco-Tena, C; Vazquez-Mellado, J; Burgos-Vargas, R

    2004-01-01

    Methods: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by χ2 or Fisher's tests. Results: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in ∼50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. Conclusion: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA. PMID:15361397

  14. Characteristics of adults and children diagnosed with tuberculosis in Lilongwe, Malawi: findings from an integrated HIV/TB clinic

    PubMed Central

    Feldacker, C.; Tweya, H.; Keiser, O.; Weigel, R.; Kalulu, M.; Fenner, L.; Egger, M.; Manda, E.; Mwafilaso, J. B.; Kamba, C.; Phiri, S.

    2013-01-01

    Objectives To describe initial registration characteristics of adult and pediatric TB patients at a large, public, integrated TB and HIV clinic in Lilongwe, Malawi, between January 2008 – December 2010. Methods Routine data on TB patient category and TB type, stratified by HIV and ART status, were used to explore differences in proportions among TB-only, TB/HIV co-infected patients not on ART, and TB/HIV co-infected patients on ART using Chi-square tests.. Trends over time illustrate strengths and weaknesses of integrated service provision. Results Among 10,143 adults, HIV ascertainment and ART uptake were high and increased over time. The proportion of relapse was highest among those on ART (5%). The proportion of smear-positive pulmonary TB (PTB) was highest among HIV-negative TB patients (34.9%); extra-pulmonary TB (EPTB) was lowest among TB-only (16.2%). Among 338 children <15 years, EPTB and smear-positive PTB were more common among TB-only patients. Time trends showed significant increases in the proportion of adults with smear-positive PTB and the proportion of adults already on ART before starting TB treatment. However, some co-infected patients still delay ART initiation. Conclusions HIV ascertainment and ART uptake among co-infected patients is successful and improving over time. However, delays in ART initiation indicate some weakness linking TB/HIV patients into ART during TB follow-up care. Improved TB diagnostics and screening efforts, especially for pediatric patients, may help improve quality care for co-infected patients. These results may aid efforts to prioritize TB and HIV prevention, education, and treatment campaigns for specific populations. PMID:22808948

  15. Bovine Tuberculosis Risk Factors for British Herds Before and After the 2001 Foot-and-Mouth Epidemic: What have we Learned from the TB99 and CCS2005 Studies?

    PubMed

    Vial, F; Miguel, E; Johnston, W T; Mitchell, A; Donnelly, C A

    2015-10-01

    Over the last couple of decades, the UK experienced a substantial increase in the incidence and geographical spread of bovine tuberculosis (TB), in particular since the epidemic of foot-and-mouth disease (FMD) in 2001. The initiation of the Randomized Badger Culling Trial (RBCT) in 1998 in south-west England provided an opportunity for an in-depth collection of questionnaire data (covering farming practices, herd management and husbandry, trading and wildlife activity) from herds having experienced a TB breakdown between 1998 and early 2006 and randomly selected control herds, both within and outside the RBCT (the so-called TB99 and CCS2005 case-control studies). The data collated were split into four separate and comparable substudies related to either the pre-FMD or post-FMD period, which are brought together and discussed here for the first time. The findings suggest that the risk factors associated with TB breakdowns may have changed. Higher Mycobacterium bovis prevalence in badgers following the FMD epidemic may have contributed to the identification of the presence of badgers on a farm as a prominent TB risk factor only post-FMD. The strong emergence of contact/trading TB risk factors post-FMD suggests that the purchasing and movement of cattle, which took place to restock FMD-affected areas after 2001, may have exacerbated the TB problem. Post-FMD analyses also highlighted the potential impact of environmental factors on TB risk. Although no unique and universal solution exists to reduce the transmission of TB to and among British cattle, there is an evidence to suggest that applying the broad principles of biosecurity on farms reduces the risk of infection. However, with trading remaining as an important route of local and long-distance TB transmission, improvements in the detection of infected animals during pre- and post-movement testing should further reduce the geographical spread of the disease.

  16. MAIT cells are activated during human viral infections.

    PubMed

    van Wilgenburg, Bonnie; Scherwitzl, Iris; Hutchinson, Edward C; Leng, Tianqi; Kurioka, Ayako; Kulicke, Corinna; de Lara, Catherine; Cole, Suzanne; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Young, Duncan; Denney, Laura; Moore, Michael D; Fabris, Paolo; Giordani, Maria Teresa; Oo, Ye Htun; Laidlaw, Stephen M; Dustin, Lynn B; Ho, Ling-Pei; Thompson, Fiona M; Ramamurthy, Narayan; Mongkolsapaya, Juthathip; Willberg, Christian B; Screaton, Gavin R; Klenerman, Paul

    2016-06-23

    Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.

  17. TB in Children in the United States

    MedlinePlus

    ... Search The CDC 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 ...

  18. Multidrug-Resistant TB

    PubMed Central

    Cox, Helen; Coomans, Fons

    2016-01-01

    Abstract The right to enjoy the benefits of scientific progress (REBSP) is a little-known but potentially valuable right that can contribute to rights-based approaches to addressing multidrug-resistant TB (MDR-TB). We argue that better understanding of the REBSP may help to advance legal and civil society action for health rights. While the REBSP does not provide an individual entitlement to have a new drug developed for MDR-TB, it sets up entitlements to expect a state to establish a legislative and policy framework aimed at developing scientific capacity to address the most important health issues and at disseminating the outcomes of scientific research. By making scientific findings available and accessible, people can be enabled to claim the use of science for social benefits. Inasmuch as the market fails to address neglected diseases such as MDR-TB, the REBSP provides a potential counterbalance to frame a positive obligation on states to both marshal their own resources and to coordinate the actions of multiple other actors towards this goal, including non-state actors. While the latter do not hold the same level of accountability as states, the REBSP can still enable the recognition of obligations at a level of “soft law” responsibilities. PMID:27780997

  19. Wavelength dependence of Verdet constant of Tb3+:Y2O3 ceramics

    NASA Astrophysics Data System (ADS)

    Snetkov, I. L.; Permin, D. A.; Balabanov, S. S.; Palashov, O. V.

    2016-04-01

    Samples of the magneto-active material—Tb3+:Y2O3 ceramics with Tb3+ ion concentrations of 10%, 20%, 30%, and 100% (Tb2O3)—were prepared and studied. The wavelength dependence of Verdet constant in the 380 nm-1750 nm range was approximated for all investigated ceramic samples and was predicted for a pure Tb2O3 material. Tb2O3 ceramics demonstrates a more than three times higher Verdet constant in comparison with terbium gallium garnet crystal or ceramics. The linear dependence of the Verdet constant on Tb3+ ion concentration in the Tb3+:Y2O3 ceramics was demonstrated. The obtained data will be useful for fabricating magneto-optical elements of Faraday devices based on Tb3+:Y2O3 with arbitrary Tb3+ ion concentration operating at room temperature in the wavelength range of 380 nm-1750 nm.

  20. Isoniazid toxicity and TB development during biological therapy of patients with psoriasis in Colombia.

    PubMed

    Cataño, Juan; Morales, Milena

    2016-10-01

    Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up.

  1. Advances and prospects for management of TB transmission between badgers and cattle.

    PubMed

    Wilson, Gavin J; Carter, Stephen P; Delahay, Richard J

    2011-07-05

    Bovine tuberculosis (bTB) is the most serious endemic disease facing the livestock industry in the United Kingdom (UK) and Republic of Ireland (RoI), where its management has been confounded by the presence of persistent infection in the Eurasian badger (Meles meles). Field evidence suggests that the social structure of badger populations can have an important influence on disease dynamics, and on the outcome of management interventions. Recent, large-scale badger culling experiments in the UK and RoI had complex epidemiological outcomes. In the UK, proactive culling led to reduced bTB incidence in cattle herds inside culled areas, but a temporary increase in adjacent areas. Reactive culling in response to herd breakdowns was associated with an increase in the incidence of bTB in cattle. In contrast, badger culling in RoI was reported to have only beneficial effects on bTB incidence in cattle. The reasons for these differences are not clear. The complexity of the evidence base for culling is highlighted by the different management approaches currently being adopted by the different authorities of the UK and RoI. It is generally accepted that a holistic approach to bTB management, which targets both cattle and wildlife, is necessary. Consequently recent research activities have also focussed on cattle and badger vaccines, and biosecurity on farms. This paper describes recent advances in our understanding of the epidemiology of bTB in badgers and the consequences of culling, and current research to develop approaches for the vaccination of badgers, and methods of managing the risks of contact between badgers and cattle in farm buildings.

  2. Pregnancy outcome in serologically indicated active Chlamydia trachomatis infection.

    PubMed

    Tadmor, O P; Shaia, M; Rosenman, H; Livshin, Y; Choukroun, C; Barr, I; Diamant, Y Z

    1993-05-01

    A serological test for chlamydial infection was administered to 281 Jerusalem women in order to determine the rate and influence of Chlamydia on pregnancy outcome. Serological indication of active infection was present in 7.8% of the tested women, while 15.3% were shown to be positive for Chlamydia. Among the ultraorthodox subpopulation of Mea Shearim, serological indication of active infection was present among 5.9% of the women, and 12.3% of this population tested positive. In comparison, women from the secular subpopulation had 12.7% serological indication of active infection and 22.95% tested positive (P < 0.01). There were no statistically significant differences between pregnancy duration, birthweight, incidence of premature uterine contractions, premature rupture of membranes, and postpartum febrile morbidity in the infected and noninfected groups. Women with a previous history of induced abortions showed a significantly higher evidence of past Chlamydia infection (9.3%) when compared with the women who did not have an infection (1.4%) (P < 0.006). Among the ultraorthodox women with positive or active infection, 41% had suffered at least one spontaneous abortion, as compared with 25% of the religious women who had no serological evidence of infection.

  3. Preparation and spectroscopic properties of rare-earth (RE) (RE = Sm, Eu, Tb, Dy, Tm)-activated K{sub 2}LnZr(PO{sub 4}){sub 3} (Ln = Y, La, Gd and Lu) phosphate in vacuum ultraviolet region

    SciTech Connect

    Zhang, Zhi-Jun; Lin, Xiao; Zhao, Jing-Tai; Zhang, Guo-Bin

    2013-02-15

    Graphical abstract: Display Omitted Highlights: ► We report the VUV spectroscopic properties of rare-earth ions in K{sub 2}LnZr(PO{sub 4}){sub 3}. ► The O{sup 2−}-Eu{sup 3+} charge transfer bands at about 220 nm have been observed. ► The 4f–5d spin-allowed and spin-forbidden transitions of Tb{sup 3+} have been observed. ► There is energy transfer between the host and rare-earth activators. -- Abstract: Rare earth (RE = Sm, Eu, Tb, Dy and Tm)-activated K{sub 2}LnZr(PO{sub 4}){sub 3} (Ln = Y, La, Gd and Lu) have been synthesized by solid-state reaction method, and their vacuum ultraviolet (VUV) excitation luminescent characteristics have been investigated. The band in the wavelength range of 130–157 nm and the other one range from 155 to 216 nm with the maximum at about 187 nm in the VUV excitation spectra of these compounds are attributed to the host lattice absorption and O–Zr charge transfer transition, respectively. The charge transfer bands (CTB) of O{sup 2−}-Sm{sup 3+}, O{sup 2−}-Dy{sup 3+} and O{sup 2−}-Tm{sup 3+}, in Sm{sup 3+}, Dy{sup 3+} and Tm{sup 3+}-activated samples, have not been obviously observed probably because the 2p electrons of oxygen are tightly bound to the zirconium ion in the host lattice. For Eu{sup 3+}-activated samples, the relatively weak O{sup 2−}-Eu{sup 3+} CTB at about 220 nm is observed. And for Tb{sup 3+}-activated samples, the bands at 223 and 258 nm are related to the 4f-5d spin-allowed and spin-forbidden transitions of Tb{sup 3+}, respectively. It is observed that there is energy transfer between the host lattice and the luminescent activators (e.g. Eu{sup 3+}, Tb{sup 3+}). From the standpoint of luminescent efficiency, color purity and chemical stability, K{sub 2}GdZr(PO{sub 4}){sub 3}:Sm{sup 3+}, Eu{sup 3+}, Tb{sup 3+} are attractive candidates for novel yellow, red, green-emitting PDP phosphors.

  4. Genome-Wide Expression Profiling Identifies Type 1 Interferon Response Pathways in Active Tuberculosis

    PubMed Central

    Ottenhoff, Tom H. M.; Zhang, Mingzi M.; Wong, Hazel E. E.; Sahiratmadja, Edhyana; Khor, Chiea Chuen; Alisjahbana, Bachti; van Crevel, Reinout; Marzuki, Sangkot; Seielstad, Mark; van de Vosse, Esther; Hibberd, Martin L.

    2012-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains the leading cause of mortality from a single infectious agent. Each year around 9 million individuals newly develop active TB disease, and over 2 billion individuals are latently infected with M.tb worldwide, thus being at risk of developing TB reactivation disease later in life. The underlying mechanisms and pathways of protection against TB in humans, as well as the dynamics of the host response to M.tb infection, are incompletely understood. We carried out whole-genome expression profiling on a cohort of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment. We identified molecular signatures involving the upregulation of type-1 interferon (α/β) mediated signaling and chronic inflammation during active TB disease in an Indonesian population, in line with results from two recent studies in ethnically and epidemiologically different populations in Europe and South Africa. Expression profiles were captured in neutrophil-depleted blood samples, indicating a major contribution of lymphocytes and myeloid cells. Expression of type-1 interferon (α/β) genes mediated was also upregulated in the lungs of M.tb infected mice and in infected human macrophages. In patients, the regulated gene expression-signature normalized during treatment, including the type-1 interferon mediated signaling and a concurrent opposite regulation of interferon-gamma. Further analysis revealed IL15RA, UBE2L6 and GBP4 as molecules involved in the type-I interferon response in all three experimental models. Our data is highly suggestive that the innate immune type-I interferon signaling cascade could be used as a quantitative tool for monitoring active TB disease, and provide evidence that components of the patient’s blood gene expression signature bear similarities to the pulmonary and macrophage response to mycobacterial infection

  5. Preventing Nosocomial MDR-TB Transmission in sub Saharan Africa: Where Are We at?

    PubMed Central

    Menon, Sonia S.

    2013-01-01

    Background: In sub Saharan Africa, the cocktail of many advanced HIV-infected susceptible hosts, poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing (DST) have resulted in HIV-infected individuals being disproportionately represented in Multi drug resistant Tuberculosis (MDR-TB) cases. The prevailing application of the WHO re-treatment protocol indiscriminately to all re-treatment cases sets the stage for an increase in mortality and MDR-TB nosocomial transmission. Method: A comprehensive search was performed of the Cochrane Infectious Diseases Group Specialized Register and Medline database including the bibliographies of the retrieved reference. Findings: The TB diagnosis paradigm which for decades relied on smear sputum and culture is likely to change with the advent of the point-of-care diagnostic, Xpert MTB/RIF assay. Until the new DST infrastructure is available, along with clinical trials for both, current and new approaches to retreatment TB in areas heavily affected by HIV and TB, there are cost effective administrative, environmental, and protective measures that may be immediately instituted. Conclusion: The severe lack of infection control practices in sub Saharan Africa may jeopardise the recent strides in MDR-TB management. Cost effective infection control measures must be immediately implemented, otherwise the development of further drug resistance may offset recent strides in MDR-TB management. Indiscriminate use of the WHO standardized retreatment protocol can lead to nosocomial transmission of MDR-TB by: -Precluding early diagnosis and prompt separation of patients who experienced treatment failure category and thereby more likely to have MDR-TB. -Leaving patients from the treatment failure category in health establishments on ineffective standard retreatment regimen until the DST results are known. -Targeting only patients who have had prior TB therapy, new severely debilitated TB patients having

  6. Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy in Tanzania

    PubMed Central

    LIU, Enju; MAKUBI, Abel; DRAIN, Paul; SPIEGELMAN, Donna; SANDO, David; LI, Nan; CHALAMILLA, Guerino; SUDFELD, Christopher R.; HERTZMARK, Ellen; FAWZI, Wafaie W.

    2015-01-01

    Objective To determine the incidence rate and risk factors of tuberculosis (TB) among HIV-infected adults accessing antiretroviral therapy (ART) in Tanzania. Design A prospective observational study among HIV-infected adults attending 47 HIV clinics in Dar es Salaam. Methods We estimated TB incidence rates among HIV-infected patients prior to and after ART initiation. We used Cox proportional hazard regressions to determine the predictors of incident TB among HIV-infected adults enrolled in the HIV care and treatment program. Results We assessed 67,686 patients for a median follow-up period of 24 (interquartile range: 8–49) months; 7,602 patients were diagnosed with active TB. The TB incidence rate was 7.9 (95% Confidence Interval (CI), 7.6–8.2)/100 person-years prior to ART initiation, and 4.4(95%CI, 4.2–4.4)/100 person-years for patients receiving ART. In multivariate analyses, patients on ART in the first 3 months had a 57% higher risk of TB (Hazard Ratio:1.57, 95%CI:1.47–1.68) compared to those not on ART, but the risk significantly decreased with increasing duration of ART. Risk factors for incident TB included being male, having low body mass index or middle upper arm circumference, lower CD4 cell count, and advanced WHO disease stage. There was seasonal variation for incident TB, with higher risk observed following the rainy seasons (May, June, and November). Conclusion In TB endemic regions, HIV-infected patients initiating ART, particularly males and those with poor nutritional status, should be closely monitored for active TB in the months following ART initiation. In addition to increasing the access to ART, interventions should be considered to improve nutritional status among HIV-infected patients. PMID:26091295

  7. Tunable color temperature solid state white light source using flux grown phosphor crystals of Eu3+, Dy3+ and Tb3+ activated calcium sodium molybdenum oxide

    NASA Astrophysics Data System (ADS)

    Khanna, A.; Dutta, P. S.

    2014-11-01

    Solid state light sources with dynamically tunable color temperature in the range of 3000-6000 K with chromaticity coordinates lying on the Planckian black body curve has been designed using mixtures of narrow emissions at 615 nm, 575 nm and 550 nm. These respective emissions lines were generated by individual phosphor crystals of trivalent rare earth (RE3+) species, europium (Eu3+), dysprosium (Dy3+) and terbium (Tb3+) activated calcium sodium molybdenum oxide (Ca1-2xNaxMoO4:RE3+x), when excited by near-ultra-violet (NUV) light emitting diode (LED) with emission wavelength of 380 nm. Highly luminescent crystals of these compounds have been grown from molten solutions (flux) of molybdenum (VI) oxide. The flux grown crystals exhibit emission intensity 2-4 times more than phosphor powders of the same compounds synthesized by traditional solid-state reactions. An optimum flux to solute ratio of 2.5 and solute dissolution temperature of 1100 °C resulted in the largest size crystals.

  8. Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient.

    PubMed

    Mätz-Rensing, K; Hartmann, T; Wendel, G M; Frick, J S; Homolka, S; Richter, E; Munk, M H; Kaup, F-J

    2015-01-01

    Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies.

  9. Microglial activation induces neuronal death in Chandipura virus infection

    PubMed Central

    Verma, Abhishek Kumar; Ghosh, Sourish; Pradhan, Sreeparna; Basu, Anirban

    2016-01-01

    Neurotropic viruses induce neurodegeneration either directly by activating host death domains or indirectly through host immune response pathways. Chandipura Virus (CHPV) belonging to family Rhabdoviridae is ranked among the emerging pathogens of the Indian subcontinent. Previously we have reported that CHPV induces neurodegeneration albeit the root cause of this degeneration is still an open question. In this study we explored the role of microglia following CHPV infection. Phenotypic analysis of microglia through lectin and Iba-1 staining indicated cells were in an activated state post CHPV infection in cortical region of the infected mouse brain. Cytokine Bead Array (CBA) analysis revealed comparatively higher cytokine and chemokine levels in the same region. Increased level of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric Oxide (NO) and Reactive Oxygen species (ROS) in CHPV infected mouse brain indicated a strong inflammatory response to CHPV infection. Hence it was hypothesized through our analyses that this inflammatory response may stimulate the neuronal death following CHPV infection. In order to validate our hypothesis supernatant from CHPV infected microglial culture was used to infect neuronal cell line and primary neurons. This study confirmed the bystander killing of neurons due to activation of microglia post CHPV infection. PMID:26931456

  10. TB or not TB?: a case of isolated testicular TB with scrotal involvement.

    PubMed

    Bhargava, A; Davenport, C; Gibbons, N; McConkey, S

    2009-06-01

    Despite the genitourinary tract being the most common site affected by extrapulmonary TB, isolated testicular TB remains a rare clinical entity. In patients with co-morbidities such as hepatic impairment, treatment proves a challenge, as first-line hepatotoxic pharmaceuticals are contraindicated. Here, we report a case of isolated testicular TB with scrotal involvement, on a background of hepatic dysfunction.

  11. Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa.

    PubMed

    Gilbert, Jennifer A; Long, Elisa F; Brooks, Ralph P; Friedland, Gerald H; Moll, Anthony P; Townsend, Jeffrey P; Galvani, Alison P; Shenoi, Sheela V

    2015-01-01

    The WHO recommends integrating interventions to address the devastating TB/HIV co-epidemics in South Africa, yet integration has been poorly implemented and TB/HIV control efforts need strengthening. Identifying infected individuals is particularly difficult in rural settings. We used mathematical modeling to predict the impact of community-based, integrated TB/HIV case finding and additional control strategies on South Africa's TB/HIV epidemics. We developed a model incorporating TB and HIV transmission to evaluate the effectiveness of integrating TB and HIV interventions in rural South Africa over 10 years. We modeled the impact of a novel screening program that integrates case finding for TB and HIV in the community, comparing it to status quo and recommended TB/HIV control strategies, including GeneXpert, MDR-TB treatment decentralization, improved first-line TB treatment cure rate, isoniazid preventive therapy, and expanded ART. Combining recommended interventions averted 27% of expected TB cases (95% CI 18-40%) 18% HIV (95% CI 13-24%), 60% MDR-TB (95% CI 34-83%), 69% XDR-TB (95% CI 34-90%), and 16% TB/HIV deaths (95% CI 12-29). Supplementing these interventions with annual community-based TB/HIV case finding averted a further 17% of TB cases (44% total; 95% CI 31-56%), 5% HIV (23% total; 95% CI 17-29%), 8% MDR-TB (68% total; 95% CI 40-88%), 4% XDR-TB (73% total; 95% CI 38-91%), and 8% TB/HIV deaths (24% total; 95% CI 16-39%). In addition to increasing screening frequency, we found that improving TB symptom questionnaire sensitivity, second-line TB treatment delays, default before initiating TB treatment or ART, and second-line TB drug efficacy were significantly associated with even greater reductions in TB and HIV cases. TB/HIV epidemics in South Africa were most effectively curtailed by simultaneously implementing interventions that integrated community-based TB/HIV control strategies and targeted drug-resistant TB. Strengthening existing TB and HIV

  12. Determinants for tuberculosis in HIV-infected adults in Northwest Ethiopia: a multicentre case–control study

    PubMed Central

    Alemu, Yihun Mulugeta; Awoke, Worku; Wilder-Smith, Annalies

    2016-01-01

    Objective The objective of this study was to identify determinants for tuberculosis (TB) among HIV-infected adults in Northwest Ethiopia. Design Case–control study. Setting Three hospitals and 10 health centres in Northwest Ethiopia. Participants A total of 446 individuals consented to participate in the study (150 cases and 296 controls). Cases were HIV-infected adults diagnosed with active TB, and controls were HIV-infected adults without active TB. Main outcome measure The link between TB and determinants was assessed using logistic regression. Determinants were categorised as sociodemographic, host-related, clinical and environmental. Results Smoking (adjusted OR (AOR) 5.47; 95% CI 2.26 to 13.22), presence of a TB patient in the family (AOR 2.66; 95% CI 1.25 to 5.66), alcohol consumption (AOR 2.49; 95% CI 1.29 to 4.80) and chewing khat (AOR 2.22; 95% CI 1.11 to 4.41) were independent determinants for increased occurrence of TB. Highly active antiretroviral therapy (HAART) (AOR 0.25; 95% CI 0.13 to 0.51), isoniazid preventive therapy (IPT) (AOR 0.22; 95% CI 0.11 to 0.41) and cotrimoxazole preventive therapy (AOR 0.32; 95% CI 0.19 to 0.55) had a protective effect against TB. Conclusions HIV-infected adults with substance abuse (tobacco smoking, khat chewing and alcohol) should be prioritised for TB screening. This study reaffirmed that HAART and IPT are some of the best strategies for reducing TB occurrence in HIV-infected adults. These findings provide impetus to intensify tracing of TB household contacts. PMID:27084271

  13. T cell reactivity against mycolyl transferase antigen 85 of M. tuberculosis in HIV-TB coinfected subjects and in AIDS patients suffering from tuberculosis and nontuberculous mycobacterial infections.

    PubMed

    Launois, Pascal; Drowart, Annie; Bourreau, Eliane; Couppie, Pierre; Farber, Claire-Michèle; Van Vooren, Jean-Paul; Huygen, Kris

    2011-01-01

    The mycolyl transferase antigen 85 complex is a major secreted protein family from mycobacterial culture filtrate, demonstrating powerful T cell stimulatory properties in most HIV-negative, tuberculin-positive volunteers with latent M.tuberculosis infection and only weak responses in HIV-negative tuberculosis patients. Here, we have analyzed T cell reactivity against PPD and Ag85 in HIV-infected individuals, without or with clinical symptoms of tuberculosis, and in AIDS patients with disease caused by nontuberculous mycobacteria. Whereas responses to PPD were not significantly different in HIV-negative and HIV-positive tuberculin-positive volunteers, responses to Ag85 were significantly decreased in the HIV-positive (CDC-A and CDC-B) group. Tuberculosis patients demonstrated low T cell reactivity against Ag85, irrespective of HIV infection, and finally AIDS patients suffering from NTM infections were completely nonreactive to Ag85. A one-year follow-up of twelve HIV-positive tuberculin-positive individuals indicated a decreased reactivity against Ag85 in patients developing clinical tuberculosis, highlighting the protective potential of this antigen.

  14. Addressing diabetes mellitus as part of the strategy for ending TB.

    PubMed

    Harries, Anthony D; Kumar, Ajay M V; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

    2016-03-01

    As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases.

  15. Addressing diabetes mellitus as part of the strategy for ending TB

    PubMed Central

    Harries, Anthony D.; Kumar, Ajay M.V.; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

    2016-01-01

    As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497

  16. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

    PubMed Central

    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang, Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection. PMID:28133458

  17. An investigation into the statistical properties of TB episodes in a South African community with high HIV prevalence.

    PubMed

    Pretorius, Carel; Dodd, Peter; Wood, Robin

    2011-02-07

    Continuous differential equations are often applied to small populations with little time spent on understanding uncertainty brought about by small-population effects. Despite large numbers of individuals being latently infected with Mycobacterium tuberculosis (TB), progression from latent infection to observable disease is a relatively rare event. For small communities, this means case counts are subject to stochasticity, and deterministic models may not be appropriate tools for interpreting transmission trends. Furthermore, the nonlinear nature of the underlying dynamics means that fluctuations are autocorrelated, which can invalidate standard statistical analyses which assume independent fluctuations. Here we extend recent work using a system of differential equations to study the HIV-TB epidemic in Masiphumelele, a community near Cape Town in South Africa [Bacaër, et al., J. Mol. Biol. 57(4), 557-593] by studying the statistical properties of active TB events. We apply van Kampen's system-size (or population-size) expansion technique to obtain an approximation to a master equation describing the dynamics. We use the resulting Fokker-Planck equation and point-process theory to derive two-time correlation functions for active TB events. This method can be used to gain insight into the temporal aspect of cluster identification, which currently relies on DNA classification only.

  18. 78 FR 40481 - Agency Information Collection Activities; Proposals, Submissions, and Approvals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... Tuberculosis Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC). Background and Brief... prevention and control of HIV infection, viral hepatitis, sexually transmitted diseases (STDs), and tuberculosis (TB), as well as for community-based HIV prevention activities, syphilis, and TB...

  19. Luminescent properties of rare earth fully activated apatites, LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb): site selective crystal field effect.

    PubMed

    Kim, Donghyeon; Park, Doyoung; Oh, Namgyeong; Kim, Jaegyeom; Jeong, Euh Duck; Kim, Seung-Joo; Kim, Sungyun; Park, Jung-Chul

    2015-02-16

    Novel LiCe9(SiO4)6O2 and LiTb9(SiO4)6O2 compounds have been successfully synthesized, and the site selectivity and occupancy of activator ions have been estimated including LiEu9(SiO4)6O2 compound. The rare earth (RE) fully occupied compounds, as well as the RE partially occupied congeners are required for the assessment of site selectivity of RE (activator) ions in apatite-type compounds. The splitting energies of the 6H and 4F Wycoff positions of LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb) compounds are calculated based on crystal field theory: ΔECe(6H) = 3849.3 cm(-1), ΔECe(4F) = 4228.1 cm(-1), ΔEEu(6H) = 3870.0 cm(-1), ΔEEu(4F) = 4092.8 cm(-1), ΔETb(6H) = 3637.6 cm(-1), ΔETb(4F) = 4396.1 cm(-1), indicating that the splitting energy for the 4F site is larger than that for the 6H site in all compounds; thus the absorption energy is higher for the 6H site. In apatite-type LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb) compounds, the Ce(3+) ions predominantly occupy the 4F site associated with the absorption band around 300 nm at lower Ce(3+) concentration, and then enter the 6H site associated the absorption band around 245 nm. For the Eu(3+)-doped compounds, the 4F site and 6H site are mixed within the charge transfer band (CTB) between 220 and 350 nm. Eu(3+) ions initially preferentially occupy the 6H site (around 290 nm) at lower Eu(3+) concentration and subsequently enter the 4F site (around 320 nm) with increasing Eu(3+) concentration. For the Tb(3+)-doped compounds, the absorption due to the two different sites is mixed within f-d absorption band between 200 and 300 nm. At lower Tb(3+) concentration, the Tb(3+) ions enter favorably 6H site around 240 nm and then enter 4F site around 270 nm. These compounds may provide a platform for modeling a new phosphor and application in the solid-state lighting field.

  20. [Management of tuberculosis (TB) cases from view points of public health].

    PubMed

    Satoh, Ken; Motomiya, Masakichi

    2011-08-01

    Tuberculosis control law was enacted in 1951 and has been the basis for the management of TB cases over the long post-war period. This law has legalized the use of public founds for the treatment of TB patients for the first time and has provided the authentic basis for mandatory hospitalization, routine health examination, vaccination, notification and registration of TB cases. However, this law was abrogated in 2001 and was joined to the comprehensive infectious diseases control law, in order to facilitate a prophylactic measure against TB infection and to protect human rights of TB patients. Concurrently the medical care system and the formalities connected to hospitalization treatment of TB patients were reviewed. The purpose of the present overview is to explain how TB cases are managed under the newly-enacted law.

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

    PubMed Central

    Blankley, Simon; Graham, Christine M.; Turner, Jacob; Berry, Matthew P. R.; Bloom, Chloe I.; Xu, Zhaohui; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; Breen, Ronan; Santis, George; Blankenship, Derek M.; Lipman, Marc; O’Garra, Anne

    2016-01-01

    Background Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. Methods A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB. Results The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. Conclusions The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics. PMID:27706152

  2. New drugs and regimens for treatment of TB

    PubMed Central

    Leibert, Eric; Rom, William N

    2013-01-01

    Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms. PMID:20586565

  3. Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages

    PubMed Central

    Moreira-Souza, Aline Cristina Abreu; Marinho, Ygor; Correa, Gladys; Santoro, Giani França; Coutinho, Claudia Mara Lara Melo; Vommaro, Rossiane Claudia; Coutinho-Silva, Robson

    2015-01-01

    Infection by the protozoan parasite Toxoplasma gondii is highly prevalent worldwide and may have serious clinical manifestations in immunocompromised patients. T. gondii is an obligate intracellular parasite that infects almost any cell type in mammalian hosts, including immune cells. The immune cells express purinergic P2 receptors in their membrane – subdivided into P2Y and P2X subfamilies - whose activation is important for infection control. Here, we examined the effect of treatment with UTP and UDP in mouse peritoneal macrophages infected with T. gondii tachyzoites. Treatment with these nucleotides reduced parasitic load by 90%, but did not increase the levels of the inflammatory mediators NO and ROS, nor did it modulate host cell death by apoptosis or necrosis. On the other hand, UTP and UDP treatments induced early egress of tachyzoites from infected macrophages, in a Ca2+-dependent manner, as shown by scanning electron microscopy analysis, and videomicroscopy. In subsequent infections, prematurely egressed parasites had reduced infectivity, and could neither replicate nor inhibit the fusion of lysosomes to the parasitophorous vacuole. The use of selective agonists and antagonists of the receptor subtypes P2Y2 and P2Y4 and P2Y6 showed that premature parasite egress may be mediated by the activation of these receptor subtypes. Our results suggest that the activity of P2Y host cell receptors controls T. gondii infection in macrophages, highlighting the importance of pyrimidinergic signaling for innate immune system response against infection. Finally the P2Y receptors should be considered as new target for the development of drugs against T. gondii infection. PMID:26192447

  4. Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages

    PubMed Central

    La Manna, Marco Pio; Orlando, Valentina; Dieli, Francesco; Di Carlo, Paola; Cascio, Antonio; Cuzzi, Gilda; Palmieri, Fabrizio; Goletti, Delia

    2017-01-01

    Tuberculosis (TB) is one of the most important cause of morbidity and death among infectious diseases, and continuous efforts are needed to improve diagnostic tools and therapy. Previous published studies showed that the absolute cells number of monocytes or lymphocytes in peripheral blood or yet the ratio of monocytes to lymphocytes displayed the ability to predict the risk of active TB. In the present study we evaluated the ratio of monocytes to lymphocytes variation and we also analyzed the ex-vivo expression of CD64 on monocytes as tools to identify biomarkers for discriminating TB stages. Significant differences were found when the average ratio of monocytes to lymphocytes of active TB patients was compared with latent TB infection (LTBI) subjects, cured TB and healthy donors (HD). By the receiver operator characteristics (ROC) curve analysis the cut-off value of 0.285, allowed the discrimination of active TB from HD, with a sensitivity of 91.04% and a specificity of 93.55% (95% of confidence interval: 0.92–0.99). The ROC curve analysis comparing TB patients and LTBI groups, led to a sensitivity and the specificity of the assay of 85.07% and 85.71%, respectively (95% of confidence interval: 0.85 to 0.96). The upregulation of CD64 expression on circulating monocytes in active TB patients could represent an additional biomarker for diagnosis of active TB. In conclusion, we found that the ML ratio or monocyte absolute count or phenotypic measures show predictive value for active TB. PMID:28208160

  5. Active cytomegalovirus infection in patients with atopic dermatitis.

    PubMed

    Hafez, Shereen F; Shehata, Iman H; Abdel Aziz, Ghada A; Kamal, Mahmoud M

    2005-01-01

    Atopic dermatitis (AD) is a complex immunologic skin disorder that is expressed when genetically predisposed individuals are exposed to certain environmental stimuli. Inspite of the high prevalence of cytomegalovirus (CMV) infection and its potent immunomodulatory activities, the relation of CMV to AD is still poorly understood and is still to be clarified. The aim of the present study was to evaluate the frequency of active CMV infection in patients with AD and its possible etiologic role in the pathogenesis of the disease. Also, we tried to find if a relation between active CMV infection and disease severity exists. The present study was carried on 31 patients with AD with various degrees of disease severity. Ten apparently healthy subjects were enrolled in the study as a control group. Anti CMV IgG antibodies were estimated by quantitative enzyme immunoassay to discriminate between recent CMV infection and CMV reactivation. Active CMV infection was diagnosed by using nested PCR to detect CMV DNA in the sera of the studied subjects. The detection rate of CMV genome was higher in patients with AD in comparison to the control group. Cytomegalovirus genome was detected in the sera of 52% (16/31) of patients with AD (87.5% of them were seropositive for anti-CMV IgG antibodies). On the other hand no CMV DNA was detected in any of the serum samples of the control subjects. The difference was statistically significant. No significant relation was found between active CMV infection and disease severity. Also, no significant statistical difference was found between the two studied groups as regards the prevalence of latent CMV infection. In addition, no significant difference was detected between anti-CMV IgG antibody levels in all seropositive subjects. Our results denote that active subclinical CMV infection is more frequent in patients with AD and may have possible immunomodulatory role in the etiopathogenesis of AD but it is not related to disease severity.

  6. Mayaro virus infection cycle relies on casein kinase 2 activity.

    PubMed

    Barroso, Madalena M S; Lima, Carla S; Silva-Neto, Mário A C; Da Poian, Andrea T

    2002-09-06

    Replication of Mayaro virus in Vero cells induces dramatic cytopathic effects and cell death. In this study, we have evaluated the role of casein kinase 2 (CK2) during Mayaro virus infection cycle. We found that CK2 was activated during the initial stages of infection ( approximately 36% after 4h). This activation was further confirmed when the enzyme was partially purified from the cellular lysate either by Mono Q 5/5Hr column or heparin-agarose column. Using this later column, we found that the elution profile of CK2 activity from infected cells was different from that obtained for control cell enzyme, suggesting a structural modification of CK2 after infection. Treatment of infected cells with a cell-permeable inhibitor of CK2, dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB), abolished the cytopathic effect in a dose-dependent manner. Together this set of data demonstrates for the first time that CK2 activity in host cells is required in Mayaro virus infection cycle.

  7. EGFR regulates macrophage activation and function in bacterial infection.

    PubMed

    Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad; Verriere, Thomas G; Olivares-Villagómez, Danyvid; Barry, Daniel P; Allaman, Margaret M; Washington, M Kay; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T

    2016-09-01

    EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis.

  8. Acute lymphoid changes and ongoing immune activation in SIV infection.

    PubMed

    Popov, J; McGraw, T; Hofmann, B; Vowels, B; Shum, A; Nishanian, P; Fahey, J L

    1992-01-01

    Two features of simian immunodeficiency virus (SIV) infection are emphasized: a transitory decrease in CD4 T cells in the first 2 weeks of infection followed by CD8 T-cell rise, and immune cell activation occurring by 4 weeks and persisting throughout the illness. The short-term changes included a fall in CD4 T cells by 2 weeks with partial recovery by 4 weeks and a CD8 rise that starts at 2 weeks. Subsequent characterization of CD4 T cells showed reduced expression of HLA-DR and CD25 (IL-2 receptor alpha chain) antigens later in SIV infection. Immune cell activation is evident in increased serum levels of neopterin and soluble CD8 antigen. Serum beta 2-microglobulin changes are less marked. Activation of CD8 T cells is reflected by increased percentages of cells expressing HLA-DR antigen. The B-cell numbers increased late in the course of SIV infection. Increased expression of the CD78 (Leu 21) activation phenotype was also seen in some monkeys. The immune activation changes (serum neopterin levels) induced by SIV infection in rhesus macaques appear to be associated with duration of illness, although the number of monkeys observed until death were too few for conclusive data. Thus, immune activation as well as T-cell deficiency may reflect significant immunopathogenic processes in SIV-induced disease.

  9. TISSUE FACTOR EXPRESSION BY MYELOID CELLS CONTRIBUTES TO PROTECTIVE IMMUNE RESPONSE AGAINST Mycobacterium tuberculosis INFECTION

    PubMed Central

    Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R.; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

    2015-01-01

    Tissue Factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TFΔ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2 like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. PMID:26471500

  10. Prevalence, Risk Factors and Social Context of Active Pulmonary Tuberculosis among Prison Inmates in Tajikistan

    PubMed Central

    Winetsky, Daniel E.; Almukhamedov, Olga; Pulatov, Dilshod; Vezhnina, Natalia; Dooronbekova, Aizhan; Zhussupov, Baurzhan

    2014-01-01

    Setting Tuberculosis (TB) is highly prevalent in prisons of the former Soviet Union. Objective To understand the behavioral, demographic and biological factors placing inmates in Tajikistan at risk for active TB. Design We administered a behavioral and demographic survey to 1317 inmates in two prison facilities in Sughd province, Tajikistan along with radiographic screening for pulmonary TB. Suspected cases were confirmed bacteriologically. Inmates undergoing TB treatment were also surveyed. In-depth interviews were conducted with former prisoners to elicit relevant social and behavioral characteristics. Results We identified 59 cases of active pulmonary TB (prevalence 4.5%). Factors independently associated with increased prevalence of active TB were: HIV-infection by self-report (PR 7.88; 95%CI 3.40–18.28), history of previous TB (PR 10.21; 95%CI 6.27–16.63) and infrequent supplemental nutrition beyond scheduled meals (PR 3.00; 95%CI 1.67–5.62). Access to supplemental nutrition was associated with frequency of visits from friends and family and ability to rely on other inmates for help. Conclusion In prison facilities of Tajikistan, HIV-infection, injection drug use and low access to supplemental nutrition were associated with prevalent cases of active pulmonary TB. Policies that reduce HIV transmission among injection drug users and improve the nutritional status of socially isolated inmates may alleviate the TB burden in Tajikistan’s prisons. PMID:24465861

  11. Platelet activation determines the severity of thrombocytopenia in dengue infection

    PubMed Central

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  12. Transcriptional profile of TB antigen-specific T cells reveals novel multifunctional features1

    PubMed Central

    Arlehamn, Cecilia Lindestam; Seumois, Gregory; Gerasimova, Anna; Huang, Charlie; Fu, Zheng; Yue, Xiaojing; Sette, Alessandro; Vijayanand, Pandurangan; Peters, Bjoern

    2014-01-01

    In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4+ T cells as important contributors. Here we show that TB-specific CD4+ T cells have a characteristic chemokine expression signature (CCR6+CXCR3+CCR4−), and that the overall number of these cells is significantly increased in LTBI donors compared to healthy subjects. We have comprehensively characterized the transcriptional signature of CCR6+CXCR3+CCR4− cells and find significant differences to conventional Th1, Th17 and Th2 cells, but no major changes between healthy and LTBI donors. CCR6+CXCR3+CCR4− cells display linage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of CCR6+CXCR3+CCR4− cells reveals characteristics important for controlling latent TB infections. PMID:25092889

  13. Active Tuberculosis Case Finding in Port-au-Prince, Haiti: Experiences, Results, and Implications for Tuberculosis Control Programs

    PubMed Central

    Delva, Guesly J.; Fort, Dumesle St.

    2016-01-01

    Background. Haiti has the highest tuberculosis (TB) prevalence in the Americas with 254 cases per 100,000 persons. Case detection relies on passive detection and TB services in many regions suffer from poor diagnostic and clinical resources. Methods. Mache Chache (“Go and Seek”) was a TB REACH Wave 3 funded TB case finding project in Port-au-Prince between July 2013 and September 2014, targeting four intervention areas with insufficient TB diagnostic performance. Results. Based on a verbal symptom screen emphasizing the presence of cough, the project identified 11,150 (11.75%) of all screened persons as TB subjects and 2.67% as smear-positive (SS+) TB cases. Enhanced case finding and strengthening of laboratory services led to a 59% increase in bacteriologically confirmed cases in the evaluation population. In addition, smear grades dropped significantly, suggesting earlier case detection. Xpert® MTB/RIF was successfully introduced and improved TB diagnosis in HIV-infected, smear-negative clinic patients, but not in HIV-negative, smear-negative TB suspects in the community. However, the number needed to screen for one additional SS+ case varied widely between clinic and community screening activities. Conclusion. Enhanced and active TB case finding in Haiti can improve TB diagnosis and care. However, screening algorithms have to be tailored to individual settings, necessitating long-term commitment. PMID:27668093

  14. Immune parameters differentiating active from latent tuberculosis infection in humans.

    PubMed

    Lee, Ji Yeon; Jung, Young Won; Jeong, Ina; Joh, Joon-Sung; Sim, Soo Yeon; Choi, Boram; Jee, Hyeon-Gun; Lim, Dong-Gyun

    2015-12-01

    Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.

  15. A Panel of Trypanosoma brucei Strains Tagged with Blue and Red-Shifted Luciferases for Bioluminescent Imaging in Murine Infection Models

    PubMed Central

    Van Reet, Nick; Van de Vyver, Hélène; Pyana, Patient Pati; Van der Linden, Anne Marie; Büscher, Philippe

    2014-01-01

    Background Genetic engineering with luciferase reporter genes allows monitoring Trypanosoma brucei (T.b.) infections in mice by in vivo bioluminescence imaging (BLI). Until recently, luminescent T.b. models were based on Renilla luciferase (RLuc) activity. Our study aimed at evaluating red-shifted luciferases for in vivo BLI in a set of diverse T.b. strains of all three subspecies, including some recently isolated from human patients. Methodology/Principal findings We transfected T.b. brucei, T.b. rhodesiense and T.b. gambiense strains with either RLuc, click beetle red (CBR) or Photinus pyralis RE9 (PpyRE9) luciferase and characterised their in vitro luciferase activity, growth profile and drug sensitivity, and their potential for in vivo BLI. Compared to RLuc, the red-shifted luciferases, CBR and PpyRE9, allow tracking of T.b. brucei AnTaR 1 trypanosomes with higher details on tissue distribution, and PpyRE9 allows detection of the parasites with a sensitivity of at least one order of magnitude higher than CBR luciferase. With CBR-tagged T.b. gambiense LiTaR1, T.b. rhodesiense RUMPHI and T.b. gambiense 348 BT in an acute, subacute and chronic infection model respectively, we observed differences in parasite tropism for murine tissues during in vivo BLI. Ex vivo BLI on the brain confirmed central nervous system infection by all luminescent strains of T.b. brucei AnTaR 1, T.b. rhodesiense RUMPHI and T.b. gambiense 348 BT. Conclusions/Significance We established a genetically and phenotypically diverse collection of bioluminescent T.b. brucei, T.b. gambiense and T.b. rhodesiense strains, including drug resistant strains. For in vivo BLI monitoring of murine infections, we recommend trypanosome strains transfected with red-shifted luciferase reporter genes, such as CBR and PpyRE9. Red-shifted luciferases can be detected with a higher sensitivity in vivo and at the same time they improve the spatial resolution of the parasites in the entire body due to the better

  16. One Episode of Self-Resolving Plasmodium yoelii Infection Transiently Exacerbates Chronic Mycobacterium tuberculosis Infection

    PubMed Central

    Blank, Jannike; Eggers, Lars; Behrends, Jochen; Jacobs, Thomas; Schneider, Bianca E.

    2016-01-01

    Malaria and tuberculosis (Tb) are two of the main causes of death from infectious diseases globally. The pathogenic agents, Plasmodium parasites and Mycobacterium tuberculosis, are co-endemic in many regions in the world, however, compared to other co-infections like HIV/Tb or helminth/Tb, malaria/Tb has been given less attention both in clinical and immunological studies. Due to the lack of sufficient human data, the impact of malaria on Tb and vice versa is difficult to estimate but co-infections are likely to occur very frequently. Due to its immunomodulatory properties malaria might be an underestimated risk factor for latent or active Tb patients particularly in high-endemic malaria settings were people experience reinfections very frequently. In the present study, we used the non-lethal strain of Plasmodium yoelii to investigate, how one episode of self-resolving malaria impact on a chronic M. tuberculosis infection. P. yoelii co-infection resulted in exacerbation of Tb disease as demonstrated by increased pathology and cellular infiltration of the lungs which coincided with elevated levels of pro- and anti-inflammatory mediators. T cell responses were not impaired in co-infected mice but enhanced and likely contributed to increased cytokine production. We found a slight but statistically significant increase in M. tuberculosis burden in co-infected animals and increased lung CFU was positively correlated with elevated levels of TNFα but not IL-10. Infection with P. yoelii induced the recruitment of a CD11c+ population into lungs and spleens of M. tuberculosis infected mice. CD11c+ cells isolated from P. yoelii infected spleens promoted survival and growth of M. tuberculosis in vitro. 170 days after P. yoelii infection changes in immunopathology and cellular immune responses were no longer apparent while M. tuberculosis numbers were still slightly higher in lungs, but not in spleens of co-infected mice. In conclusion, one episode of P. yoelii co-infection

  17. Multiple host kinases contribute to Akt activation during Salmonella infection.

    PubMed

    Roppenser, Bernhard; Kwon, Hyunwoo; Canadien, Veronica; Xu, Risheng; Devreotes, Peter N; Grinstein, Sergio; Brumell, John H

    2013-01-01

    SopB is a type 3 secreted effector with phosphatase activity that Salmonella employs to manipulate host cellular processes, allowing the bacteria to establish their intracellular niche. One important function of SopB is activation of the pro-survival kinase Akt/protein kinase B in the infected host cell. Here, we examine the mechanism of Akt activation by SopB during Salmonella infection. We show that SopB-mediated Akt activation is only partially sensitive to PI3-kinase inhibitors LY294002 and wortmannin in HeLa cells, suggesting that Class I PI3-kinases play only a minor role in this process. However, depletion of PI(3,4) P2/PI(3-5) P3 by expression of the phosphoinositide 3-phosphatase PTEN inhibits Akt activation during Salmonella invasion. Therefore, production of PI(3,4) P2/PI(3-5) P3 appears to be a necessary event for Akt activation by SopB and suggests that non-canonical kinases mediate production of these phosphoinositides during Salmonella infection. We report that Class II PI3-kinase beta isoform, IPMK and other kinases identified from a kinase screen all contribute to Akt activation during Salmonella infection. In addition, the kinases required for SopB-mediated activation of Akt vary depending on the type of infected host cell. Together, our data suggest that Salmonella has evolved to use a single effector, SopB, to manipulate a remarkably large repertoire of host kinases to activate Akt for the purpose of optimizing bacterial replication in its host.

  18. Luminescent properties of Tb-activated rare-earth oxyapatite silicate MLn4Si3O13 (M = Ca, Sr, Ln = La, Gd)

    NASA Astrophysics Data System (ADS)

    Yamane, A.; Kunimoto, T.; Ohmi, K.; Honma, T.; Kobayashi, H.

    2006-09-01

    Rare-earth oxyapatites MLn4Si3O13 (M = Ca, Sr, Ba Ln = La, Gd) have been proposed as a new plasma display panel (PDP) host material to overcome the problems of Zn2SiO4:Mn commercial green phosphor, such as luminance degradation and poor surface charge. Tb-doped MLn4Si3O13 phosphor powders show a green luminescence with the CIE color coordinate (x, y) = (0.337, 0.562). The PL excitation band lies continuously in the wavelength region from 130 to 260 nm. The photoluminescence (PL) peak intensity of SrGd4Si3O13:Tb is comparable with that of Zn2SiO4:Mn. The phosphor is a candidate for a green PDP phosphor for Xe2 excitation.

  19. Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.

    PubMed

    Barouch, Dan H; Ghneim, Khader; Bosche, William J; Li, Yuan; Berkemeier, Brian; Hull, Michael; Bhattacharyya, Sanghamitra; Cameron, Mark; Liu, Jinyan; Smith, Kaitlin; Borducchi, Erica; Cabral, Crystal; Peter, Lauren; Brinkman, Amanda; Shetty, Mayuri; Li, Hualin; Gittens, Courtney; Baker, Chantelle; Wagner, Wendeline; Lewis, Mark G; Colantonio, Arnaud; Kang, Hyung-Joo; Li, Wenjun; Lifson, Jeffrey D; Piatak, Michael; Sekaly, Rafick-Pierre

    2016-04-21

    The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

  20. UV-VUV-excited photoluminescence of RE-activated CaLaP{sub 3}O{sub 10} (RE=Eu,Tb)

    SciTech Connect

    Wu Chunfang; Wang Yuhua . E-mail: wyh@lzu.edu.cn; Liu Wenjing

    2006-12-15

    Monazite-type polyphosphate CaLaP{sub 3}O{sub 10} was synthesized by solid-state reaction at 1000 deg. C and their photoluminescence of Eu{sup 3+} and Tb{sup 3+} in CaLaP{sub 3}O{sub 10} under ultraviolet (UV) and vacuum-ultraviolet (VUV) excitation were evaluated for the first time. The emission spectra of CaLaP{sub 3}O{sub 10}:Eu{sup 3+}showed that Eu{sup 3+} are in a site with inversion symmetry because the magnetic dipole transition {sup 5} D {sub 0}-{sup 7} F {sub 1} was the strongest both upon 254 and 147 nm excitation. Monitored at 621 nm the excitation spectra consisted of host absorption bands, charge transfer band of Eu-O and the intraconfiguration 4f {sup 6} transition of Eu{sup 3+}. Green phosphor CaLaP{sub 3}O{sub 10}:Tb{sup 3+}exhibited better color purity when excited by 147 nm than that excited by 254 nm. With monitored at 542 nm the host absorption bands of CaLaP{sub 3}O{sub 10}:Tb{sup 3+} were also observed. Besides the host absorption bands there were strong f-d and weak f-f transitions of Tb{sup 3+}. - Graphical abstract: Excitation spectra of CaLa{sub 0.85}P{sub 3}O{sub 10}:0.15Eu{sup 3+} ({lambda} {sub em}=620 nm)

  1. Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity.

    PubMed

    Gilio, Joyce M; Marcondes, Marcelo F; Ferrari, Débora; Juliano, Maria A; Juliano, Luiz; Oliveira, Vitor; Machado, Maurício F M

    2017-04-01

    Metacaspases are members of the cysteine peptidase family and may be implicated in programmed cell death in plants and lower eukaryotes. These proteases exhibit calcium-dependent activity and specificity for arginine residues at P1. In contrast to caspases, they do not require processing or dimerization for activity. Indeed, unprocessed metacaspase-2 of Trypanosoma brucei (TbMCA2) is active; however, it has been shown that cleavages at Lys(55) and Lys(268) increase TbMCA2 hydrolytic activity on synthetic substrates. The processed TbMCA2 comprises 3 polypeptide chains that remain attached by non-covalent bonds. Replacement of Lys(55) and Lys(268) with Gly via site-directed mutagenesis results in non-processed but enzymatically active mutant, TbMCA2 K55/268G. To investigate the importance of this processing for the activity and specificity of TbMCA2, we performed activity assays comparing the non-processed mutant (TbMCA2 K55/268G) with the processed TbMCA2 form. Significant differences between TbMCA2 WT (processed form) and TbMCA2 K55/268G (non-processed form) were observed. Specifically, we verified that although non-processed TbMCA2 is active when assayed with small synthetic substrates, the TbMCA2 form does not exhibit hydrolytic activity on large substrates such as azocasein, while processed TbMCA2 is able to readily digest this protein. Such differences can be relevant for understanding the physiological regulation and function of TbMCA2.

  2. LL-37 Immunomodulatory Activity during Mycobacterium tuberculosis Infection in Macrophages

    PubMed Central

    Torres-Juarez, Flor; Cardenas-Vargas, Albertina; Montoya-Rosales, Alejandra; González-Curiel, Irma; Garcia-Hernandez, Mariana H.; Enciso-Moreno, Jose A.; Hancock, Robert E. W.

    2015-01-01

    Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 during M. tuberculosis infection has not been clarified. Monocyte-derived macrophages were infected with M. tuberculosis strain H37Rv and then treated with 1, 5, or 15 μg/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor β (TGF-β) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines. PMID:26351280

  3. Agreement between QuantiFERON®-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts

    PubMed Central

    2014-01-01

    Background Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people. We determined the prevalence of Mycobacterium tuberculosis infection by TST and QuantiFERON®-TB Gold In-Tube (QFT-GIT) and assessed agreement between the two test methods and factors associated with positivity in either test in Warao Amerindian children in Venezuela. Furthermore, progression to active TB disease was evaluated for up to 12 months. Methods 163 HIV-negative childhood household contacts under 16 years of age were enrolled for TST, QFT-GIT and chest X-ray (CXR). Follow-up was performed at six and 12 months. Factors associated with TST and QFT-GIT positivity were studied using generalized estimation equations logistic regression models. Results At baseline, the proportion of TST positive children was similar to the proportion of children with a positive QFT-GIT (47% vs. 42%, p = 0.12). Overall concordance between QFT-GIT and TST was substantial (kappa 0.76, 95% CI 0.46-1.06). Previous BCG vaccination was not associated with significantly increased positivity in either test (OR 0.68, 95% CI 0.32-1.5 for TST and OR 0.51, 95% CI 0.14-1.9 for QFT-GIT). Eleven children were diagnosed with active TB at baseline. QFT-GIT had a higher sensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95% CI 24-83%) while specificities were similar (respectively 58% and 55%). Five initially asymptomatic childhood contacts progressed to active TB disease during follow-up. Conclusion Replacement of TST by the QFT-GIT for detection of M. tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantial concordance and TST positivity was not affected by previous BCG vaccination. The QFT-GIT had a higher sensitivity than the TST for the detection of TB disease. However, the value of the QFT

  4. Rapid detection of Mycobacterium tuberculosis in sputum by Patho-TB kit in comparison with direct microscopy and culture.

    PubMed

    Ben-Selma, Walid; Ben-Kahla, Imen; Marzouk, Manel; Ferjeni, Asma; Ghezal, Samira; Ben-Said, Moncef; Boukadida, Jalel

    2009-11-01

    The usefulness of a new rapid diagnostic test (Patho-TB) using antibodies specific to mycobacterial antigens was evaluated for the rapid discrimination between pulmonary tuberculosis (TB) and non-TB pulmonary diseases on sputa. One hundred sputa collected from 79 active TB patients and from 21 patients with non-TB pulmonary diseases (asthma and chronic obstructive pulmonary disease) were enrolled into the study and tested for the presence of Mycobacterium tuberculosis by Ziehl-Neelsen smear, Patho-TB kit, and Löwenstein-Jensen culture. The sensitivity, specificity, positive predictive value, and negative predictive value of the Patho-TB test were 95%, 100%, 100%, and 84%, respectively. Patho-TB test is simple, quick, and easy to perform. Its sensitivity, specificity, and positive predictive value are satisfactory. Therefore, it could be used as a screening test in poorly equipped laboratories of TB endemic areas.

  5. BUTIMBA: Intensifying the Hunt for Child TB in Swaziland through Household Contact Tracing

    PubMed Central

    Alonso Ustero, Pilar; Golin, Rachel; Anabwani, Florence; Mzileni, Bulisile; Sikhondze, Welile; Stevens, Robert

    2017-01-01

    Background Limited data exists to inform contact tracing guidelines in children and HIV-affected populations. We evaluated the yield and additionality of household contact and source case investigations in Swaziland, a TB/HIV high-burden setting, while prioritizing identification of childhood TB. Methods In partnership with 7 local TB clinics, we implemented standardized contact tracing of index cases (IC) receiving TB treatment. Prioritizing child contacts and HIV-affected households, screening officers screened contacts for TB symptoms and to identify risk factors associated with TB. We ascertained factors moderating the yield of contact tracing and measured the impact of our program by additional notifications. Results From March 2013 to November 2015, 3,258 ICs (54% bacteriologically confirmed; 70% HIV-infected; 85% adults) were enrolled leading to evaluation of 12,175 contacts (median age 18 years, IQR 24–42; 45% children; 9% HIV-infected). Among contacts, 196 TB cases (56% bacteriologically confirmed) were diagnosed resulting in a program yield of 1.6% for all forms of TB. The number needed to screen (NNS) to identify a bacteriologically confirmed TB case or all forms TB case traced from a child IC <5 years was respectively 62% and 40% greater than the NNS for tracing from an adult IC. In year one, we demonstrated a 32% increase in detection of bacteriologically confirmed child TB. Contacts were more likely to have TB if <5 years (OR = 2.0), HIV-infected (OR = 4.9), reporting ≥1 TB symptoms (OR = 7.7), and sharing a bed (OR = 1.7) or home (OR = 1.4) with the IC. There was a 1.4 fold increased chance of detecting a TB case in households known to be HIV-affected. Conclusion Contact tracing prioritizing children is not only feasible in a TB/HIV high-burden setting but contributes to overall case detection. Our findings support WHO guidelines prioritizing contact tracing among children and HIV-infected populations while highlighting potential to integrate TB

  6. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

    PubMed Central

    2011-01-01

    Background Rhodococcus equi (R.equi) is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis) is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART). Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection. PMID:22168333

  7. Tuberculosis Screening on a Health Science Campus: Use of QuantiFERON-TB Gold Test for Students and Employees

    ERIC Educational Resources Information Center

    Veeser, Peggy Ingram; Smith, Phillip Karl; Handy, Barry; Martin, Sharon R.

    2007-01-01

    Detecting and managing "Mycobacterium tuberculosis" (TB) infection in a health-science center population is a clinical dilemma. Tuberculin skin tests are still the preferred method for detecting present or past infection of TB. The authors discuss the performance of whole blood interferon gamma release assay test commercially known as…

  8. LAG3 expression in active Mycobacterium tuberculosis infections.

    PubMed

    Phillips, Bonnie L; Mehra, Smriti; Ahsan, Muhammad H; Selman, Moises; Khader, Shabaana A; Kaushal, Deepak

    2015-03-01

    Mycobacterium tuberculosis (MTB) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. MTB modulates several aspects of the host immune response. Lymphocyte-activation gene 3 (LAG3) is a protein with a high affinity for the CD4 receptor and is expressed mainly by regulatory T cells with immunomodulatory functions. To understand the function of LAG3 during MTB infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects of natural human infection in rhesus macaques (Macaca mulatta), was used. We show that the expression of LAG3 is highly induced in the lungs and particularly in the granulomatous lesions of macaques experimentally infected with MTB. Furthermore, we show that LAG3 expression is not induced in the lungs and lung granulomas of animals exhibiting latent tuberculosis infection. However, simian immunodeficiency virus-induced reactivation of latent tuberculosis infection results in an increased expression of LAG3 in the lungs. This response is not observed in nonhuman primates infected with non-MTB bacterial pathogens, nor with simian immunodeficiency virus alone. Our data show that LAG3 was expressed primarily on CD4(+) T cells, presumably by regulatory T cells but also by natural killer cells. The expression of LAG3 coincides with high bacterial burdens and changes in the host type 1 helper T-cell response.

  9. Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013

    PubMed Central

    Sandy, Charles; Masuka, Nyasha; Hazangwe, Patrick; Choto, Regis C.; Mutasa-Apollo, Tsitsi; Nkomo, Brilliant; Sibanda, Edwin; Mugurungi, Owen; Siziba, Nicholas

    2017-01-01

    Background. In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology. This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results. Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46–282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35–4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10–1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44–2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22–0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion. There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART. PMID:28352474

  10. Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation.

    PubMed

    Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B; Purcell, Olivia M; Didier, Peter J; Russell-Lodrigue, Kasi; Weaver, Scott C; Roy, Chad J; MacLean, Andrew G

    2016-04-01

    Chikungunya, "that which bends up" in the Makonde dialect, is an emerging global health threat, with increasing incidence of neurological complications. Until 2013, Chikungunya infection had been largely restricted to East Africa and the Indian Ocean, with cases within the USA reported to be from foreign travel. However, in 2014, over 1 million suspected cases were reported in the Americas, and a recently infected human could serve as an unwitting reservoir for the virus resulting in an epidemic in the continental USA. Chikungunya infection is increasingly being associated with neurological sequelae. In this study, we sought to understand the role of astrocytes in the neuropathogenesis of Chikungunya infection. Even after virus has been cleared form the circulation, astrocytes were activated with regard to TLR2 expression. In addition, white matter astrocytes were hypertrophic, with increased arbor volume in gray matter astrocytes. Combined, these would alter the number and distribution of synapses that each astrocyte would be capable of forming. These results provide the first evidence that Chikungunya infection induces morphometric and innate immune activation of astrocytes in vivo. Perturbed glia-neuron signaling could be a major driving factor in the development of Chikungunya-associated neuropathology.

  11. Contact investigation after a fatal case of extensively drug-resistant tuberculosis (XDR-TB) in an aircraft, Germany, July 2013.

    PubMed

    An der Heiden, Maria; Hauer, Barbara; Fiebig, Lena; Glaser-Paschke, Gisela; Stemmler, Markus; Simon, Claudia; Rüsch-Gerdes, Sabine; Gilsdorf, Andreas; Haas, Walter

    2017-03-23

    In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired.

  12. The macrophage in HIV-1 infection: from activation to deactivation?

    PubMed

    Herbein, Georges; Varin, Audrey

    2010-04-09

    Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-gamma display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease.

  13. RNase L Activates the NLRP3 Inflammasome During Viral Infections

    PubMed Central

    Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi; Loo, Yueh-Ming; Gale, Michael; Núñez, Gabriel; Silverman, Robert H.

    2015-01-01

    SUMMARY The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1β. Although virus infection activates the NLRP3 inflammasome, the underlying events remain incompletely understood. We report that virus activation of the NLRP3 inflammasome involves the 2′,5′-oligoadenylate (2-5A) synthetase (OAS)/RNase L system, a component of the interferon-induced antiviral response that senses double stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs. The absence of RNase L reduces IL-1β production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1β production but require the presence of 2′,3′-cyclic phosphorylated termini characteristic of RNase L activity. Additionally, these cleavage products stimulate NLRP3 complex formation with the DExD/H-box helicase, DHX33, and mitochondrial adapter protein, MAVS, which are each required for effective NLRP3 inflammasome activation. Thus, RNA cleavage events catalyzed by RNase L are required for optimal inflammasome activation during viral infections. PMID:25816776

  14. Active tuberculosis among Iraqi schoolchildren with positive skin tests and their household contacts.

    PubMed

    Al Kubaisy, W; Al Dulayme, A; Hashim, D S

    2003-07-01

    In a prospective cohort study in Iraq, schoolchildren with a positive tuberculin skin test during the nationwide survey in 2000 were followed up in 2002 to determine prevalence of latent tuberculosis (TB) infection and risk factors among household contacts. Of 205 children, 191 remained skin-test positive in 2002. Based on X-ray and clinical examination, 9 children (4.4%) were active TB cases. Among 834 household contacts, there were 144 new TB cases, giving a cumulative incidence of 17.3%. Risk factors for TB among household contacts were: age > or = 15 years; technical/professional job; smoking; low body mass index; diabetes mellitus; steroid therapy; and closeness of contact with the index cases. Based on past history of TB in index children and their contacts, 77.2% of new TB cases were attributable to household contacts.

  15. Haemophagocytic lymphohistiocytosis associated with Mycobacterium tuberculosis infection

    PubMed Central

    Hui, Yee Man Tracy; Pillinger, Toby; Luqmani, Asad; Cooper, Nichola

    2015-01-01

    Haemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal condition that can be primary or secondary. Secondary HLH can occur in association with infections, most commonly viral infections, but has also been reported in association with Mycobacterium tuberculosis (TB). Prompt identification of the underlying cause of HLH is important as it guides treatment decisions. Early initiation of appropriate treatment (eg, anti-TB treatment) reduces morbidity and mortality. We present a case of HLH associated with TB infection. Initial TB investigations were negative and standard combination chemoimmunotherapy for HLH resulted in a limited clinical response. On apparent relapse of HLH, further investigation revealed TB with changes on CT chest, granuloma on bone marrow and eventual positive TB culture on bronchoalveolar lavage. Subsequent treatment with quadruple anti-TB treatment resulted in rapid clinical response and disease remission. We advocate continued monitoring for TB infection in patients with HLH, and prophylaxis or full treatment for those at high risk. PMID:25870214

  16. Activated mouse eosinophils protect against lethal respiratory virus infection.

    PubMed

    Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I; Luo, Janice L; Fischer, Elizabeth R; Lee, James J; Lee, Nancy A; Domachowske, Joseph B; Rosenberg, Helene F

    2014-01-30

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine-driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense.

  17. Infection with Helicobacter pylori Is Associated with Protection against Tuberculosis

    PubMed Central

    Perry, Sharon; de Jong, Bouke C.; Solnick, Jay V.; la Luz Sanchez, Maria de; Yang, Shufang; Lin, Philana Ling; Hansen, Lori M.; Talat, Najeeha; Hill, Philip C.; Hussain, Rabia; Adegbola, Richard A.; Flynn, JoAnne; Canfield, Don; Parsonnet, Julie

    2010-01-01

    Background Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings We first examined M. tuberculosis-specific IFN-γ and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-γ responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36–0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63–2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12–0.80], p = 0.04). Conclusions/Significance H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for

  18. Marine peptides and their anti-infective activities.

    PubMed

    Kang, Hee Kyoung; Seo, Chang Ho; Park, Yoonkyung

    2015-01-16

    Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present.

  19. Marine Peptides and Their Anti-Infective Activities

    PubMed Central

    Kang, Hee Kyoung; Seo, Chang Ho; Park, Yoonkyung

    2015-01-01

    Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present. PMID:25603351

  20. Impact of Latent Infection Treatment in Indigenous Populations

    PubMed Central

    Yuhara, Lucia Suemi; Sacchi, Flávia Patussi Correia; Croda, Julio

    2013-01-01

    The aims of the present study were to identify risk factors associated with latent tuberculosis (TB), examine the development of active disease among contacts, and assess the effectiveness of treating latent infection in indigenous Brazilians from January 2006 to December 2011. This was a retrospective study consisting of 1,371 tuberculosis contacts, 392 of whom underwent treatment for latent infection. Morbidity-from-TB data were obtained from the Information System for Disease Notification (SINAN) database, and the contacts’ data were collected from the clinical records using forms employed by Special Department of Indigenous Health (SESAI) multidisciplinary teams, according to SESAI’s instructions. The variables that were associated with latent infection among the contacts were age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02–1.04) and close contact with a smear-positive index case (OR: 2.26, 95% CI: 1.59–3.22). The variables associated with the development of active TB among the contacts were a tuberculin skin test (TST) ≥10 mm (relative risk [RR]: 1.12, 95% CI: 1.07–1.17), age (RR: 1.01, 95% CI: 1.00–1.03), and treatment of latent infection (RR: 0.03, 95% CI: 0.01–0.27). The estimated number of latent infection treatments needed to prevent one case of active TB among the contacts was 51 treatments (95% CI: 33–182). In contacts with TST ≥10 mm, 10 (95% CI: 6–19) latent infection treatments were necessary to prevent one case of active TB. Age and close contact with a smear-positive index case were associated with latent TB. Screening with TST is a high priority among individuals contacting smear-positive index cases. Age and TST are associated with the development of active TB among contacts, and treatment of latent infection is an effective measure to control TB in indigenous communities. PMID:23936264

  1. Immune Activation and Cardiovascular Disease in Chronic HIV Infection

    PubMed Central

    Longenecker, Chris T.; Sullivan, Claire; Baker, Jason V.

    2016-01-01

    Purpose of review To describe the potential contribution of immune activation in the pathogenesis of HIV-associated cardiovascular disease (CVD)—a leading cause of morbidity and mortality among HIV positive persons with access to antiretroviral therapy (ART). Recent findings We review recent literature that suggests abnormalities in both adaptive and innate immunity contributes to CVD risk among persons with HIV infection. In particular, potentially atherogenic T-cell mechanisms include persistent high-level T-cell activation (and associated pro-inflammatory mechanisms), as well as the presence of co-pathogens (e.g., CMV) providing an ongoing stimulus for cytotoxic T-cell responses. More recent data has then emphasized the potential impact of monocyte/macrophage-mediated inflammation and injury within atherosclerotic lesions. The pathology driving innate immune activation many not fully reverse with ART treatment, highlighting the need for interventions that target inflammation as a CVD prevention strategy. Summary Premature CVD among persons with HIV infection is due, in part, to persistent abnormalities in immune activation and systemic inflammation despite viral suppression. Prevention strategies for persons with HIV infection include those that target traditional CVD risk factors as well as newer candidate treatments with potential immunomodulatory benefits. PMID:26599166

  2. Gelsolin activity controls efficient early HIV-1 infection

    PubMed Central

    2013-01-01

    Background HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-receptor interactions and that generates the tension at the plasma membrane necessary to potentiate fusion pore formation, thereby favouring early HIV-1 infection. However, it remains unclear whether the dynamic processing of F-actin and the amount of cortical actin available during the initial virus-cell contact are required to such events. Results Here we show that gelsolin restructures cortical F-actin during HIV-1 Env-gp120-mediated signalling, without affecting cell-surface expression of receptors or viral co-receptor signalling. Remarkably, efficient HIV-1 Env-mediated membrane fusion and infection of permissive lymphocytes were impaired when gelsolin was either overexpressed or silenced, which led to a loss or gain of cortical actin, respectively. Indeed, HIV-1 Env-gp120-induced F-actin reorganization and viral receptor capping were impaired under these experimental conditions. Moreover, gelsolin knockdown promoted HIV-1 Env-gp120-mediated aberrant pseudopodia formation. These perturbed-actin events are responsible for the inhibition of early HIV-1 infection. Conclusions For the first time we provide evidence that through its severing of cortical actin, and by controlling the amount of actin available for reorganization during HIV-1 Env-mediated viral fusion, entry and infection, gelsolin can constitute a barrier that restricts HIV-1 infection of CD4+ lymphocytes in a pre-fusion step. These findings provide important insights into the complex molecular and actin-associated dynamics events that underlie early viral infection. Thus, we propose that gelsolin is a new factor that can limit HIV-1 infection acting at a pre-fusion step

  3. Sheep as a Potential Source of Bovine TB: Epidemiology, Pathology and Evaluation of Diagnostic Techniques.

    PubMed

    Muñoz-Mendoza, M; Romero, B; Del Cerro, A; Gortázar, C; García-Marín, J F; Menéndez, S; Mourelo, J; de Juan, L; Sáez, J L; Delahay, R J; Balseiro, A

    2016-12-01

    Bovine tuberculosis (TB) infection is infrequently diagnosed in sheep. Most reports are from single individual cases or flock outbreaks. However, in Spain several outbreaks have been reported recently, all of which had epidemiological links with TB-infected cattle herds. A total of 897 sheep suspected of being infected with TB and belonging to 23 flocks cohabiting with TB-infected cattle herds and/or goats were tested between 2009 and 2013 in Galicia (north-western Spain), using pathological, immunological and molecular techniques. Of these, 50.44% were positive by culture, 83.23% by histopathology and 24.92%, 4.86% and 59.42% by single intradermal tuberculin test (SITT), interferon-γ and ELISA, respectively. Results suggest that in circumstances akin to those in our study, sheep may be considered as a potential source of TB. We conclude that under similar conditions, serious consideration should be given to TB testing sheep, as they may represent a potential risk to other susceptible co-habiting species. The SITT and ELISA are recommended as the simplest and most cost-effective initial approaches for the diagnosis of TB in sheep under field conditions. However, when possible, interferon-γ should be applied to increase sensitivity.

  4. Indole-2-carboxamide-based MmpL3 Inhibitors Show Exceptional Antitubercular Activity in an Animal Model of Tuberculosis Infection.

    PubMed

    Stec, Jozef; Onajole, Oluseye K; Lun, Shichun; Guo, Haidan; Merenbloom, Benjamin; Vistoli, Giulio; Bishai, William R; Kozikowski, Alan P

    2016-07-14

    Our team had previously identified certain indolecarboxamides that represented a new chemical scaffold that showed promising anti-TB activity at both an in vitro and in vivo level. Based on mutational analysis using bacteria found resistant to one of these indolecarboxamides, we identified the trehalose monomycolate transporter MmpL3 as the likely target of these compounds. In the present work, we now further elaborate on the SAR of these compounds, which has led in turn to the identification of a new analog, 4,6-difluoro-N-((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)-1H-indole-2-carboxamide (26), that shows excellent activity against drug-sensitive (MIC = 0.012 μM; SI ≥ 16000), multidrug-resistant (MDR), and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains, has superior ADMET properties, and shows excellent activity in the TB aerosol lung infection model. Compound 26 is also shown to work in synergy with rifampin. Because of these properties, we believe that indolecarboxamide 26 is a possible candidate for advancement to human clinical trials.

  5. Viral hepatitis and HIV-associated tuberculosis: Risk factors and TB treatment outcomes in Thailand

    PubMed Central

    Sirinak, Chawin; Kittikraisak, Wanitchaya; Pinjeesekikul, Duangporn; Charusuntonsri, Pricha; Luanloed, Phinai; Srisuwanvilai, La-ong; Nateniyom, Sriprapa; Akksilp, Somsak; Likanonsakul, Sirirat; Sattayawuthipong, Wanchai; Burapat, Channawong; Varma, Jay K

    2008-01-01

    Background The occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients. Methods Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines. Results Of 769 enrolled patients, 752 (98%) had serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg, 237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated liver function tests compared with 69 (15%) patients non-reactive to any viral marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1–4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0–3.0). Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0–23.2) and living in Bangkok (AOR, 15.8; CI, 9.4–26.5). The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker. Conclusion Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus infection, were

  6. Activity of terbinafine in experimental fungal infections of laboratory animals.

    PubMed Central

    Petranyi, G; Meingassner, J G; Mieth, H

    1987-01-01

    The allylamine derivative terbinafine is the first antifungal agent with primary fungicidal properties against dermatophytes which acts systemically after oral application as well as locally after topical application. Comparative oral studies carried out with griseofulvin and ketoconazole in model infections such as guinea pig trichophytosis and microsporosis revealed terbinafine to be superior to the reference compounds both clinically and mycologically. An excellent antimycotic activity of terbinafine was also demonstrable after topical treatment of guinea pig dermatophytoses caused by Trichophyton mentagrophytes or Microsporum canis. Results of comparative chemotherapeutic studies carried out with econazole and tolnaftate demonstrated superior efficacy of terbinafine in the treatment of both trichophytosis and microsporosis. Skin infections of guinea pigs caused by Candida albicans and vaginal candidiasis in rats proved to be responsive to a topical application of terbinafine also. However, the reference compounds, clotrimazole and miconazole, exhibited activity superior to that of terbinafine in both models. PMID:3435103

  7. Multiple Skin Colored Nodules on both Legs in Patient with Positive QuantiFERON®-TB Gold Test

    PubMed Central

    Choi, Mi Soo; Hong, Seung Phil; Park, Byung Cheol

    2017-01-01

    Nodular tuberculid (NT) was originally described by Jordaan et al. in 2000 in 4 patients from South Africa. It appeared as nodules on the legs; the pathologic changes were situated in the deep dermis and adjacent subcutaneous fat. A 34-year-old woman visited our hospital with subcutaneous skin-colored or slightly erythematous round to oval nodules. Skin biopsies revealed granulomatous inflammation at the dermo-subcutaneous junction with vasculitis. Chest X-ray, tuberculosus (TB)-polymerase chain reaction and TB culture of the skin specimen were normal. A QuantiFERON®-TB Gold test (QUIAGEN, Germany) was positive, which suggested a diagnosis of latent TB infection. The patient was treated with anti-TB medication and her condition has not recurred. Herein, we report a case of a patient with latent TB diagnosed by a positive QuantiFERON®-TB Gold test whose skin lesions had the clinical and histopathologic features of NT. PMID:28223755

  8. Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection.

    PubMed

    López-García, Sonia; Castañeda-Sanchez, Jorge Ismael; Jiménez-Arellanes, Adelina; Domínguez-López, Lilia; Castro-Mussot, Maria Eugenia; Hernández-Sanchéz, Javier; Luna-Herrera, Julieta

    2015-08-06

    Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-β) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-β and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated).

  9. In Silico identification of M. TB proteins with diagnostic potential

    PubMed Central

    2013-01-01

    TB, caused by Mycobacterium tuberculosis (MTB), is one of the major global infectious diseases. For the pandemic control, early diagnosis with sensitive and specific methods is fundamental. With the advent of bioinformatics’ tools, the identification of several proteins involved in the pathogenesis of TB (TB) has been possible. In the present work, the MTB genome was explored to look for molecules with possible antigenic properties for their evaluation as part of new generation diagnostic kits based on the release of cytokines. Seven proteins from the MTB proteome and some of their combinations suited the computational test and the results suggested their potential use for the diagnosis of infection in the following population groups: Cuba, Mexico, Malaysia and sub-Saharan Africa. Our predictions were performed using public bioinformatics tools plus three computer programs, developed by our group, to facilitate information retrieval and processing. PMID:23458073

  10. The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review

    PubMed Central

    2009-01-01

    Background In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship. Methods A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken. Results There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol. Conclusion The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed. PMID:19961618

  11. Relationship between interleukin-5 production and variations in eosinophil counts during HIV infection in West Africa: influence of Mycobacterium tuberculosis infection.

    PubMed

    Diagbouga, S; Aldebert, D; Fumoux, F; Capron, M; Ledru, E

    1999-02-01

    Eosinophils are important effectors of the non-specific immune response and we studied whether perturbations in the production of the type 2 cytokine, interleukin-5 (IL-5), could account for the variations in eosinophil counts observed in human immunodeficiency virus (HIV) infection. HIV-infected patients without helminthiasis were investigated in a cross-sectional study in West Africa. Eosinophil counts were significantly higher in CDC-B patients than in controls, but were dramatically decreased at the CDC-C stage. Phorbol 12-myristate 13-acetate (PMA)+ ionomycin-induced IL-5 production by peripheral blood mononuclear cells (PBMC) was decreased from the A stage of the disease, and significant correlations were observed between IL-5 production and eosinophil counts in tuberculosis (TB)-negative HIV-1-positive, TB-positive HIV-1-positive and TB-positive HIV-negative patient groups. Nevertheless, the production of IL-5 was not decreased in HIV-positive patients with TB, in contrast to HIV-positive patients without TB presenting with the same ranges of CD4+ counts. Our data suggest that, during HIV infection, the impairment in IL-5 production is one of the factors associated with the 'paradoxal' eosinopenia observed in tropical areas, but that IL-5 production during active TB is compensated by cellular subsets, yet to be identified.

  12. TB incidence and characteristics in the remote gulf province of Papua New Guinea: a prospective study

    PubMed Central

    2014-01-01

    Background The incidence and characteristics of tuberculosis (TB) in remote areas of Papua New Guinea (PNG) are largely unknown. The purpose of our study was to determine the incidence of TB in the Gulf Province of PNG and describe disease characteristics, co-morbidities and drug resistance profiles that could impact on disease outcomes and transmission. Methods Between March 2012 and June 2012, we prospectively collected data on 274 patients presenting to Kikori Hospital with a presumptive diagnosis of TB, and on hospital inpatients receiving TB treatment during the study period. Sputum was collected for microscopy, GeneXpert analysis, culture and genotyping of isolates. Results We estimate the incidence of TB in Kikori to be 1290 per 100,000 people (95% CI 1140 to 1460) in 2012. The proportion of TB patients co-infected with HIV was 1.9%. Three of 32 TB cases tested were rifampicin resistant. Typing of nine isolates demonstrated allelic diversity and most were related to Beijing strains. Conclusions The incidence of TB in Kikori is one of the highest in the world and it is not driven by HIV co-infection. The high incidence and the presence of rifampicin resistant warrant urgent attention to mitigate substantial morbidity in the region. PMID:24555577

  13. Deregulated lncRNAs in B Cells from Patients with Active Tuberculosis

    PubMed Central

    Fu, Yurong; Xu, Xianqin; Xue, Junfang; Duan, Wenping; Yi, Zhengjun

    2017-01-01

    Role of lncRNAs in human adaptive immune response to TB infection is largely unexplored. To address this issue, here we characterized lncRNA expression profile in primary human B cell response to TB infection using microarray assay. Several lncRNAs and mRNAs were chosen for RT-qPCR validation. Bioinformatics prediction was applied to delineate function of the deregulated mRNAs. We found that 844 lncRNAs and 597 mRNAs were differentially expressed between B cell samples from individuals with or without TB. KEGG pathway analysis for the deregulated mRNAs indicated a number of pathways, such as TB, TLR signaling pathway and antigen processing and presentation. Moreover, corresponding to the dysregulation of many lncRNAs, we also found that their adjacent protein-coding genes were also deregulated. Functional annotation for the corresponding mRNAs showed that these lncRNAs were mainly associated with TLR signaling, TGF-β signaling. Interestingly, SOCS3, which is a critical negative regulator of cytokine response to TB infection and its nearby lncRNA XLOC_012582, were highly expressed in active TB B cells. Subsequent RT-qPCR results confirmed the changes. Whether upregulated XLOC_012582 causes SOCS3 overexpression and is eventually involved in the context of exacerbations of active TB represents an interesting issue that deserves to be further explored. Taken together, for the first time, we identified a set of deregulated lncRNAs in active TB B cells and their functions were predicted. Such findings provided novel insight into the pathogenesis of TB and further studies should focus on the function and pathogenic mechanisms of the lncRNAs involved in active TB. PMID:28125665

  14. Smart spotting of pulmonary TB cavities using CT images.

    PubMed

    Swanly, V Ezhil; Selvam, L; Kumar, P Mohan; Renjith, J Arokia; Arunachalam, M; Shunmuganathan, K L

    2013-01-01

    One third of the world's population is thought to have been infected with mycobacterium tuberculosis (TB) with new infection occurring at a rate of about one per second. TB typically attacks the lungs. Indication of cavities in upper lobes of lungs shows the high infection. Traditionally, it has been detected manually by physicians. But the automatic technique proposed in this paper focuses on accurate detection of disease by computed tomography (CT) using computer-aided detection (CAD) system. The various steps of the detection process include the following: (i) image preprocessing, which is done by techniques such as resizing, masking, and Gaussian smoothening, (ii) image egmentation that is implemented by using mean-shift model and gradient vector flow (GVF) model, (iii) feature extraction that can be achieved by Gradient inverse coefficient of variation and circularity measure, and (iv) classification using Bayesian classifier. Experimental results show that its perfection of detecting cavities is very accurate in low false positive rate (FPR).

  15. Temperature-dependent structure of Tb-doped magnetite nanoparticles

    SciTech Connect

    Rice, Katherine P.; Russek, Stephen E. Shaw, Justin M.; Usselman, Robert J.; Evarts, Eric R.; Silva, Thomas J.; Nembach, Hans T.; Geiss, Roy H.; Arenholz, Elke; Idzerda, Yves U.

    2015-02-09

    High quality 5 nm cubic Tb-doped magnetite nanoparticles have been synthesized by a wet-chemical method to investigate tailoring of magnetic properties for imaging and biomedical applications. We show that the Tb is incorporated into the octahedral 3+ sites. High-angle annular dark-field microscopy shows that the dopant is well-distributed throughout the particle, and x-ray diffraction measurements show a small lattice parameter shift with the inclusion of a rare-earth dopant. Magnetization and x-ray magnetic circular dichroism data indicate that the Tb spins are unpolarized and weakly coupled to the iron spin lattice at room temperature, and begin to polarize and couple to the iron oxide lattice at temperatures below 50 K. Broadband ferromagnetic resonance measurements show no increase in magnetic damping at room temperature for Tb-doped nanoparticles relative to undoped nanoparticles, further confirming weak coupling between Fe and Tb spins at room temperature. The Gilbert damping constant, α, is remarkably low for the Tb-doped nanoparticles, with α = 0.024 ± 0.003. These nanoparticles, which have a large fixed moment, a large fluctuating moment and optically active rare-earth elements, are potential high-relaxivity T1 and T2 MRI agents with integrated optical signatures.

  16. Temperature-dependent structure of Tb-doped magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Rice, Katherine P.; Russek, Stephen E.; Geiss, Roy H.; Shaw, Justin M.; Usselman, Robert J.; Evarts, Eric R.; Silva, Thomas J.; Nembach, Hans T.; Arenholz, Elke; Idzerda, Yves U.

    2015-02-01

    High quality 5 nm cubic Tb-doped magnetite nanoparticles have been synthesized by a wet-chemical method to investigate tailoring of magnetic properties for imaging and biomedical applications. We show that the Tb is incorporated into the octahedral 3+ sites. High-angle annular dark-field microscopy shows that the dopant is well-distributed throughout the particle, and x-ray diffraction measurements show a small lattice parameter shift with the inclusion of a rare-earth dopant. Magnetization and x-ray magnetic circular dichroism data indicate that the Tb spins are unpolarized and weakly coupled to the iron spin lattice at room temperature, and begin to polarize and couple to the iron oxide lattice at temperatures below 50 K. Broadband ferromagnetic resonance measurements show no increase in magnetic damping at room temperature for Tb-doped nanoparticles relative to undoped nanoparticles, further confirming weak coupling between Fe and Tb spins at room temperature. The Gilbert damping constant, α, is remarkably low for the Tb-doped nanoparticles, with α = 0.024 ± 0.003. These nanoparticles, which have a large fixed moment, a large fluctuating moment and optically active rare-earth elements, are potential high-relaxivity T1 and T2 MRI agents with integrated optical signatures.

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

    PubMed

    Bell, Lucy C K; Pollara, Gabriele; Pascoe, Mellissa; Tomlinson, Gillian S; Lehloenya, Rannakoe J; Roe, Jennifer; Meldau, Richard; Miller, Robert F; Ramsay, Alan; Chain, Benjamin M; Dheda, Keertan; Noursadeghi, Mahdad

    2016-03-01

    Increased risk of tuberculosis (TB) associated with HIV-1 infection is primarily attributed to deficient T helper (Th)1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART) exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis. We sought to define these effects in patients with active TB by transcriptional profiling of tuberculin skin tests (TST) to make comprehensive molecular level assessments of in vivo human immune responses at the site of a standardised mycobacterial challenge. We showed that the TST transcriptome accurately reflects the molecular pathology at the site of human pulmonary TB, and used this approach to investigate immune dysregulation in HIV-1/TB co-infected patients with distinct clinical phenotypes associated with TST reactivity or anergy and unmasking TB immune reconstitution inflammatory syndrome (IRIS) after initiation of ART. HIV-1 infected patients with positive TSTs exhibited preserved Th1 responses but deficient immunoregulatory IL10-inducible responses. Those with clinically negative TSTs revealed profound anergy of innate as well as adaptive immune responses, except for preservation of type 1 interferon activity, implicated in impaired anti-mycobacterial immunity. Patients with unmasking TB IRIS showed recovery of Th1 immunity to normal levels, but exaggerated Th2-associated responses specifically. These mechanisms of immune dysregulation were localised to the tissue microenvironment and not evident in peripheral blood. TST

  18. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  19. Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study

    PubMed Central

    2011-01-01

    Background Concomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV. Methods We conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values. Results From a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome. Conclusion The results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB. PMID:22176628

  20. Antiviral activity of lanatoside C against dengue virus infection.

    PubMed

    Cheung, Yan Yi; Chen, Karen Caiyun; Chen, Huixin; Seng, Eng Khuan; Chu, Justin Jang Hann

    2014-11-01

    Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.

  1. WHO's End TB Strategy: From stopping to ending the global TB epidemic.

    PubMed

    Uplekar, Mukund; Raviglione, Mario

    2015-10-01

    The 67th World Health Assembly of 2014 adopted the "End TB Strategy" with a vision of making the world free of tuberculosis (TB) and with the goal of ending the global TB epidemic by the year 2035. World Health Organization's "End TB Strategy" captures this holistic response in its four principles and three pillars. The three high-level indicators of the "End TB Strategy" - reductions in TB deaths, reductions in the TB incidence rate and the percentage of TB patients and their households experiencing catastrophic costs - are relevant to all countries.

  2. Litigation as TB Rights Advocacy

    PubMed Central

    2016-01-01

    Abstract One thousand people die every day in India as a result of TB, a preventable and treatable disease, even though the Constitution of India, government schemes, and international law guarantee available, accessible, acceptable, quality health care. Failure to address the spread of TB and to provide quality treatment to all affected populations constitutes a public health and human rights emergency that demands action and accountability. As part of a broader strategy, health activists in India employ Public Interest Litigation (PIL) to hold the state accountable for rights violations and to demand new legislation, standards for patient care, accountability for under-spending, improvements in services at individual facilities, and access to government entitlements in marginalized communities. Taking inspiration from right to health PIL cases (PILs), lawyers in a New Delhi-based rights organization used desk research, fact-findings, and the Right To Information Act to build a TB PIL for the Delhi High Court, Sanjai Sharma v. NCT of Delhi and Others (2015). The case argues that inadequate implementation of government TB schemes violates the Constitutional rights to life, health, food, and equality. Although PILs face substantial challenges, this paper concludes that litigation can be a crucial advocacy and accountability tool for people living with TB and their allies. PMID:27781000

  3. Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro

    PubMed Central

    Tschan-Plessl, Astrid; Stern, Martin; Schmied, Laurent; Retière, Christelle; Hirsch, Hans H.; Garzoni, Christian; van Delden, Christian; Boggian, Katia; Mueller, Nicolas J.; Berger, Christoph; Villard, Jean; Manuel, Oriol; Meylan, Pascal; Terszowski, Grzegorz

    2016-01-01

    Background Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. Methods We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls. Results We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P < 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P < 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern. Most importantly, we observed a significantly higher NK cell degranulation and IFNγ production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P < 0.001; IFNγ: mean increase, 6.6%; 95% CI, 1.6-11.1; P < 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNγ: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002). Conclusions We report

  4. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

    PubMed

    Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

    2010-11-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs.

  5. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites

    PubMed Central

    Ammerman, Michelle L.; Presnyak, Vladimir; Fisk, John C.; Foda, Bardees M.; Read, Laurie K.

    2010-01-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5′ ends of pan-edited RNAs than at their 3′ ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3′ to 5′ progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3′ ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA–RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3′ to 5′ progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

  6. Subunit-selective proteasome activity profiling uncovers uncoupled proteasome subunit activities during bacterial infections.

    PubMed

    Misas-Villamil, Johana C; van der Burgh, Aranka M; Grosse-Holz, Friederike; Bach-Pages, Marcel; Kovács, Judit; Kaschani, Farnusch; Schilasky, Sören; Emon, Asif Emran Khan; Ruben, Mark; Kaiser, Markus; Overkleeft, Hermen S; van der Hoorn, Renier A L

    2017-01-24

    The proteasome is a nuclear - cytoplasmic proteolytic complex involved in nearly all regulatory pathways in plant cells. The three different catalytic activities of the proteasome can have different functions but tools to monitor and control these subunits selectively are not yet available in plant science. Here, we introduce subunit-selective inhibitors and dual-color fluorescent activity-based probes for studying two of the three active catalytic subunits of the plant proteasome. We validate these tools in two model plants and use this to study the proteasome during plant-microbe interactions. Our data reveals that Nicotiana benthamiana incorporates two different paralogs of each catalytic subunit into active proteasomes. Interestingly, both β1 and β5 activities are significantly increased upon infection with pathogenic Pseudomonas syringae pv. tomato DC3000 lacking hopQ1-1 (PtoDC3000(ΔhQ)) whilst the activity profile of the β1 subunit changes. Infection with wild-type PtoDC3000 causes proteasome activities that range from strongly induced β1 and β5 activities to strongly suppressed β5 activities, revealing that β1 and β5 activities can be uncoupled during bacterial infection. These selective probes and inhibitors are now available to the plant science community and can be widely and easily applied to study the activity and role of the different catalytic subunits of the proteasome in different plant species. This article is protected by copyright. All rights reserved.

  7. TB vaccines in clinical development.

    PubMed

    Ginsberg, Ann M; Ruhwald, Morten; Mearns, Helen; McShane, Helen

    2016-08-01

    The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on TB Vaccines in Clinical Development, and Clinical Research: Data and Findings. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30].

  8. Using theory to interpret beliefs in migrants diagnosed with latent TB.

    PubMed

    Wyss, Lora L; Alderman, M Kay

    2006-11-16

    Tuberculosis (TB) is a serious health threat to migrant farm workers in the Midwestern United States. This article describes characteristics of migrant culture and lifestyle, economic, and health challenges that may impact screening, diagnosis, and adherence with complex medication regimens associated with TB. A brief overview of TB discusses the historical perspective of the disease and describes the stages, transmission, and incidence among migrant populations. Several theoretical models, such as the Health Belief Model (HBM) and social cognitive theory, were considered by the authors to guide understanding of migrant beliefs about TB. A qualitative research study conducted with 23 Hispanic migrants with latent TB infection is presented. Discussion of the research findings describes environmental, cognitive, and social factors that were barriers to screening, diagnosis, and treatment. The article concludes with a description of recent migrant health clinic updates designed to improve the worker' health status and considerations for environmental and educational change.

  9. Vaccines for TB: Lessons from the Past Translating into Future Potentials

    PubMed Central

    Tye, Gee Jun; Lew, Min Han; Choong, Yee Siew; Lim, Theam Soon; Sarmiento, Maria Elena; Acosta, Armando; Norazmi, Mohd Nor

    2015-01-01

    Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB. PMID:26146643

  10. [Guidelines for the diagnosis and treatment of latent tuberculosis infection and active tuberculosis in patients with inflammatory joint diseases proposed for treatment with tumour necrosis factor alpha antagonist drugs].

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2006-01-01

    The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test.

  11. A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette–Guérin-vaccinated Individuals

    PubMed Central

    Peña, Delfina; Rovetta, Ana I.; Hernández Del Pino, Rodrigo E.; Amiano, Nicolás O.; Pasquinelli, Virginia; Pellegrini, Joaquín M.; Tateosian, Nancy L.; Rolandelli, Agustín; Gutierrez, Marisa; Musella, Rosa M.; Palmero, Domingo J.; Gherardi, María M.; Iovanna, Juan; Chuluyan, H. Eduardo; García, Verónica E.

    2015-01-01

    IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette–Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens. BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited. QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly, whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people. PMID:26425695

  12. The frequency distribution of vitamin D Receptor fok I gene polymorphism among Ugandan pulmonary TB patients

    PubMed Central

    Acen, Ester L.; Worodria, William; Mulamba, Peter; Kambugu, Andrew; Erume, Joseph

    2016-01-01

    Background: Mycobacterium tuberculosis (TB) is still a major problem globally and especially in Africa. Vitamin D deficiency has been linked to TB in the past and studies have found vitamin D deficiency to be common among Ugandan TB patients. The functional activity of vitamin D is dependent on the genotype of the vitamin D receptor (VDR) polymorphic genes. Recent findings have indicated that VDR polymorphisms may cause increased resistance or susceptibility to TB. The vitamin D ligand and its receptor play a pivotal role in innate immunity by eliciting antimicrobial activity, which is important in prevention of TB. The fok I vitamin D receptor gene has extensively been examined in TB patients but findings so far have been inconclusive. Objectives: This study sought to investigate the frequency distribution of the VDR fok I gene polymorphisms in pulmonary TB patients and controls. Methods: A pilot case control study of 41 newly diagnosed TB patients and 41 healthy workers was set up. Vitamin D receptor fok I gene was genotyped. Results: The frequency distribution of fok I genotype in Ugandan TB patients was 87.8% homozygous-dominant (FF), 7.3% (Ff) heterozygous and 4.8% (ff) homozygous recessive. For normal healthy subjects the frequencies were (FF) 92.6%, (Ff) 2.4% and (ff) 4.8%. No significant difference was observed in the FF and ff genotypes among TB patients and controls. The Ff heterozygous genotype distribution appeared more in TB patients than in controls. A significant difference was observed in the fok I genotype among gender p value 0.02. No significant difference was observed in ethnicity, p value 0.30. Conclusions: The heterozygous Ff fok I genotype may be associated with TB in the Ugandan population. PMID:27785354

  13. Mitral valve repair for active culture positive infective endocarditis

    PubMed Central

    Doukas, G; Oc, M; Alexiou, C; Sosnowski, A W; Samani, N J; Spyt, T J

    2006-01-01

    Objective To describe the clinical and echocardiographic outcome after mitral valve (MV) repair for active culture positive infective MV endocarditis. Patients and methods Between 1996 and 2004, 36 patients (mean (SD) age 53 (18) years) with positive blood culture up to three weeks before surgery (or positive culture of material removed at operation) and intraoperative evidence of endocarditis underwent MV repair. Staphylococci and streptococci were the most common pathogens. All patients had moderate or severe mitral regurgitation (MR). Mean New York Heart Association (NYHA) class was 2.3 (1.0). Follow up was complete (mean 38 (19) months). Results Operative mortality was 2.8% (one patient). At follow up, endocarditis has not recurred. One patient developed severe recurrent MR and underwent valve replacement and one patient had moderate MR. There were two late deaths, both non‐cardiac. Kaplan‐Meier five year freedom from recurrent moderate to severe MR, freedom from repeat operation, and survival were 94 (4)%, 97 (3)%, and 93 (5)%, respectively. At the most recent review the mean NYHA class was 1.17 (0.3) (p < 0.0001). At the latest echocardiographic evaluation, left atrial diameters, left ventricular end diastolic diameter, and MV diameter were significantly reduced (p < 0.05) compared with preoperative values. Conclusions MV repair for active culture positive endocarditis is associated with low operative mortality and provides satisfactory freedom from recurrent infection, freedom from repeat operation, and survival. Hence, every effort should be made to repair infected MVs and valves should be replaced only when repair is not possible. PMID:15951395

  14. Is TB in Your Curriculum?

    ERIC Educational Resources Information Center

    Kerr, Joanne; Elwell, Jack

    2002-01-01

    Points out the importance of effective health education to fight against tuberculosis (TB) which is the number one fatal infectious disease around the world. Describes a science curriculum on tuberculosis that includes information on the facts about tuberculosis, a forum on tuberculosis, and evaluation. (Contains 17 references.) (YDS)

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

    PubMed

    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

    2015-12-01

    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 approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

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

    PubMed Central

    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 Jr, 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 approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. PMID:26405286

  17. Active Community-Based Case Finding for Tuberculosis With Limited Resources

    PubMed Central

    Karki, Bindu; Kittel, Guenter; Bolokon, Ignatius; Duke, Trevor

    2016-01-01

    Papua New Guinea is one of the 14 highest-burden countries for tuberculosis (TB) infection, but few community-based studies exist. We evaluated a low-cost method of active community case finding in Kabwum and Wasu in Morobe Province, Papua New Guinea. Over 3 months we visited 26 villages and screened adults and children for symptoms and signs of TB. Sputum samples were examined using smear microscopy. A total of 1700 people had chronic symptoms, of which 267 were suspicious for TB on further examination. Sputum from 230 symptomatic adults yielded 97 samples that were positive for acid-fast bacilli. In addition, 15 cases of extrapulmonary TB in adults and 17 cases of TB in children were identified. One hundred and thirty people were identified with active TB disease among the source population of approximately 17 000, giving an estimated prevalence of 765 per 100 000. One hundred and six (82%) cases were not previously diagnosed. The cost per case identified was US$146. It is feasible to conduct active community-based case finding and treatment initiation for TB with limited resources and in remote areas, and in Papua New Guinea the yield was high. Active case finding and follow-up of treatment in villages is needed to address the hidden burden of TB in Papua New Guinea and other high-burden Asia Pacific countries. PMID:28033717

  18. Antimicrobial activity of Lactobacillus against microbial flora of cervicovaginal infections

    PubMed Central

    Dasari, Subramanyam; Shouri, Raju Naidu Devanaboyaina; Wudayagiri, Rajendra; Valluru, Lokanatha

    2014-01-01

    Objective To assess the probiotic nature of Lactobacillus in preventing cervical pathogens by studying the effectiveness of antimicrobial activity against vaginal pathogens. Methods Lactobacilli were isolated from healthy vaginal swabs on selective media and different pathogenic bacteria were isolated by using different selective media. The Lactobacillus strains were tested for the production of hydrogen peroxide and antimicrobial compounds along with probiotic properties. Results Of the 10 isolated Lactobacillus strains, strain 1, 3 and 6 are high hydrogen peroxide producers and the rest were low producers. Results of pH and amines tests indicated that pH increased with fishy odour in the vaginal fluids of cervicovaginal infection patients when compared with vaginal fluids of healthy persons. The isolates were found to be facultative anaerobic, Gram-positive, non-spore-forming, non-capsule forming and catalase-negative bacilli. The results of antimicrobial activity of compounds indicated that 280 and 140 µg/mL was the minimum concentration to inhibit the growth of both pathogens and test organisms respectively. Conclusions The results demonstrated that Lactobacillus producing antimicrobial compounds inhibits the growth of cervical pathogens, revealing that the hypothesis of preventing vaginal infection by administering probiotic organisms has a great appeal to patients, which colonize the vagina to help, restore and maintain healthy vagina.

  19. [Immunotherapy for MDR-TB (multi-drug resistant tuberculosis)--its feasibility].

    PubMed

    Tsuyuguchi, I

    1999-06-01

    MDR-TB is known to be man-made-disease. Inappropriate treatment of tuberculosis is responsible for the development of MDR-TB. MDR-TB is often accompanied with the immunosuppression of the host. Given that we are unable to develop another potent anti-TB drug in near future, immunotherapy directed at combating immunosuppression and enhancing the host's own immune response is an attractive approach to supplement conventional chemotherapy for MDR-TB. Patients with AIDS and patients with abnormalities of macrophage function have frequent problems with TB. This is suggesting that the host defenses involved in protection against mycobacteria include T-cell and monocyte/macrophage functions. That is cell-mediated immunity. Diverse cytokines are known to play an important role in anti-TB cell-mediated immunity, including IL-2, IL-12, IL-18 and IFN-gamma. Various animal experiments are indicating that administration of these cytokine (s) did recover the suppressed immunity and rescued the host from death by tuberculous infection. However, we have to keep it in mind that the results obtained from animal model of mycobacterial infection on the study of pathogenesis and immune responses in TB is not always applicable to the understanding of human TB. Clinical trial of inhalation therapy with IFN-gamma showed some improvement for drug-resistant TB. Cytokine treatment, however, often gave some deleterious side effects such as high fever, malaise, general edema and even the death of the host. Clinical trials with M. vaccae have been extensively conducted by UK group. The mechanisms underlying its possible therapeutic action remain to be clarified, but when administered at an appropriate dose, it has been shown to elicit a strong Th1 immune response. From the practical view point of immunotherapy for TB, surrogate markers of disease eradication and protective immunity are urgently required. Such markers would facilitate clinical trials by providing early evidence that test

  20. Changes in cell-mediated immune response after lung resection surgery for MDR-TB patients.

    PubMed

    Park, Seung-Kyu; Hong, Sunghee; Eum, Seok-Yong; Lee, In Hee; Shin, Donk Ok; Cho, Jang Eun; Cho, Sungae; Cho, Sang-Nae

    2011-07-01

    The immune responses of multidrug-resistant tuberculosis (MDR-TB) patients undergoing lung resection surgery were investigated in order to understand the mechanism of strong immune suppression in MDR-TB. We examined changes in cell-mediated immune response (CMI) of a total of sixteen MDR-TB patients, three of them extensively drug-resistant tuberculosis (XDR-TB) patients, after the removal of the heavily diseased lung section. The IFN-γ response to Mycobacterium tuberculosis culture filtrate proteins (Mtb-CFP), one of the most important CMI to defend TB, showed a statistically significant elevation in 2-4 months after operation when compared to the preoperative CMI in patients who were converted into AFB negative and cured in two years' follow-up, suggesting that the recovery of CMI may be one of the key factors in the successful treatment of MDR-TB. Interestingly, IL-10 response to Mtb-CFP was also elevated in 2-4 months after surgery in cured patients although both proliferative response and PBMC composition were not significantly changed. Infection with first- or second-line drugs resistant Mtb reduces the efficiency of chemotherapeutic treatment of MDR-TB to about 50%. Thus, this study suggests that chemotherapeutic treatment of MDR-TB may be more effective when combined with accompanying therapy that increases CMI, includes lung resection surgery.

  1. [Tuberculosis annual report 2009. Series 1. Summary of TB notification statistics in 2009].

    PubMed

    2011-02-01

    Annual reports of tuberculosis (TB) statistics in Japan have been compiled mainly using the output of the database obtained through the nationwide computerized tuberculosis surveillance system which has been operated since 1987. This system has been revised several times, with the latest revision conducted in 2007 when much new information was added. Therefore, a plan was drawn up to provide TB epidemiological statistics in Japan on "Kekkaku" and a series of ten reports was already issued as "TB Annual Report 2008". This is the first report of a new series for "TB Annual Report 2009". The report can be summarized as follows. The TB notification (incidence) rate fell below 20 per 100,000 in 2007 and continued to decline, reaching 19.0 in 2009. However, 24,170 TB patients were newly notified in 2009. For sputum smear positive pulmonary TB, the patient count was 9,675 with an incidence rate of 7.6 per 100,000 in 2009. Since June 2007, it has been legally compulsory to notify latent TB infections (LTBI) requiring treatment; the number in 2009 was 4119 cases.

  2. Cross section measurement of the 159Tb(n, γ)Tb160 nuclear reaction

    NASA Astrophysics Data System (ADS)

    Dzysiuk, N.; Kadenko, I.; Gressier, V.; Koning, A. J.

    2015-04-01

    The cross section of the 159Tb(n, γ)Tb160 reaction was measured in four mono-energetic neutron fields of energy 3.7, 4.3, 5.4, and 6.85 MeV, respectively, with the activation technique applied to metal discs of natural composition. To ensure an acceptable precision of the results all major sources of uncertainties were taken into account. Calculations of detector efficiency, incident neutron spectrum and correction factors were performed with the Monte Carlo code (MCNPX), whereas theoretical excitation functions were calculated with the TALYS-1.2 code and compared to the experimental cross section values. This paper presents both measurements and calculation leading to the cross section values.

  3. Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria.

    PubMed

    Chang, Charlotte A; Meloni, Seema Thakore; Eisen, Geoffrey; Chaplin, Beth; Akande, Patrick; Okonkwo, Prosper; Rawizza, Holly E; Tchetgen Tchetgen, Eric; Kanki, Phyllis J

    2015-12-01

    Background.  Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods.  This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results.  Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7-27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4(+) cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions.  The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections.

  4. MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis

    PubMed Central

    Azman, Andrew S.; Cobelens, Frank G.; Dowdy, David W.

    2017-01-01

    Background In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality. Methods We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology. Results Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4–52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6–55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20–74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025. Conclusions Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected

  5. Hyponatremia in pulmonary TB: evidence of ectopic antidiuretic hormone production.

    PubMed

    Lee, Paul; Ho, Ken K Y

    2010-01-01

    Hyponatremia is among the most common biochemical abnormalities in hospital inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of several causes of hyponatremia, particularly in patients with pulmonary diseases. The mechanism of SIADH associated with pulmonary infection is, however, poorly understood. We report an unusual case of hyponatremia in a man with pulmonary TB and central diabetes insipidus with biochemical evidence of ectopic antidiuretic hormone production as a possible mechanism causing hyponatremia.

  6. Thermal and optical properties of Tb(III), Eu(III) and Tb(III)/Eu(III) co-complexed silicone fluorinated acrylate copolymer

    NASA Astrophysics Data System (ADS)

    Zhai, Yinfeng; Xie, Hongde; Cai, Haijun; Cai, Peiqing; Seo, Hyo Jin

    2015-07-01

    Tb(III), Eu(III) and Tb(III)/Eu(III) activated silicone fluorinated acrylate (SFA) have been successfully synthesized using the method of semi-continuous emulsion polymerization. The copolymers are characterized by flourier transform infrared (FT-IR), thermal gravity analysis (TGA), photoluminescence excitation (PLE) and emission (PL) spectroscopy. The copolymer containing Tb(III) and Eu(III) ions display green and red luminescent colors under UV light excitation, respectively. The TGA curves show the thermal decomposition temperatures of the copolymers are up to about 300 °C. The PL spectra show a strong green emission at 546 nm (5D4 → 7F5) of Tb(III) complexed copolymers, and show a prominent red emission at 615 nm (5D0 → 7F2) of Eu(III) complexed copolymers. Different concentrations of Eu(III) and Tb(III) ions are introduced into the copolymer and the energy transfer from Tb(III) to Eu(III) ions in the copolymer was found. Thus, based on the results it can be suggested that SFA:Eu(III), SFA:Tb(III) and SFA:Tb(III)/Eu(III) can be used potentially as luminescent materials.

  7. Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice

    PubMed Central

    Shen, Hongbo; Wang, Feifei; Zeng, Gucheng; Shen, Ling; Cheng, Han; Huang, Dan; Wang, Richard; Rong, Lijun; Chen, Zheng W.

    2016-01-01

    While there is an urgent need to develop new and effective drugs for treatment of tuberculosis (TB) and multi-drug resistant TB (MDR-TB), repurposing FDA (U.S. Food and Drug Administration) -approved drugs for development of anti-TB agents may decrease time and effort from bench to bedside. Here, we employed host cell-based high throughput screening (HTS) assay to screen and characterize FDA-approved, off-patent library drugs for anti-Mycobacterium tuberculosis (MTB) activities. The cell-based HTS allowed us to identify an anti-cancer drug of bis-biguanide dihydrochloride (BBD) as potent anti-mycobacteria agent. Further characterization showed that BBD could inhibit intracellular and extracellular growth of M. smegmatis and slow-growing M. bovis BCG. BBD also potently inhibited replication of clinically-isolated MTB and MDR-TB strains. The proof-of-concept study showed that BBD treatment of MTB-infected mice could significantly decrease CFU counts in the lung and spleen. Notably, comparative evaluation showed that MTB CFU counts in BBD-treated mice were lower than those in rifampicin-treated mice. No apparent BBD side effects were found in BBD-treated mice. Thus, our findings support further studies to develop BBD as a new and effective drug against TB and MDR-TB. PMID:27601302

  8. Granulocytic Myeloid Derived Suppressor Cells Expansion during Active Pulmonary Tuberculosis Is Associated with High Nitric Oxide Plasma Level

    PubMed Central

    El Daker, Sary; Sacchi, Alessandra; Tempestilli, Massimo; Carducci, Claudia; Goletti, Delia; Vanini, Valentina; Colizzi, Vittorio; Lauria, Francesco Nicola; Martini, Federico; Martino, Angelo

    2015-01-01

    Tuberculosis (TB) is still the principal cause of death caused by a single infectious agent, and the balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. The aim of this work was to study the role of myeloid-derived suppressor cells (MDSCs) during active pulmonary tuberculosis at the site of infection. We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma. We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB. Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy. PMID:25879532

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

    PubMed

    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.

  10. TMC207 becomes bedaquiline, a new anti-TB drug.

    PubMed

    Palomino, Juan Carlos; Martin, Anandi

    2013-09-01

    TB still represents a serious public health problem. The latest reports estimate an incidence of 8.7 million cases in 2011 and 1.4 million deaths. Drug resistance contributed an estimated 630,000 cases of multidrug-resistant TB, making control of the disease harder. Recent reports show cases of TB that were almost resistant to all available antibiotics. Therefore, there is an urgent need to develop new anti-TB drugs with the potential of reducing the current length of treatment. Bedaquiline, formerly TMC207, is a new diarylquinoline antibiotic with specific activity against Mycobacterium tuberculosis and several nontuberculous mycobacteria. It acts by inhibiting ATP synthase, interfering with the energy generation needed by the bacterial cell. Based on clinical evaluations for safety, tolerability and efficacy, bedaquiline has recently received accelerated approval for the treatment of pulmonary multidrug-resistant TB in adults. This article will review the main aspects related to the chemistry, microbiology, pharmacology, efficacy and tolerability of bedaquiline.

  11. Eugenol nanocapsule for enhanced therapeutic activity against periodontal infections.

    PubMed

    Pramod, Kannissery; Aji Alex, M R; Singh, Manisha; Dang, Shweta; Ansari, Shahid H; Ali, Javed

    2016-01-01

    Eugenol is a godsend to dental care due to its analgesic, local anesthetic, and anti-inflammatory and antibacterial effects. The aim of the present research work was to prepare, characterize and evaluate eugenol-loaded nanocapsules (NCs) against periodontal infections. Eugenol-loaded polycaprolactone (PCL) NCs were prepared by solvent displacement method. The nanometric size of the prepared NCs was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The in vitro drug release was found to follow a biphasic pattern and followed Michaelis-Menten like model. The percentage cell viability values near to 100 in the cell viability assay indicated that the NCs are not cytotoxic. In the in vivo studies, the eugenol NC group displayed significant difference in the continuity of epithelium of the interdental papilla in comparison to the untreated, pure eugenol and placebo groups. The in vivo performance of the eugenol-loaded NCs using ligature-induced periodontitis model in rats indicated that eugenol-loaded NCs could prevent septal bone resorption in periodontitis. On the basis of our research findings it could be concluded that eugenol-loaded PCL NCs could serve as a novel colloidal drug delivery system for enhanced therapeutic activity of eugenol in the treatment of periodontal infections.

  12. Developing vaccines to prevent sustained infection with Mycobacterium tuberculosis: Conference proceedings: National Institute of Allergy and Infectious Diseases, Rockville, Maryland USA, November 7, 2014.

    PubMed

    2015-06-12

    On November 7, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a conference entitled "Vaccine Prevention of Sustained Mycobacterium tuberculosis Infection." The purpose of this meeting was to explore the biologic plausibility, potential public health and economic impact, and regulatory feasibility in attempting to develop a vaccine to prevent sustained infection with Mycobacterium tuberculosis (Mtb). Currently there are two main goals for tuberculosis (TB) vaccine development, to develop a vaccine that could serve as a booster to Bacille Calmette-Guérin (BCG) vaccination and prevent active TB in adolescents and adults, and to develop an improved vaccine to replace BCG in infants. Although prevention of sustained Mtb infection is being used as a proof of biological activity for vaccines in mid-Phase 2 development, there currently are no plans for pursuing a prevention of Mtb infection licensure indication for TB vaccines. Ultimately, pursuing a prevention of sustained Mtb infection indication for TB vaccines, in parallel with ongoing efforts to develop vaccines to prevent active TB disease, was deemed a potentially important effort, but would require further resources, particularly to improve diagnostic assays, to increase the regulatory feasibility of this endeavor.

  13. Seasonal dynamics of tuberculosis epidemics and implications for multidrug-resistant infection risk assessment.

    PubMed

    Lin, Y-J; Liao, C-M

    2014-02-01

    Understanding how seasonality shapes the dynamics of tuberculosis (TB) is essential in determining risks of transmission and drug resistance in (sub)tropical regions. We developed a relative fitness-based multidrug-resistant (MDR) TB model incorporated with seasonality and a probabilistic assessment model to assess infection risk in Taiwan regions. The model accurately captures the seasonal transmission and population dynamics of TB incidence during 2006-2008 and MDR TB in high TB burden areas during 2006-2010 in Taiwan. There is ~3% probability of having exceeded 50% of the population infected attributed to MDR TB. Our model not only provides insight into the understanding of the interactions between seasonal dynamics of TB and environmental factors but is also capable of predicting the seasonal patterns of TB incidence associated with MDR TB infection risk. A better understanding of the mechanisms of TB seasonality will be critical in predicting the impact of public control programmes.

  14. Striking the Right Balance Determines TB or Not TB

    PubMed Central

    BoseDasgupta, Somdeb; Pieters, Jean

    2014-01-01

    Mycobacterium tuberculosis continues to be one of the most successful pathogens on earth. Upon inhalation of M. tuberculosis by a healthy individual, the host immune system will attempt to eliminate these pathogens using a combination of immune defense strategies. These include the recruitment of macrophages and other phagocytes to the site of infection, production of cytokines that enhance the microbicidal capacity of the macrophages, as well as the activation of distinct subsets of leukocytes that work in concert to fight the infection. However, being as successful as it is, M. tuberculosis has evolved numerous strategies to subvert host immunity at virtual every level. As a consequence, one third of the world inhabitants carry M. tuberculosis, and tuberculosis continuous to cause disease in more than 8 million people with deadly consequences in well over 1 million patients each year. In this review, we discuss several of the strategies that M. tuberculosis employs to circumvent host immunity, as well as describe some of the mechanisms that the host uses to counter such subversive strategies. As for many other infectious diseases, the ultimate outcome is usually defined by the relative strength of the virulence strategies employed by the tubercle bacillus versus the arsenal of immune defense mechanisms of the infected host. PMID:25339950

  15. Antiviral Activity of HPMPC (Cidofovir) Against ORF Virus Infected Lambs

    PubMed Central

    Scagliarini, A.; McInnes, C.J.; Gallina, L.; Dal, Pozzo F.; Scagliarini, L.; Snoeck, R.; Prosperi, S.; Sales, J.; Gilray, J.A.; Nettleton, P.F.

    2007-01-01

    (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPC, cidofovir, CDV, Vistide®) is an acyclic nucleoside analogue with a potent and selective activity against a broad spectrum of DNA viruses including the poxviruses. In this study we present the results of different treatment regimens in lambs experimentally infected with orf virus with different cidofovir formulations prepared in Beeler basis and Unguentum M. Our results show that choice of excipient, concentration of cidofovir and treatment regimen were all important to the clinical outcome of the therapy. Whilst one particular regimen appeared to exacerbate the lesion, treatment with 1% w/v cidofovir cream, prepared in Beeler Basis, for 4 consecutive days did result in milder lesions that resolved more quickly than untreated lesions. Furthermore the scabs of the treated animals contained significantly lower amounts of viable virus meaning there should be less contamination of the environment with virus than would normally occur. PMID:17049627

  16. A review of the literature on the economics of vaccination against TB.

    PubMed

    Tu, Hong-Anh T; Vu, Hoa D; Rozenbaum, Mark H; Woerdenbag, Herman J; Postma, Maarten J

    2012-03-01

    The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

  17. Co-Fe-Tb (202)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 2 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from B-Be-Fe to Co-W-Zr' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Co-Fe-Tb (202)' with the content:

  18. B-Fe-Tb (148)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 2 http://dx.doi.org/10.1007/9getType="URL"/> 'Systems from B-Be-Fe to Co-W-Zr' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'B-Fe-Tb (148)' with the content:

  19. Infection

    DTIC Science & Technology

    2010-09-01

    standing, diagnosis, and treatment of musculoskeletal infections. Key Words: musculoskeletal infection, biofilm , bacteria, biomaterial (J Orthop Trauma...form a biofilm , or slime layer.1 The recurrence of infections is often the result of microbial biofilm formation on the implant, enabling the persistence...Klebsiella pneumoniae). Staphylococcus species is by far the most studied pathogen in musculoskeletal infections and can produce a multilayered biofilm

  20. Usefulness of interferon-γ release assay for the diagnosis of latent tuberculosis infection in young children

    PubMed Central

    Kim, Young Kwang; Kim, Hae Ryun; Lee, Mi Kyung; Lim, In Seok

    2016-01-01

    Purpose Latent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-γ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI. Methods We performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011–June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol. Results Among 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-γ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-γ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects. Conclusion The lack of decrease in interferon-γ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients. PMID:27462354

  1. Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia

    PubMed Central

    Lemma, Fitsum A.; Mekonnen, Daniel A.; Alemu, Zelalem E.; Kelkay, Tessema Z.

    2016-01-01

    Bovine tuberculosis (bTB) infection is generally correlated with individual cattle’s age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife—including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia’s highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in

  2. Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate influenza viral infection.

    PubMed

    Kohio, Hinissan P; Adamson, Amy L

    2013-09-01

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection.

  3. TB and HIV Therapeutics: Pharmacology Research Priorities.

    PubMed

    Dooley, Kelly E; Kim, Peter S; Williams, Sharon D; Hafner, Richard

    2012-01-01

    An unprecedented number of investigational drugs are in the development pipeline for the treatment of tuberculosis. Among patients with tuberculosis, co-infection with HIV is common, and concurrent treatment of tuberculosis and HIV is now the standard of care. To ensure that combinations of anti-tuberculosis drugs and antiretrovirals are safe and are tested at doses most likely to be effective, selected pharmacokinetic studies based on knowledge of their metabolic pathways and their capacity to induce or inhibit metabolizing enzymes of companion drugs must be conducted. Drug interaction studies should be followed up by evaluations in larger populations to evaluate safety and pharmacodynamics more fully. Involving patients with HIV in trials of TB drugs early in development enhances the knowledge gained from the trials and will ensure that promising new tuberculosis treatments are available to patients with HIV as early as possible. In this review, we summarize current and planned pharmacokinetic and drug interaction studies involving investigational and licensed tuberculosis drugs and antiretrovirals and suggest priorities for tuberculosis-HIV pharmacokinetic, pharmacodynamic, and drug-drug interaction studies for the future. Priority studies for children and pregnant women with HIV and tuberculosis co-infection are briefly discussed.

  4. Tuberculosis trends in the U.S. Armed Forces, active component, 1998-2012.

    PubMed

    Mancuso, James D; Aaron, Christopher L

    2013-05-01

    Members of the Armed Forces represent a segment of the U.S. population that may be at increased risk for tuberculosis (TB) infection, disease, and transmission due to overseas service in endemic areas and residence in congregate settings. The purpose of this study was to examine recent surveillance trends and risk factors associated with TB disease in the active component U.S. military. The rate of TB in the U.S. military -0.6 per 100,000 population (n=128) over the interval from 1998 to 2012 - was lower than the age-adjusted rate among the U.S. population (adjusted rate ratio=0.20) over the same time interval. During the last five years of the surveillance period, the most common factor associated with the diagnosis of TB disease during military service was latent infection at time of accession; also, as many as nine (24%) cases of TB were associated with deployment to Iraq or other military exposures. TB control activities should continue to mitigate unique military exposures such as crowding during recruit training and deployments to TB endemic areas.

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

    PubMed

    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.

  6. Combination of gene expression patterns in whole blood discriminate between tuberculosis infection states

    PubMed Central

    2014-01-01

    Background Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by non-genetic factors, may also determine whether individuals progress to active TB. Methods We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts. Results The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts. Conclusions Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts. PMID:24885723

  7. TB vaccine development and the End TB Strategy: importance and current status.

    PubMed

    Fletcher, Helen A; Schrager, Lewis

    2016-04-01

    TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates.

  8. Treatment guidelines for latent tuberculosis infection.

    PubMed

    2014-01-01

    The treatment of latent tuberculosis infection (LTBI) has been established as valid for patients at high risk for developing active tuberculosis. Treatment of LTBI is also considered an important strategy for eliminating tuberculosis (TB) in Japan. In recent years, interferon-gamma release assays have come into widespread use; isoniazid (INH) preventive therapy for HIV patients has come to be recommended worldwide; and there have been increases in both types of biologics used in the treatment of immune diseases as well as the diseases susceptible to treatment. In light of the above facts, the Prevention Committee and the Treatment Committee of the Japanese Society for Tuberculosis have jointly drafted these guidelines. In determining subjects for LTBI treatment, the following must be considered: 1) risk of TB infection/ development; 2) infection diagnosis; 3) chest image diagnosis; 4) the impact of TB development; 5) the possible manifestation of side effects; and 6) the prospects of treatment completion. LTBI treatment is actively considered when relative risk is deemed 4 or higher, including risk factors such as the following: HIV/AIDS, organ transplants (immunosuppressant use), silicosis, dialysis due to chronic renal failure, recent TB infection (within 2 years), fibronodular shadows in chest radiographs (untreated old TB), the use of biologics, and large doses of corticosteroids. Although the risk is lower, the following risk factors require consideration of LTBI treatment when 2 or more of them are present: use of oral or inhaled corticosteroids, use of other immunosuppressants, diabetes, being underweight, smoking, gastrectomy, and so on. In principle, INH is administered for a period of 6 or 9 months. When INH cannot be used, rifampicin is administered for a period of 4 or 6 months. It is believed that there are no reasons to support long-term LTBI treatment for immunosuppressed patients in Japan, where the risk of infection is not considered markedly high

  9. Dramatic effect of redox pre-treatments on the CO oxidation activity of Au/Ce(0.50)Tb(0.12)Zr(0.38)O(2-x) catalysts prepared by deposition-precipitation with urea: a nano-analytical and nano-structural study.

    PubMed

    del Río, Eloy; López-Haro, Miguel; Cíes, José M; Delgado, Juan J; Calvino, José J; Trasobares, Susana; Blanco, Ginesa; Cauqui, Miguel A; Bernal, Serafín

    2013-08-04

    Nano-structural and nano-analytical studies show that the dramatic difference in CO oxidation activity observed between two Au/Ce0.50Tb0.12Zr0.38O2-x samples prepared by deposition-precipitation with urea and further activated under oxidising or reducing conditions is due to the poisoning effect of a very thin layer of carbon grown on the pre-reduced catalyst.

  10. Microglia activation in a pediatric rabbit model of tuberculous meningitis

    PubMed Central

    Tucker, Elizabeth W.; Pokkali, Supriya; Zhang, Zhi; DeMarco, Vincent P.; Klunk, Mariah; Smith, Elizabeth S.; Ordonez, Alvaro A.; Penet, Marie-France; Bhujwalla, Zaver; Kannan, Sujatha

    2016-01-01

    ABSTRACT Central nervous system (CNS) tuberculosis (TB) is the most severe form of extra-pulmonary TB and disproportionately affects young children where the developing brain has a unique host response. New Zealand white rabbits were infected with Mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. Control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologic and pathologic changes. The presence of meningitis and tuberculomas was demonstrated histologically and by in vivo magnetic resonance imaging (MRI). The extent of microglial activation was quantified by in vitro immunohistochemistry as well as non-invasive in vivo imaging of activated microglia/macrophages with positron emission tomography (PET). Subarachnoid infection induced characteristic leptomeningeal and perivascular inflammation and TB lesions with central necrosis, a cellular rim and numerous bacilli on pathologic examination. Meningeal and rim enhancement was visible on MRI. An intense microglial activation was noted in M. tuberculosis-infected animals in the white matter and around the TB lesions, as evidenced by a significant increase in uptake of the tracer 124I-DPA-713, which is specific for activated microglia/macrophages, and confirmed by quantification of Iba-1 immunohistochemistry. Neurobehavioral analyses demonstrated signs similar to those noted in children with delayed maturation and development of neurological deficits resulting in significantly worse composite behavior scores in M. tuberculosis-infected animals. We have established a rabbit model that mimics features of TB meningitis in young children. This model could provide a platform for evaluating novel therapies, including host-directed therapies, against TB meningitis relevant to a young child's developing brain. PMID:27935825

  11. Using a mathematical model to evaluate the efficacy of TB control measures.

    PubMed Central

    Gammaitoni, L.; Nucci, M. C.

    1997-01-01

    We evaluated the efficacy of recommended tuberculosis (TB) infection control measures by using a deterministic mathematical model for airborne contagion. We examined the percentage of purified protein derivative conversions under various exposure conditions, environmental controlstrategies, and respiratory protective devices. We conclude that environmental control cannot eliminate the risk for TB transmission during high-risk procedures; respiratory protective devices, and particularly high-efficiency particulate air masks, may provide nearly complete protection if used with air filtration or ultraviolet irradiation. Nevertheless, the efficiency of these control measures decreases as the infectivity of the source case increases. Therefore, administrative control measures (e.g., indentifying and isolating patients with infectious TB) are the most effective because they substantially reduce the rate of infection. PMID:9284378

  12. Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

    PubMed Central

    Brust, Belinda; Lecoufle, Mélanie; Tuaillon, Edouard; Dedieu, Luc; Canaan, Stéphane; Valverde, Viviane; Kremer, Laurent

    2011-01-01

    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 biomarkers providing high

  13. Mortality among MDR-TB Cases: Comparison with Drug-Susceptible Tuberculosis and Associated Factors

    PubMed Central

    Chung-Delgado, Kocfa; Guillen-Bravo, Sonia; Revilla-Montag, Alejandro; Bernabe-Ortiz, Antonio

    2015-01-01

    Background An increase in multidrug-resistant tuberculosis (MDR-TB) cases is evident worldwide. Its management implies a complex treatment, high costs, more toxic anti-tuberculosis drug use, longer treatment time and increased treatment failure and mortality. The aims of this study were to compare mortality between MDR and drug-susceptible cases of tuberculosis, and to determine risk factors associated with mortality among MDR-TB cases. Methods and Results A retrospective cohort study was performed using data from clinical records of the National Strategy for Prevention and Control of Tuberculosis in Lima, Peru. In the first objective, MDR-TB, compared to drug-susceptible cases, was the main exposure variable and time to death, censored at 180 days, the outcome of interest. For the second objective, different variables obtained from clinical records were assessed as potential risk factors for death among MDR-TB cases. Cox regression analysis was used to determine hazard ratios (HR) and 95% confidence intervals (95%CI). A total of 1,232 patients were analyzed: mean age 30.9 ±14.0 years, 60.0% were males. 61 patients (5.0%) died during treatment, whereas the MDR-TB prevalence was 19.2%. MDR-TB increased the risk of death during treatment (HR = 7.5; IC95%: 4.1–13.4) when compared to presumed drug-susceptible cases after controlling for potential confounders. Education level (p = 0.01), previous TB episodes (p<0.001), diabetes history (p<0.001) and HIV infection (p = 0.04) were factors associated with mortality among MDR-TB cases. Conclusions MDR-TB is associated with an increased risk of death during treatment. Lower education, greater number of previous TB episodes, diabetes history, and HIV infection were independently associated with mortality among MDR-TB cases. New strategies for appropriate MDR-TB detection and management should be implemented, including drug sensitivity tests, diabetes and HIV screening, as well as guarantee for a complete adherence to

  14. Prioritizing Healthcare Delivery in a Conflict Zone Comment on "TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo".

    PubMed

    Wood, Robin; Richardson, Eugene T

    2013-09-01

    Nowhere are the barriers to a functional health infrastructure more clearly on display than in the Goma region of Democratic Republic of Congo. Kaboru et al. report poorly integrated services for HIV and TB in this war-torn region. Priorities in conflict zones include provision of security, shelter, food, clean water and prevention of sexual violence. In Goma, immediate health priorities include emergency treatment of cholera, malaria, respiratory illnesses, provision of maternal care, millions of measles vaccinations, and management of an ongoing rabies epidemic. It is a daunting task to determine an essential package of medical services in a setting where there are so many competing priorities, where opportunity costs are limited and epidemiologic information is scarce. Non-governmental agencies sometimes add to the challenge via an insidious reduction of state sovereignty and the creation of new levels of income inequality. Kaboru et al. have successfully highlighted many of the complexities of rebuilding and prioritizing healthcare in a conflict zone.

  15. Green photoluminescence from Zn3N2:Tb films prepared by magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Zhang, Z.-X.; Pan, X.-J.; Liu, L.-X.; Ma, Z.-W.; Zhao, H.-T.; Jia, L.; Xie, E.-Q.

    2009-01-01

    Terbium (Tb)-doped Zn3N2 thin films were prepared on glass and Si substrates by direct current magnetron sputtering in a mixture of pure argon and nitrogen gases. Glancing incidence x-ray diffraction patterns indicated that Zn3N2:Tb thin films were of cubic structure. Raman spectra showed only two Raman-active phonon modes located at 258 and 565 cm-1. The indirect optical band gap of Zn3N2:Tb was determined as 2.4 eV. The sharp characteristic emission lines corresponding to Tb3+ intra-4f shell transitions were resolved in the photoluminescence spectra at room temperature. Those results suggest that Tb-doped Zn3N2 may be a suitable material for visible optoelectronic devices.

  16. Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons

    PubMed Central

    2014-01-01

    Background Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia’s largest prison. Methods From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. Results Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other

  17. Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies.

    PubMed

    Kramnik, Igor; Beamer, Gillian

    2016-03-01

    A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co-evolution shaped M . tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data. In mice, there is clear genetic basis for susceptibility. Although the spectra of human and mouse TB do not completely overlap, comparison of human TB with mouse lesions across genetically diverse strains firmly establishes points of convergence. By embracing the genetic heterogeneity of the mouse population, we gain tremendous advantage in the quest for suitable in vivo models. Below, we review genetically defined mouse models that recapitulate a key element of M.tb pathogenesis-induction of necrotic TB lesions in the lungs-and discuss how these models may reflect TB stratification and pathogenesis in humans. The approach ensures that roles that mouse models play in basic and translational TB research will continue to increase allowing researchers to address fundamental questions of TB pathogenesis and bacterial physiology in vivo using this well-defined, reproducible, and cost-efficient system. Combination of the new generation mouse models with advanced imaging technologies will also allow rapid and inexpensive assessment of experimental vaccines and therapies prior to testing in larger animals and clinical trials.

  18. Tunable luminescence properties and energy transfer in LaAl₁₁O₁₈:Eu,Tb phosphor.

    PubMed

    Mendhe, M S; Puppalwar, S P; Dhoble, S J

    2016-05-01

    Eu(2+) and Tb(3+) singly doped and co-doped LaAl11O18 phosphors were prepared by a combustion method using urea as a fuel. The phase structure and photoluminescence (PL) properties of the prepared phosphors were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence excitation and emission spectra. When the content of Eu(2+) was fixed at 0.01, the emission chromaticity coordinates could be adjusted from blue to green region by tuning the contents of Tb(3+) ions from 0.01 to 0.03 through an energy transfer (ET) process. The fluorescence data collected from the samples with different contents of Tb(3+) into LaAl11O18: Eu, show the enhanced green emission at 545 nm associated with (5)D(4)-(7)F(5) transitions of Tb(3+). The enhancement was attributed to ET from Eu(2+) to Tb(3+), and therefore Eu(2+) ion acts as a sensitizer (an energy donor) while Tb(3+) ion as an activator. The ET from Eu(2+) to Tb(3+) is performed through dipole-dipole interaction. The ET efficiency and critical distance were also calculated. The present Eu(2+)-Tb(3+) co-doped LaAl11O18 phosphor will have potential application for UV convertible white light-emitting diodes.

  19. Tuberculosis in cattle herds are sentinels for Mycobacterium bovis infection in European badgers (Meles meles): the Irish Greenfield Study.

    PubMed

    Murphy, D; Gormley, E; Collins, D M; McGrath, G; Sovsic, E; Costello, E; Corner, L A L

    2011-07-05

    In Ireland badgers are removed in response to tuberculosis (TB) breakdowns in cattle herds (focal culling). Prevalence studies, conducted using a detailed post mortem and bacteriological examination, showed that 36-50% of badgers were infected with Mycobacterium bovis. Focal culling forms part of the medium term national strategy for the control of bovine TB in cattle and is based on the premise that badgers in areas with herd breakdowns have a higher prevalence of infection than the badger population at large. However, the hypothesis that cattle can be used as sentinels for infection in the badger population has never been formally tested. In this study we tested the hypothesis by determining the infection prevalence in badgers in areas where there had been historically, a consistently low prevalence of infection in cattle. Low cattle TB prevalence areas were defined as those herds with ≤ 2 standard reactors in the annual round of skin testing over the preceding 5 years (Greenfield sites). Using GIS, and adjusting for variation in land use, previous culling and cattle density, 198 Greenfield sites were identified and surveyed, and 138 areas with badger setts or signs of badger activity were identified. A single badger was removed from 87 sites and all were examined using detailed post mortem and bacteriological procedures. A prevalence of M. bovis infection of 14.9% was found in the Greenfield site badgers. This prevalence was significantly lower (P<0.001) than in badgers removed during focal culling (36.6%). The results validate the use of cattle as sentinels for TB in badgers and support the medium term national strategy for the control of bovine TB. The geographic variation in M. bovis infection prevalence in the Irish badger populations will be used when devising strategies for the incorporation of badger vaccination into the long term bovine TB control programme.

  20. High level of IFN-γ released from whole blood of human tuberculosis infections following stimulation with Rv2073c of Mycobacterium tuberculosis.

    PubMed

    Tan, Kun; Zhang, Jingyan; Teng, Xindong; Liang, Jinping; Wang, Xiaochun; Yuan, Xuefeng; Tian, Maopeng; Fan, Xionglin

    2015-07-01

    More efficacious and specific biomarkers are urgently needed for better control of tuberculosis (TB), the second leading infectious cause of mortality worldwide. The region of difference 9 (RD9) presents the genome of the causative pathogen Mycobacterium tuberculosis rather than other species of the genus Mycobacterium, which might be promising targets for specific diagnosis, vaccine development and pathogenesis. In this study, two proteins Rv2073c and Rv2074, encoded by the RD9 were expressed and purified from Escherichia coli system. Following stimulation with both proteins, the levels of IFN-γ secreted by T cells from a total of 49 whole blood samples obtained from clinically diagnosed active TB patients, patients with latent TB infections (LTBIs), and healthy donors, were compared with those of the incubation with recombinant fusion protein of CFP21 and MPT64 (rCM). Our results demonstrated that only Rv2073c could induce a higher level of IFN-γ in TB infections than healthy controls and there was a positive correlation between Rv2073c- and rCM-specific IFN-γ levels in TB infections and healthy donors, respectively. These findings indicate that Rv2073c might be a promising antigen for specific diagnostic reagents and vaccine candidates of TB.

  1. Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study

    PubMed Central

    2013-01-01

    Background The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART). Methods Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations. Results Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively]. Conclusions Ocular

  2. A single-phase full-color phosphor based on Ba3MgSi2O8 co-activated with Eu2+, Tb3+, and Mn2+

    NASA Astrophysics Data System (ADS)

    Birkel, Alexander; DeCino, Nicholas A.; Cozzan, Clayton; Mikhailovsky, Alexander A.; Hong, Byung-Chul; Seshadri, Ram

    2015-10-01

    We present a rapid and energy-efficient microwave-assisted approach to prepare a single-phase full-color phosphor based on Ba3MgSi2O8. The samples were prepared using a citric acid based sol-gel preparation pathway with a microwave-assisted heating step, which reduces the time required for the final heat treatment to less than 30 min. Thermogravimetric analysis was utilized to optimize the solution-based preparation prior to microwave heating. The structural properties of the obtained luminescent materials have been thoroughly investigated by means of X-ray powder diffraction and Rietveld analyses. To study the optical behavior, the excitation and emission spectra were recorded. Full-color emission is achieved using Eu2+ (blue), Tb3+ (green), and Mn2+ (red) as the activator ions. The thermally robust emission was investigated using temperature-dependent luminescence spectroscopy. The energy-transfer processes within the samples were studied using time-dependent spectroscopy, and the quantum yield of this true color phosphor as a function of the composition was determined.

  3. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    SciTech Connect

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  4. Screening and treatment of latent tuberculosis infection among HIV-infected patients in resource-rich settings.

    PubMed

    Lin, Ada W C; Lau, Susanna K P; Woo, Patrick C Y

    2016-01-01

    Current international guidelines recommend screening and treatment of latent tuberculosis (TB) infection in HIV-infected patients in all settings. The main factors affecting the risk of TB in HIV-infected patients include the level of immunosuppression, coverage of antiretroviral therapy and local TB burden. In resource-rich settings where antiretroviral therapy is more accessible and HIV-infected patients are expected to be diagnosed at an earlier stage, local TB burden remains a key factor on their risk of TB. This article reviewed the epidemiology of latent TB infection among the adult HIV-infected patients, and the use and benefit of screening and treatment of latent TB infection in resource-rich settings in the past decade. While such practice should be continued in countries with medium or high TB burden, targeted screening and treatment only for HIV-infected patients with additional risk factors for TB might be a more practical option in resource-rich countries with low TB burden.

  5. HIV-Mycobacterium tuberculosis co-infection: a 'danger-couple model' of disease pathogenesis.

    PubMed

    Shankar, Esaki M; Vignesh, Ramachandran; Ellegård, Rada; Barathan, Muttiah; Chong, Yee K; Bador, M Kahar; Rukumani, Devi V; Sabet, Negar S; Kamarulzaman, Adeeba; Velu, Vijayakumar; Larsson, Marie

    2014-03-01

    Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co-infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV-TB co-infection.

  6. Activation and Exhaustion of Adaptive Immune Cells in Hepatitis B Infection.

    PubMed

    Gogoi, Dimpu; Borkakoty, Biswajyoti; Biswas, Dipankar; Mahanta, Jagadish

    2015-09-01

    In hepatitis B virus (HBV) infection, the immune reaction is responsible for viral clearance and preventing their spread within the host. However, the immune system is dysfunctional in patients with chronic HBV infection, leading to an inadequate immune response against the virus. A major factor contributing to inefficient immune function is the phenomenon of immune exhaustion. Hence, understanding immune activation and exhaustion during HBV infection is important, as it would provide insight in developing immunotherapy to control chronic HBV infection. The aim of this review is to highlight the existing information on immune effector functions and immune exhaustion in response to HBV infection.

  7. Alcohol and drug use disorders, HIV status and drug resistance in a sample of Russian TB patients

    PubMed Central

    Fleming, M. F.; Krupitsky, E.; Tsoy, M.; Zvartau, E.; Brazhenko, N.; Jakubowiak, W.; E. McCaul, M.

    2006-01-01

    SUMMARY SETTING: Alcohol use, tuberculosis (TB) drug resistance and human immunodeficiency virus (HIV) risk behavior are of increasing concern in Russian TB patients. DESIGN: A prevalence study of alcohol use and HIV risk behavior was conducted in a sample of 200 adult men and women admitted to TB hospitals in St Petersburg and Ivanovo, Russia. RESULTS: Of the subjects, 72% were men. The mean age was 41. Active TB was diagnosed using a combination of chest X-ray, sputum smears and sputum cultures. Sixty-two per cent met DSM-IV criteria for current alcohol abuse or dependence. Drug use was uncommon, with only two patients reporting recent intravenous heroin use. There was one case of HIV infection. The mean total risk assessment battery score was 3.4. Depression was present in 60% of the sample, with 17% severely depressed. Alcohol abuse/dependence was associated with an eight-fold increase in drug resistance (OR 8.58; 95% CI 2.09-35.32). Patients with relapsing or chronic TB were more likely to meet the criteria for alcohol abuse/dependence (OR 2.56; 95% CI 1.0-6.54). CONCLUSION: Alcohol use disorders are common in patients being treated for active TB, and are associated with significant morbidity. Additional surveys are needed to examine the relationship between alcohol use disorders and anti-tuberculosis drug resistance. CONTEXTE: Chezles patients tuberculeux russes, l’utilisation d’alcool, la résistance aux médicaments antituberculeux et un comportement à risque pour le virus de l’immunodéficience humaine (VIH) sont des sujets croissants d’inquiétude. SCHÉMA: Une étude: de prévalence de l’utilisation d’alcool et du comportement à risque pour le VIH a été menée sur un échantillon de 200 hommes et femmes adultes, admis dans des hôpitaux pour la tuberculose (TB) de Saint-Pétersbourg et d’Ivanovo en Russie. RÉSULTATS: Il y avait 72% d’hommes dans l’échantillon. L’âge moyen est de 41 ans. On a diagnostiqué la TB active par l

  8. A species-specific activation of Toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by Mycobacterial infections.

    PubMed

    Ma, Yan; Han, Fei; Liang, Jinping; Yang, Jiali; Shi, Juan; Xue, Jing; Yang, Li; Li, Yong; Luo, Meihui; Wang, Yujiong; Wei, Jun; Liu, Xiaoming

    2016-03-01

    Pulmonary tuberculosis caused by a Mycobacterium infection remains a major public health problem in most part of the world, in part owing to the transmission of its pathogens between hosts including human, domestic and wild animals. To date, molecular mechanisms of the pathogenesis of TB are still incompletely understood. In addition to alveolar macrophages, airway epithelial cells have also been recently recognized as main targets for Mycobacteria infections. In an effort to understand the pathogen-host interaction between Mycobacteria and airway epithelial cells in domestic animals, in present study, we investigated the Toll-like receptor (TLR) signaling in bovine and sheep airway epithelial cells in response to an infection of Mycobacterium tuberculosis avirulent H37Ra stain or Mycobacterium bovis BCG vaccine strain, using primary air-liquid interface (ALI) bronchial epithelial culture models. Our results revealed a host and pathogen species-specific TLR-mediated recognition of pathogen-associated molecular patterns (PAMPs), induction and activation of TLR signaling pathways, and substantial induction of inflammatory response in bronchial epithelial cells in response to Mycobacteria infections between these two species. Interestingly, the activation TLR signaling in bovine bronchial epithelial cells induced by Mycobacteria infection was mainly through a myeloid differentiation factor 88 (MyD88)-independent TLR signaling pathway, while both MyD88-dependent and independent TLR signaling cascades could be induced in sheep epithelial cells. Equally noteworthy, a BCG infection was able to induce both MyD88-dependent and independent signaling in sheep and bovine airway epithelial cells, but more robust inflammatory responses were induced in sheep epithelial cells relative to the bovines; whereas an H37Ra infection displayed an ability to mainly trigger a MyD88-independent TLR signaling cascade in these two host species, and induce a more extent expression of

  9. What is Multidrug and Extensively Drug Resistant TB?

    MedlinePlus

    ... org > Lung Health and Diseases > Lung Disease Lookup > Tuberculosis (TB) What Is Multidrug and Extensively Drug Resistant TB? Multidrug-resistant tuberculosis ( MDR TB ) is a very dangerous form of ...

  10. TB in Correctional Facilities Is a Public Health Concern

    MedlinePlus

    ... component to TB elimination in the United States. Tuberculosis (TB) is a disease caused by bacteria that ... is essential to these efforts. More Information Reported Tuberculosis in the United States, 2012 TB in Correctional ...

  11. Tuberculosis: infection control in hospital and at home.

    PubMed

    Jarvis, Miles

    This article examines infection control issues relating to tuberculosis (TB) in acute and community settings. Background information on TB is discussed briefly along with key challenges to global and national control. A programme to prevent infection composed of specific hierarchical levels is outlined, using national and international guidance, and suggestions are made for infection control in the community. The article will be useful for nurses involved in the care of patients with confirmed or suspected TB.

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

    PubMed

    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.

  13. West Nile virus infection does not induce PKR activation in rodent cells.

    PubMed

    Elbahesh, H; Scherbik, S V; Brinton, M A

    2011-12-05

    dsRNA-activated protein kinase (PKR) is activated by viral dsRNAs and phosphorylates eIF2a reducing translation of host and viral mRNA. Although infection with a chimeric West Nile virus (WNV) efficiently induced PKR and eIF2a phosphorylation, infections with natural lineage 1 or 2 strains did not. Investigation of the mechanism of suppression showed that among the cellular PKR inhibitor proteins tested, only Nck, known to interact with inactive PKR, colocalized and co-immunoprecipitated with PKR in WNV-infected cells and PKR phosphorylation did not increase in infected Nck1,2-/- cells. Several WNV stem-loop RNAs efficiently activated PKR in vitro but not in infected cells. WNV infection did not interfere with intracellular PKR activation by poly(I:C) and similar virus yields were produced by control and PKR-/- cells. The results indicate that PKR phosphorylation is not actively suppressed in WNV-infected cells but that PKR is not activated by the viral dsRNA in infected cells.

  14. Estimating the cost of TB and its social impact on TB patients and their households.

    PubMed

    Onazi, O; Gidado, M; Onazi, M; Daniel, O; Kuye, J; Obasanya, O; Odusote, T; Gande, S

    2015-06-21

    Illness often poses a significant financial burden on individuals and their households, and tuberculosis (TB) is no exception. Although TB treatment is free in Nigeria, patients are likely to incur costs due to multiple visits during treatment. The purpose of this study was 1) to examine the health-seeking behaviour of TB patients and the costs borne by TB patients in Nigeria, and 2) to assess the social impact of TB disease on TB patients and their families/households. Of 260 TB patients surveyed, the majority (74.7%) were aged between 20 and 49 years. TB patients expended an average of US$52.02 (N = 8323.58, at the rate of US$1 = N = 160) per person on all visits associated with diagnosis and receipt of diagnostic test results. Overall, households experienced a shortfall of about US$57.30 (N = 9174.72) or 24.9% of income loss due to TB illness. Further analysis revealed that 9.7% of TB patients relied on children of school age or below to finance the costs of TB illness.

  15. Estimating the cost of TB and its social impact on TB patients and their households

    PubMed Central

    Onazi, O.; Gidado, M.; Onazi, M.; Daniel, O.; Kuye, J.; Obasanya, O.; Odusote, T.; Gande, S.

    2015-01-01

    Illness often poses a significant financial burden on individuals and their households, and tuberculosis (TB) is no exception. Although TB treatment is free in Nigeria, patients are likely to incur costs due to multiple visits during treatment. The purpose of this study was 1) to examine the health-seeking behaviour of TB patients and the costs borne by TB patients in Nigeria, and 2) to assess the social impact of TB disease on TB patients and their families/households. Of 260 TB patients surveyed, the majority (74.7%) were aged between 20 and 49 years. TB patients expended an average of US$52.02 (N = 8323.58, at the rate of US$1 = N = 160) per person on all visits associated with diagnosis and receipt of diagnostic test results. Overall, households experienced a shortfall of about US$57.30 (N = 9174.72) or 24.9% of income loss due to TB illness. Further analysis revealed that 9.7% of TB patients relied on children of school age or below to finance the costs of TB illness. PMID:26400384

  16. Infection

    MedlinePlus

    ... 23(4):251-69. Association for Professionals in Infection Control and Epidemiology (APIC) guideline. Back to Top Administration ... : Hospital Scope | Glossary | References | Site Map | Credits Freedom of ...

  17. 'Z(S)-MDR-TB' versus 'Z(R)-MDR-TB': improving treatment of MDR-TB by identifying pyrazinamide susceptibility.

    PubMed

    Zhang, Ying; Chiu Chang, Kwok; Leung, Chi-Chiu; Wai Yew, Wing; Gicquel, Brigitte; Fallows, Dorothy; Kaplan, Gilla; Chaisson, Richard E; Zhang, Wenhong

    2012-07-01

    Indispensable for shortening treatment of drug-susceptible tuberculosis (TB), pyrazinamide (PZA, Z) is also essential in the treatment of multidrug-resistant (MDR)-TB. While resistance to PZA in MDR-TB is associated with poor treatment outcome, bacillary susceptibility to PZA along with the use of fluoroquinolone (FQ) and second-line injectable drugs (SLIDs) may predict improved treatment success in MDR-TB. Despite a high prevalence of PZA resistance among MDR-TB patients (10%-85%), PZA susceptibility testing is seldom performed because of technical challenges. To improve treatment of MDR-TB, we propose to: (i) classify MDR-TB into PZA-susceptible MDR-TB (Z(S)-MDR-TB) and PZA-resistant MDR-TB (Z(R)-MDR-TB); (ii) use molecular tests such as DNA sequencing (pncA, gyrA, rrs, etc.) to rapidly identify Z(S)-MDR-TB versus Z(R)-MDR-TB and susceptibility profile for FQ and SLID; (iii) refrain from using PZA in Z(R)-MDR-TB; and (iv) explore the feasibility of shortening the treatment duration of Z(S)-MDR-TB with a regimen comprising PZA plus at least two bactericidal agents especially new agents like TMC207 or PA-824 or delamanid which the bacilli are susceptible to, with one or two other agents. These measures may potentially shorten therapy, save costs, and reduce side effects of MDR-TB treatment.

  18. Magnetoresistance in nanostructured Tb/Ti and Tb/Si multilayers

    SciTech Connect

    Svalov, A. V.; Kurlyandskaya, G. V.; Vas'kovskiy, V. O.; Sorokin, A. N.; Diercks, D.

    2011-01-15

    Magnetic, magnetoresistive and structural properties were studied for [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers which were prepared by rf-sputtering. The thickness of the Tb layers varied from 1.5 to 12 nm. The thickness of 2 nm nonmagnetic spacers of Ti or Si was kept constant. Both anisotropic and isotropic magnetoresistance was observed in [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers. A decrease in the thickness of the terbium layers led to a decrease in the anisotropic contribution to the total magnetoresistance. The negative isotropic magnetoresistanse in [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers can be attributed to the giant magnetoresistance (GMR) and/or high field isotropic magnetoresistance. The structure of the samples of both types enabled the existence of the GMR effect.

  19. E-ADA activity in serum of lambs experimentally infected with Haemonchus contortus.

    PubMed

    Da Silva, Aleksandro S; Fausto, Guilherme C; Grando, Thirssa H; Cadore, Carlos A; Pimentel, Victor C; Jaques, Jeandre A; Schetinger, Maria R C; Monteiro, Silvia G; Leal, Marta L R

    2013-08-01

    The aim of this study was to evaluate adenosine deaminase (E-ADA) activity in sera of lambs experimentally infected with Haemonchus contortus. We used 12 lambs divided into 2 groups; Group A had 5 healthy, non-infected animals (control) and Group B had 7 healthy animals infected with H. contortus . Lambs were infected orally with 500 larvae (L3) per animal every 2 days, for a period of 20 days, and later the infection was confirmed by examination of feces (eggs per gram [EPG] via fecal egg count). Blood collection was performed at days 0, 20, 40, 60, and 80 post-infection (PI) for analysis of E-ADA activity. Animals in Group A showed negative EPG throughout the experiment unlike those from Group B that had elevated EPG counts. E-ADA activity was reduced in the serum of animals infected with H. contortus when compared to non-infected controls at days 20, 40, 60, and 80 PI. Therefore, it is concluded that infection with H. contortus influences the E-ADA activity in lambs.

  20. Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar.

    PubMed

    Thi, A M; Shewade, H D; Kyaw, N T T; Oo, M M; Aung, T K; Aung, S T; Oo, H N; Win, T; Harries, A D

    2016-06-21

    Contexte : Programme intégré de prise en charge du virus de l'immunodéficience humaine (VIH), Mandalay, Myanmar.Objectifs : Chez les patients atteints de tuberculose (TB) et VIH enrôlés entre 2011 et 2014, déterminer la date du début du traitement antirétroviral (TAR) en relation avec le traitement antituberculeux (ATT) et son association avec le résultat d'ATT.Schéma : Etude rétrospective de cohorte.Résultats : Sur 1708 patients TB-VIH, 1565 (92%) ont débuté l'ATT en premier et 143 (8%) ont commencé le TAR en premier. Le résultat du traitement a été manquant pour 226 patients qui n'ont pas été inclus. Chez les patients ayant débuté l'ATT en premier, le délai médian de mise en route du TAR a été de 8,6 semaines. L'initiation du TAR a été retardée d'un délai médian de 8 semaines chez 830 (53%) patients. Parmi ces patients, 7% ont eu un résultat médiocre, avec une anémie qui a constitué un facteur de risque indépendant. Chez les patients ayant débuté le TAR en premier, le délai médian de mise en route de l'ATT a été de 21,6 semaines. L'ATT a été initié au cours des 3 mois chez 56 (39%) patients. Le traitement a échoué chez 12% des patients et chez 20% de ceux qui ont débuté l'ATT dans les 3 mois. Les patients ayant des CD4 <100/mm(3) ont eu un risque quatre fois plus élevé d'échec.Conclusions: La chronologie du TAR en rapport avec l'ATT n'a pas été un facteur de risque indépendant d'échec du traitement. Un dépistage extensif de la TB avec des tests de diagnostic rapides et sensibles chez les personnes infectées par le VIH et un suivi étroit de l'anémie et de l'immunosuppression sont recommandés afin d'améliorer encore le résultat du traitement de TB parmi les patients TB-VIH.

  1. MiR-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through TLR2/MyD88/NF-κB pathway by targeting TLR2.

    PubMed

    Gu, Xing; Gao, Yan; Mu, De-Guang; Fu, En-Qing

    2017-03-19

    Autophagy plays a pivotal role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M.tb.). The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the influence of miR-23a-5p on the activation of macrophage autophagy during M.tb. infection in bone marrow-derived macrophages (BMDMs) and murine RAW264.7 cells. Here, we demonstrated that M.tb.-infection of macrophages lead to markedly enhanced expression of miR-23a-5p in a time- and dose-dependent manner. Furthermore, forced expression of miR-23a-5p accelerated the survival rate of intracellular mycobacteria, while transfection with miR-23a-5p inhibitors attenuated mycobacterial survival. More importantly, overexpression of miR-23a-5p dramatically prevented M.tb.-induced activation of autophagy in macrophages, whereas inhibitors of miR-23a-5p remarkably accelerated M.tb.-induced autophagy. Mechanistically, miR-23a-5p is able to modulate TLR2/MyD88/NF-κB signaling activity by targeting TLR2 in RAW264.7 cells in response to M.tb.-infection. Collectively, these findings demonstrated that miR-23a-5p modulated the innate host defense by promoting mycobacteria survival and inhibiting the activation of autophagy against M.tb. through TLR2/MyD88/NF-κB pathway by targeting TLR2, which may provide a promising therapeutic target for tuberculosis.

  2. Understanding social context on TB cases

    NASA Astrophysics Data System (ADS)

    Ariyanto, Y.; Wati, D. M.

    2017-01-01

    Tuberculosis (TB) nowadays still becomes one of the world’s deadliest communicable disease. More than half were in South-East Asia and Western Pacific Regions, including Indonesia. As developing country, Indonesia remains classic problems in overcoming TB, that is discontinuation on treatment. Most of discontinuation on treatment among TB patients are affected by diagnostic delay that caused by patient delay. These phenomena occur in many areas, rural to suburb, coastal to plantation, and so on, and they are related with social context among community that could be social capital for each community to deal with TB. Jember as one of county in East Java is known as plantation area. It also has a high prevalence of TB. This study focused on understanding about social context among community, especially on plantation area. This cross-sectional study involved in three districts of Jember, those are Tanggul, Pakusari, and Kalisat. The data were obtained directly from the TB patients, local community, and Primary Health Care (PHC) where the patients recorded. Spatial analysis and social network analysis (SNA) were applied to obtain health seeking behavior pattern among the TB patients coincide the community. Most of TB patients had already chosen health professionals to lead the treatment, although some of them remained to choose self-medication. Meanwhile, SNA showed that religious leader was considered as main part of countermeasures of TB. But they didn’t ever become central figures. So it can be concluded that there are other parts among community who can contribute due to combatting on TB.

  3. Systematic expression profiling analysis mines dys-regulated modules in active tuberculosis based on re-weighted protein-protein interaction network and attract algorithm.

    PubMed

    Sun, Ying; Weng, Yan; Zhang, Ying; Yan, Xiang; Guo, Lei; Wang, Jia; Song, Xin; Yuan, Ying; Chang, Fu-Ye; Wang, Chun-Ling

    2017-03-18

    About 90% of tuberculosis (TB) patients latently infected with Mycobacterium tuberculosis (Mtb) show no symptoms, yet have a 10% chance in lifetime to progress active TB. Nevertheless, current diagnosis approaches need improvement in efficiency and sensitivity. The objective of this work was to detect potential signatures for active TB to further improve the understanding of the biological roles of functional modules involved in this disease. First, targeted networks of active TB and control groups were established via re-weighting protein-protein interaction (PPI) networks using Pearson's correlation coefficient (PCC). Candidate modules were detected from the targeted networks, and the modules with Jaccard score >0.7 were defined as attractors. After that, identification of dys-regulated modules was conducted from the attractors using attract method, Subsequently, gene oncology (GO) enrichment analyses were implemented for genes in the dys-regulated modules. We obtained 33 and 65 candidate modules from the targeted networks of control and active TB groups, respectively. Overall, 13 attractors were identified. Using the cut-off criteria of false discovery rate <0.05, there were 4 dys-regulated modules (Module 1, 2, 3, and 4). Based on the GO annotation results, genes in Modules 1, 2 and 4 were only involved in translation. Most genes in Module 1, 2 and 4 were associated with ribosomes. Accordingly, these dys-regulated modules might serve as potential biomarkers of active TB, facilitating the development for a more efficient, and sensitive diagnostic assay for active TB.

  4. Effects of immunomodulators on functional activity of innate immunity cells infected with Streptococcus pneumoniae.

    PubMed

    Plekhova, N G; Kondrashova, N M; Somova, L M; Drobot, E I; Lyapun, I N

    2015-02-01

    Low activity of bactericidal enzymes was found in innate immunity cells infected with S. pneumonia. The death of these cells was fastened under these conditions. On the contrary, treatment with antibiotic maxifloxacin was followed by an increase in activity of bactericidal enzymes in phagocytes and induced their death via necrosis. Analysis of the therapeutic properties of immunomodulators tinrostim and licopid in combination with maxifloxacin showed that these combinations correct functional activity of cells infected with S. pneumonia.

  5. Tuberculosis and HIV co-infection-focus on the Asia-Pacific region.

    PubMed

    Trinh, Q M; Nguyen, H L; Nguyen, V N; Nguyen, T V A; Sintchenko, V; Marais, B J

    2015-03-01

    Tuberculosis (TB) is the leading opportunistic disease and cause of death in patients with HIV infection. In 2013 there were 1.1 million new TB/HIV co-infected cases globally, accounting for 12% of incident TB cases and 360,000 deaths. The Asia-Pacific region, which contributes more than a half of all TB cases worldwide, traditionally reports low TB/HIV co-infection rates. However, routine testing of TB patients for HIV infection is not universally implemented and the estimated prevalence of HIV in new TB cases increased to 6.3% in 2013. Although HIV infection rates have not seen the rapid rise observed in Sub-Saharan Africa, indications are that rates are increasing among specific high-risk groups. This paper reviews the risks of TB exposure and progression to disease, including the risk of TB recurrence, in this vulnerable population. There is urgency to scale up interventions such as intensified TB case-finding, isoniazid preventive therapy, and TB infection control, as well as HIV testing and improved access to antiretroviral treatment. Increased awareness and concerted action is required to reduce TB/HIV co-infection rates in the Asia-Pacific region and to improve the outcomes of people living with HIV.

  6. Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement

    PubMed Central

    Dara, Masoud; de Colombani, Pierpaolo; Petrova-Benedict, Roumyana; Centis, Rosella; Zellweger, Jean-Pierre; Sandgren, Andreas; Heldal, Einar; Sotgiu, Giovanni; Jansen, Niesje; Bahtijarevic, Rankica; Migliori, Giovanni Battista

    2012-01-01

    The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants. A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011. Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country. The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support). PMID:22653772

  7. Salamanders increase their feeding activity when infected with the pathogenic chytrid fungus Batrachochytrium dendrobatidis.

    PubMed

    Hess, Alexandra; McAllister, Caroline; DeMarchi, Joseph; Zidek, Makenzie; Murone, Julie; Venesky, Matthew D

    2015-10-27

    Immune function is a costly line of defense against parasitism. When infected with a parasite, hosts frequently lose mass due to these costs. However, some infected hosts (e.g. highly resistant individuals) can clear infections with seemingly little fitness losses, but few studies have tested how resistant hosts mitigate these costly immune defenses. We explored this topic using eastern red-backed salamanders Plethodon cinereus and the fungal pathogen Batrachochytrium dendrobatidis (Bd). Bd is generally lethal for amphibians, and stereotypical symptoms of infection include loss in mass and deficits in feeding. However, individuals of P. cinereus can clear their Bd infections with seemingly few fitness costs. We conducted an experiment in which we repeatedly observed the feeding activity of Bd-infected and non-infected salamanders. We found that Bd-infected salamanders generally increased their feeding activity compared to non-infected salamanders. The fact that we did not observe any differences in mass change between the treatments suggests that increased feeding might help Bd-infected salamanders minimize the costs of an effective immune response.

  8. Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

    PubMed Central

    Efsen, Anne Marie W.; Schultze, Anna; Post, Frank A.; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F.; Losso, Marcelo H.; Toibaro, Javier; Skrahin, Aliaksandr; Miro, Jose M.; Caylà, Joan A.; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Podlekareva, Daria N.; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

    2015-01-01

    Objectives Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and Methods Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001). Conclusions In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART. PMID:26716686

  9. Soil Moisture Active Passive (SMAP) Project Algorithm Theoretical Basis Document SMAP L1B Radiometer Data Product: L1B_TB

    NASA Technical Reports Server (NTRS)

    Piepmeier, Jeffrey; Mohammed, Priscilla; De Amici, Giovanni; Kim, Edward; Peng, Jinzheng; Ruf, Christopher; Hanna, Maher; Yueh, Simon; Entekhabi, Dara

    2016-01-01

    The purpose of the Soil Moisture Active Passive (SMAP) radiometer calibration algorithm is to convert Level 0 (L0) radiometer digital counts data into calibrated estimates of brightness temperatures referenced to the Earth's surface within the main beam. The algorithm theory in most respects is similar to what has been developed and implemented for decades for other satellite radiometers; however, SMAP includes two key features heretofore absent from most satellite borne radiometers: radio frequency interference (RFI) detection and mitigation, and measurement of the third and fourth Stokes parameters using digital correlation. The purpose of this document is to describe the SMAP radiometer and forward model, explain the SMAP calibration algorithm, including approximations, errors, and biases, provide all necessary equations for implementing the calibration algorithm and detail the RFI detection and mitigation process. Section 2 provides a summary of algorithm objectives and driving requirements. Section 3 is a description of the instrument and Section 4 covers the forward models, upon which the algorithm is based. Section 5 gives the retrieval algorithm and theory. Section 6 describes the orbit simulator, which implements the forward model and is the key for deriving antenna pattern correction coefficients and testing the overall algorithm.

  10. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  11. HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytes

    PubMed Central

    Gonçalves, Lígia Antunes; Rodo, Joana; Rodrigues-Duarte, Lurdes; de Moraes, Luciana Vieira; Penha-Gonçalves, Carlos

    2017-01-01

    Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium-infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite. PMID:28220125

  12. In situ localization of ATPase activity in cells of plants infected by maize dwarf mosaic potyvirus.

    PubMed

    Chen, S; Das, P; Hari, V

    1994-01-01

    Cells of healthy maize plants as well as those infected by maize dwarf mosaic potyvirus were examined by electron microscopy for the location of ATPase activity. In healthy and virus infected plants, ATPase activity was found in plasma membranes, chloroplast thylakoid membranes, nuclear membranes and in mitochondria. In virus-infected cells, ATPase activity was also observed in cytoplasmic vesicles which were found in close proximity to the virus-specific cytoplasmic inclusion bodies (CI), at the ends of the arms of the CI and in plasmodesmata.

  13. Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

    SciTech Connect

    Rainio, Eeva-Marja; Ahlfors, Helena; Ruuska, Marja; Kieff, Elliott; Koskinen, Paeivi J. . E-mail: paivi.koskinen@btk.fi

    2005-03-15

    Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth.

  14. Activation of Hypoxia Inducible Factor 1 Is a General Phenomenon in Infections with Human Pathogens

    PubMed Central

    Werth, Nadine; Beerlage, Christiane; Rosenberger, Christian; Yazdi, Amir S.; Edelmann, Markus; Amr, Amro; Bernhardt, Wanja; von Eiff, Christof; Becker, Karsten; Schäfer, Andrea; Peschel, Andreas; Kempf, Volkhard A. J.

    2010-01-01

    Background Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Methodology/Principal Findings Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Conclusions/Significance Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections. PMID:20644645

  15. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins.

    PubMed

    Granstedt, Andrea E; Bosse, Jens B; Thiberge, Stephan Y; Enquist, Lynn W

    2013-09-10

    A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy.

  16. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

    PubMed

    Zhen, Anjie; Rezek, Valerie; Youn, Cindy; Lam, Brianna; Chang, Nelson; Rick, Jonathan; Carrillo, Mayra; Martin, Heather; Kasparian, Saro; Syed, Philip; Rice, Nicholas; Brooks, David G; Kitchen, Scott G

    2017-01-03

    Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.

  17. Human granuloma in vitro model, for TB dormancy and resuscitation.

    PubMed

    Kapoor, Nidhi; Pawar, Santosh; Sirakova, Tatiana D; Deb, Chirajyoti; Warren, William L; Kolattukudy, Pappachan E

    2013-01-01

    Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human tuberculosis.

  18. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point

    PubMed Central

    Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K. Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G. Suarez, Pedro

    2016-01-01

    A child’s risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76–4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID:27196627

  19. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point.

    PubMed

    Tadesse, Yared; Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G Suarez, Pedro

    2016-01-01

    A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges.

  20. Enhanced luminescence of Tb3 + due to efficient energy transfer from Ce3 + in a nanocrystalline Lu2Si2O7 host lattice

    NASA Astrophysics Data System (ADS)

    Sokolnicki, J.

    2010-07-01

    Nanocrystalline lutetium pyrosilicate Lu2Si2O7 (LPS) doped with Tb3 + (LPS:Tb) or Ce3 + /Tb3 + (LPS:Ce, Tb) was obtained at 1250 °C by the reaction of nanostructured Lu2O3 and colloidal SiO2. X-ray diffraction analysis confirmed the crystallization of a single phase of LPS at the indicated temperature. Different concentrations of active ions allowed us to study the influence of Ce3 + co-doping on Tb3 + emission. Tb3 + -doped LPS yields both the blue emission ^{5}\\mathrm {D}_{3} \\to {}^{7}\\mathrm {F}_{J} (J = 3, 4, 5, 6) and the green emission ^{5}\\mathrm {D}_{4} \\to {}^{7}\\mathrm {F}_{J} (J = 3, 4, 5, 6) of Tb3 + . The green emission of Tb3 + is enhanced remarkably in both the cathodoluminescence and photoluminescence spectra because of energy transfer from Ce3 + to Tb3 + ions, both of which are present in the host lattice. Based on the optical luminescence and luminescence excitation spectra, the optimal Tb3 + doping level for maximum light output was established to be 9 mol% and the highest enhancement of Tb3 + luminescence by Ce3 + co-doping was detected using a 1:3 ratio of Ce3 + /Tb3 + concentration. Two different crystallographic sites of Tb3 + in the LPS lattice were detected in the luminescence and excitation spectra of samples with higher Tb3 + concentrations (6-9 mol%). The single-exponential decay profile of 5D4 emission for the less concentrated samples and the double-exponential decay for the higher doping level are in agreement with this observation. Calculation of colour coordinates shows that LPS:Ce(0.25%)Tb(3%) emits white light.

  1. Syphilis superinfection activates expression of human immunodeficiency virus I in latently infected rabbits.

    PubMed Central

    Tseng, C. K.; Hughes, M. A.; Hsu, P. L.; Mahoney, S.; Duvic, M.; Sell, S.

    1991-01-01

    Superinfection of latently human immunodeficiency virus (HIV)-infected rabbits with either Treponema pallidum or Shope fibroma virus (SFV) activates HIV expression. In addition, HIV-infected rabbits demonstrate prolonged cutaneous lesions (chancres) after intracutaneous challenge with T. pallidum, the causative agent of syphilis. Rabbits were infected by intravenous inoculation of 3 x 10(7) human T-cell lymphotrophic virus type III (HTLV-III)/B10 (HIV-1)-infected H9 (human) cells. Five weeks after initial infection, integrated HIV-1-specific DNA sequences were detected in the DNA of the peripheral blood lymphocytes of only one of eight rabbits using polymerase chain reactions (PCR); human DNA could not be detected at this time. Furthermore HIV infection could not be demonstrated by either seroconversion or PCR during the next 6 months. All HIV-infected rabbits remained clinically healthy and had normal white blood cell counts. Six months after HIV infection, four HIV-infected and two noninfected controls were superinfected with 10(6) T. pallidum in eight skin sites in the shaved skin of the back, and four infected and two control animals were challenged with an intradermal injection with SFV. After infection with either syphilis or SFV, the DNA from the white blood cells of all eight HIV-infected rabbits contained HIV sequences, and HIV sequences were demonstrated in dermal mononuclear cells of the syphilitic lesions by in situ hybridization. The SFV-induced tumors were rejected normally in the HIV-infected rabbits, but four of the four rabbits challenged with T. pallidum had delayed development of cutaneous lesions and three of four demonstrated larger and more prolonged lesions. White blood counts, mitogen responses, and interleukin-2 production remained within normal limits, and seroconversion for HIV was not detected. Three of four rabbits in a second group, challenged with T. pallidum 4 months after HIV-inoculation, also had delayed healing of syphilitic

  2. Perspectives on the History of Bovine TB and the Role of Tuberculin in Bovine TB Eradication

    PubMed Central

    Good, Margaret; Duignan, Anthony

    2011-01-01

    Tuberculosis remains a significant disease of animals and humans worldwide. Bovine tuberculosis is caused by Mycobacteria with an extremely wide host range and serious, although currently probably underdiagnosed, zoonotic potential. Where bovine tuberculosis controls are effective, human zoonotic TB, due to Mycobacterium bovis or M. caprae, is uncommon and clinical cases are infrequent in cattle. Therefore, the control and ultimate eradication of bovine tuberculosis is desirable. Tuberculin tests are the primary screening tool used in bovine eradication. The choice of tuberculin test is dependent on the environment in which it is to be used. Tuberculin potency is critical to test performance, and the accurate determination of potency is therefore particularly important. The design of a control or eradication programme should take into consideration the fundamental scientific knowledge, the epidemiological profile of disease, the experience of other eradication programmes, and the presence, in the same ecosystem, of maintenance hosts, in which infection is self-sustaining and which are capable of transmitting infection. A control or eradication programme will necessarily require modification as it progresses and must be under constant review to identify the optimal desirable goals, the efficacy of policy, and constraints to progress. PMID:21547209

  3. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  4. Infection,

    DTIC Science & Technology

    1980-10-16

    inapparent infection. A refeeding program may thus become complicated by the sudden appearance of a life-threatening infectious illness (3). (3) The...Beisel, W. R. 23 Unusually low serum concentrations of inorganic phosphate have been reported in patients with gram-negative sepsis and in Reye’s syndrome ...infection should be corrected by a well-managed program of convalescent-period refeeding . This aspect of nutritional support is too often ignored. On the

  5. Adenosine deaminase activity in serum, erythrocytes and lymphocytes of rats infected with Leptospira icterohaemorrhagiae.

    PubMed

    Tonin, Alexandre A; Pimentel, Victor C; da Silva, Aleksandro S; de Azevedo, Maria Isabel; Souza, Viviane C G; Wolkmer, Patrícia; Rezer, João F P; Badke, Manoel R T; Leal, Daniela B R; Schetinger, Maria Rosa C; Monteiro, Silvia G; Lopes, Sonia T A

    2012-04-01

    Leptospirosis is a systemic disease of humans and domestic animals, mainly dogs, cattle and swine. The course of human leptospirosis varies from mild to severe fatal forms and the most severe form of human leptospirosis is principally caused by Leptospira interrogans serovar icterohaemorrhagiae (L. icterohaemorrhagiae). The enzyme adenosine deaminase (ADA) plays an important role in the production and differentiation of blood cells. The aim of this study was to evaluate the activity of ADA in serum, erythrocytes and lymphocytes of rats infected with L. icterohaemorrhagiae, as compared with non-infected rats. Twenty-four adult rats, divided into two uniform groups (A and B) were used for the enzymatic assays. The animals in Group B were inoculated intraperitoneally with 2×10(8) leptospires/rat, and the rodents in Group A (control) were not-inoculated. Blood collection was performed on days 5 and 15 post-infection (PI) and the blood used to assess the ADA activity. The infection by L.icterohaemorrhagiae altered erythrocyte count, hemoglobin concentration and hematocrit, causing a decrease in all these parameters on day 15 PI. Lymphocytes decreased significantly on day 15 PI, and ADA activity in serum was inhibited in infected rats on days 5 and 15 PI and its activity in erythrocytes were increased on day 5 PI. On day 5 PI, we found an increase in ADA activity in erythrocytes of infected rats. No correlation was observed between hematocrit and erythrocyte ADA activity on days 5 and 15 PI. The ADA activity was inhibited in rats infected on day 15 PI. A positive correlation (r(2)=60) was also observed between the number of lymphocytes and ADA activity in lymphocytes on day 15 PI (P<0.05). In conclusion, our results showed that the ADA activity is altered in serum, lymphocytes and erythrocytes in experimental infection by L.icterohaemorrhagiae in rats, concomitantly with hematological parameters.

  6. Epstein-Barr virus infection-induced inflammasome activation in human monocytes

    PubMed Central

    Torii, Yuka; Murata, Takayuki; Yoshiyama, Hironori; Kimura, Hiroshi; Ito, Yoshinori

    2017-01-01

    Inflammasomes are cytoplasmic sensors that regulate the activity of caspase-1 and the secretion of interleukin-1β (IL-1β) or interleukin-18 (IL-18) in response to foreign molecules, including viral pathogens. They are considered to be an important link between the innate and adaptive immune responses. However, the mechanism by which inflammasome activation occurs during primary Epstein-Barr virus (EBV) infection remains unknown. Human B lymphocytes and epithelial cells are major targets of EBV, although it can also infect a variety of other cell types. In this study, we found that EBV could infect primary human monocytes and the monocyte cell line, THP-1, inducing inflammasome activation. We incubated cell-free EBV with THP-1 cells or primary human monocytes, then confirmed EBV infection using confocal microscopy and flow cytometry. Lytic and latent EBV genes were detected by real-time RT-PCR in EBV-infected monocytes. EBV infection of THP-1 cells and primary human monocytes induced caspase-dependent IL-1β production, while EBV infection of B-cell or T-cell lines did not induce IL-1β production. To identify the sensor molecule responsible for inflammasome activation during EBV infection, we examined the mRNA and the protein levels of NLR family pyrin domain-containing 3 (NLRP3), absent in melanoma 2 (AIM2), and interferon-inducible protein 16 (IFI16). Increased AIM2 levels were observed in EBV-infected THP-1 cells and primary human monocytes, whereas levels of IFI16 and NLRP3 did not show remarkable change. Furthermore, knockdown of AIM2 by small interfering RNA attenuated caspase-1 activation. Taken together, our results suggest that EBV infection of human monocytes induces caspase-1-dependent IL-1β production, and that AIM2, acting as an inflammasome, is involved in this response. PMID:28369146

  7. Human lymphokine-activated killer cells are cytotoxic against cells infected with Toxoplasma gondii

    PubMed Central

    1992-01-01

    Experiments were conducted to determine whether human lymphokine- activated killer (LAK) cells are cytotoxic against cells infected with Toxoplasma gondii. Nylon wool nonadherent (NWNA) peripheral blood lymphocytes, as well as purified natural killer cell (NK) (CD3- CD16+ CD56+) and T (CD3+ CD16- CD56-) cells obtained from five healthy T. gondii seronegative volunteers exhibited minimal cytotoxic activity against T. gondii-infected cells. When standard LAK (S-LAK) cell preparations were induced by incubation of NWNA cells with recombinant interleukin 2, induction of remarkable cytotoxic activity against T. gondii-infected cells. When standard in LAK cell preparations from each of the volunteers. The phenotype of the LAK precursor and effector cells varied depending on the target cell used. Whereas the precursor and the effector cells of most of the LAK activity against K562 and Daudi cells were cells with NK phenotype, when T. gondii-infected cells were used as targets, both cells with NK and T cell phenotypes were precursors and effectors of the lysis. When cytotoxic activity of S-LAK cells was compared with the activity of adherent LAK (A-LAK) cells, A- LAK cells displayed higher cytotoxic activity against T. gondii- infected cells, as well as against K562 and Daudi cells. Cold target inhibition experiments suggested that there is a subset of LAK effector cells capable of lysing both T. gondii-infected cells and Daudi cells, whereas other subsets preferentially or exclusively lyse one of these target cells. PMID:1460415

  8. [Development and study of structure-activity relationship of drugs against Mycobacterium tuberculosis].

    PubMed

    Baska, Ferenc; Székely, Edina Rita; Szántai-Kis, Csaba; Bánhegyi, Péter; Hegymegi-Barakonyi, Bálint; Németh, Gábor; Breza, Nóra; Zsákai, Lilian; Greff, Zoltán; Pató, János; Kéri, György; Orfi, Lászlo

    2013-01-01

    Tuberculosis is considered to be one of the major health problem not only in the less developed countries but in the economically developed countries as well. Roughly one third of the world's population are infected with Mycobacterium tuberculosis and a significant part of them are carriers of latent tuberculosis. From ten percent of these latent infections are developing the active TB disease and fifty percent of them die from the illness without appropriate treatment. The drug-resistant Mycobacterium tuberculosis (MDR-TB, XDR-TB) and TB-HIV co-infection attracted attention to the most serious infectious disease. Inhibition of alternative signaling pathways were an important part of the research strategies for cancer and inflammatory diseases in recent years. In case of Mycobacterium tuberculosis such pathways were also identified, for example, three serine-threonine kinases (PknA, PknB, PknG) which are necessary and essential for bacterial growth. In this paper we summarize our best anti-TB active compounds, their biological effects and structure-activity relationships using in silico modeling, biochemical measurements and tests on active bacteria.

  9. Indoor environmental control of tuberculosis and other airborne infections.

    PubMed

    Nardell, E A

    2016-02-01

    Tuberculosis (TB) remains the airborne infection of global importance, although many environmental interventions to control TB apply to influenza and other infections with airborne potential. This review focuses on the global problem and the current state of available environmental interventions. TB transmission is facilitated in overcrowded, poorly ventilated congregate settings, such as hospitals, clinics, prisons, jails, and refugee camps. The best means of TB transmission control is source control- to identify unsuspected infectious cases and to promptly begin effective therapy. However, even with active case finding and rapid diagnostics, not every unsuspected case will be identified, and environmental control measures remain the next intervention of choice. Natural ventilation is the main means of air disinfection and has the advantage of wide availability, low cost, and high efficacy-under optimal conditions. It is usually not applicable all year in colder climates and may not be effective when windows are closed on cold nights in warm climates, for security, and for pest control. In warm climates, windows may be closed when air conditioning is installed for thermal comfort. Although mechanical ventilation, if properly installed and maintained, can provide adequate air disinfection, it is expensive to install, maintain, and operate. The most cost-effective way to achieve high levels of air disinfection is upper room germicidal irradiation. The safe and effective application of this poorly defined intervention is now well understood, and recently published evidence-based application guidelines will make implementation easier.

  10. From Wasting to Obesity: The Contribution of Nutritional Status to Immune Activation in HIV Infection.

    PubMed

    Koethe, John R; Heimburger, Douglas C; PrayGod, George; Filteau, Suzanne

    2016-10-01

    The impact of human immunodeficiency virus (HIV) infection on innate and adaptive immune activation occurs in the context of host factors, which serve to augment or dampen the physiologic response to the virus. Independent of HIV infection, nutritional status, particularly body composition, affects innate immune activation through a variety of conditions, including reduced mucosal barrier defenses and microbiome dysbiosis in malnutrition and the proinflammatory contribution of adipocytes and stromal vascular cells in obesity. Similarly, T-cell activation, proliferation, and cytokine expression are reduced in the setting of malnutrition and increased in obesity, potentially due to adipokine regulatory mechanisms restraining energy-avid adaptive immunity in times of starvation and exerting a paradoxical effect in overnutrition. The response to HIV infection is situated within these complex interactions between host nutritional health and immunologic function, which contribute to the varied phenotypes of immune activation among HIV-infected patients across a spectrum from malnutrition to obesity.

  11. Effects of malaria (Plasmodium relicturm) on activity budgets of experimentally-infected juvenile Apapane (Himatione sanquinea)

    USGS Publications Warehouse

    Yorinks, N.; Atkinson, C.T.

    2000-01-01

    We used behavioral, physiological, and parasitological measures to document effects of acute malarial infections on activity budgets of experimentally infected juvenile Apapane (Himatione sanguinea). Five of eight birds died within 20 to 32 days after exposure to a single infective mosquito bite. Infected Apapane devoted less time to locomotory activities involving flight, walking or hopping, and stationary activities such as singing, preening, feeding, and probing. The amount of time spent sitting was positively correlated with parasitemia and increased dramatically after infection and between treatment and control groups. Birds that succumbed to infection experienced a significant loss of body mass and subcutaneous fat, whereas surviving Apapane were better able to maintain body condition and fat levels. When rechallenged with the parasite five months after initial infection, surviving birds experienced no increase in parasitemia, indicating that they had become immune to reinfection. Regardless of the outcome, infected birds experienced acute illness that would have left them unable to forage or to escape from predators in the wild.

  12. Field evaluation of a blood based test for active tuberculosis in endemic settings.

    PubMed

    Khaliq, Aasia; Ravindran, Resmi; Hussainy, Syed Fahadulla; Krishnan, Viwanathan V; Ambreen, Atiqa; Yusuf, Noshin Wasim; Irum, Shagufta; Rashid, Abdul; Jamil, Muhammad; Zaffar, Fareed; Chaudhry, Muhammad Nawaz; Gupta, Puneet K; Akhtar, Muhammad Waheed; Khan, Imran H

    2017-01-01

    Over 9 million new active tuberculosis (TB) cases emerge each year from an enormous pool of 2 billion individuals latently infected with Mycobacterium tuberculosis (M. tb.) worldwide. About 3 million new TB cases per year are unaccounted for, and 1.5 million die. TB, however, is generally curable if diagnosed correctly and in a timely manner. The current diagnostic methods for TB, including state-of-the-art molecular tests, have failed in delivering the capacity needed in endemic countries to curtail this ongoing pandemic. Efficient, cost effective and scalable diagnostic approaches are critically needed. We report a multiplex TB serology panel using microbead suspension array containing a combination of 11 M.tb. antigens that demonstrated overall sensitivity of 91% in serum/plasma samples from TB patients confirmed by culture. Group wise sensitivities for sputum smear positive and negative patients were 95%, and 88%, respectively. Specificity of the test was 96% in untreated COPD patients and 91% in general healthy population. The sensitivity of this test is superior to that of the frontline sputum smear test with a comparable specificity (30-70%, and 93-99%, respectively). The multiplex serology test can be performed with scalability from 1 to 360 patients per day, and is amenable to automation for higher (1000s per day) throughput, thus enabling a scalable clinical work flow model for TB endemic countries. Taken together, the above results suggest that well defined antibody profiles in blood, analyzed by an appropriate technology platform, offer a valuable approach to TB diagnostics in endemic countries.

  13. Assessing the Macro-Level Correlates of Malware Infections Using a Routine Activities Framework.

    PubMed

    Holt, Thomas J; Burruss, George W; Bossler, Adam M

    2016-12-01

    The ability to gain unauthorized access to computer systems to engage in espionage and data theft poses a massive threat to individuals worldwide. There has been minimal focus, however, on the role of malicious software, or malware, which can automate this process. This study examined the macro-correlates of malware infection at the national level by using an open repository of known malware infections and utilizing a routine activities framework. Negative inflated binomial models for counts indicated that nations with greater technological infrastructure, more political freedoms, and with less organized crime financial impact were more likely to report malware infections. The number of Computer Emergency Response Teams (CERTs) in a nation was not significantly related with reported malware infection. The implications of the study for the understanding of malware infection, routine activity theory, and target-hardening strategies are discussed.

  14. Immune activation and induction of memory: lessons learned from controlled human malaria infection with Plasmodium falciparum.

    PubMed

    Scholzen, Anja; Sauerwein, Robert W

    2016-02-01

    Controlled human malaria infections (CHMIs) are a powerful tool to assess the efficacy of drugs and/or vaccine candidates, but also to study anti-malarial immune responses at well-defined time points after infection. In this review, we discuss the insights that CHMI trials have provided into early immune activation and regulation during acute infection, and the capacity to induce and maintain immunological memory. Importantly, these studies show that a single infection is sufficient to induce long-lasting parasite-specific T- and B-cell memory responses, and suggest that blood-stage induced regulatory responses can limit inflammation both in ongoing and potentially future infections. As future perspective of investigation in CHMIs, we discuss the role of innate cell subsets, the interplay between innate and adaptive immune activation and the potential modulation of these responses after natural pre-exposure.

  15. Intestinal autophagy activity is essential for host defense against Salmonella typhimurium infection in Caenorhabditis elegans.

    PubMed

    Curt, Alexander; Zhang, Jiuli; Minnerly, Justin; Jia, Kailiang

    2014-08-01

    Salmonella typhimurium infects both intestinal epithelial cells and macrophages. Autophagy is a lysosomal degradation pathway that is present in all eukaryotes. Autophagy has been reported to limit the Salmonella replication in Caenorhabditis elegans and in mammals. However, it is unknown whether intestinal autophagy activity plays a role in host defense against Salmonella infection in C. elegans. In this study, we inhibited the autophagy gene bec-1 in different C. elegans tissues and examined the survival of these animals following Salmonella infection. Here we show that inhibition of the bec-1 gene in the intestine but not in other tissues confers susceptibility to Salmonella infection, which is consistent with recent studies in mice showing that autophagy is involved in clearance of Salmonella in the intestinal epithelial cells. Therefore, the intestinal autophagy activity is essential for host defense against Salmonella infection from C. elegans to mice, perhaps also in humans.

  16. Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and Their Microparticles.

    PubMed

    Hare, Nathan J; Lee, Ling Y; Loke, Ian; Britton, Warwick J; Saunders, Bernadette M; Thaysen-Andersen, Morten

    2017-01-06

    Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of frontline alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M. tb infection. Infection promoted a dramatic regulation of the macrophage proteome. Most notably, significant infection-dependent down-regulation (4-26 fold) of 11 lysosomal exoglycosidases, e.g., β-galactosidase, β-hexosaminidases and α-/β-mannosidases, was observed. Relative weak infection-driven transcriptional regulation of these exoglycosidases and a stronger augmentation of the extracellular hexosaminidase activity demonstrated that the lysosome-centric changes may originate predominantly from infection-induced secretion of the lysosomal content. The macrophages showed heterogeneous N-glycan profiles and displayed significant up-regulation of complex-type glycosylation and concomitant down-regulation of paucimannosylation upon infection. Complementary intact N-glycopeptide analysis supported a subcellular-specific manipulation of the glycosylation machinery and altered glycosylation patterns of lysosomal N-glycoproteins within infected macrophages. Interestingly, the corresponding macrophage-derived MPs displayed unique N-glycome and proteome signatures supporting a preferential packaging from plasma membranes. The MPs were devoid of infection-dependent N-glycosylation signatures, but interestingly displayed increased levels of the glyco-initiating oligosaccharyltransferase complex and associated α-glucosidases that correlated with increased formation, N-glycan precursor levels

  17. The Relationship between Active Trachoma and Ocular Chlamydia trachomatis Infection before and after Mass Antibiotic Treatment

    PubMed Central

    Ramadhani, Athumani M.; Derrick, Tamsyn; Macleod, David; Holland, Martin J.; Burton, Matthew J.

    2016-01-01

    Background Trachoma is a blinding disease, initiated in early childhood by repeated conjunctival infection with the obligate intracellular bacterium Chlamydia trachomatis. The population prevalence of the clinical signs of active trachoma; ‘‘follicular conjunctivitis” (TF) and/or ‘‘intense papillary inflammation” (TI), guide programmatic decisions regarding the initiation and cessation of mass drug administration (MDA). However, the persistence of TF following resolution of infection at both the individual and population level raises concerns over the suitability of this clinical sign as a marker for C. trachomatis infection. Methodology/Principle Findings We systematically reviewed the literature for population-based studies and those including randomly selected individuals, which reported the prevalence of the clinical signs of active trachoma and ocular C. trachomatis infection by nucleic acid amplification test. We performed a meta-analysis to assess the relationship between active trachoma and C. trachomatis infection before and after MDA. TF and C. trachomatis infection were strongly correlated prior to MDA (r = 0.92, 95%CI 0.83 to 0.96, p<0.0001); the relationship was similar when the analysis was limited to children. A moderate correlation was found between TI and prevalence of infection. Following MDA, the relationship between TF and infection prevalence was weaker (r = 0.60, 95%CI 0.25 to 0.81, p = 0.003) and there was no correlation between TI and C. trachomatis infection. Conclusions/Significance Prior to MDA, TF is a good indicator of the community prevalence of C. trachomatis infection. Following MDA, the prevalence of TF tends to overestimate the underlying infection prevalence. In order to prevent unnecessary additional rounds of MDA and to accurately ascertain when elimination goals have been reached, a cost-effective test for C. trachomatis that can be administered in low-resource settings remains desirable. PMID:27783678

  18. Inhibition of cyclooxygenase activity reduces rotavirus infection at a postbinding step.

    PubMed

    Rossen, John W A; Bouma, Janneke; Raatgeep, Rolien H C; Büller, Hans A; Einerhand, Alexandra W C

    2004-09-01

    Elevated levels of prostaglandins (PGs), products of cyclooxygenases (COXs), are found in the plasma and stool of rotavirus-infected children. We sought to determine the role of COXs, PGs, and the signal transduction pathways involved in rotavirus infection to elucidate possible new targets for antiviral therapy. Human intestinal Caco-2 cells were infected with human rotavirus Wa or simian rotavirus SA-11. COX-2 mRNA expression and secreted PGE2 levels were determined at different time points postinfection, and the effect of COX inhibitors on rotavirus infection was studied by an immunofluorescence assay (IFA). To reveal the signal transduction pathways involved, the effect of MEK, protein kinase A (PKA), p38 mitogen-activated protein kinase (MAPK), and NF-kappaB inhibitors on rotavirus infection was analyzed. In infected Caco-2 cells, increased COX-2 mRNA expression and secreted PGE2 levels were detected. Indomethacin (inhibiting both COX-1 and COX-2) and specific COX-1 and COX-2 inhibitors reduced rotavirus infection by 85 and 50%, respectively, as measured by an IFA. Indomethacin reduced virus infection at a postbinding step early in the infection cycle, inhibiting virus protein synthesis. Indomethacin did not seem to affect viral RNA synthesis. Inhibitors of MEK, PKA, p38 MAPK, and NF-kappaB decreased rotavirus infection by at least 40%. PGE2 counteracted the effect of the COX and PKA inhibitors but not of the MEK, p38 MAPK, and NF-kappaB inhibitors. Conclusively, COXs and PGE2 are important mediators of rotavirus infection at a postbinding step. The ERK1/2 pathway mediated by PKA is involved in COX induction by rotavirus infection. MAPK and NF-kappaB pathways are involved in rotavirus infection but in a PGE2-independent manner. This report offers new perspectives in the search for therapeutic agents in treatment of severe rotavirus-mediated diarrhea in children.

  19. Rift Valley fever virus infection induces activation of the NLRP3 inflammasome.

    PubMed

    Ermler, Megan E; Traylor, Zachary; Patel, Krupen; Schattgen, Stefan A; Vanaja, Sivapriya K; Fitzgerald, Katherine A; Hise, Amy G

    2014-01-20

    Inflammasome activation is gaining recognition as an important mechanism for protection during viral infection. Here, we investigate whether Rift Valley fever virus, a negative-strand RNA virus, can induce inflammasome responses and IL-1β processing in immune cells. We have determined that RVFV induces NLRP3 inflammasome activation in murine dendritic cells, and that this process is dependent upon ASC and caspase-1. Furthermore, absence of the cellular RNA helicase adaptor protein MAVS/IPS-1 significantly reduces extracellular IL-1β during infection. Finally, direct imaging using confocal microscopy shows that the MAVS protein co-localizes with NLRP3 in the cytoplasm of RVFV infected cells.

  20. Lessons learned about opportunistic infections in southeast Asia.

    PubMed

    Nissapatorn, Veeranoot

    2008-07-01

    Southeast Asia is a region where the number of people infected with HIV/AIDS is one of the fastest growing in the world. Tuberculosis (TB) has grown along with the HIV epidemic. TB is not only the most common AIDS-defining illness but is also the leading cause of morbidity and mortality in AIDS patients. Cryptococcosis (meningitis or disseminated) is one of the most common opportunistic infections in AIDS patients. Cryptococcal meningitis is the first in the differential diagnosis considered with meningeal irritation. Penicillosis, a unique systemic mycosis, is an important emerging public health problem and has been classified as an AIDS defining illness in endemic areas like Thailand. Pneumocystis carinii (jiroveci) pneumonia has been one of the most important opportunistic infections in AIDS patients. Among parasitic infections, cryptosporidiosis is the most common intestinal protozoan infection relating to diarrhea in AIDS patients and toxoplasmosis is the only parasitic infection of the nervous system with a substantial incidence, up to 14.8%. Cytomegalovirus (CMV) retinitis has a lower prevalence compared to other opportunistic infections. In the era of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has significantly reduced in the past few years. Subsequently, the phenomena of immune restoration inflammatory syndrome (IRIS) in AIDS patients has been reported in this region as a result of HAART.

  1. Mycobacterium tuberculosis Infection Interferes with HIV Vaccination in Mice

    PubMed Central

    Ignatowicz, Lech; Mazurek, Jolanta; Leepiyasakulchai, Chaniya; Sköld, Markus; Hinkula, Jorma; Källenius, Gunilla; Pawlowski, Andrzej

    2012-01-01

    Tuberculosis (TB) has emerged as the most prominent bacterial disease found in human immunodeficiency virus (HIV)-positive individuals worldwide. Due to high prevalence of asymptomatic Mycobacterium tuberculosis (Mtb) infections, the future HIV vaccine in areas highly endemic for TB will often be administrated to individuals with an ongoing Mtb infection. The impact of concurrent Mtb infection on the immunogenicity of a HIV vaccine candidate, MultiHIV DNA/protein, was investigated in mice. We found that, depending on the vaccination route, mice infected with Mtb before the administration of the HIV vaccine showed impairment in both the magnitude and the quality of antibody and T cell responses to the vaccine components p24Gag and gp160Env. Mice infected with Mtb prior to intranasal HIV vaccination exhibited reduced p24Gag-specific serum IgG and IgA, and suppressed gp160Env-specific serum IgG as compared to respective titers in uninfected HIV-vaccinated controls. Importantly, in Mtb-infected mice that were HIV-vaccinated by the intramuscular route the virus neutralizing activity in serum was significantly decreased, relative to uninfected counterparts. In addition mice concurrently infected with Mtb had fewer p24Gag-specific IFN-γ-expressing T cells and multifunctional T cells in their spleens. These results suggest that Mtb infection might interfere with the outcome of prospective HIV vaccination in humans. PMID:22848444

  2. Immunomodulation by vitamin D: implications for TB

    PubMed Central

    Chun, Rene F; Adams, John S; Hewison, Martin

    2011-01-01

    TB remains a major cause of mortality throughout the world. Low vitamin D status has been linked to increased risk of TB and other immune disorders. These observations suggest a role for vitamin D as a modulator of normal human immune function. This article will detail the cellular and molecular mechanisms by which vitamin D regulates the immune system and how vitamin D insufficiency may lead to immune dysregulation. The importance of vitamin D bioavailability as a mechanism for defining the immunomodulatory actions of vitamin D and its impact on TB will also be discussed. The overall aim will be to provide a fresh perspective on the potential benefits of vitamin D supplementation in the prevention and treatment of TB. PMID:22046197

  3. The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy

    PubMed Central

    Jung, Yu Jung; Woo, Hye In; Jeon, Kyeongman; Koh, Won-Jung; Jang, Dong Kyoung; Cha, Hoon Suk; Koh, Eun Mi; Lee, Nam Yong; Kang, Eun-Suk

    2015-01-01

    Objective We compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring. Methods Before starting TNF-α antagonist therapy, 156 consecutive patients with rheumatic diseases were screened for LTBI using QFT-GIT and T-SPOT.TB tests. According to our study protocol, QFT-GIT-positive patients received LTBI treatment. Patients positive by any IGRAs were subjected to follow-up IGRA tests after completing LTBI-treatment and/or during TNF-α antagonist therapy. Results At the initial LTBI screening, 45 (28.9%) and 70 (44.9%) patients were positive by QFT-GIT and T-SPOT.TB, respectively. The agreement rate between IGRA results was 78.8% (k = 0.56; 95% confidence interval [95% CI] = 0.43 to 0.68). Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by T-SPOT.TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-α antagonist therapy. By the end of the follow-up period (218 to 1,264 days), four patients (4/137, 2.9%) developed active tuberculosis (TB) diseases during receiving TNF-α antagonist therapy. Among them, one was Q-T+, one was Q+T-, and the remaining two were Q-T- at the initial screening (Q, QuantiFERON-TB Gold In-Tube; T, T-SPOT.TB; +, positive; -, negative). Two (2/4, 50%) patients with TB reactivation had at least one prior risk factor consistent with previous TB infection. Conclusion This study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in at-risk patients for a more sensitive diagnosis in countries with an intermediate TB burden. PMID:26474294

  4. HIV Infection and Geographically Bound Transmission of Drug-Resistant Tuberculosis, Argentina

    PubMed Central

    López, Beatriz; Ambroggi, Marta; Palmero, Domingo; Salvadores, Bernardo; Gravina, Elida; Mazzeo, Eduardo; Imaz, Susana; Barrera, Lucía

    2012-01-01

    During 2003–2009, the National Tuberculosis (TB) Laboratory Network in Argentina gave 830 patients a new diagnosis of multidrug-resistant (MDR) TB and 53 a diagnosis of extensively drug- resistant (XDR) TB. HIV co-infection was involved in nearly one third of these cases. Strain genotyping showed that 7 major clusters gathered 56% of patients within restricted geographic areas. The 3 largest clusters corresponded to epidemic MDR TB strains that have been undergoing transmission for >10 years. The indigenous M strain accounted for 29% and 40% of MDR and XDR TB cases, respectively. Drug-resistant TB trends in Argentina are driven by spread of a few strains in hotspots where the rate of HIV infection is high. To curb transmission, the national TB program is focusing stringent interventions in these areas by strengthening infection control in large hospitals and prisons, expediting drug resistance detection, and streamlining information-sharing systems between HIV and TB programs. PMID:23092584

  5. Nitroimidazoles for the treatment of TB: past, present and future

    PubMed Central

    Mukherjee, Tathagata; Boshoff, Helena

    2011-01-01

    Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed. PMID:21879846

  6. [Start of TB case-registration and case-management system in Japan].

    PubMed

    Shimao, Tadao

    2010-07-01

    Institute of Tuberculosis) to study how to register TB cases, how to collect information and how to improve patients' adherence to treatment. Registration index cards were prepared in each HC arranged alphabetically to avoid double register. The formula of registration card was indicated in Fig. 1 and 2. Small hollows were made in the lower part of the card, and registration card container with 45 metal bars in the bottom as shown in Fig. 3 was prepared. By setting 30 cards dislocating one each hollow as shown in Fig. 3, in one card container with 30 rows, altogether 600 registration cards were stored. In most right part of the card, important information such as activity of the case, treatment status, expected time of next home visit, expiring time of public support for TB treatment, etc. are indicated by different color metal signals. This new system was applied in 216 HCs, about one fourth of all HCs in Japan in 1959, another 200 HCs were added in 1960, and finally from 1961, the new system of registration and case-management started in the whole country after making minor amendments based on experience in 1959 and 1960. Quality of TB case-management improved much after the introduction of new system, and annual statistics not only newly registered TB cases but also on prevalence of active as well as registered cases was available since then, and this was the starting point of TB surveillance system started in 1986.

  7. Anti-infection activity of nanostructured titanium percutaneous implants with a postoperative infection model

    NASA Astrophysics Data System (ADS)

    Tan, Jing; Li, Yiting; Liu, Zhiyuan; Qu, Shuxin; Lu, Xiong; Wang, Jianxin; Duan, Ke; Weng, Jie; Feng, Bo

    2015-07-01

    The titanium percutaneous implants were widely used in clinic; however, they have an increased risk of infection since they breach the skin barrier. Lack of complete skin integration with the implants can cause infection and implant removal. In this work, three titania nanotubes (TNT) with different diameters, 50 nm (TNT-50), 100 nm (TNT-100) and 150 nm (TNT-150) arrays were prepared on titanium surfaces by anodization, pure titanium (pTi) was used as control. Samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle analysis. The antibacterial efficiency of TNT was evaluated in vitro against Staphylococcus aureus under the visible light. The results indicated that TNT-100 had the highest antibacterial efficiency under the visible light. Subsequently, TNT implants and pTi implants were placed subcutaneously to the dorsum of New Zealand White rabbits, 108 CFU S. aureus was inoculated into the implant sites 4 h after surgery. The TNF-alpha and IL-1alpha were determined using enzyme linked immunoassay (ELISA). TNT implants revealed less inflammatory factor release than pTi implants with or without injected S. aureus liquid. According to the histological results, the TNT implants displayed excellent tissue integration. Whereas, pTi implants were surrounded with fibrotic capsule, and the skin tissue was almost separated from the implant surface. Therefore, the TNT significantly inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. The immersion test in the culture medium suggested that one of causes be probably more proteins adsorbed on TNT than on pTi.

  8. Economic Support to Patients in HIV and TB Grants in Rounds 7 and 10 from the Global Fund to Fight AIDS, Tuberculosis and Malaria

    PubMed Central

    Richter, Linda M.; Lönnroth, Knut; Desmond, Chris; Jackson, Robin; Jaramillo, Ernesto; Weil, Diana

    2014-01-01

    People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible. PMID:24489702

  9. Analysis of 161Tb by radiochemical separation and liquid scintillation counting

    DOE PAGES

    Jiang, J.; Davies, A.; Arrigo, L.; ...

    2015-12-05

    The determination of 161Tb activity is problematic due to its very low fission yield, short half-life, and the complication of its gamma spectrum. At AWE, radiochemically purified 161Tb solution was measured on a PerkinElmer 1220 QuantulusTM Liquid Scintillation Spectrometer. Since there was no 161Tb certified standard solution available commercially, the counting efficiency was determined by the CIEMAT/NIST Efficiency Tracing method. The method was validated during a recent inter-laboratory comparison exercise involving the analysis of a uranium sample irradiated with thermal neutrons. Lastly, the measured 161Tb result was in excellent agreement with the result using gamma spectrometry and the result obtainedmore » by Pacific Northwest National Laboratory.« less

  10. Effect of hydrogen passivation on the photoluminescence of Tb ions in silicon rich silicon oxide films

    NASA Astrophysics Data System (ADS)

    Zatryb, G.; Klak, M. M.; Wojcik, J.; Misiewicz, J.; Mascher, P.; Podhorodecki, A.

    2015-12-01

    In this work, silicon-rich silicon oxide films containing terbium were prepared by means of plasma enhanced chemical vapor deposition. The influence of hydrogen passivation on defects-mediated non-radiative recombination of excited Tb3+ ions was investigated by photoluminescence, photoluminescence excitation, and photoluminescence decay measurements. Passivation was found to have no effect on shape and spectral position of the excitation spectra. In contrast, a gradual increase in photoluminescence intensity and photoluminescence decay time was observed upon passivation for the main 5D4-7F5 transition of Tb3+ ions. This observation was attributed to passivation of non-radiative recombination defects centers with hydrogen. It was found that the number of emitted photons increases upon passivation as a result of two effects: (1) longer Tb3+ lifetime in the 5D4 excited state and (2) optical activation of new Tb3+ emitters. The obtained results were discussed and compared with other experimental reports.

  11. Analysis of 161Tb by radiochemical separation and liquid scintillation counting

    SciTech Connect

    Jiang, J.; Davies, A.; Arrigo, L.; Friese, J.; Seiner, B. N.; Greenwood, L.; Finch, Z.

    2015-12-05

    The determination of 161Tb activity is problematic due to its very low fission yield, short half-life, and the complication of its gamma spectrum. At AWE, radiochemically purified 161Tb solution was measured on a PerkinElmer 1220 QuantulusTM Liquid Scintillation Spectrometer. Since there was no 161Tb certified standard solution available commercially, the counting efficiency was determined by the CIEMAT/NIST Efficiency Tracing method. The method was validated during a recent inter-laboratory comparison exercise involving the analysis of a uranium sample irradiated with thermal neutrons. Lastly, the measured 161Tb result was in excellent agreement with the result using gamma spectrometry and the result obtained by Pacific Northwest National Laboratory.

  12. Tuberculosis and HIV co-infection: screening and treatment strategies.

    PubMed

    Venkatesh, Kartik K; Swaminathan, Soumya; Andrews, Jason R; Mayer, Kenneth H

    2011-06-18

    Globally, tuberculosis (TB) and HIV interact in deadly synergy. The high burden of TB among HIV-infected individuals underlies the importance of TB diagnosis, treatment and prevention for clinicians involved in HIV care. Despite expanding access to antiretroviral therapy (ART) to treat HIV infection in resource-limited settings, many individuals i