Science.gov

Sample records for active tuberculosis tb

  1. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Overview In developed countries, such as the ... thought to be infected with TB bacteria, Mycobacterium tuberculosis ( Mtb ). TB is a chronic bacterial infection. It ...

  2. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Research The New Challenge for TB Research NIAID ... HIV/AIDS Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Research Agenda (PDF) TB Research at NIAID Research ...

  3. Tuberculosis (TB): Treatment

    MedlinePlus

    ... Departments & Divisions Home Conditions Tuberculosis Treating Tuberculosis Treating Tuberculosis Make an Appointment Refer a Patient Ask a ... bones is treated longer. NEXT: Preventive Treatment Diagnosing Tuberculosis History of TB Our Specialists Charles L. Daley, ...

  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. Active Case Finding of Tuberculosis (TB) in an Emergency Room in a Region with High Prevalence of TB in Brazil

    PubMed Central

    Silva, Denise Rossato; Müller, Alice Mânica; Tomasini, Karina da Silva; Dalcin, Paulo de Tarso Roth; Golub, Jonathan E.; Conde, Marcus Barreto

    2014-01-01

    Setting Public hospital emergency room (ER) in Porto Alegre, Brazil, a setting with high prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) infection. Objective To determine the prevalence of PTB, using a symptom based active case finding (ACF) strategy in the ER of a public hospital in an area with high prevalence of TB and HIV, as well as variables associated with pulmonary TB diagnosis. Methods Cross sectional study. All patients ≥18 years seeking care at the ER were screened for respiratory symptoms and those with cough ≥2 weeks were invited to provide a chest radiograph and two unsupervised samples of sputum for acid-fast bacilli smear and culture. Results Among 31,267 admissions, 6,273 (20.1%) reported respiratory symptoms; 197 reported cough ≥2 weeks, of which pulmonary TB was diagnosed in 30. In multivariate analysis, the variables associated with a pulmonary tuberculosis diagnosis were: age (OR 0.94, 95% CI: 0.92–0.97; p<0.0001), sputum production (OR 0.18, 95% CI 0.06–0.56; p = 0.003), and radiographic findings typical of TB (OR 12.11, 95% CI 4.45–32.93; p<0.0001). Conclusions This study identified a high prevalence of pulmonary TB among patients who sought care at the emergency department of a tertiary hospital, emphasizing the importance of regular screening of all comers for active TB in this setting. PMID:25211158

  7. 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

  8. 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 ...

  9. 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 ...

  10. First-Line Treatment for Tuberculosis (TB), Drug Resistant TB -- A Visual Tour

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Drugs First-Line Treatment of TB for Drug- ... ago. See how these drugs work . Multidrug-Resistant Tuberculosis (MDR TB) and Second-Line Treatments MDR TB ...

  11. Active tuberculosis case finding and detection of drug resistance among HIV-infected patients: A cross-sectional study in a TB endemic area, Gondar, Northwest Ethiopia

    PubMed Central

    Alemayehu, Martha; Gelaw, Baye; Abate, Ebba; Wassie, Liya; Belyhun, Yeshambel; Bekele, Shiferaw; Kempker, Russell R.; Blumberg, Henry M.; Aseffa, Abraham

    2016-01-01

    Background Tuberculosis (TB) patients co-infected with human immunodeficiency virus (HIV) often lack the classic symptoms of pulmonary tuberculosis, making the diagnosis difficult. Current practices in resource-limited settings often indicate that these co-infected patients are diagnosed when they clinically manifest disease symptoms, resulting in a delayed diagnosis and despite continued transmission. The aim of this study is to determine the prevalence of undiagnosed pulmonary tuberculosis cases through active case finding and including multidrug-resistant TB (MDR-TB) among HIV-infected patients. Materials and methods A total of 250 HIV-infected patients, aged 18 years and above were evaluated in a cross-sectional design between February 2012 and November 2012. Socio-demographic and clinical data were collected using a structured questionnaire. Sputum samples were collected from all participants for acid fast bacilli (AFB) direct smear microscopy and Mycobacteria culture. A PCR-based RD9 deletion and genus typing, as well as first-line anti-TB drug susceptibility testing, was performed for all culture-positive isolates. Results Following active TB case finding, a total of 15/250 (6%) cases were diagnosed as TB cases, of whom 9/250 (3.6%) were detected by both smear microscopy and culture and the remaining 6/250 (2.4%) only by culture. All the 15 isolates were typed through RD9 typing of which 10 were Mycobacterium tuberculosis species; 1 belonged to Mycobacterium genus and 4 isolates were non-tuberculous mycobacteria. The prevalence of undiagnosed pulmonary TB disease among the study participants was 4.4%, which implies the possibility of identifying even more undiagnosed cases through active case finding. A multivariate logistic regression showed a statistically significant association between the presence of pneumonia infection and the occurrence of TB (OR = 4.81, 95% CI (1.08–21.43), p = 0.04). In addition, all the isolates were sensitive to all first

  12. Tuberculosis: Learn the Signs and Symptoms of TB Disease

    MedlinePlus

    ... What's this? Submit Button Past Emails CDC Features Tuberculosis (TB) Disease: Symptoms & Risk Factors Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Tuberculosis (TB) is a disease caused by bacteria that ...

  13. The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

    PubMed

    Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

    2016-01-01

    Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.

  14. Tuberculosis: The Connection between TB and HIV (the AIDS Virus)

    MedlinePlus

    ... Task Force Tuberculosis: The Connection between TB and HIV Recommend on Facebook Tweet Share Compartir Order this ... if I am infected with both TB and HIV? If you have HIV, it is important to ...

  15. Tuberculosis specific responses following therapy for TB: Impact of HIV co-infection.

    PubMed

    Siddiqui, S; Sarro, Y; Diarra, B; Diallo, H; Guindo, O; Dabitao, D; Tall, M; Hammond, A; Kassambara, H; Goita, D; Dembele, P; Traore, B; Hengel, R; Nason, M; Warfield, J; Washington, J; Polis, M; Diallo, S; Dao, S; Koita, O; Lane, H C; Catalfamo, M; Tounkara, A

    2015-07-01

    Characterizing perturbations in the immune response to tuberculosis in HIV can develop insights into the pathogenesis of coinfection. HIV+ TB+ and TB monoinfected (TB+) subjects recruited from clinics in Bamako prior to initiation of TB treatment were evaluated at time-points following initiation of therapy. Flow cytometry assessed CD4+/CD8+ T cell subsets and activation markers CD38/HLA-DR. Antigen specific responses to TB proteins were assessed by intracellular cytokine detection and proliferation. HIV+ TB+ subjects had significantly higher markers of immune activation in the CD4+ and CD8+ T cells compared to TB+ subjects. HIV+ TB+ had lower numbers of TB-specific CD4+ T cells at baseline. Plasma IFNγ levels were similar between HIV+ TB+ and TB+ subjects. No differences were observed in in-vitro proliferative capacity to TB antigens between HIV+ TB+ and TB+ subjects. Subjects with HIV+ TB+ coinfection demonstrate in vivo expansion of TB-specific CD4+ T cells. Immunodeficiency associated with CD4+ T cell depletion may be less significant compared to immunosuppression associated with HIV viremia or untreated TB infection.

  16. 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.

  17. Diagnostic 'omics' for active tuberculosis.

    PubMed

    Haas, Carolin T; Roe, Jennifer K; Pollara, Gabriele; Mehta, Meera; Noursadeghi, Mahdad

    2016-01-01

    The decision to treat active tuberculosis (TB) is dependent on microbiological tests for the organism or evidence of disease compatible with TB in people with a high demographic risk of exposure. The tuberculin skin test and peripheral blood interferon-γ release assays do not distinguish active TB from a cleared or latent infection. Microbiological culture of mycobacteria is slow. Moreover, the sensitivities of culture and microscopy for acid-fast bacilli and nucleic acid detection by PCR are often compromised by difficulty in obtaining samples from the site of disease. Consequently, we need sensitive and rapid tests for easily obtained clinical samples, which can be deployed to assess patients exposed to TB, discriminate TB from other infectious, inflammatory or autoimmune diseases, and to identify subclinical TB in HIV-1 infected patients prior to commencing antiretroviral therapy. We discuss the evaluation of peripheral blood transcriptomics, proteomics and metabolomics to develop the next generation of rapid diagnostics for active TB. We catalogue the studies published to date seeking to discriminate active TB from healthy volunteers, patients with latent infection and those with other diseases. We identify the limitations of these studies and the barriers to their adoption in clinical practice. In so doing, we aim to develop a framework to guide our approach to discovery and development of diagnostic biomarkers for active TB. PMID:27005907

  18. Extensively Drug-Resistant Tuberculosis (XDR TB)

    MedlinePlus

    ... other federal agencies and international partners to raise awareness and enhance strategies for TB prevention worldwide by: Strengthening TB services for people living with HIV/AIDS; Guiding preparedness and outbreak investigation responses; Improving ...

  19. An Update on Global Tuberculosis (TB)

    PubMed Central

    Talip, Balkis A.; Sleator, Roy D.; Lowery, Colm J.; Dooley, James S.G.; Snelling, William J.

    2013-01-01

    Tuberculosis globally results in almost 2 million human deaths annually, with 1 in 4 deaths from tuberculosis being human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related. Primarily a pathogen of the respiratory system, aerobic Mycobacterium tuberculosis complex (MTBC) infects the lungs via the inhalation of infected aerosol droplets generated by people with pulmonary disease through coughing. This review focuses on M. tuberculosis transmission, epidemiology, detection methods and technologies. PMID:24847176

  20. Drug Resistance Pattern of Mycobacterium tuberculosis Isolates From Patients Referred to TB Reference Laboratory in Ahvaz

    PubMed Central

    Badie, Fereshteh; Arshadi, Maniya; Mohsenpoor, Maryam; Gharibvand, Soodabeh S.

    2015-01-01

    Objectives Tuberculosis remains one of the top three infectious disease killers. The prevalence of multidrug-resistant tuberculosis (MDR-TB) has increased substantially in the past 20 years. When drug resistance is not detected, MDR-TB patients cannot access life-saving treatment; this puts their communities at risk of ongoing MDR-TB transmission. We aimed to determine the patterns of resistance to antituberculosis drugs among Mycobacterium tuberculosis isolates from Khuzestan province in Iran. Methods A total of 850 clinical specimens from patients suspected of active TB were cultured in 2015. Drug susceptibility testing to the first line antiTB drugs for culture positive MTB was performed on Lowenstein–Jensen medium using the proportion method. Results Of 850 cultured specimens, 272 (32%) were culture positive for mycobacteria. Of 64 MTB isolates that were analyzed by the proportion method, 62 (96.8%) were pan-susceptible and two (3.1%) were MDR. Conclusion An important way to prevent the emergence of MDR and XDR TB, and the principles of full implementation of the strategy is directly observed treatment, short-course (DOTS). The efficient diagnosis and timely treatment of MDR-TB patients can prevent disease transmission, reduce the risk of drug resistance developing, and avoid further lung damage. PMID:26981340

  1. Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

    PubMed Central

    Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; Mc Neeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Oramasionwu, Gloria E; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H. Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

    2015-01-01

    Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle. PMID:25957923

  2. Tuberculosis and Diabetes

    MedlinePlus

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

  3. 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 ...

  4. Tuberculosis preventive therapy: an underutilised strategy to reduce individual risk of TB and contribute to TB control.

    PubMed

    Churchyard, Gavin J; Chaisson, Richard E; Maartens, Gary; Getahun, Haileyesus

    2014-05-01

    Tuberculosis (TB) remains a global health problem, and South Africa (SA) has one of the world's worst TB epidemics. The World Health Organization (WHO) estimated in 1999 that one-third of the world's population was latently infected with TB. In SA up to 88% of HIV-uninfected young adults (31 - 35 years) are latently infected with TB. In the most recent meta-analysis, 6 - 12 months of isoniazid preventive therapy (IPT) was associated with a lower incidence of active TB than placebo (relative risk (RR) 0.68; 95% confidence interval (CI) 0.54 - 0.85), with the greatest benefit among individuals with a positive tuberculin skin test (TST) (RR 0.38; 95% CI 0.25 - 0.57). A clinical trial of IPT given with antiretroviral therapy (ART) for 12 months reduced TB incidence by 37% compared with ART alone (hazard ratio (HR) 0.63; 95% CI 0.41 - 0.94). The effect of IPT is limited in high-burden countries. IPT for 36 months v. 6 months reduced TB incidence among HIV-positive, TST-positive participants by 74% (HR 0.26; 95% CI 0.09 - 0.80). A study of more than 24 000 goldminers confirmed that IPT is safe, with only 0.5% experiencing adverse events. A meta-analysis of studies of IPT since 1951 did not show an increased risk of developing resistance. Alternative TB preventive therapy regimens, including high-dose isoniazid and rifapentine given weekly for 3 months, have been shown to have similar efficacy to IPT. Mathematical modelling suggests that scaling up continuous IPT targeted to HIV-positive persons, when used in combination with other treatment and prevention strategies, may substantially improve TB control. PMID:25212199

  5. 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.

  6. Activities of the Korean Institute of Tuberculosis

    PubMed Central

    Ryoo, Sungweon; Kim, Hee Jin

    2014-01-01

    The Korean National Tuberculosis Association (KNTA) set up the Korean Institute of Tuberculosis (KIT) in 1970 to foster research and technical activities pertaining to tuberculosis (TB). The KNTA/KIT had successfully conducted a countrywide TB prevalence survey from 1965 to 1995 at 5-year intervals. The survey results (decline in TB rates) established Korea as a country that had successfully implemented national control programs for TB. The KIT developed the Korea Tuberculosis Surveillance System and the Laboratory Management Information System, both of which were transferred to the Korea Centers for Disease Control and Prevention after its establishment. The KIT functions as a central and supranational reference TB laboratory for microbiological and epidemiological research and provides training and education for health-care workers and medical practitioners. Recently, the KIT has expanded its activities to countries such as Ethiopia, Laos, and Timor-Leste to support TB control and prevention. The KIT will continue to support research activities and provide technical assistance in diagnosing the infection until it is completely eliminated in Korea. PMID:25861580

  7. 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.

  8. Too Busy for TB: Managing a Case of Tuberculosis Disease in the School Setting.

    PubMed

    Galemore, Cynthia A

    2016-03-01

    School nurses actively monitor the school population for signs of communicable disease on a daily basis. State regulations outline reportable diseases and provide guidance to control disease outbreak, including management of disease outbreak in the school setting. The purpose of this article is to review strategies recently used in managing a tuberculosis (TB) outbreak at a large high school in Kansas. A timeline of events is presented along with a discussion of the differences between latent TB infection and TB disease. Partnering across agencies and departments enabled the timely testing of over 400 individuals and subsequent management of individuals testing positive for latent TB infection. Public information officers provided necessary guidance to communicate to audiences both internally and externally. PMID:26822133

  9. TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

    PubMed

    Houben, R M G J; Lalli, M; Sumner, T; Hamilton, M; Pedrazzoli, D; Bonsu, F; Hippner, P; Pillay, Y; Kimerling, M; Ahmedov, S; Pretorius, C; White, R G

    2016-01-01

    Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it

  10. TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

    PubMed

    Houben, R M G J; Lalli, M; Sumner, T; Hamilton, M; Pedrazzoli, D; Bonsu, F; Hippner, P; Pillay, Y; Kimerling, M; Ahmedov, S; Pretorius, C; White, R G

    2016-03-24

    Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it

  11. Pathogen-derived biomarkers for active tuberculosis diagnosis.

    PubMed

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

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by members of Mycobacterium tuberculosis complex. Despite the availability of effective treatments, TB remains a major public health concern in most low and middle-income countries, representing worldwide the second leading cause of death from an infectious disease. Inadequate case detection and failures to classify the disease status hamper proper TB control. The limitations of the conventional diagnostic methods have encouraged much research activities in this field, but there is still an urgent need for an accurate point of care test for active TB diagnosis. A rapid, precise, and inexpensive TB diagnostic test would allow an earlier implementation of an appropriate treatment and the reduction of disease transmission. Pathogen-derived molecules present in clinical specimens of affected patients are being validated for that purpose. This short review aims to summarize the available data regarding biomarkers derived from M. tuberculosis, and their current usage in active TB diagnosis.

  12. Pro- and anti-inflammatory cytokines in tuberculosis: a two-edged sword in TB pathogenesis.

    PubMed

    Etna, Marilena Paola; Giacomini, Elena; Severa, Martina; Coccia, Eliana Marina

    2014-12-01

    A major challenge in tuberculosis (TB) is to improve current vaccination and therapeutic strategies and this requires a fine understanding of the mechanisms that mediate protection and pathogenesis. We need to discern how the host perceives Mycobacterium tuberculosis (Mtb) infection, what are the danger signals that activate the immune system and, in turn, how the immune response controls the life-cycle of Mtb. Cytokines, because of their nature of soluble mediators, represent key elements in mediating and tuning these complex processes. In this review, we provide an overview of recent studies on cytokines expression and function in active (mainly human) TB. Understanding of the balance between pro- and anti-inflammatory networks is crucial to refine our knowledge on the immune responses directed against Mtb.

  13. Tuberculosis

    MedlinePlus

    Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with ...

  14. 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 ...

  15. Tuberculosis

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Tuberculosis KidsHealth > For Teens > Tuberculosis Print A A A Text Size What's in ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...

  16. Tackling tuberculosis: Insights from an international TB Summit in London

    PubMed Central

    Maitra, Arundhati; Danquah, Cynthia A; Scotti, Francesca; Howard, Tracey K; Kamil, Tengku K; Bhakta, Sanjib

    2015-01-01

    Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID:26151309

  17. Phenotypic variability in childhood TB: implications for diagnostic endpoints in tuberculosis vaccine trials.

    PubMed

    Mulenga, Humphrey; Moyo, Sizulu; Workman, Lesley; Hawkridge, Tony; Verver, Suzanne; Tameris, Michele; Geldenhuys, Hennie; Hanekom, Willem; Mahomed, Hassan; Hussey, Gregory; Hatherill, Mark

    2011-06-10

    The endpoint definition for infant tuberculosis (TB) vaccine trials should match the TB disease phenotype expected in the control arm of the study population. Our aim was to analyse selected combinations of the clinical, radiological, and microbiological features of pulmonary TB among children investigated under vaccine trial conditions, in order to estimate case frequency for a range of expected TB phenotypes. Two thousand one hundred and eighty five South African children were investigated over a nine-year period (2001-2009). Evidence of TB exposure and classical symptoms were several times more common than chest radiography (CXR) compatible with TB, or positive Mycobacterium tuberculosis culture. Discordance between clinical, radiological, and microbiological features was common in individual children. Up to one third of children with compatible CXR, and up to half the children who were M. tuberculosis culture positive, were asymptomatic. The culture positive rate fell over time, although rates of TB exposure and compatible chest radiography increased. Consequently, the annual incidence of diagnostic combinations that included M. tuberculosis culture fell to <0.2%. However, in this study population (children <2 years of age), annual incidence of the TB disease phenotype that included the triad of TB exposure, symptoms, and compatible CXR, approached 1% (n=848 per 100,000). These findings allow modelling of expected TB case frequency in multi-centre infant TB vaccine trials, based upon benchmarking of diagnostic data against the key indicator variables that constitute the building blocks of a trial endpoint. PMID:21527304

  18. 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

  19. 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

  20. 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

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

    PubMed

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

    2016-05-01

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

  2. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States.

    PubMed

    Mazurek, Gerald H; Jereb, John; Lobue, Phillip; Iademarco, Michael F; Metchock, Beverly; Vernon, Andrew

    2005-12-16

    On May 2, 2005, a new in vitro test, QuantiFERON-TB Gold (QFT-G, Cellestis Limited, Carnegie, Victoria, Australia), received final approval from the U.S. Food and Drug Administration as an aid for diagnosing Mycobacterium tuberculosis infection. This test detects the release of interferon-gamma (IFN-g) in fresh heparinized whole blood from sensitized persons when it is incubated with mixtures of synthetic peptides representing two proteins present in M. tuberculosis: early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). These antigens impart greater specificity than is possible with tests using purified protein derivative as the tuberculosis (TB) antigen. In direct comparisons, the sensitivity of QFT-G was statistically similar to that of the tuberculin skin test (TST) for detecting infection in persons with untreated culture-confirmed tuberculosis (TB). The performance of QFT-G in certain populations targeted by TB control programs in the United States for finding latent TB infection is under study. Its ability to predict who eventually will have TB disease has not been determined, and years of observational study of substantial populations would be needed to acquire this information. In July 2005, CDC convened a meeting of consultants and researchers with expertise in the field to review scientific evidence and clinical experience with QFT-G. On the basis of this review and discussion, CDC recommends that QFT-G may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers). This report provides specific cautions for interpreting negative QFT-G results in persons from selected populations. This report is aimed at public health officials, health-care providers, and laboratory workers with responsibility for TB control activities in the United States.

  3. 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

  4. 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

  5. Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls.

    PubMed

    Biselli, R; Mariotti, S; Sargentini, V; Sauzullo, I; Lastilla, M; Mengoni, F; Vanini, V; Girardi, E; Goletti, D; D' Amelio, R; Nisini, R

    2010-08-01

    Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-gamma and interleukin (IL)-2 profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-gamma distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.

  6. The relationship between chitotriosidase activity and tuberculosis.

    PubMed

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

    2015-11-01

    Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future. PMID:26418349

  7. Pharmacokinetics and dose response of anti-TB drugs in rat infection model of tuberculosis.

    PubMed

    Kumar, Naveen; Vishwas, K G; Kumar, Mahesh; Reddy, Jitendar; Parab, Manish; Manikanth, C L; Pavithra, B S; Shandil, R K

    2014-05-01

    Robust and physiologically relevant infection models are required to investigate pharmacokinetic-pharmacodynamic (PK/PD) correlations for anti-tuberculosis agents at preclinical discovery. We have validated an inhalation-based rat infection model of tuberculosis harbouring mycobacteria in a replicating state, that is suitable for investigating pharmacokinetics and drug action of anti-tubercular agents. A reproducible and actively replicating lung infection was established in Wistar rats by inhalation of a series of graded inocula of Mycobacterium tuberculosis. Following an initial instillation of ∼10(5) log10 CFU/lung, M. tuberculosis grew logarithmically for the first 3 weeks, and then entered into a chronic phase with no net increase in pulmonary bacterial loads. Dose response of front-line anti-TB drugs was investigated following pharmacokinetic measurements in the plasma of infected rats. Rifampicin, Isoniazid, and Ethambutol dosed per orally exhibited bactericidality and good dose response with maximal effect of 5.66, 4.66, and 4.80 log10 CFU reductions in the lungs, respectively. In contrast, Pyrazinamide was merely bacteriostatic with 1.92 log10 CFU/lung reduction and did not reduce the bacterial burden beyond the initial bacterial loads present at beginning of treatment in spite of high Pyrazinamide blood levels. Rat infection model with actively replicating bacilli provides a physiologically distinct and pharmacologically relevant model that can be exploited to distinguish investigational compounds in to bacteriostatic or bactericidal scaffolds. We propose that this rat infection model though need more drug substance, can be used in early discovery settings to investigate pharmacology of novel anti-tubercular agents for the treatment of active pulmonary tuberculosis.

  8. [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.

  9. 'TB or not TB?' Problems of differential diagnosis of cutaneous mycobacteriosis and tuberculosis--A Case Study and interdisciplinary discussion.

    PubMed

    Szmygin-Milanowska, Katarzyna; Grzywa-Celińska, Anna; Zwolska, Zofia; Krawczyk, Paweł; Guz, Leszek; Milanowski, Janusz

    2016-01-01

    The diagnosis of cutaneous tuberculosis poses a serious challenge due to many skin diseases of different etiology resembling the lesions caused by the TB (tuberculosis) bacillus, and difficulties in confirming the disease. The presented case concerns skin lesions in a hobby aquarist stung in the finger of the left hand by a fish. The resulting inflammatory infiltration was to be cutaneous tuberculosis or mycobacteriosis caused by MOTT (Mycobacterium other than tuberculosis). Laboratory, pathomorphologic, genetic and microbiologic tests of samples obtained from the patient, fish and water in the aquarium gave ambiguous results. A multidisciplinary discussion is presented on the difficulties in the differential diagnosis, problems with a clear interpretation of the results of various conducted tests, and possible ways of transmission of the infection, relevant to the described example.

  10. 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.

  11. Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis (MDR- TB) Compared with Non-MDR-TB Infections in Peninsular Malaysia

    PubMed Central

    Elmi, Omar Salad; Hasan, Habsah; Abdullah, Sarimah; Mat Jeab, Mat Zuki; Ba, Zilfalil; Naing, Nyi Nyi

    2016-01-01

    Background Treating patients with multidrug-resistant tuberculosis (MDR-TB) strains is more complicated, complex, toxic, expensive, than treating patients with susceptible TB strains. This study aims to compare the treatment outcomes and potential factors associated between patients with MDR-TB and non MDR TB infections in peninsular Malaysia. Methods This study was a retrospective cohort study. Data were collected from the medical records of all registered MDR-TB patients and Non-MDR-TB patients at five TB hospitals in peninsular Malaysia from January 2010 to January 2014. Results A total of 314 subjects were studied, including 105 MDR-TB cases and 209 non-MDR-TB. After TB treatment, 24.8% of the MDR-TB patients and 17.7% of non MDR TB relapsed; 17.1% of the MDR-TB patients and 16.3% of non MDR TB defaulted from TB treatment. A significant difference seen in treatment success rate 17.1% for MDR-TB; 63.1% for non MDR TB (P < 0.001)). Mortality rate were 8.9% for MDR-TB; 13.2% for non MDR TB. Multivariable analysis showed the potential factors associated with poor treatment outcomes were presence of HIV infection (AOR, 1.09; 95%CI: 1.05, 1.75; P = 0.001) and previous TB treatment (AOR, 4.87; 95%CI: 2.84, 8.38; P = 0.001). Conclusion This study revealed that the treatment success rate in patients with non MDR TB infection was higher than MDR-TB. Unsuccessful treatment was seen in MDR-TB associated with potential factors such as history of TB treatment, and presence of HIV infection. PMID:27660541

  12. Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis (MDR- TB) Compared with Non-MDR-TB Infections in Peninsular Malaysia

    PubMed Central

    Elmi, Omar Salad; Hasan, Habsah; Abdullah, Sarimah; Mat Jeab, Mat Zuki; Ba, Zilfalil; Naing, Nyi Nyi

    2016-01-01

    Background Treating patients with multidrug-resistant tuberculosis (MDR-TB) strains is more complicated, complex, toxic, expensive, than treating patients with susceptible TB strains. This study aims to compare the treatment outcomes and potential factors associated between patients with MDR-TB and non MDR TB infections in peninsular Malaysia. Methods This study was a retrospective cohort study. Data were collected from the medical records of all registered MDR-TB patients and Non-MDR-TB patients at five TB hospitals in peninsular Malaysia from January 2010 to January 2014. Results A total of 314 subjects were studied, including 105 MDR-TB cases and 209 non-MDR-TB. After TB treatment, 24.8% of the MDR-TB patients and 17.7% of non MDR TB relapsed; 17.1% of the MDR-TB patients and 16.3% of non MDR TB defaulted from TB treatment. A significant difference seen in treatment success rate 17.1% for MDR-TB; 63.1% for non MDR TB (P < 0.001)). Mortality rate were 8.9% for MDR-TB; 13.2% for non MDR TB. Multivariable analysis showed the potential factors associated with poor treatment outcomes were presence of HIV infection (AOR, 1.09; 95%CI: 1.05, 1.75; P = 0.001) and previous TB treatment (AOR, 4.87; 95%CI: 2.84, 8.38; P = 0.001). Conclusion This study revealed that the treatment success rate in patients with non MDR TB infection was higher than MDR-TB. Unsuccessful treatment was seen in MDR-TB associated with potential factors such as history of TB treatment, and presence of HIV infection.

  13. GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism

    PubMed Central

    Beste, Dany JV; Hooper, Tracy; Stewart, Graham; Bonde, Bhushan; Avignone-Rossa, Claudio; Bushell, Michael E; Wheeler, Paul; Klamt, Steffen; Kierzek, Andrzej M; McFadden, Johnjoe

    2007-01-01

    Background An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling of M. tuberculosis. Results GSMN-TB, a genome-scale metabolic model of M. tuberculosis, was constructed, consisting of 849 unique reactions and 739 metabolites, and involving 726 genes. The model was calibrated by growing Mycobacterium bovis bacille Calmette Guérin in continuous culture and steady-state growth parameters were measured. Flux balance analysis was used to calculate substrate consumption rates, which were shown to correspond closely to experimentally determined values. Predictions of gene essentiality were also made by flux balance analysis simulation and were compared with global mutagenesis data for M. tuberculosis grown in vitro. A prediction accuracy of 78% was achieved. Known drug targets were predicted to be essential by the model. The model demonstrated a potential role for the enzyme isocitrate lyase during the slow growth of mycobacteria, and this hypothesis was experimentally verified. An interactive web-based version of the model is available. Conclusion The GSMN-TB model successfully simulated many of the growth properties of M. tuberculosis. The model provides a means to examine the metabolic flexibility of bacteria and predict the phenotype of mutants, and it highlights previously unexplored features of M. tuberculosis metabolism. PMID:17521419

  14. Advanced development of the digital tuberculosis tester for MDR-TB screening

    NASA Astrophysics Data System (ADS)

    Smith, Jason E.; Simkulet, Michelle D.; Gutin, Alexander; Gutin, Alexy; Bardarov, Savco; Jacobs, William R., Jr.; Castracane, James; Tang, Oliver; Riska, Paul

    2001-05-01

    Tuberculosis (TB) remains the leading cause of death in the world from a single infectious disease, and the threat is becoming more critical with the spread of multi-drug resistant Tuberculosis (MDR-TB). TB detection, and susceptibility testing for drug resistant strain identification, is advancing with the development of Luciferase Reporter Mycobacteriophages (LRM). LRM will emit visible light at very low intensity when in the presence of live mycobacteria cells such as Tuberculosis strains. InterScience, Inc., together with its collaboration, is developing a highly sensitive, real-time digital detection system for the analysis of luminescent assays. Recent advances in system sensitivity, design, and implementation, as well as preliminary results of the development of individual test cartridges, will be presented. The ultimate goal of this work is to provide a versatile luminescence detection tool for widespread research and clinical applications.

  15. 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

  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. 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. PMID:23061988

  18. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain.

    PubMed

    Halim, Mohd Zakihalani A; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-03-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968.

  19. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain

    PubMed Central

    Halim, Mohd Zakihalani A.; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-01-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. PMID:26981419

  20. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain.

    PubMed

    Halim, Mohd Zakihalani A; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-03-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. PMID:26981419

  1. World TB Day 2016: an interview with leading experts in tuberculosis research.

    PubMed

    Phillips, Patrick P J; Fletcher, Helen A; Abubakar, Ibrahim; Lipman, Marc C I; McHugh, Timothy D

    2016-01-01

    In this interview, we talk to leading tuberculosis (TB) experts from University College London and the London School of Hygiene and Tropical Medicine about the current challenges in TB research. The video of this interview is available here: https://www.youtube.com/watch?v=75Die7MQBec&feature=youtu.be . The video can also be downloaded via Additional file 1. PMID:27007648

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Bayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis.

    PubMed

    Ekins, Sean; Casey, Allen C; Roberts, David; Parish, Tanya; Bunin, Barry A

    2014-03-01

    The search for compounds active against Mycobacterium tuberculosis is reliant upon high-throughput screening (HTS) in whole cells. We have used Bayesian machine learning models which can predict anti-tubercular activity to filter an internal library of over 150,000 compounds prior to in vitro testing. We used this to select and test 48 compounds in vitro; 11 were active with MIC values ranging from 0.4 μM to 10.2 μM, giving a high hit rate of 22.9%. Among the hits, we identified several compounds belonging to the same series including five quinolones (including ciprofloxacin), three molecules with long aliphatic linkers and three singletons. This approach represents a rapid method to prioritize compounds for testing that can be used alongside medicinal chemistry insight and other filters to identify active molecules. Such models can significantly increase the hit rate of HTS, above the usual 1% or lower rates seen. In addition, the potential targets for the 11 molecules were predicted using TB Mobile and clustering alongside a set of over 740 molecules with known M. tuberculosis target annotations. These predictions may serve as a mechanism for prioritizing compounds for further optimization.

  5. Antitubercular activity of disulfiram, an antialcoholism drug, against multidrug- and extensively drug-resistant Mycobacterium tuberculosis isolates.

    PubMed

    Horita, Yasuhiro; Takii, Takemasa; Yagi, Tetsuya; Ogawa, Kenji; Fujiwara, Nagatoshi; Inagaki, Emi; Kremer, Laurent; Sato, Yasuo; Kuroishi, Ryuji; Lee, Yoosa; Makino, Toshiaki; Mizukami, Hajime; Hasegawa, Tomohiro; Yamamoto, Ryuji; Onozaki, Kikuo

    2012-08-01

    The antimycobacterial activities of disulfiram (DSF) and diethyldithiocarbamate (DDC) against multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) clinical isolates were evaluated in vitro. Both DSF and DDC exhibited potent antitubercular activities against 42 clinical isolates of M. tuberculosis, including MDR/XDR-TB strains. Moreover, DSF showed remarkable bactericidal activity ex vivo and in vivo. Therefore, DSF might be a drug repurposed for the treatment of MDR/XDR-TB. PMID:22615274

  6. Antitubercular Activity of Disulfiram, an Antialcoholism Drug, against Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Isolates

    PubMed Central

    Horita, Yasuhiro; Yagi, Tetsuya; Ogawa, Kenji; Fujiwara, Nagatoshi; Inagaki, Emi; Kremer, Laurent; Sato, Yasuo; Kuroishi, Ryuji; Lee, YooSa; Makino, Toshiaki; Mizukami, Hajime; Hasegawa, Tomohiro; Yamamoto, Ryuji; Onozaki, Kikuo

    2012-01-01

    The antimycobacterial activities of disulfiram (DSF) and diethyldithiocarbamate (DDC) against multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) clinical isolates were evaluated in vitro. Both DSF and DDC exhibited potent antitubercular activities against 42 clinical isolates of M. tuberculosis, including MDR/XDR-TB strains. Moreover, DSF showed remarkable bactericidal activity ex vivo and in vivo. Therefore, DSF might be a drug repurposed for the treatment of MDR/XDR-TB. PMID:22615274

  7. 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

  8. A model to predict anti-tuberculosis activity: value proposition for marine microorganisms.

    PubMed

    Liu, Miaomiao; Grkovic, Tanja; Zhang, Lixin; Liu, Xueting; Quinn, Ronald J

    2016-08-01

    The development of new antibiotics effective against all strains of tuberculosis (TB) is needed. To evaluate the potential of marine microbe-derived natural products as anti-TB leads, we analyzed and compared the physico-chemical properties of 39 current TB drugs and candidates against 60 confirmed mycobacteria-active natural products. We showed that anti-TB natural products sourced from marine microbes have a large overlap with TB drug-like space. A model to predict potential anti-TB drugs is proposed. PMID:27406906

  9. 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 ...

  10. Multicenter evaluation of Seegene Anyplex TB PCR for the detection of Mycobacterium tuberculosis in respiratory specimens.

    PubMed

    Lim, Jinsook; Kim, Jimyung; Kim, Jong Wan; Ihm, Chunhwa; Sohn, Yong-Hak; Cho, Hyun-Jung; Kim, Jayoung; Koo, Sun Hoe

    2014-07-01

    Culture is the gold standard for diagnosis of tuberculosis, but it takes 6 to 8 weeks to confirm the result. This issue is complemented by the detection method using polymerase chain reaction, which is now widely used in a routine microbiology laboratory. In this study, we evaluated the performance of the Seegene Anyplex TB PCR to assess its diagnostic sensitivity and specificity, and compared its results with the Roche Cobas TaqMan MTB PCR, one of the most widely used assays in the world. Five university hospitals located in the Chungcheong area in South Korea participated in the study. A total of 1,167 respiratory specimens ordered for acid-fast bacilli staining and culture were collected for four months, analyzed via the Seegene Anyplex TB PCR, and its results were compared with the Roche Cobas TaqMan MTB PCR. For detection of Mycobacterium tuberculosis, the diagnostic sensitivity and specificity of the Anyplex TB PCR were 87.5% and 98.2% respectively, whereas those of the Cobas TaqMan were 92.0% and 98.0% respectively (p value > 0.05). For smear-positive specimens, the sensitivity of the Anyplex TB PCR was 95.2%, which was exactly the same as that of the Cobas TaqMan. For smear-negative specimens, the sensitivity of the Anyplex TB PCR was 69.2%, whereas that of the Cobas TaqMan TB PCR was 84.6%. For detection of MTB, the Seegene Anyplex TB PCR showed excellent diagnostic performance, and high sensitivity and specificity, which were comparable to the Roche Cobas TaqMan MTB PCR. In conclusion, the Anyplex TB PCR can be a useful diagnostic tool for the early detection of tuberculosis in clinical laboratories.

  11. PEPFAR support for the scaling up of collaborative TB/HIV activities.

    PubMed

    Howard, Andrea A; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L

    2012-08-15

    The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

  12. Modified TB rapid test by proteinase K for rapid diagnosis of pleural tuberculosis.

    PubMed

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

    2016-03-01

    The diagnosis of pleural tuberculosis continues to be a challenge due to the low sensitivity of traditional diagnostic methods. Better and more rapid tests are needed for diagnosis of pleural TB. In this study, pleural fluids were tested with rapid test to determine Mycobacterium tuberculosis (MTB antigen). Affinity chromatography was used to purify specific polyclonal antibodies against MTB antigen. Pleural samples after decontamination were treated with proteinase K. Rapid test for pleural fluids was prepared by specific antibody. Rapid test was performed on 85 pleural fluid patients. The patients had a mean age of 46.55 ± 15.96 years and 38 were men. The performance of rapid test, using proteinase K, was found to be the most impressive: sensitivity 93%, specificity 94%, PPV 90%, and NPV 96% compared with adenosine deaminase test (ADA), PCR, smear, and culture. The present study did demonstrate that modified TB rapid test can substantially improve the diagnosis of extrapulmonary TB.

  13. Impact of awareness drives and community-based active tuberculosis case finding in Odisha, India.

    PubMed

    Parija, D; Patra, T K; Kumar, A M V; Swain, B K; Satyanarayana, S; Sreenivas, A; Chadha, V K; Moonan, P K; Oeltmann, J E

    2014-09-01

    India's Revised National Tuberculosis Control programme employs passive case detection. The new sputum smear-positive case detection rate is less than 70% in Odisha State. During April-June 2012, active case finding (ACF) was conducted through awareness drives and field-based tuberculosis (TB) screening in select communities with the lowest case detection rates. During the campaign, 240 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 11% relative to April-June 2011 in intervention communities compared to an 0.8% increase in non-intervention communities. ACF brought TB services closer to the community and increased TB case detection.

  14. Tetrahdroxysqualene from Rhus taitensis Shows Antimycobacterial Activity Against Mycobacterium tuberculosis

    PubMed Central

    Noro, Jeffrey C.; Barrows, Louis R.; Gideon, Osia G.; Ireland, Chris M.; Koch, Michael; Matainaho, Teatulohi; Piskaut, Pius; Pond, Christopher D.; Bugni, Tim S.

    2010-01-01

    Tuberculosis has become a major health problem, in particular with the emergence of extremely drug resistant tuberculosis (XDRTB). In our search for new therapeutic leads against TB, we isolated a new triterpene (1) from the plant Rhus taitensis collected in Papua New Guinea. Tetrahydroxysqualene (1) was isolated using bioassay-guided fractionation of the methanolic extract of R. taitensis leaves and twigs. The structure of tetrahydroxysqualene (1) was elucidated on the basis of HRESIMS and 1D and 2D NMR spectra. Tetrahydroxysqualene (1) exhibited anti–tuberculosis activity with an MIC of 10.0 μg/mL while showing only modest cytotoxicity. PMID:18710283

  15. HGV&TB: a comprehensive online resource on human genes and genetic variants associated with tuberculosis.

    PubMed

    Sahajpal, Ruchika; Kandoi, Gaurav; Dhiman, Heena; Raj, Sweety; Scaria, Vinod; Bhartiya, Deeksha; Hasija, Yasha

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by fastidious pathogen Mycobacterium tuberculosis. TB has emerged as one of the major causes of mortality in the developing world. Role of host genetic factors that modulate disease susceptibility have not been studied widely. Recent studies have reported few genetic loci that provide impetus to this area of research. The availability of tools has enabled genome-wide scans for disease susceptibility loci associated with infectious diseases. Till now, information on human genetic variations and their associated genes that modulate TB susceptibility have not been systematically compiled. In this work, we have created a resource: HGV&TB, which hosts genetic variations reported to be associated with TB susceptibility in humans. It currently houses information on 307 variations in 98 genes. In total, 101 of these variations are exonic, whereas 78 fall in intronic regions. We also analysed the pathogenicity of the genetic variations, their phenotypic consequences and ethnic origin. Using various computational analyses, 30 variations of the 101 exonic variations were predicted to be pathogenic. The resource is freely available at http://genome.igib.res.in/hgvtb/index.html. Using integrative analysis, we have shown that the disease associated variants are selectively enriched in the immune signalling pathways which are crucial in the pathophysiology of TB. Database URL: http://genome.igib.res.in/hgvtb/index.html

  16. Incidence of and Risk Factors for Tuberculosis (TB) in Gastric Cancer Patients in an Area Endemic for TB

    PubMed Central

    Fang, Wen-Liang; Hung, Yi-Ping; Liu, Chia-Jen; Lan, Yuan-Tzu; Huang, Kuo-Hung; Chen, Ming-Huang; Lo, Su-Shun; Shyr, Yi-Ming; Wu, Chew-Wun; Yang, Muh-Hwa; Chen, Tzeng-Ji; Chao, Yee

    2015-01-01

    Abstract To date, there have been few reports investigating the relationship between tuberculosis (TB) and gastric cancer. We conducted a nationwide population-based matched cohort study using data retrieved from Taiwan's National Health Insurance Research Database to determine the incidence of and risk factors for TB in patients diagnosed with gastric cancer. From 2000 to 2011, we identified 36,972 gastric cancer patients and normal subjects from the general population matched for age, sex, and comorbidities at a 1:1 ratio. The data were analyzed using Cox proportional hazards models. Compared with the matched cohort, gastric cancer patients exhibited a higher risk for TB (adjusted hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.65–3.05, P < 0.001), and those with TB exhibited higher mortality (adjusted HR 1.59, 95% CI 1.41–1.79, P < 0.001). Old age (adjusted HR 2.40, 95% CI 1.92–2.99, P < 0.001), male sex (adjusted HR 2.13, 95% CI 1.76–2.57, P < 0.001), diabetes mellitus (adjusted HR 1.28, 95% CI 1.05–1.56, P = 0.013), and chronic obstructive pulmonary disease (COPD) (adjusted HR 1.44, 95% CI 1.19–1.75, P < 0.001) were identified as independent risk factors for TB in gastric cancer patients. Dyslipidemia was an independent protective factor for both TB (adjusted HR 2.13, 95% CI 1.73–2.62, P < 0.001) and mortality (adjusted HR 1.11, 95% CI 1.08–1.15, P < 0.001) in gastric cancer patients. Old age, male sex, diabetes mellitus, and COPD were independent risk factors for TB in gastric cancer. High-risk gastric cancer patients, especially those in TB-endemic areas, should be regularly screened for TB. PMID:26632751

  17. Construction of two Listeria ivanovii attenuated strains expressing Mycobacterium tuberculosis antigens for TB vaccine purposes.

    PubMed

    Lin, Qingqing; Zhou, Mengying; Xu, Zongkai; Khanniche, Asma; Shen, Hao; Wang, Chuan

    2015-02-20

    Bacillus Calmette-Guerin (BCG) has failed in complete control of tuberculosis (TB), thus, novel tuberculosis vaccines are urgently needed. We have constructed several TB vaccine candidates, which are characterized by the use of Listeria ivanovii (LI) strain as an antigen delivery vector. Two L. ivanovii attenuated recombinant strains L. ivanovii△actAplcB-Rv0129c and L. ivanovii△actAplcB-Rv3875 were successfully screened. Results from genome PCR and sequencing showed that the Mycobacterium tuberculosis antigen gene cassette coding for Ag85C or ESAT-6 protein respectively had been integrated into LI genome downstream of mpl gene. Western blot confirmed the secretion of Ag85C or ESAT-6 protein from the recombinant LI strains. These two recombinant strains showed similar growth curves as wide type strain in vitro. In vivo, they transiently propagated in mice spleen and liver, and induced specific CD8(+) IFN-γ secretion. Therefore, in this paper, two novel LI attenuated strains expressing specific TB antigens were successfully constructed. The promising growth characteristics in mice immune system and the capability of induction of IFN-γ secretion make them of potential interest for development of TB vaccines.

  18. 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

  19. ART uptake, its timing and relation to anti-tuberculosis treatment outcomes among HIV-infected TB patients

    PubMed Central

    Harries, A. D.; Mutasa-Apollo, T.; Sandy, C.; Murimwa, T.; Mugurungi, O.

    2012-01-01

    Setting: All public health facilities in two provinces of Zimbabwe. Objective: To determine, among tuberculosis (TB) patients with human immunodeficiency virus (HIV) registered in 2010, 1) the proportion started on antiretroviral treatment (ART), 2) the timing of ART in relation to the start of anti-tuberculosis treatment, and 3) whether timing of ART influenced anti-tuberculosis treatment outcomes. Design: Retrospective cohort study. Results: Of the 2655 HIV-positive TB patients, 1115 (42%) were documented as receiving ART. Of these, 178 (16%) started ART prior to anti-tuberculosis treatment. Of those who started after anti-tuberculosis treatment, 17% started within 2 weeks, 43% between 2 and 8 weeks and 40% after 8 weeks. Treatment success in the cohort was 82%, with 14% deaths before completion of anti-tuberculosis treatment. Not receiving ART during anti-tuberculosis treatment was associated with lower anti-tuberculosis treatment success (adjusted RR 0.70, 95%CI 0.53–0.91) and more deaths (adjusted RR 3.43, 95%CI 2.2–5.36). There were no differences in TB treatment outcomes by timing of ART initiation. Conclusion: ART uptake is low given the improved treatment outcomes in those put on ART during anti-tuberculosis treatment. Better integration of HIV and TB services is needed to ensure increased coverage and earlier ART uptake. PMID:26392951

  20. Tuberculosis incidence among contacts of active pulmonary tuberculosis

    PubMed Central

    Cailleaux-Cezar, M.; de A. Melo, D.; Xavier, G. M.; de Salles, C. L. G.; de Mello, F. C. Q.; Ruffino-Netto, A.; Golub, J. E.; Efron, A.; Chaisson, R. E.; Conde, M. B.

    2013-01-01

    SUMMARY BACKGROUND Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients aged ≤15 years with a tuberculin skin test (TST) ≥10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST ≥15 mm regardless of previous BCG vaccination. OBJECTIVE To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN Retrospective cohort study. Contacts aged between 12 and 15 years and those aged >15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100 000 population. Risk of TB was greater among the 349 contacts with TST ≥5 mm (5.4%) compared to the 318 contacts with TST < 5 mm (0.9%; RR 6.04, 95%CI 1.7–20.6). CONCLUSION The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration ≥5 mm was the only variable that predicted the development of TB disease within 2 years. PMID:19146746

  1. 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.

  2. 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

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

    PubMed

    Delva, Guesly J; Francois, Ingrid; Claassen, Cassidy W; Dorestan, Darwin; Bastien, Barbara; Medina-Moreno, Sandra; Fort, Dumesle St; Redfield, Robert R; Buchwald, Ulrike K

    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

  4. Diagnostic value of blood gene expression signatures in active tuberculosis in Thais: a pilot study.

    PubMed

    Satproedprai, N; Wichukchinda, N; Suphankong, S; Inunchot, W; Kuntima, T; Kumpeerasart, S; Wattanapokayakit, S; Nedsuwan, S; Yanai, H; Higuchi, K; Harada, N; Mahasirimongkol, S

    2015-06-01

    Tuberculosis (TB) is a major global health problem. Routine laboratory tests or newly developed molecular detection are limited to the quality of sputum sample. Here we selected genes specific to TB by a minimum redundancy-maximum relevancy package using publicly available microarray data and determine level of selected genes in blood collected from a Thai TB cohort of 40 active TB patients, 38 healthy controls and 18 previous TB patients using quantitative real-time PCR. FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15, MAFB and KAZN had significantly higher expression level in active TB individuals as compared with healthy controls and previous TB cases (P<0.01). A mathematical method was applied to calculate TB predictive score, which contains the level of expression of seven genes and this score can identify active TB cases with 82.5% sensitivity and 100% specificity as compared with conventional culture confirmation. In addition, TB predictive scores in active TB patients were reduced to normal after completion of standard short-course therapy, which was mostly in concordant with the disease outcome. These finding suggested that blood gene expression measurement and TB Sick Score could have potential value in terms of diagnosis of TB and anti-TB treatment monitoring.

  5. 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…

  6. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis

    PubMed Central

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

    2016-01-01

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

  7. 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

  8. Taking forward the World TB Day 2016 theme 'Unite to End Tuberculosis' for the WHO Africa Region.

    PubMed

    Ntoumi, Francine; Kaleebu, Pontiano; Macete, Eusebio; Mfinanga, Sayoki; Chakaya, Jeremiah; Yeboah-Manu, Dorothy; Bates, Matthew; Mwaba, Peter; Maeurer, Markus; Petersen, Eskild; Zumla, Alimuddin

    2016-05-01

    Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100000 population-more than double the global average of 133 per 100000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is 'Unite to End TB'. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host-Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed.

  9. Giving TB wheels: Public transportation as a risk factor for tuberculosis transmission.

    PubMed

    Feske, Marsha L; Teeter, Larry D; Musser, James M; Graviss, Edward A

    2011-12-01

    Previous geospatial analysis of the well-defined Houston Tuberculosis Initiative (HTI) database identified an association between the use of city-bus transportation (inclusive of time onboard) and Tuberculosis (TB) incidence in Houston/Harris County census tracts (paper submitted). This paper is an extension of those findings. Contact investigations on school buses have reported a high rate of positive tuberculin skin tests in the persons traveling with the index case and have shown an association with bus ride duration. In Houston, city bus routes are veins connecting even the most diverse of populations within the metropolitan area. Among HTI participants, TB patients who reported weekly bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis (MTB), yet 75% of bus riders were clustered with a mean cluster size of 50.14, indicating recent transmission, compared to 56% of non-bus riders (OR = 2.4, p < 0.001) with a mean cluster size of 28.9 (p < 0.01). Individual bus routes, including one route servicing the local hospitals, were found to be risk factors for endemic MTB clustered strains and the routes themselves geographically connect the census tracts previously identified as having endemic TB.

  10. Tuberculosis: General Information

    MedlinePlus

    TB Elimination Tuberculosis: General Information What is TB? Tuberculosis (TB) is a disease caused by germs that are spread from person ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination CS227840_A What Does a Positive Test ...

  11. Immunopathogenesis of tuberculosis and novel mechanisms of vaccine activity.

    PubMed

    Schrager, Lewis K; Izzo, Angelo; Velmurugan, Kamalakannan

    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 Immunopathogenesis of Tuberculosis, and Immunopathogenesis and Novel Mechanisms of Vaccine Activity. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. PMID:27450395

  12. Symptom Screening Among HIV-Infected Pregnant Women Is Acceptable and Has High Negative Predictive Value for Active Tuberculosis

    PubMed Central

    Chandrasekhar, Aditya; Gupte, Nikhil; Patil, Sandesh; Bhosale, Ramesh; Sambarey, Pradeep; Ghorpade, Shivahari; Nayak, Uma; Garda, Laila; Sastry, Jayagowri; Bharadwaj, Renu; Bollinger, Robert C.

    2011-01-01

    We evaluated tuberculosis (TB) screening among 799 human immunodeficiency virus (HIV)–infected pregnant women in India. Eleven (1.4%) had active TB. The negative predictive value of screening using cough, fever, night sweats, or weight loss was 99.3%. Tuberculin skin test and targeted chest radiography provided no substantial benefit. TB symptom screening, as recommended by the World Health Organization, is effective for ruling out TB in HIV-infected pregnant women. PMID:21940417

  13. Active case finding of tuberculosis: historical perspective and future prospects

    PubMed Central

    Golub, J. E.; Mohan, C. I.; Comstock, G. W.; Chaisson, R. E.

    2015-01-01

    SUMMARY Despite a history of remarkable scientific achievements in microbiology and therapeutics, tuberculosis (TB) continues to pose an extraordinary threat to human health. Case finding and treatment of TB disease are the principal means of controlling transmission and reducing incidence. This review presents a historical perspective of active case finding (ACF) of TB, detailing case detection strategies that have been used over the last century. This review is divided into the following sections: mass radiography, house-to-house surveys, out-patient case detection, enhanced case finding, high-risk populations and cost-effectiveness. The report concludes with a discussion and recommendations for future case finding strategies. Understanding the strengths and weaknesses of these methods will help inform and shape ACF as a TB control policy in the twenty-first century. PMID:16333924

  14. 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 ...

  15. 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.

  16. [Human resource capacity building on TB laboratory work for TB control program--through the experience of international TB laboratory training course for TB control at the Research Institute of Tuberculosis, JATA, Japan].

    PubMed

    Fujiki, Akiko; Kato, Seiya

    2008-06-01

    The international training course on TB laboratory work for national tuberculosis program (NTP) has been conducted at the Research Institute of Tuberculosis since 1975 funded by Japan International Cooperation Agency in collaboration with WHO Western Pacific Regional Office. The aim of the course is to train key personnel in TB laboratory field for NTP in resource-limited countries. The course has trained 265 national key personnel in TB laboratory service from 57 resource-limited countries in the last 33 years. The number of participants trained may sound too small in the fight against the large TB problem in resource-limited countries. However, every participant is playing an important role as a core and catalyst for the TB control program in his/her own country when they were back home. The curriculum is composed of technical aspects on TB examination, mainly sputum microscopy in addition since microscopy service is provided at many centers that are deployed in a widely spread area, the managerial aspect of maintaining quality TB laboratory work at the field laboratory is another component of the curriculum. Effective teaching methods using materials such as artificial sputum, which is useful for panel slide preparation, and technical manuals with illustrations and pictures of training procedure have been developed through the experience of the course. These manuals are highly appreciated and widely used by the front line TB workers. The course has also contributed to the expansion of EQA (External Quality Assessment) system on AFB microscopy for the improvement of the quality of TB laboratory service of NTP. The course is well-known for not only having a long history, but also for its unique learning method emphasizing "Participatory Training", particularly for practicum sessions to master the skills on AFB microscopy. The method in learning AFB microscopy, which was developed by the course, was published as a training manual by IUATLD, RIT and USAID. As it is

  17. Factors Associated with a Strong Response to the T-SPOT.TB in Patients with Extrapulmonary Tuberculosis.

    PubMed

    Lee, Yu-Mi; Kim, Sun-Mi; Park, Su Jin; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

    2014-12-01

    Limited data are available on which factors are associated with strong immunologic responses to T-SPOT.TB. We investigated the factors associated with strong positive responses in patients with extrapulmonary tuberculosis (E-TB). Of 173 patients with E-TB who gave positive results on T-SPOT.TB, 26 (15%) with a strong positive response (defined as ≥1,000 spot-forming units (SFU)/2.5×10(5) PBMC to ESAT-6 or CFP-10) and 71 (41%) with a low positive response (≤ 99 SFU (6-99 SFU)/2.5×10(5) PBMC) were further analyzed. Miliary TB was independently associated with a strong positive response to T-SPOT.TB, while advanced age and immunosuppression were independently associated with weak positive T-SPOT.TB responses.

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

    PubMed Central

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

    2015-01-01

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

  19. 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 ...

  20. Rapid Screening of MDR-TB in Cases of Extra Pulmonary Tuberculosis Using Geno Type MTBDRplus

    PubMed Central

    Kumari, Richa; Tripathi, Rajneesh; Pandey, Alok Prakash; Banerjee, Tuhina; Sinha, Pallavi; Anupurba, Shampa

    2016-01-01

    Background Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes. Methods A total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ) media. Phenotypic drug susceptibility testing (DST) was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method. Results Of 510 specimens cultured, the total culture positivity obtained was 11.8% (60) encompassing 54 (10.6%) Mycobacterium tuberculosis and 6 (1.2%) non-tubercular mycobacteria (NTM). DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB) in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours. Conclusion The problem of MDR in extra pulmonary tuberculosis (EPTB) cannot be overlooked and

  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. Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.

    PubMed

    Dejene, Sintayehu W; Heitkönig, Ignas M A; Prins, Herbert H T; Lemma, Fitsum A; Mekonnen, Daniel A; Alemu, Zelalem E; Kelkay, Tessema Z; de Boer, Willem F

    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

  3. B in TB: B Cells as Mediators of Clinically Relevant Immune Responses in Tuberculosis.

    PubMed

    Rao, Martin; Valentini, Davide; Poiret, Thomas; Dodoo, Ernest; Parida, Shreemanta; Zumla, Alimuddin; Brighenti, Susanna; Maeurer, Markus

    2015-10-15

    The protective role of B cells and humoral immune responses in tuberculosis infection has been regarded as inferior to cellular immunity directed to the intracellular pathogen Mycobacterium tuberculosis. However, B-cell-mediated immune responses in tuberculosis have recently been revisited in the context of B-cell physiology and antigen presentation. We discuss in this review the diverse functions of B cells in tuberculosis, with a focus on their biological and clinical relevance to progression of active disease. We also present the peptide microarray platform as a promising strategy to discover unknown antigenic targets of M. tuberculosis that could contribute to the better understanding of epitope focus of the humoral immune system against M. tuberculosis.

  4. 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

    2016-01-01

    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

  5. 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

  6. Role of complement activation and antibody in the interaction between Mycobacterium tuberculosis and human macrophages.

    PubMed

    Manivannan, S; Rao, Narayan V; Ramanathan, V D

    2012-08-01

    Mycobacterium tuberculosis-specific antibodies possess immunomodulatory effects during tuberculosis infection. Prior sensitization to environmental mycobacteria is known to suppress immune responses against BCG and M. tuberculosis. Mycobacteria-induced antibodies can influence events such as complement activation and phagocytosis during infectious process. In the present study role of anti-M. tuberculosis IgG (anti-M. tb IgG) antibody during interaction between M. tuberculosis and human macrophages mediated through complement has been examined in vitro. Anti-M. tb IgG antibody significantly enhanced complement activation by M. tuberculosis. Phagocytosis of M. tuberculosis by macrophages increased significantly in the presence of complement and/or antibody. Moreover, antibody enhanced phagocytosis in the presence of complement. Addition of antibody alone or in combination with complement also augmented intracellular viability of bacilli within macrophages. Results of this study showed that anti-mycobacterial antibody enhances complement activation and anti-M. tb IgG antibody probably modulates effects of complement during early stages of tuberculosis infection.

  7. [Treatment of tuberculosis].

    PubMed

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

    2015-01-01

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

  8. [Use of molecular-biological microchip TB-BIOCHIP-2 for detecting of Mycobacterium tuberculosis with multidrug resistance to fluoroquinolones in patients with new detected and chronic tuberculosis].

    PubMed

    Nosova, E Iu; Galkina, K Iu; Antonova, O V; Garmash, Iu Iu; Skotnikova, O I; Moroz, A M

    2008-01-01

    At present the left-handed "respiratory" quinolones such as moxifloxacin and levofloxacin are the most promising drugs for therapy of multidrug resistant tuberculosis (MDR). Fast and specific diagnostics of sensitivity of M. tuberculosis (MBT) with MDR to this group of drugs is required for timely prescription of adequate chemotherapy and its correction in case of MBT resistance to fluoroquinolones. A new generation of biological microchips - TB-BIOCHIP-2 makes possible to detect 9 mutation types in quinolones resistant determination region (QRDR) of gene. About 800 samples from 169 patients in Antituberculosis center were studied. In patients with new detected tuberculosis 23.5% MBT resistant to isoniazid and rifampicin (MDR) and sensitive to fluoroquinolones were revealed. In patients with chronic tuberculosis 65.5% MBT-MDR were revealed. Our results were confirmed with detecting ofloxacin resistance on Lowenstein - Jensen. In addition efficiency of TB-BIOCHIP-2 to control drug testing sensitivity of MBT-MDR on fluoroquinolones was confirmed.

  9. Experience of active tuberculosis case finding in nearly 5 million households in India.

    PubMed

    Prasad, B M; Satyanarayana, S; Chadha, S S; Das, A; Thapa, B; Mohanty, S; Pandurangan, S; Babu, E R; Tonsing, J; Sachdeva, K S

    2016-03-21

    In India, to increase tuberculosis (TB) case detection under the National Tuberculosis Programme, active case finding (ACF) was implemented by the Global Fund-supported Project Axshya, among high-risk groups in 300 districts. Between April 2013 and December 2014, 4.9 million households covering ~20 million people were visited. Of 350 047 presumptive pulmonary TB cases (cough of ⩾2 weeks) identified, 187 586 (54%) underwent sputum smear examination and 14 447 (8%) were found to be smear-positive. ACF resulted in the detection of a large number of persons with presumptive pulmonary TB and smear-positive TB. Ensuring sputum examination of all those with presumptive TB was a major challenge.

  10. TB-SA antibody test for diagnosis and monitoring treatment outcome of sputum smear negative pulmonary tuberculosis patients.

    PubMed

    Li, Xinxu; Xu, Hancheng; Jiang, Shiwen; Jing, Kuanhe; Wang, Li; Liu, Xiaoqiu; Li, Weibin; Zhang, Hui; Wang, Lixia

    2011-09-01

    The objectives of this study were to evaluate the suitability of the TB-SA antibody test to diagnose tuberculosis in sputum smear negative (SS-) pulmonary tuberculosis (TB) patients and its applicability for monitoring treatment outcomes in these patients. This study was conducted in three counties/districts in Chongqing Municipality, Liaoning Province, China between June 2005 and June 2007. A total of 432 SS suspected pulmonary TB patients were recruited and their blood was collected prior to treatment, at the end of 1 month of treatment, 2 months of treatment and 6 months of treatment (E6MT). The serum samples were analyzed with a TB-SA antibody test kit. Of the 432 SS suspected pulmonary TB patients, serum samples were obtained at all time points in 316 patients and analyzed. The 316 patients were divided into three groups according to sputum smear and sputum culture results and the chest X-ray results before treatment and at E6MT. Ten point four percent were SS-/culture positive (C+), 73.1% were SS-/culture negative (C-) with X-rays abnormalities, and 16.5% were SS-/C- without X-rays abnormalities. The positive rates for TB-SA antibody in the three groups were 57.6, 44.6 and 44.2%, respectively, before treatment, and 18.2, 19.1 and 26.9%, respectively, at E6MT. There was a significant decrease in TB-SA antibody positivity with treatment for all 3 groups. The TB-SA antibody test may be a useful adjunct to diagnose tuberculosis in SS- pulmonary TB patients, and may be useful for monitoring treatment outcomes of SS- pulmonary TB patients. PMID:22299440

  11. Cost-comparison of different management policies for tuberculosis patients in Italy. AIPO TB Study Group.

    PubMed Central

    Migliori, G. B.; Ambrosetti, M.; Besozzi, G.; Farris, B.; Nutini, S.; Saini, L.; Casali, L.; Nardini, S.; Bugiani, M.; Neri, M.; Raviglione, M. C.

    1999-01-01

    Although in developing countries the treatment of tuberculosis (TB) cases is among the most cost-effective health interventions, few studies have evaluated the cost-effectiveness of TB control in low-prevalence countries. The aim of the present study was to carry out an economic analysis in Italy that takes into account both the perspective of the resource-allocating authority (i.e. the Ministry of Health) and the broader social perspective, including a cost description based on current outcomes applied to a representative sample of TB patients nationwide (admission and directly observed treatment (DOT) during the initial intensive phase of treatment); a cost-comparison analysis of two alternative programmes: current policy based on available data (scenario 1) and an hypothetical policy oriented more towards outpatient care (scenario 2) (both scenarios included the option of including or not including DOT outside hospital admission, and incentives) were compared in terms of cost per case treated successfully. Indirect costs (such as loss of productivity) were included in considerations of the broader social perspective. The study was designed as a prospective monitoring activity based on the supervised collection of forms from a representative sample of Italian TB units. Individual data were collected and analysed to obtain a complete economic profile of the patients enrolled and to evaluate the effectiveness of the intervention. A separate analysis was done for each scenario to determine the end-point at different levels of cure rate (50-90%). The mean length of treatment was 6.6 months (i.e. patients hospitalized during the intensive phase; length of stay was significantly higher in smear-positive patients and in human immunodeficiency virus (HIV) seropositive patients). Roughly six direct smear and culture examinations were performed during hospital admission and three during ambulatory treatment. The cost of a single bed day was US$186.90, whereas that of a

  12. inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis

    PubMed Central

    2013-01-01

    Background Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. Results We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research

  13. Direct inhibitors of InhA active against Mycobacterium tuberculosis

    PubMed Central

    Manjunatha, Ujjini H.; Rao, Srinivasa P. S.; Kondreddi, Ravinder Reddy; Noble, Christian G.; Camacho, Luis R.; Tan, Bee H.; Ng, Seow H.; Ng, Pearly Shuyi; Ma, N. L.; Lakshminarayana, Suresh B.; Herve, Maxime; Barnes, S. Whitney; Yu, Weixuan; Kuhen, Kelli; Blasco, Francesca; Beer, David; Walker, John R.; Tonge, Peter J.; Glynne, Richard; Smith, Paul W.; Diagana, Thierry T.

    2015-01-01

    New chemotherapeutic agents are urgently required to combat the global spread of multi-drug resistant tuberculosis (MDR-TB). The mycobacterial enoyl reductase, InhA, is one of the few clinically-validated targets in tuberculosis drug discovery. Here, we report the identification of a new class of direct InhA inhibitors, the 4-hydroxy-2-pyridones, using phenotypic high-throughput whole-cell screening. This class of orally-active compounds showed potent bactericidal activity against common isoniazid-resistant TB clinical isolates. Biophysical studies revealed that 4-hydroxy-2-pyridones bound specifically to InhA in an NADH-dependent manner and blocked the enoyl-substrate binding pocket. The lead compound NITD-916 directly blocked InhA in a dose-dependent manner and showed in vivo efficacy in acute and established mouse models of infection by Mycobacterium tuberculosis. Collectively, our structural and biochemical data open up new avenues for rational structure-guided optimization of the 4-hydroxy-2-pyridone class of compounds for the treatment of MDR-TB. PMID:25568071

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

    PubMed

    Souza de Lima, D; Ogusku, M M; Sadahiro, A; Pontillo, A

    2016-07-01

    Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection.

  15. The Risk of Depressive Disorder Among Contacts of Tuberculosis Patients in a TB-endemic Area: A Population-based Cohort Study.

    PubMed

    Pan, Sheng-Wei; Yen, Yung-Feng; Feng, Jia-Yih; Su, Vincent Yi-Fong; Kou, Yu Ru; Su, Wei-Juin

    2015-10-01

    Tuberculosis (TB) disease may be transmitted to close contacts of index cases, causing physical illness. No studies have investigated the risk of developing depressive disorder among TB contacts in a TB-endemic area.Adult participants with a new diagnosis of TB contact (ICD-9-CM codes V01.1 plus chest radiographic order) since January 1, 2008, were identified from the National Health Insurance Research Database in Taiwan. A control cohort matched for age (±5 y), sex, enrolled years, and income level was selected. These 2 cohorts were followed until December 31, 2012, and observed for the development of depressive disorder. The Kaplan-Meier method and the log-rank test were used to examine the difference in cumulative incidences of depressive disorder between groups. Cox proportional-hazard models were used to calculate adjusted hazard ratios (aHRs) for depressive disorder.The TB contact cohort consisted of 9046 patients and matched controls of 36,184 ones. The mean age of TB contacts was 44.7 years, and 56.0% of them were women. During a mean follow-up period of 2.5 years, 127 (1.40%) TB contacts and 521 (1.44%) matched controls developed depressive disorder. TB exposure was found to be an independent risk factor of depressive disorder in women (aHR 1.34, 95% confidence interval [CI] 1.07-1.68), but not in men (aHR 0.71, 95% CI 0.48-1.06) after adjusting for age, comorbidities, and income levels. The risk of depression was significantly higher for female TB contacts than for matched controls in the first and second years (aHR 1.49, 95% CI 1.03-2.14; and aHR 1.53, 95% CI 1.05-2.23, respectively), but not thereafter. Of note, 67 (0.74%) TB contacts and 88 (0.24%) matched controls developed active TB, but none of them had subsequent depressive disorder during follow-up periods.Female TB contacts had an increased risk of depression within the first 2 years after exposure. Clinicians should consider conducting depression evaluations in addition to routine TB contact

  16. 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.

  17. Rapid diagnosis of active tuberculosis by detecting antibodies from lymphocyte secretions.

    PubMed

    Raqib, Rubhana; Rahman, Jubayer; Kamaluddin, A K M; Kamal, S M Mostafa; Banu, Fauzia A; Ahmed, Shakeel; Rahim, Zeaur; Bardhan, Pradip K; Andersson, Jan; Sack, David A

    2003-08-01

    In the present study, we investigated the tuberculosis (TB) diagnostic performance of an assay on the basis of detection of TB-specific antibodies from peripheral blood mononuclear cells (PBMCs), to determine whether antibodies in lymphocyte secretions obtained from PBMCs would better reflect active disease than antibodies in serum. PBMCs from patients with and without TB cultured in various concentrations for different times were assessed. Immunoglobulin G (IgG) specific for antigen (bacille Calmette-Guérin [BCG] vaccine and purified protein derivative [PPD]) was measured in lymphocyte secretions. Patients with active TB had higher BCG- or PPD-specific IgG antibody responses than patients without TB or healthy subjects (P=.001). This method can be used as a quick diagnostic aid to facilitate rapid detection of TB cases.

  18. Meropenem-clavulanic acid has high in vitro activity against multidrug-resistant Mycobacterium tuberculosis.

    PubMed

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

    2015-01-01

    We investigated the activity of meropenem-clavulanic acid (MEM-CLA) against 68 Mycobacterium tuberculosis isolates. We included predominantly multi- and extensively drug-resistant tuberculosis (MDR/XDR-TB) isolates, since the activity of MEM-CLA for resistant isolates has previously not been studied extensively. Using Middlebrook 7H10 medium, all but four isolates showed an MIC distribution of 0.125 to 2 mg/liter for MEM-CLA, below the non-species-related breakpoint for MEM of 2 mg/liter defined by EUCAST. MEM-CLA is a potential treatment option for MDR/XDR-TB.

  19. Genomic Diversity of Mycobacterium tuberculosis Complex Strains in Cantabria (Spain), a Moderate TB Incidence Setting

    PubMed Central

    Pérez del Molino Bernal, Inmaculada C.; Lillebaek, Troels; Pedersen, Mathias K.; Martinez-Martinez, Luis; Folkvardsen, Dorte B.; Agüero, Jesús; Rasmussen, E. Michael

    2016-01-01

    Background Tuberculosis (TB) control strategies are focused mainly on prevention, early diagnosis, compliance to treatment and contact tracing. The objectives of this study were to explore the frequency and risk factors of recent transmission of clinical isolates of Mycobacterium tuberculosis complex (MTBC) in Cantabria in Northern Spain from 2012 through 2013 and to analyze their clonal complexity for better understanding of the transmission dynamics in a moderate TB incidence setting. Methods DNA from 85 out of 87 isolates from bacteriologically confirmed cases of MTBC infection were extracted directly from frozen stocks and genotyped using the mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) method. The MIRU-VNTRplus database tool was used to identify clusters and lineages and to build a neighbor joining (NJ) phylogenetic tree. In addition, data were compared to the SITVIT2 database at the Pasteur Institute of Guadeloupe. Results The rate of recent transmission was calculated to 24%. Clustering was associated with being Spanish-born. A high prevalence of isolates of the Euro-American lineage was found. In addition, MIRU-VNTR profiles of the studied isolates corresponded to previously found MIRU-VNTR types in other countries, including Spain, Belgium, Great Britain, USA, Croatia, South Africa and The Netherlands. Six of the strains analyzed represented clonal variants. Conclusion Transmission of MTBC is well controlled in Cantabria. The majority of TB patients were born in Spain. The population structure of MTBC in Cantabria has a low diversity of major clonal lineages with the Euro-American lineage predominating. PMID:27315243

  20. 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

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

    PubMed

    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

    2015-09-01

    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

  2. Incidence of and Risk Factors for Tuberculosis (TB) in Gastric Cancer Patients in an Area Endemic for TB: A Nationwide Population-based Matched Cohort Study.

    PubMed

    Fang, Wen-Liang; Hung, Yi-Ping; Liu, Chia-Jen; Lan, Yuan-Tzu; Huang, Kuo-Hung; Chen, Ming-Huang; Lo, Su-Shun; Shyr, Yi-Ming; Wu, Chew-Wun; Yang, Muh-Hwa; Chen, Tzeng-Ji; Chao, Yee

    2015-11-01

    To date, there have been few reports investigating the relationship between tuberculosis (TB) and gastric cancer.We conducted a nationwide population-based matched cohort study using data retrieved from Taiwan's National Health Insurance Research Database to determine the incidence of and risk factors for TB in patients diagnosed with gastric cancer. From 2000 to 2011, we identified 36,972 gastric cancer patients and normal subjects from the general population matched for age, sex, and comorbidities at a 1:1 ratio. The data were analyzed using Cox proportional hazards models.Compared with the matched cohort, gastric cancer patients exhibited a higher risk for TB (adjusted hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.65-3.05, P < 0.001), and those with TB exhibited higher mortality (adjusted HR 1.59, 95% CI 1.41-1.79, P < 0.001). Old age (adjusted HR 2.40, 95% CI 1.92-2.99, P < 0.001), male sex (adjusted HR 2.13, 95% CI 1.76-2.57, P < 0.001), diabetes mellitus (adjusted HR 1.28, 95% CI 1.05-1.56, P = 0.013), and chronic obstructive pulmonary disease (COPD) (adjusted HR 1.44, 95% CI 1.19-1.75, P < 0.001) were identified as independent risk factors for TB in gastric cancer patients. Dyslipidemia was an independent protective factor for both TB (adjusted HR 2.13, 95% CI 1.73-2.62, P < 0.001) and mortality (adjusted HR 1.11, 95% CI 1.08-1.15, P < 0.001) in gastric cancer patients.Old age, male sex, diabetes mellitus, and COPD were independent risk factors for TB in gastric cancer. High-risk gastric cancer patients, especially those in TB-endemic areas, should be regularly screened for TB.

  3. Latent and Active Tuberculosis: Evaluation of Injecting Drug Users

    PubMed Central

    Mamani, Mojgan; Majzoobi, Mohammad Mahdi; Torabian, Saadat; Mihan, Ronak; Alizadeh, Kamyab

    2013-01-01

    Background There is a high risk of tuberculosis (TB) infection among injecting drug users (IDUs). Objectives This study aimed to determine the frequency of latent and active TB infection among IDUs. Materials and Methods In a cross-sectional study between 2008 and 2009, IDUs referred to the methadone maintenance treatment (MMT) centers in Hamedan-Iran, undergone tuberculin skin test (PPD; purified protein derivative) were recruited. The participants with positive results for PPD test (> 5 mm and > 10 mm in HIV positive and negative cases), undergone other complementary procedures such as chest-X-ray and sputum smear test. Results Overall, 268 IDUs between 18 and 70 (mean: 34.5 [8.2]) years were included in the study. PPD test had positive findings in 49 cases (18.3%). There was no significant difference of PPD positivity between HIV positive and negative participants (17.7% vs. 18.5%). An active TB was found among IDUs. Conclusions The high prevalence of latent and active TB among IDUs indicates the need for TB screening tests among this population. PMID:24616784

  4. Active Tuberculosis Case Finding Interventions Among Immigrants, Refugees and Asylum Seekers in Italy

    PubMed Central

    Schepisi, Monica Sañé; Gualano, Gina; Piselli, Pierluca; Mazza, Marta; D’Angelo, Donatella; Fasciani, Francesca; Barbieri, Alberto; Rocca, Giorgia; Gnolfo, Filippo; Olivani, Piefranco; Ferrarese, Maurizio; Codecasa, Luigi Ruffo; Palmieri, Fabrizio; Girardi, Enrico

    2016-01-01

    In Italy tuberculosis (TB) is largely concentrated in vulnerable groups such as migrants and in urban settings. We analyzed three TB case finding interventions conducted at primary centers and mobile clinics for regular/irregular immigrants and refugees/asylum seekers performed over a four-year period (November 2009-March 2014) at five different sites in Rome and one site in Milan, Italy. TB history and presence of symptoms suggestive of active TB were investigated by verbal screening through a structured questionnaire in migrants presenting for any medical condition to out-patient and mobile clinics. Individuals reporting TB history or symptoms were referred to a TB clinic for diagnostic workup. Among 6347 migrants enrolled, 891 (14.0%) reported TB history or symptoms suggestive of active TB and 546 (61.3%) were referred to the TB clinic. Of them, 254 (46.5%) did not present for diagnostic evaluation. TB was diagnosed in 11 individuals representing 0.17% of those screened and 3.76% of those evaluated. The overall yield of this intervention was in the range reported for other TB screening programs for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. PMID:27403270

  5. Active Tuberculosis Case Finding Interventions Among Immigrants, Refugees and Asylum Seekers in Italy.

    PubMed

    Schepisi, Monica Sañé; Gualano, Gina; Piselli, Pierluca; Mazza, Marta; D'Angelo, Donatella; Fasciani, Francesca; Barbieri, Alberto; Rocca, Giorgia; Gnolfo, Filippo; Olivani, Piefranco; Ferrarese, Maurizio; Codecasa, Luigi Ruffo; Palmieri, Fabrizio; Girardi, Enrico

    2016-06-24

    In Italy tuberculosis (TB) is largely concentrated in vulnerable groups such as migrants and in urban settings. We analyzed three TB case finding interventions conducted at primary centers and mobile clinics for regular/irregular immigrants and refugees/asylum seekers performed over a four-year period (November 2009-March 2014) at five different sites in Rome and one site in Milan, Italy. TB history and presence of symptoms suggestive of active TB were investigated by verbal screening through a structured questionnaire in migrants presenting for any medical condition to out-patient and mobile clinics. Individuals reporting TB history or symptoms were referred to a TB clinic for diagnostic workup. Among 6347 migrants enrolled, 891 (14.0%) reported TB history or symptoms suggestive of active TB and 546 (61.3%) were referred to the TB clinic. Of them, 254 (46.5%) did not present for diagnostic evaluation. TB was diagnosed in 11 individuals representing 0.17% of those screened and 3.76% of those evaluated. The overall yield of this intervention was in the range reported for other TB screening programs for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. PMID:27403270

  6. Quantitative evaluation of T-cell response after specific antigen stimulation in active and latent tuberculosis infection in adults and children.

    PubMed

    Latorre, Irene; De Souza-Galvão, Malú; Ruiz-Manzano, Juan; Lacoma, Alicia; Prat, Cristina; Fuenzalida, Loreto; Altet, Neus; Ausina, Vicente; Domínguez, Jose

    2009-11-01

    We have evaluated the quantitative T-cell response after specific Mycobacterium tuberculosis antigen stimulation in active tuberculosis (TB) and latent TB infection (LTBI) patients. In adults, the median number of T cells after RD1 antigen stimulation was significantly higher in active TB patients than in LTBI patients. In children, the number of responder T cells against the specific antigens was higher in active TB than in LTBI patients, although the differences were not significant. In summary, in patients with suspected clinical TB, although there is overlapping in the number of responder T cells between both groups, a T-cell count above the described threshold could suggest active TB, especially in patients with a high probability of having active TB and low probability of having LTBI. In addition, the results are consistent with the current evidence that T-cell response may indicate mycobacterial burden and disease activity.

  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. Tuberculosis

    MedlinePlus

    ... to address TB and HIV coinfection around the world? The President’s U.S. President's Emergency Plan for AIDS ... of those suffering from HIV/AIDS around the world. PEPFAR’s Global Fund to Fight AIDS, Tuberculosis and ...

  9. Use of Anti-Retroviral Therapy in Tuberculosis Patients on Second-Line Anti-TB Regimens: A Systematic Review

    PubMed Central

    Arentz, Matthew; Pavlinac, Patricia; Kimerling, Michael E.; Horne, David J.; Falzon, Dennis; Schünemann, Holger J.; Royce, Sarah; Dheda, Keertan; Walson, Judd L.

    2012-01-01

    Introduction Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB. Methods We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events. Results Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6–7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3–0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm3 and less than 50 cells/mm3, and when correcting for drug resistance pattern. Limitations We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias. Discussion While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB. PMID:23144818

  10. [The present and future prospects in rapid molecular diagnosis of tuberculosis and MDR-TB (First Part)].

    PubMed

    Tănăsescu, Mihaela; Didilescu, Cristian; Marica, Constantin

    2013-01-01

    Tuberculosis is still one of the diseases with a major medical and social impact, and in terms of early diagnosis (which would imply a fair treatment and established at the time), difficulties related to the delay bacilli isolation in culture, decreased susceptibility testing methods to antituberculosis drugs, lack of methods for differentiation of M. Tuberculosis complex germs of non TB Mycobacteria, may have important clinical implications. Traditional testing of anti-TB drug susceptibility on solid Löwenstein-Jensen medium (gold standard) or liquid media can only be performed using grown samples. Determining the time it takes up to 42 days on solid media and 12 days for liquid media. For MDR/XDR TB cases is absolutely essential to reduce the detection time. In these cases prove their usefulness rapid diagnostic methods. Automatic testing in liquid medium, molecular hybridization methods are currently recommended by the current WHO guidelines. Rapid diagnosis of MDR-TB is extremely useful for the early establishment of an effective treatment tailored more accurately on the spectrum of sensitivity of the resistant strain (thus reducing the risk of developing additional resistance to other drugs) and control the spread of these strains. Genetic diagnostic methods, approved and recommended by the WHO, can reduce the time of diagnosis of TB case and, importantly, the case of MDR TB. They do not replace the current standard diagnostic methods and resistance profile, but complete them in selected cases. PMID:24273995

  11. [The present and future prospects in rapid molecular diagnosis of tuberculosis and MDR-TB (First Part)].

    PubMed

    Tănăsescu, Mihaela; Didilescu, Cristian; Marica, Constantin

    2013-01-01

    Tuberculosis is still one of the diseases with a major medical and social impact, and in terms of early diagnosis (which would imply a fair treatment and established at the time), difficulties related to the delay bacilli isolation in culture, decreased susceptibility testing methods to antituberculosis drugs, lack of methods for differentiation of M. Tuberculosis complex germs of non TB Mycobacteria, may have important clinical implications. Traditional testing of anti-TB drug susceptibility on solid Löwenstein-Jensen medium (gold standard) or liquid media can only be performed using grown samples. Determining the time it takes up to 42 days on solid media and 12 days for liquid media. For MDR/XDR TB cases is absolutely essential to reduce the detection time. In these cases prove their usefulness rapid diagnostic methods. Automatic testing in liquid medium, molecular hybridization methods are currently recommended by the current WHO guidelines. Rapid diagnosis of MDR-TB is extremely useful for the early establishment of an effective treatment tailored more accurately on the spectrum of sensitivity of the resistant strain (thus reducing the risk of developing additional resistance to other drugs) and control the spread of these strains. Genetic diagnostic methods, approved and recommended by the WHO, can reduce the time of diagnosis of TB case and, importantly, the case of MDR TB. They do not replace the current standard diagnostic methods and resistance profile, but complete them in selected cases.

  12. 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

  13. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa.

    PubMed

    Lebina, Limakatso; Fuller, Nigel; Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Abraham, Pattamukkil; Variava, Ebrahim; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62-3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52-2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield. PMID:27493800

  14. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa

    PubMed Central

    Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62–3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52–2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield. PMID:27493800

  15. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa.

    PubMed

    Lebina, Limakatso; Fuller, Nigel; Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Abraham, Pattamukkil; Variava, Ebrahim; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62-3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52-2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield.

  16. Listening to Those at the Frontline: Patient and Healthcare Personnel Perspectives on Tuberculosis Treatment Barriers and Facilitators in High TB Burden Regions of Argentina.

    PubMed

    Iribarren, Sarah J; Rubinstein, Fernando; Discacciati, Vilda; Pearce, Patricia F

    2014-01-01

    Purpose. In Argentina, tuberculosis (TB) control measures have not achieved key treatment targets. The purpose of this study was to identify modes of treatment delivery and explore patient and healthcare personnel perceptions of barriers and facilitators to treatment success. Methods. We used semistructured group and individual interviews for this descriptive qualitative study. Eight high burden municipalities were purposively selected. Patients in treatment for active TB (n = 16), multidisciplinary TB team members (n = 26), and TB program directors (n = 12) at local, municipal, regional, and national levels were interviewed. Interviews were recorded, transcribed verbatim, and analyzed using thematic analysis. Results. Modes of treatment delivery varied across municipalities and types of healthcare facility and were highly negotiated with patients. Self-administration of treatment was common in hospital-based and some community clinics. Barriers to TB treatment success were concentrated at the system level. This level relied heavily on individual personal commitment, and many system facilitators were operating in isolation or in limited settings. Conclusions. We outline experiences and perspectives of the facilitating and challenging factors at the individual, structural, social, and organizational levels. Establishing strong patient-healthcare personnel relationships, responding to patient needs, capitalizing on community resources, and maximizing established decentralized system could mitigate some of the barriers.

  17. Co-infection of long-standing extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) and non-tuberculosis mycobacteria: A case report.

    PubMed

    Izadi, Nafiseh; Derakhshan, Mohammad; Samiei, Amin; Ghazvini, Kiarash

    2015-01-01

    We report a 69-years-old Iranian HIV negative male patient, with long-standing pulmonary tuberculosis (eleven years) co-infected with non-tuberculosis mycobacteria. Despite of initiation of first line anti-tuberculosis therapy after diagnosis the patient poorly respond because of low compliance with anti-TB treatment. After several incomplete treatments the smear was still positive and thus drug susceptibility tests were performed on isolated organism which revealed that the organisms was resistant not only against isoniazid and rifampin but also against Ofloxacin (OFX), Capreomycin (CAP), p-aminosalicylic acid (PAS), ethionamide (ETH), Kanamycin (KAN), ciprofloxacin (Cip), amikacin (AMK) and cycloserine (CYC). Persistence and resistance of infection had led us to do more investigation using molecular methods, which revealed co-infection with Non-tuberculosis mycobacteria (NTM). The patient is still alive with cough and shortness of breath. PMID:26236585

  18. Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis

    PubMed Central

    Khan, Nooruddin; Alam, Kaiser; Nair, Shiny; Valluri, Vijaya Lakshmi; Murthy, Kolluri J. R.; Mukhopadhyay, Sangita

    2008-01-01

    Accurate diagnosis of tuberculosis (TB) infection is critical for the treatment, prevention, and control of TB. Conventional diagnostic tests based on purified protein derivative (PPD) do not achieve the required diagnostic sensitivity. Therefore, in this study, we have evaluated the immunogenic properties of Rv1168c, a member of the PPE family, in comparison with PPD, which is routinely used in the tuberculin test, and Hsp60 and ESAT-6, well-known immunodominant antigens of Mycobacterium tuberculosis. In a conventional enzyme immunoassay, the recombinant Rv1168c protein displayed stronger immunoreactivity against the sera obtained from patients with clinically active TB than did PPD, Hsp60, or ESAT-6 and could distinguish TB patients from Mycobacterium bovis BCG-vaccinated controls. Interestingly, Rv1168c antigen permits diagnosis of smear-negative pulmonary TB as well as extrapulmonary TB cases, which are often difficult to diagnose by conventional tests. The immunodominant nature of Rv1168c makes it a promising candidate to use in serodiagnosis of TB. In addition, our studies also show that Rv1168c is a potent T-cell antigen which elicits a strong gamma interferon response in sensitized peripheral blood mononuclear cells obtained from TB patients. PMID:18400969

  19. A reduction in anti-tuberculosis drug resistance after the implementation of the national "STOP TB" program in central Taiwan, 2003-2007.

    PubMed

    Huang, Wei-Chang; Chen, Chao-Hsien; Huang, Chen-Cheng; Wu, Kun-Ming; Chiou, Chien-Shun; Lin, Chen-Fu; Chen, Jiann-Hwa; Shen, Gwan-Han

    2013-01-01

    The aim of this study was to determine the performance of the national "STOP TB" program in central Taiwan during 2003-2007 by examining trends in the combined drug resistance to first-line anti-tuberculosis (TB) drugs among clinical Mycobacterium tuberculosis isolates. Using 4,819 clinical M. tuberculosis isolates obtained from two mycobacteriology referral laboratories, the resistance to drugs was measured and analyzed along with the treatment outcomes in notified TB patients. The proportion of isolates showing total resistance and multidrug-resistant tuberculosis (MDR-TB) isolates were 17.7% and 3.67%, respectively. More number of MDR-TB isolates showed high-level resistance to isoniazid (84.18%) and streptomycin (SM) (30.51%); low-level resistance to ethambutol (EMB) (61.58%), SM (41.81%), and pyrazinamide (66.1%); and resistance to ofloxacin (30.4%). However, fewer isolates showed high-level resistance to EMB (19.77%), levofloxacin (17.9%), moxifloxacin (19.6%), kanamycin (8.9%), amikacin (8.9%), and capreomycin (8.9%). Of these MDR-TB isolates, 7.1% were extensively drug-resistant. Trends in combined drug resistance to all the first-line anti-TB drugs and the incidence of MDR-TB were stable during the 2 years (2003-2004) before the implementation of the national "STOP TB" program. After the "STOP TB" program, there were significant declines in the incidence of MDR-TB during 2005-2007 in central Taiwan as well as improved TB-treatment outcomes. Thus, the national "STOP TB" program had a significant positive impact on TB control in central Taiwan.

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

    PubMed Central

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

    2014-01-01

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

  1. 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

  2. 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

  3. 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.

  4. Discriminating Active Tuberculosis from Latent Tuberculosis Infection by flow cytometric measurement of CD161-expressing T cells

    PubMed Central

    Yang, Qianting; Xu, Qian; Chen, Qi; Li, Jin; Zhang, Mingxia; Cai, Yi; Liu, Haiying; Zhou, Yiping; Deng, Guofang; Deng, Qunyi; Zhou, Boping; Kornfeld, Hardy; Chen, Xinchun

    2015-01-01

    Interferon-gamma Release Assays (IGRAs) significantly increases the possibility for early diagnosis of tuberculosis, but IGRAs alone cannot discriminate active TB from LTBI. Therefore, fast and reliable discrimination of active tuberculosis, especially bacteriology negative tuberculosis, from LTBI is a great necessity. Here we established an assay based on flow cytometric multiparameter assay assessing expression of CD161 along with CD3, CD4, and CD8, whereby a set of indices formulated by the percentages of CD3+CD161+, CD3+CD4+CD161+ and CD3+CD8+CD161+ T cells multiplied with lymphocyte/monocyte ratio were established. Application of the CD3+CD8+CD161+ index to compare a cohort of active tuberculosis with a cohort of LTBI or health control yielded 0.7662 (95% confidence interval [CI] 0.6559–0.8552) or 0.7922 (95%  CI 0.6846–0.8763) for sensitivity and 0.9048 (95%  CI 0.8209–0.9580) or 0.8939 (95% CI 0.8392–0.9349) for specificity when the TB cohort was AFB+; the corresponding results were 0.7481 (95%  CI 0.6648–0.8198) or 0.7557 (95%  CI 0.6730–0.8265) for sensitivity and 0.8571 (95%  CI 0.7637–0.9239) or 0.8603 (95%  CI 0.8008–0.9075) for specificity when the TB cohort was AFB−. Our results reveal that in combination with IGRAs, CD161-based indices provide a novel, fast diagnostic solution addressing the limitation of current tuberculosis diagnostics. PMID:26643453

  5. Discriminating Active Tuberculosis from Latent Tuberculosis Infection by flow cytometric measurement of CD161-expressing T cells.

    PubMed

    Yang, Qianting; Xu, Qian; Chen, Qi; Li, Jin; Zhang, Mingxia; Cai, Yi; Liu, Haiying; Zhou, Yiping; Deng, Guofang; Deng, Qunyi; Zhou, Boping; Kornfeld, Hardy; Chen, Xinchun

    2015-12-08

    Interferon-gamma Release Assays (IGRAs) significantly increases the possibility for early diagnosis of tuberculosis, but IGRAs alone cannot discriminate active TB from LTBI. Therefore, fast and reliable discrimination of active tuberculosis, especially bacteriology negative tuberculosis, from LTBI is a great necessity. Here we established an assay based on flow cytometric multiparameter assay assessing expression of CD161 along with CD3, CD4, and CD8, whereby a set of indices formulated by the percentages of CD3(+)CD161(+), CD3(+)CD4(+)CD161(+) and CD3(+)CD8(+)CD161(+) T cells multiplied with lymphocyte/monocyte ratio were established. Application of the CD3(+)CD8(+)CD161(+) index to compare a cohort of active tuberculosis with a cohort of LTBI or health control yielded 0.7662 (95% confidence interval [CI] 0.6559-0.8552) or 0.7922 (95% CI 0.6846-0.8763) for sensitivity and 0.9048 (95% CI 0.8209-0.9580) or 0.8939 (95% CI 0.8392-0.9349) for specificity when the TB cohort was AFB(+); the corresponding results were 0.7481 (95% CI 0.6648-0.8198) or 0.7557 (95% CI 0.6730-0.8265) for sensitivity and 0.8571 (95% CI 0.7637-0.9239) or 0.8603 (95% CI 0.8008-0.9075) for specificity when the TB cohort was AFB(-). Our results reveal that in combination with IGRAs, CD161-based indices provide a novel, fast diagnostic solution addressing the limitation of current tuberculosis diagnostics.

  6. Understanding the gender aspects of tuberculosis: a narrative analysis of the lived experiences of women with TB in slums of Delhi, India.

    PubMed

    Khan, Koushambhi Basu

    2012-01-01

    There have been few ethnographic studies on gender aspects of tuberculosis (TB). In this article, drawing on a qualitative study on TB in Delhi slums and through an intersectional analysis of group interviews and personal narratives of women living with TB, I bring forth the "genderization" of TB and the associated sufferings for women. With my findings I demonstrate how gender, in conjunction with other social forces, influences the disease outcomes and stigmatizes women, how lives in slums are uniquely organized by multiple discourses that contribute to the gender makings of TB, and, finally, how women strategize to reduce their burden of illness.

  7. From HIV to tuberculosis and back again: a tale of activism in 2 pandemics.

    PubMed

    Harrington, Mark

    2010-05-15

    Tuberculosis (TB) and human immunodeficiency virus (HIV) infections are the deadliest chronic infections globally. Although each is deadly alone, they are deadlier together, with TB causing one-quarter of AIDS-related deaths and HIV infecting at least 15% of patients with TB worldwide. Historically, the 2 diseases were treated through specific, vertical programs. Strong activism and massive scientific investment have boosted the global response to AIDS, whereas TB has suffered from weak advocacy and anemic research funding. However, since 2004, there has been increasing collaboration and convergence between programs to control the 2 diseases, driven by the recognition that program cooperation leads to synergistic gains in strengthening responses to the 2 diseases and to health systems in general. Progress to date is incomplete, however, and countries must rededicate themselves to scaling up prevention and treatment programs for TB and HIV infection toward universal access, while pursuing accelerated research efforts to develop effective vaccines, better treatments, and cures for both diseases.

  8. 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. PMID:26980495

  9. Adverse Events in Healthy Individuals and MDR-TB Contacts Treated with Anti-Tuberculosis Drugs Potentially Effective for Preventing Development of MDR-TB: A Systematic Review

    PubMed Central

    Langendam, Miranda W.; Tiemersma, Edine W.; van der Werf, Marieke J.; Sandgren, Andreas

    2013-01-01

    A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58–100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption. PMID:23326464

  10. Hepatitis C Virus Infection Is Associated With an Increased Risk of Active Tuberculosis Disease

    PubMed Central

    Wu, Ping-Hsun; Lin, Yi-Ting; Hsieh, Kun-Pin; Chuang, Hung-Yi; Sheu, Chau-Chyun

    2015-01-01

    Abstract Tuberculosis (TB) and hepatitis C virus (HCV) infection contribute to major disease mortality and morbidity worldwide. However, the causal link between HCV infection and TB risk remains unclear. We conducted a population-based cohort study to elucidate the association between HCV infection and TB disease by analyzing Taiwan National Health Insurance Database. We enrolled 5454 persons with HCV infection and 54,274 age- and sex-matched non-HCV-infected persons between January 1998 and December 2007. Time-dependent Cox proportional hazards regression analysis was used to measure the association between HCV infection and active TB disease. Incidence rate of active TB disease was higher among HCV infection than in control (134.1 vs 89.1 per 100,000 person-years; incidence rate ratio 1.51; P = 0.014). HCV infection was significantly associated with active TB disease in multivariate Cox regression (adjusted hazard ratio [HR] 3.20; 95% confidence interval [CI], 1.85–5.53; P < 0.001) and competing death risk event analysis (adjusted HR 2.11; 95% CI, 1.39–3.20; P < 0.001). Multivariate stratified analysis further revealed that HCV infection was a risk of active TB disease in most strata. This nationwide cohort study suggests that HCV infection is associated with a higher risk of developing active TB disease. PMID:26287416

  11. On the spread and control of MDR-TB epidemics: an examination of trends in anti-tuberculosis drug resistance surveillance data

    PubMed Central

    Cohen, Ted; Jenkins, Helen E.; Lu, Chunling; McLaughlin, Megan; Floyd, Katherine; Zignol, Matteo

    2015-01-01

    SUMMARY Background Multidrug resistant tuberculosis (MDR-TB) poses serious challenges for tuberculosis control in many settings, but trends of MDR-TB have been difficult to measure. Methods We analyzed surveillance and population-representative survey data collected worldwide by the World Health Organization between 1993 and 2012. We examined setting-specific patterns associated with linear trends in the estimated per capita rate of MDR-TB among new notified TB cases to generate hypotheses about factors associated with trends in the transmission of highly drug resistant tuberculosis. Results 59 countries and 39 sub-national settings had at least three years of data, but less than 10% of the population in the WHO-designated 27-high MDR-TB burden settings were in areas with sufficient data to track trends. Among settings in which the majority of MDR-TB was autochthonous, we found 10 settings with statistically significant linear trends in per capita rates of MDR-TB among new notified TB cases. Five of these settings had declining trends (Estonia, Latvia, Macao, Hong Kong, and Portugal) ranging from decreases of 3-14% annually, while five had increasing trends (four individual oblasts of the Russian Federation and Botswana) ranging from 14-20% annually. In unadjusted analysis, better surveillance indicators and higher GDP per capita were associated with declining MDR-TB, while a higher existing absolute burden of MDR-TB was associated with an increasing trend. Conclusions Only a small fraction of countries in which the burden of MDR-TB is concentrated currently have sufficient surveillance data to estimate trends in drug-resistant TB. Where trend analysis was possible, smaller absolute burdens of MDR-TB and more robust surveillance systems were associated with declining per capita rates of MDR-TB among new notified cases. PMID:25458783

  12. ESAT-6 (EsxA) and TB10.4 (EsxH) based vaccines for pre- and post-exposure tuberculosis vaccination.

    PubMed

    Hoang, Truc; Aagaard, Claus; Dietrich, Jes; Cassidy, Joseph P; Dolganov, Gregory; Schoolnik, Gary K; Lundberg, Carina Vingsbo; Agger, Else Marie; Andersen, Peter

    2013-01-01

    The ESX systems from Mycobacterium tuberculosis are responsible for the secretion of highly immunogenic proteins of key importance for bacterial survival and growth. The two prototypic proteins, ESAT-6 (EsxA from ESX-1) and TB10.4 (EsxH from ESX-3) share a lot of characteristics regarding genome organization, size, antigenic properties, and vaccine potential but the two molecules clearly have very different roles in bacterial physiology. To further investigate the role of ESAT-6 and TB10.4 as preventive and post-exposure tuberculosis vaccines, we evaluated four different fusion-protein vaccines; H1, H4, H56 and H28, that differ only in these two components. We found that all of these vaccines give rise to protection in a conventional prophylactic vaccination model. In contrast, only the ESAT-6-containing vaccines resulted in significant protection against reactivation, when administered post-exposure. This difference in post-exposure activity did not correlate with a difference in gene expression during infection or a differential magnitude or quality of the vaccine-specific CD4 T cells induced by ESAT-6 versus TB10.4-containing vaccines. The post-exposure effect of the ESAT-6 based vaccines was found to be influenced by the infectious load at the time-point of vaccination and was abolished in chronically infected animals with high bacterial loads at the onset of vaccination. Our data demonstrate that there are specific requirements for the immune system to target an already established tuberculosis infection and that ESAT-6 has a unique potential in post-exposure vaccination strategies.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27695679

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

    PubMed Central

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

    2016-01-01

    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.

  15. Disseminated tuberculosis

    MedlinePlus

    Tuberculosis (TB) infection can develop after breathing in droplets sprayed into the air from a cough or sneeze by ... bacterium. The resulting lung infection is called primary TB. The usual site of TB is the lungs ( ...

  16. Yield of intensified tuberculosis case-finding activities using Xpert® MTB/RIF among risk groups in Nepal

    PubMed Central

    Baral, S.; Shrestha, P.; Puri, M.; Kandel, S.; Lamichanne, B.; Elsey, H.; Brouwer, M.; Goel, S.; Chinnakali, P.

    2016-01-01

    Setting: Twenty-two districts of Nepal, where intensified case-finding (ICF) activities for tuberculosis (TB) were implemented among risk groups under the TB REACH initiative in collaboration with the National TB Programme from July 2013 to November 2015. Objectives: To assess the yield of TB screening using an algorithm with smear microscopy followed by Xpert® MTB/RIF. Design: A descriptive study using routinely collected data. Results: Of 145 679 individuals screened, 28 574 (19.6%) had presumptive TB; 1239 (4.3%) of these were diagnosed with TB and 1195 (96%) were initiated on anti-tuberculosis treatment. The yield of screening was highest among people living with the human immunodeficiency virus (PLHIV) (6.1%), followed by household contacts (3.5%) and urban slum dwellers (0.5%). Among other risk groups, such as prisoners, factory workers, refugees and individuals with diabetes, the yield was less than 0.5%. The number needed to screen to diagnose an active TB case was 17 for PLHIV, 29 for household contacts and 197 for urban slum dwellers. Of 11 525 patients from ICF and the routine programme, 112 (1%) were diagnosed with multidrug-resistant TB. Conclusion: There was a substantial yield of TB cases among risk groups such as PLHIV and household contacts. Although the yield in urban slum dwellers was found to be moderate, some intervention should nonetheless be targeted because of the large population and poor access to care in this group. PMID:27358808

  17. Putting Tuberculosis (TB) To Rest: Transformation of the Sleep Aid, Ambien, and “Anagrams” Generated Potent Antituberculosis Agents

    PubMed Central

    2015-01-01

    Zolpidem (Ambien, 1) is an imidazo[1,2-a]pyridine-3-acetamide and an approved drug for the treatment of insomnia. As medicinal chemists enamored by how structure imparts biological function, we found it to have strikingly similar structure to the antitubercular imidazo[1,2-a]pyridine-3-carboxyamides. Zolpidem was found to have antituberculosis activity (MIC of 10–50 μM) when screened against replicating Mycobacterium tuberculosis (Mtb) H37Rv. Manipulation of the Zolpidem structure, notably, to structural isomers (“anagrams”), attains remarkably improved potency (5, MIC of 0.004 μM) and impressive potency against clinically relevant drug-sensitive, multi- and extensively drug-resistant Mtb strains (MIC < 0.03 μM). Zolpidem anagrams and analogues were synthesized and evaluated for their antitubercular potency, toxicity, and spectrum of activity against nontubercular mycobacteria and Gram-positive and Gram-negative bacteria. These efforts toward the rational design of isomeric anagrams of a well-known sleep aid underscore the possibility that further optimization of the imidazo[1,2-a]pyridine core may well “put TB to rest”. PMID:25984566

  18. Intra- and Extracellular Activities of Trimethoprim-Sulfamethoxazole against Susceptible and Multidrug-Resistant Mycobacterium tuberculosis

    PubMed Central

    Schön, T.; Simonsson, U. S. H.; Bruchfeld, J.; Larsson, M.; Juréen, P.; Sturegård, E.; Giske, C. G.; Ängeby, K.

    2014-01-01

    We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC0–24/MIC) using ≥25 as a potential target, the cumulative fraction response was ≥90% at doses of ≥2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB. PMID:25246405

  19. Relationship between education and training activities and tuberculosis case detection in Fiji, 2008-2011.

    PubMed

    Delai, M Y; Gounder, S; Tayler-Smith, K; Van den Bergh, R; Harries, A D

    2012-12-21

    Due to concerns about under-reporting of the tuberculosis (TB) case burden in Fiji, efforts have been put into national training, education and awareness activities in the formal health sector and among village health workers, health volunteers and the community since 2010. There has been an absolute increase in TB registrations, and TB case notification rates during the period of training activities in 2010 (21.3 per 100 000 population) and 2011 (23.6/100 000) were significantly increased compared with TB case notification rates in 2008 (12.4/100 000) and 2009 (14.6/100 000), when no training activities took place (P < 0.01). These findings support the use of ongoing training efforts.

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

    PubMed Central

    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

    2016-01-01

    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

  1. 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

  2. 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

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

    PubMed Central

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

    2015-01-01

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

  4. Infectious Diseases (ID) Learning Unit: How Rapidly to Evaluate for Active Tuberculosis Disease in Low-Prevalence Settings

    PubMed Central

    Chida, Natasha; Shah, Maunank

    2016-01-01

    With declining tuberculosis (TB) incidence in low-prevalence settings, many clinicians are likely unaware that the approach to diagnosing active TB is evolving with newer technologies. Rapid molecular assays are commercially available, and more are likely to enter the market in the coming years. These tests, such as the Xpert MTB/RIF, which can detect TB and drug-resistance in 2 hours, are increasingly used in settings with higher TB prevalence; however, uptake has been slower in low-prevalence settings. Newer algorithms incorporating rapid TB diagnostics have the ability to alter current clinical and infection control practice patterns. In this learning unit, we review current and newly available tests for the detection of active TB disease and their usage in low-prevalence settings. PMID:27186583

  5. [Tuberculosis].

    PubMed

    Iinuma, Y

    2000-11-01

    The incidence of tuberculosis in Japan is the highest among developed countries, with approximately 42,000 new cases reported in 1997, marking the first increase in 38 years. The growing incidence among the elderly and group infections among young adults may be responsible for this increase. Infection with tubercle bacilli(TB) occurs via airborne transmission, which involves dissemination of either airborne droplet nuclei on evaporated droplets that may remain suspended in the air for long periods of time. Microorganisms carried in this manner can be dispersed widely by air currents, therefore, special air handling and ventilation are required to prevent airborne transmission. Patients with infectious TB must be placed in a single room with negative pressure and a ventilation rate of 6 or more air changes per hour. Health care workers must wear an N95 mask when entering the room, and if an incident involving possible TB infection occurs in the hospital, the concerned people should be examined for Tuberculin reaction. Two to 12 weeks after the TB infection has occurred, the tuberculin reaction converts to positive. However, most Japanese people have been vaccinated with BCG, so assessment of the results is difficult. A comparison of the diameter of erythema before and after the potential infection may be the most confirmatory. If latent TB infection is suspected, preventive therapy with isoniazid must be considered. Special biohazard systems in the clinical laboratory and autopsy room have also been proposed to prevent TB dispersal. DOTS(Directly Observed Treatment, Short-course) is useful to prevent the emergence of multi-drug-resistant TB. In some areas of Japan that have low levels of compliance with TB therapy, trials of DOTS have been started. PMID:11132556

  6. Activity against multidrug-resistant Mycobacterium tuberculosis in Mexican plants used to treat respiratory diseases.

    PubMed

    Jimenez-Arellanes, Adelina; Meckes, Mariana; Ramirez, Raquel; Torres, Javier; Luna-Herrera, Julieta

    2003-09-01

    The increase of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) demands the search for alternative antimycobacterial drugs. The aim of this study was to evaluate plants used in Mexican traditional medicine to treat respiratory diseases for activity against MDR-TB. A group of 22 plants was screened for activity against Mycobacterium tuberculosis H37Rv and Mycobacterium avium at concentrations from 50 to 200 microg/mL. The antimycobacterial effect was determined by a microcolorimetric assay with Alamar blue dye. None of the aqueous extracts had antimycobacterial activity. Hexane extracts from Artemisia ludoviciana, Chamaedora tepejilote, Lantana hispida, Juniperus communis and Malva parviflora, and methanol extracts from Artemisia ludoviciana and Juniperus communis inhibited the growth of Mycobacterium tuberculosis. Mycobacterium avium was inhibited by Juniperus communis hexane extract and by Malva parviflora methanol extract. The active extracts were tested against monoresistant variants of Mycobacterium tuberculosis H37Rv (isoniazid, rifampin, streptomycin and ethambutol resistant) and the hexane extract of Lantana hispida showed the best activity. Lantana hispida hexane extract was also active against a group of MDR-TB clinical isolates. In contrast, it did not inhibit the growth of non-tuberculous mycobacteria. The hexane extract of Lantana hispida was fractionated by column chromatography and one of its fractions (FVI) inhibited the growth of all the MDR-TB clinical isolates at concentrations up to 25 microg/mL. This study supports the fact that selecting plants by ethnobotanical criteria enhances the probability of finding species with activity against mycobacteria, and our results point to Lantana hispida as an important source of potential compounds against MDR-TB.

  7. Pulmonary tuberculosis: clinical features and patient management.

    PubMed

    Gough, Andrea; Kaufman, Gerri

    Pulmonary tuberculosis (TB) is a common infectious disease and a major cause of illness and death throughout the world, particularly in developing countries. This article explores the difference between latent TB infection and active TB disease, and discusses the pharmacological management of TB and issues around adherence to medication. Although TB is usually managed by specialist teams it is essential that all practitioners have an understanding of the signs and symptoms of the disease to ensure early referral and accurate diagnosis. PMID:21888103

  8. Global Tuberculosis Report 2015

    MedlinePlus

    ... Feed Youtube Twitter Facebook Google + iTunes Play Store Tuberculosis (TB) Menu Tuberculosis The End TB Strategy Areas ... data News, events and features About us Global tuberculosis report 2015 This is the twentieth global report ...

  9. 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.

  10. TGS-TB: Total Genotyping Solution for Mycobacterium tuberculosis Using Short-Read Whole-Genome Sequencing.

    PubMed

    Sekizuka, Tsuyoshi; Yamashita, Akifumi; Murase, Yoshiro; Iwamoto, Tomotada; Mitarai, Satoshi; Kato, Seiya; Kuroda, Makoto

    2015-01-01

    Whole-genome sequencing (WGS) with next-generation DNA sequencing (NGS) is an increasingly accessible and affordable method for genotyping hundreds of Mycobacterium tuberculosis (Mtb) isolates, leading to more effective epidemiological studies involving single nucleotide variations (SNVs) in core genomic sequences based on molecular evolution. We developed an all-in-one web-based tool for genotyping Mtb, referred to as the Total Genotyping Solution for TB (TGS-TB), to facilitate multiple genotyping platforms using NGS for spoligotyping and the detection of phylogenies with core genomic SNVs, IS6110 insertion sites, and 43 customized loci for variable number tandem repeat (VNTR) through a user-friendly, simple click interface. This methodology is implemented with a KvarQ script to predict MTBC lineages/sublineages and potential antimicrobial resistance. Seven Mtb isolates (JP01 to JP07) in this study showing the same VNTR profile were accurately discriminated through median-joining network analysis using SNVs unique to those isolates. An additional IS6110 insertion was detected in one of those isolates as supportive genetic information in addition to core genomic SNVs. The results of in silico analyses using TGS-TB are consistent with those obtained using conventional molecular genotyping methods, suggesting that NGS short reads could provide multiple genotypes to discriminate multiple strains of Mtb, although longer NGS reads (≥ 300-mer) will be required for full genotyping on the TGS-TB web site. Most available short reads (~100-mer) can be utilized to discriminate the isolates based on the core genome phylogeny. TGS-TB provides a more accurate and discriminative strain typing for clinical and epidemiological investigations; NGS strain typing offers a total genotyping solution for Mtb outbreak and surveillance. TGS-TB web site: https://gph.niid.go.jp/tgs-tb/. PMID:26565975

  11. TGS-TB: Total Genotyping Solution for Mycobacterium tuberculosis Using Short-Read Whole-Genome Sequencing.

    PubMed

    Sekizuka, Tsuyoshi; Yamashita, Akifumi; Murase, Yoshiro; Iwamoto, Tomotada; Mitarai, Satoshi; Kato, Seiya; Kuroda, Makoto

    2015-01-01

    Whole-genome sequencing (WGS) with next-generation DNA sequencing (NGS) is an increasingly accessible and affordable method for genotyping hundreds of Mycobacterium tuberculosis (Mtb) isolates, leading to more effective epidemiological studies involving single nucleotide variations (SNVs) in core genomic sequences based on molecular evolution. We developed an all-in-one web-based tool for genotyping Mtb, referred to as the Total Genotyping Solution for TB (TGS-TB), to facilitate multiple genotyping platforms using NGS for spoligotyping and the detection of phylogenies with core genomic SNVs, IS6110 insertion sites, and 43 customized loci for variable number tandem repeat (VNTR) through a user-friendly, simple click interface. This methodology is implemented with a KvarQ script to predict MTBC lineages/sublineages and potential antimicrobial resistance. Seven Mtb isolates (JP01 to JP07) in this study showing the same VNTR profile were accurately discriminated through median-joining network analysis using SNVs unique to those isolates. An additional IS6110 insertion was detected in one of those isolates as supportive genetic information in addition to core genomic SNVs. The results of in silico analyses using TGS-TB are consistent with those obtained using conventional molecular genotyping methods, suggesting that NGS short reads could provide multiple genotypes to discriminate multiple strains of Mtb, although longer NGS reads (≥ 300-mer) will be required for full genotyping on the TGS-TB web site. Most available short reads (~100-mer) can be utilized to discriminate the isolates based on the core genome phylogeny. TGS-TB provides a more accurate and discriminative strain typing for clinical and epidemiological investigations; NGS strain typing offers a total genotyping solution for Mtb outbreak and surveillance. TGS-TB web site: https://gph.niid.go.jp/tgs-tb/.

  12. Novel pyridazino[4,3-b]indoles with dual inhibitory activity against Mycobacterium tuberculosis and monoamine oxidase.

    PubMed

    Velezheva, Valeriya S; Brennan, Patrick J; Marshakov, Vladimir Yu; Gusev, Dmitrij V; Lisichkina, Inessa N; Peregudov, Alexander S; Tchernousova, Larisa N; Smirnova, Tatiana G; Andreevskaya, Sofia N; Medvedev, Alexei E

    2004-06-17

    Tuberculosis is one of the most common infectious diseases known to man. About 37% of the world's population (about 1.86 billion people) are infected with Mycobacterium tuberculosis. According to the World Health Organization, every year approximately 8 million people develop active tuberculosis and almost 2 million of those die from the disease. The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing. The present drug regimen for treating tuberculosis has been in existence for 30 years. New drugs that will shorten total treatment duration, improve the treatment of MDR-TB, and address latent tuberculosis are the most urgent need of tuberculosis control programs. A new series of synthetic 3-amino-4-arylpyridazino[4,3-b]indoles (pyridazinoindoles) were identified as inhibitors of Mycobacterium tuberculosis. The design, synthesis, and antimycobacterial activity of these compounds are described. While the most active compounds are still not comparable to the front-line drugs rifampicin and isoniazid, they do show promise. Most of the pyridazinoindoles with appreciable antituberculosis activity also inhibit monoamine oxidase, suggestive of a novel inhibitory effect on mycobacterial redox reactions. PMID:15189042

  13. Comparison of QuantiFERON-TB gold in tube test versus tuberculin skin test for screening of latent tuberculosis infection in Saudi Arabia: A population-based study

    PubMed Central

    Balkhy, Hanan H.; El Beltagy, Kamel; El-Saed, Aiman; Aljasir, Badr; Althaqafi, Abdulhakeem; Alothman, Adel F.; Alshalaan, Mohammad; Al-Jahdali, Hamdan

    2016-01-01

    OBJECTIVES: To compare QuantiFERON-TB gold in tube (QFT-GIT) test with tuberculin skin test (TST) in detecting latent tuberculosis infection (LTBI) among a general population in Saudi Arabia. METHODS: A population-based cross-sectional study was conducted between July 2010 and March 2013 among individuals randomly selected from the list of those receiving care at primary healthcare centers in three provinces of Saudi Arabia; Central, Western, and Eastern provinces. Those younger than 5 years, immunocompromised, had a current or previous history of active TB, LTBI, or who were receiving anti-TB medications were excluded. Informed consent was obtained before the study questionnaire was completed. Participants were then evaluated for LTBI using QFT-GIT test followed immediately by TST. RESULTS: Of the 1369 subjects included in the final analysis, QFT-GIT was positive in 124 (9.1%) and TST was positive in 127 (9.3%). Positive concordance was observed in 49 (3.6%) subjects while negative concordance was observed in 1167 (85.2%) subjects. The overall agreement between the two tests was 88.8% with a significant kappa (κ) test (κ = 0.332, P < 0.001). Concordance was significantly higher in younger age, female gender, single status, students, primary education, living in middle-sized families, and never smoked. CONCLUSIONS: The overall agreement of TST and QFT-GIT for the detection of LTBI among a Saudi general population was 88.8%. QFT-GIT is probably comparable to TST for detecting LTBI in an intermediate TB burden country with high at birth bacille calmette guerin vaccination coverage. Further prospective studies are needed to compare the ability of both tests to predict TB disease. PMID:27512509

  14. 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.

  15. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB.

    PubMed

    Barr, David A; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R; Sloan, Derek J

    2016-05-01

    Faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates 'persister' phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli.

  16. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB

    PubMed Central

    Barr, David A.; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R.; Sloan, Derek J.

    2016-01-01

    Summary Faster elimination of drug tolerant ‘persister’ bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates ‘persister’ phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli. PMID:27156626

  17. 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.

  18. Strong Antibody Responses to Mycobacterium tuberculosis PE-PGRS62 Protein Are Associated with Latent and Active Tuberculosis▿

    PubMed Central

    Koh, Kah Wee; Soh, Shu E; Seah, Geok Teng

    2009-01-01

    Mycobacterium tuberculosis has a unique family of PE-PGRS proteins with conserved N-terminal domains (PE) containing site-specific proline-glutamine residues and polymorphic GC-rich repetitive sequences (PGRS). Tuberculosis (TB) patients produce antibodies against some such proteins, but it is not clear whether these responses correlate with disease. Clinical groups with different mycobacterium exposure were studied for their seroreactivity to PE-PGRS17 and PE-PGRS62 proteins and their respective PE domains. There were minimal antibody responses against both PE domains and full-length PE-PGRS17, even in patients with active TB. However, patients with active and latent TB showed significantly higher PE-PGRS62-specific immunoglobulin G antibody responses than treated TB patients and mycobacterium-reactive TB contacts without latent infection. Latently infected persons had high anti-PE-PGRS62 responses but low responses to the 38-kDa antigen commonly used for TB serology, while treated TB cases showed the opposite response. Thus, patterns of seroreactivity to PE-PGRS62 correlate with clinical status and are associated with latent TB infection. PMID:19487480

  19. Ofloxacin resistance in Mycobacterium tuberculosis is associated with efflux pump activity independent of resistance pattern and genotype.

    PubMed

    Sun, Zhaogang; Xu, Yuhui; Sun, Yong; Liu, Yi; Zhang, Xuxia; Huang, Hairong; Li, Chuanyou

    2014-12-01

    Drug-resistance to ofloxacin (OFX) in Mycobacterium tuberculosis is due to missense mutations in gyrA and other factors, such as alterations in the activity of drug efflux pumps. In this study, we identified 8 extensively drug resistant tuberculosis (XDR-TB), 40 multidrug resistant TB (MDR-TB), 38 polydrug resistant TB (PDR-TB), and 16 single OFX-resistant TB from 102 clinical isolates. We tested the effect of three efflux inhibitors, reserpine, verapamil, and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), on changes in the OFX minimum inhibitory concentration (MIC) using Resazurin microtitre assay. These three inhibitors changed the MICs from 2- to 32-fold, with CCCP having the strongest effect. A total of 55%, 74%, and 83% of the tested isolates had changes in MIC of more than two-fold by reserpine, verapamil, and CCCP, respectively. The inhibitors led to similar fold-changes of OFX MICs in the XDR, MDR, PDR, and single OFX-resistant isolates. For each inhibitor, a higher resistance to OFX was associated with the greater efflux pump activity. There were no significant differences in the effect of efflux pump inhibitors upon Beijing and non-Beijing M. tuberculosis genotypes. Taken together, these results indicate that the efflux pump activity was greater in the isolates higher resistant to OFX and had similar effects on isolates with different drug resistant pattern, and had similar effects on Beijing and non-Beijing genotypes.

  20. 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.

  1. Toward an Evidence-Based Nonclinical Road Map for Evaluating the Efficacy of New Tuberculosis (TB) Drug Regimens: Proceedings of a Critical Path to TB Drug Regimens-National Institute of Allergy and Infectious Diseases In Vivo Pharmacology Workshop for TB Drug Development

    PubMed Central

    Nuermberger, Eric; Sizemore, Christine; Romero, Klaus

    2016-01-01

    Novel tuberculosis (TB) drug regimens are urgently needed, and their development will be enabled by improved preclinical approaches that more effectively inform and ensure safe selection of clinical candidates and drug combination/regimens. An evidence-based approach for the assessment of nonclinical models supporting TB drug development has been proposed by a joint partnership between the National Institute of Allergy and Infectious Diseases (NIAID) and the Critical Path to TB Drug Regimens (CPTR) Consortium. PMID:26824941

  2. Evaluation of the MeltPro TB/STR assay for rapid detection of streptomycin resistance in Mycobacterium tuberculosis.

    PubMed

    Zhang, Ting; Hu, Siyu; Li, Guoli; Li, Hui; Liu, Xiaoli; Niu, Jianjun; Wang, Feng; Wen, Huixin; Xu, Ye; Li, Qingge

    2015-03-01

    Rapid and comprehensive detection of drug-resistance is essential for the control of tuberculosis, which has facilitated the development of molecular assays for the detection of drug-resistant mutations in Mycobacterium tuberculosis. We hereby assessed the analytical and clinical performance of an assay for streptomycin-resistant mutations. MeltPro TB/STR is a closed-tube, dual-color, melting curve analysis-based, real-time PCR test designed to detect 15 streptomycin-resistant mutations in rpsL 43, rpsL 88, rrs 513, rrs 514, rrs 517, and rrs 905-908 of M. tuberculosis. Analytical studies showed that the accuracy was 100%, the limit of detection was 50-500 bacilli per reaction, the reproducibility in the form of Tm variation was within 1.0 °C, and we could detect 20% STR resistance in mixed bacterial samples. The cross-platform study demonstrated that the assay could be performed on six models of real-time PCR instruments. A multicenter clinical study was conducted using 1056 clinical isolates, which were collected from three geographically different healthcare units, including 709 STR-susceptible and 347 STR-resistant isolates characterized on Löwenstein-Jensen solid medium by traditional drug susceptibility testing. The results showed that the clinical sensitivity and specificity of the MeltPro TB/STR was 88.8% and 95.8%, respectively. Sequencing analysis confirmed the accuracy of the mutation types. Among all the 8 mutation types detected, rpsL K43R (AAG → AGG), rpsL K88R (AAG → AGG) and rrs 514 A → C accounted for more than 90%. We concluded that MeltPro TB/STR represents a rapid and reliable assay for the detection of STR resistance in clinical isolates.

  3. 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.

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

    PubMed Central

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

    2011-01-01

    While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998–2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The 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. PMID:21392424

  5. High and equitable tuberculosis awareness coverage in the community-driven Axshya TB control project in India.

    PubMed

    Thapa, B; Chadha, S S; Das, A; Mohanty, S; Tonsing, J

    2015-03-21

    Data from surveys on knowledge, attitudes and practice (KAP) on tuberculosis (TB) conducted under the Axshya project at two time points (baseline 2010-2011 and mid-line 2012-2013) were analysed for changes in coverage and equity of TB awareness after project interventions. Overall coverage increased from 84% at baseline to 88% at midline (5% increase, P < 0.05). In comparison to baseline results, coverage at the midline survey had significantly increased, from 81% to 87% among the rural population, from 81% to 86% among women, from 73% to 85% in the ⩾55 years age group, from 71% to 80% among illiterates and from 73% to 81% in the south zone (P < 0.05). The equity gap among the different study groups (settlement, sex, age, education and zones) decreased from 6-23% at baseline to 3-11% during the midline survey. The maximum decline was observed for type of settlement (rural vs. urban), from 10% to 3% (P < 0.05). This community-driven TB control project has achieved high and equitable coverage of TB awareness, offering valuable lessons for the global community. PMID:26400604

  6. Kinetic mechanism determination and analysis of metal requirement of dehydroquinate synthase from Mycobacterium tuberculosis H37Rv: an essential step in the function-based rational design of anti-TB drugs.

    PubMed

    de Mendonça, Jordana Dutra; Adachi, Osao; Rosado, Leonardo Astolfi; Ducati, Rodrigo Gay; Santos, Diogenes Santiago; Basso, Luiz Augusto

    2011-01-01

    The number of new cases of tuberculosis (TB) arising each year is increasing globally. Migration, socio-economic deprivation, HIV co-infection and the emergence of drug-resistant strains of Mycobacterium tuberculosis, the main causative agent of TB in humans, have all contributed to the increasing number of TB cases worldwide. Proteins that are essential to the pathogen survival and absent in the host, such as enzymes of the shikimate pathway, are attractive targets to the development of new anti-TB drugs. Here we describe the metal requirement and kinetic mechanism determination of M. tuberculosis dehydroquinate synthase (MtDHQS). True steady-state kinetic parameters determination and ligand binding data suggested that the MtDHQS-catalyzed chemical reaction follows a rapid-equilibrium random mechanism. Treatment with EDTA abolished completely the activity of MtDHQS, and addition of Co(2+) and Zn(2+) led to, respectively, full and partial recovery of the enzyme activity. Excess Zn(2+) inhibited the MtDHQS activity, and isotitration microcalorimetry data revealed two sequential binding sites, which is consistent with the existence of a secondary inhibitory site. We also report measurements of metal concentrations by inductively coupled plasma atomic emission spectrometry. The constants of the cyclic reduction and oxidation of NAD(+) and NADH, respectively, during the reaction of MtDHQS was monitored by a stopped-flow instrument, under single-turnover experimental conditions. These results provide a better understanding of the mode of action of MtDHQS that should be useful to guide the rational (function-based) design of inhibitors of this enzyme that can be further evaluated as anti-TB drugs.

  7. Sputum is a surrogate for bronchoalveolar lavage for monitoring Mycobacterium tuberculosis transcriptional profiles in TB patients.

    PubMed

    Garcia, Benjamin J; Loxton, Andre G; Dolganov, Gregory M; Van, Tran T; Davis, J Lucian; de Jong, Bouke C; Voskuil, Martin I; Leach, Sonia M; Schoolnik, Gary K; Walzl, Gerhard; Strong, Michael; Walter, Nicholas D

    2016-09-01

    Pathogen-targeted transcriptional profiling in human sputum may elucidate the physiologic state of Mycobacterium tuberculosis (M. tuberculosis) during infection and treatment. However, whether M. tuberculosis transcription in sputum recapitulates transcription in the lung is uncertain. We therefore compared M. tuberculosis transcription in human sputum and bronchoalveolar lavage (BAL) samples from 11 HIV-negative South African patients with pulmonary tuberculosis. We additionally compared these clinical samples with in vitro log phase aerobic growth and hypoxic non-replicating persistence (NRP-2). Of 2179 M. tuberculosis transcripts assayed in sputum and BAL via multiplex RT-PCR, 194 (8.9%) had a p-value <0.05, but none were significant after correction for multiple testing. Categorical enrichment analysis indicated that expression of the hypoxia-responsive DosR regulon was higher in BAL than in sputum. M. tuberculosis transcription in BAL and sputum was distinct from both aerobic growth and NRP-2, with a range of 396-1020 transcripts significantly differentially expressed after multiple testing correction. Collectively, our results indicate that M. tuberculosis transcription in sputum approximates M. tuberculosis transcription in the lung. Minor differences between M. tuberculosis transcription in BAL and sputum suggested lower oxygen concentrations or higher nitric oxide concentrations in BAL. M. tuberculosis-targeted transcriptional profiling of sputa may be a powerful tool for understanding M. tuberculosis pathogenesis and monitoring treatment responses in vivo.

  8. Sputum is a surrogate for bronchoalveolar lavage for monitoring Mycobacterium tuberculosis transcriptional profiles in TB patients.

    PubMed

    Garcia, Benjamin J; Loxton, Andre G; Dolganov, Gregory M; Van, Tran T; Davis, J Lucian; de Jong, Bouke C; Voskuil, Martin I; Leach, Sonia M; Schoolnik, Gary K; Walzl, Gerhard; Strong, Michael; Walter, Nicholas D

    2016-09-01

    Pathogen-targeted transcriptional profiling in human sputum may elucidate the physiologic state of Mycobacterium tuberculosis (M. tuberculosis) during infection and treatment. However, whether M. tuberculosis transcription in sputum recapitulates transcription in the lung is uncertain. We therefore compared M. tuberculosis transcription in human sputum and bronchoalveolar lavage (BAL) samples from 11 HIV-negative South African patients with pulmonary tuberculosis. We additionally compared these clinical samples with in vitro log phase aerobic growth and hypoxic non-replicating persistence (NRP-2). Of 2179 M. tuberculosis transcripts assayed in sputum and BAL via multiplex RT-PCR, 194 (8.9%) had a p-value <0.05, but none were significant after correction for multiple testing. Categorical enrichment analysis indicated that expression of the hypoxia-responsive DosR regulon was higher in BAL than in sputum. M. tuberculosis transcription in BAL and sputum was distinct from both aerobic growth and NRP-2, with a range of 396-1020 transcripts significantly differentially expressed after multiple testing correction. Collectively, our results indicate that M. tuberculosis transcription in sputum approximates M. tuberculosis transcription in the lung. Minor differences between M. tuberculosis transcription in BAL and sputum suggested lower oxygen concentrations or higher nitric oxide concentrations in BAL. M. tuberculosis-targeted transcriptional profiling of sputa may be a powerful tool for understanding M. tuberculosis pathogenesis and monitoring treatment responses in vivo. PMID:27553415

  9. Potential Role of M. tuberculosis Specific IFN-γ and IL-2 ELISPOT Assays in Discriminating Children with Active or Latent Tuberculosis

    PubMed Central

    Chiappini, Elena; Della Bella, Chiara; Bonsignori, Francesca; Sollai, Sara; Amedei, Amedeo; Galli, Luisa; Niccolai, Elena; Singh, Mahavir; D'Elios, Mario M.; de Martino, Maurizio

    2012-01-01

    Background Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI). Objective Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB. Methods Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens. Results Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs. Conclusion Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB. PMID:23029377

  10. 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

  11. 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

    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

  12. 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. PMID:27364701

  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. Predictive value of the tuberculin skin test and QuantiFERON-tuberculosis Gold In-Tube test for development of active tuberculosis in hemodialysis patients

    PubMed Central

    Seyhan, Ekrem Cengiz; Gunluoglu, Gulşah; Gunluoglu, Mehmet Zeki; Tural, Seda; Sökücü, Sinem

    2016-01-01

    BACKGROUND: Hemodialysis (HD) patients are at increased risk of reactivation of latent tuberculosis infection (LTBI) compared with the general population. QuantiFERON-TB Gold (QFT-G) for LTBI detection is more promising than tuberculin skin test (TST) in HD patients. AIM: In our study, we evaluated the value of the TST and QFT-G In-Tube (QFG-IT) test in the development of active tuberculosis (TB), in the HD patients, and in healthy controls. METHODS: The study enrolled 95 HD patients and ninety age-matched, healthy controls. The TST and QFG-IT were performed. All the subjects were followed up 5 years for active TB disease. RESULTS: Compared to the healthy controls, a high prevalence of LTBI was found in the HD patients by QFG-IT (41% vs. 25%). However, no significant difference was detected by TST (32% vs. 31%). Four HD patients and one healthy control progressed to active TB disease within the 5-year follow-up. For active TB discovered subjects, QFG-IT was positive in all, but TST was positive in two (one patient and one healthy control). In HD patients; sensitivity, specificity, positive and negative predictive values of QFG-IT, and TST for active TB was 100% and 25%, 62% and 67%, 10%, and 3%, and 100% and 95%, respectively. Receiver operating curve analysis revealed that the results are significantly different (P = 0.04). CONCLUSION: QFG-IT test is a more useful diagnostic method than TST for detecting those who will progress to active TB in HD patients. PMID:27168859

  15. The increased risk of active tuberculosis disease in patients with dermatomyositis – a nationwide retrospective cohort study

    PubMed Central

    Wu, Ping-Hsun; Lin, Yi-Ting; Yang, Yi-Hsin; Lin, Yu-Chih; Lin, Yi-Ching

    2015-01-01

    The risk of active tuberculosis (TB) in patients with dermatomyositis (DM) is poorly understood. The cohort study aimed to investigate the association between DM and the risk of active TB disease. We conducted a population based study on 4,958 patients with newly diagnosed DM and 19,832 matched controls according to age, sex, and index date between 1998 and 2008. The hazard ratios (HRs) and cumulative incidences of active TB disease between DM patients and controls were analyzed. During the study period, a total of 85 (1.7%) DM patients developed active TB disease, which was significantly higher than that of non-DM patients (0.64%). The incidence rate of active TB disease was higher among DM patients than controls (incidence rate ratio 2.95; 95% confidence interval [CI], 2.24 to 3.88). The Cox regression model demonstrated significantly higher active TB disease rate among DM patients compared with controls (adjusted HR, 2.64; 95% CI, 1.97 to 3.54; p < 0.001) after adjusting for age, sex, and underlying medical disorders. The most significant risk factors for developing active TB included male sex, diabetes mellitus comorbidity, and use of corticosteroids and azathioprine in DM patients. In conclusion, DM patients are at a greater risk for active TB disease. PMID:26573418

  16. The association between sterilizing activity and drug distribution into tuberculosis lesions.

    PubMed

    Prideaux, Brendan; Via, Laura E; Zimmerman, Matthew D; Eum, Seokyong; Sarathy, Jansy; O'Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, Tae Sun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N; Barry, Clifton E; Dartois, Véronique

    2015-10-01

    Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside. In contrast, moxifloxacin, which is active in vitro against a subpopulation of Mycobacterium tuberculosis that persists in specific niches under drug pressure and has achieved treatment shortening in mice, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug-resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration may contribute to treatment outcome has wide implications for TB. PMID:26343800

  17. Highly active antiretroviral therapy and tuberculosis control in Africa: synergies and potential.

    PubMed Central

    Harries, Anthony D.; Hargreaves, Nicola J.; Chimzizi, Rehab; Salaniponi, Felix M.

    2002-01-01

    HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and TB (tuberculosis) are two of the world's major pandemics, the brunt of which falls on sub-Saharan Africa. Efforts aimed at controlling HIV/AIDS have largely focused on prevention, little attention having been paid to care. Work on TB control has concentrated on case detection and treatment. HIV infection has complicated the control of tuberculosis. There is unlikely to be a decline in the number of cases of TB unless additional strategies are developed to control both this disease and HIV simultaneously. Such strategies would include active case-finding in situations where TB transmission is high, the provision of a package of care for HIV-related illness, and the application of highly active antiretroviral therapy. The latter is likely to have the greatest impact, but for this therapy to become more accessible in Africa the drugs would have to be made available through international support and a programme structure would have to be developed for its administration. It could be delivered by means of a structure based on the five-point strategy called DOTS, which has been adopted for TB control. However, it may be unrealistic to give TB control programmes the responsibility for running such a programme. A better approach might be to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy complementing the preventive work already being undertaken by AIDS control programmes. TB programmes could contribute towards the development and implementation of this strategy. PMID:12132003

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

    PubMed Central

    Eisenhut, Michael; Hargreaves, Dougal S.; Scott, Anne; Housley, David; Walters, Andrew; Mulla, Rohinton

    2016-01-01

    Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p < 0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p < 0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection. PMID:27433370

  19. The impact of IFN-γ receptor on SLPI expression in active tuberculosis: association with disease severity.

    PubMed

    Tateosian, Nancy L; Pasquinelli, Virginia; Hernández Del Pino, Rodrigo E; Ambrosi, Nella; Guerrieri, Diego; Pedraza-Sánchez, Sigifredo; Santucci, Natalia; D'Attilio, Luciano; Pellegrini, Joaquín; Araujo-Solis, María A; Musella, Rosa M; Palmero, Domingo J; Hernandez-Pando, Rogelio; Garcia, Verónica E; Chuluyan, H Eduardo

    2014-05-01

    Interferon (IFN)-γ displays a critical role in tuberculosis (TB), modulating the innate and adaptive immune responses. Previously, we reported that secretory leukocyte protease inhibitor (SLPI) is a pattern recognition receptor with anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb). Herein, we determined whether IFN-γ modulated the levels of SLPI in TB patients. Plasma levels of SLPI and IFN-γ were studied in healthy donors (HDs) and TB patients. Peripheral blood mononuclear cells from HDs and patients with TB or defective IFN-γ receptor 1* were stimulated with Mtb antigen and SLPI, and IFN-γR expression levels were measured. Both SLPI and IFN-γ were significantly enhanced in plasma from those with TB compared with HDs. A direct association between SLPI levels and the severity of TB was detected. In addition, Mtb antigen stimulation decreased the SLPI produced by peripheral blood mononuclear cells from HDs, but not from TB or IFN-γR patients. Neutralization of IFN-γ reversed the inhibition of SLPI induced by Mtb antigen in HDs, but not in TB patients. Furthermore, recombinant IFN-γ was unable to modify the expression of SLPI in TB patients. Finally, IFN-γR expression was lower in TB compared with HD peripheral blood mononuclear cells. These results show that Mtb-induced IFN-γ down-modulated SLPI levels by signaling through the IFN-γR in HDs. This inhibitory mechanism was not observed in TB, probably because of the low expression of IFN-γR detected in these individuals.

  20. Untreated Active Tuberculosis in Pregnancy with Intraocular Dissemination: A Case Report and Review of the Literature

    PubMed Central

    LoBue, Stephen; Adams, Daniel; Oladipo, Yewande; Posso, Ramses; Mapp, Tiffany; Santiago, Crystal; Jain, Manisha; Marino, William D.; Henderson, Cassandra E.

    2015-01-01

    Background. Tuberculosis (TB) is a disease that affects hundreds of millions of people across the world. However, the incidence in developed countries has decreased over the past decades causing physicians to become unfamiliar with its unspecific symptoms. Pregnant individuals are especially difficult because many symptoms of active TB can mimic normal physiological changes of pregnancy. We present a case report of a 26-year-old multiparous woman, G4P3003, at 38-week gestation with a history of positive PPD who emigrated from Ghana 6 years ago. She came to the hospital with an initial complaint of suprapubic pain, pressure, and possible leakage of amniotic fluid for the past week. Patient also complained of a productive cough for the past 3 to 4 months with a decrease in vision occurring with the start of pregnancy. Visual acuity was worse than 20/200 in both eyes. Definitive diagnosis of active TB was delayed due to patient refusal of chest X-ray. Fortunately, delay in diagnosis was minimized since patient delivered within 24 hours of admission. Active TB was confirmed with intraocular dissemination. Patient had optic atrophy OS (left eye) and papillitis, choroiditis, and uveitis OD (right eye) due to TB infiltration. Fetus was asymptomatic and anti-TB therapy was started for both patients. PMID:26693374

  1. Seasonal Variations in Notification of Active Tuberculosis Cases in China, 2005–2012

    PubMed Central

    Li, Xin-Xu; Wang, Li-Xia; Zhang, Hui; Du, Xin; Jiang, Shi-Wen; Shen, Tao; Zhang, Yan-Ping; Zeng, Guang

    2013-01-01

    Background Although seasonal variation in tuberculosis (TB) incidence has been described in many countries, it remains unknown in China. Methods A time series decomposition analysis (X-12-ARIMA) was performed to examine the seasonal variation in active TB cases nationwide from 2005 through 2012 in China. Seasonal amplitude was calculated for the evaluation of TB seasonal variation. Results A total of 7.78 million active TB cases were reported over a period of 8 years. A spring peak (April) was observed with seasonal amplitude of 46.3%, compared with the winter trough (February). Most cases in provinces with subtropical and tropical monsoon climate showed lower amplitudes than those in temperate continental, plateau and mountain climate regions. The magnitude of seasonality varied inversely with annual average temperature, r (95% CI) = -0.71 (-0.79, -0.61). The seasonal amplitudes were 56.7, 60.5, 40.6, 46.4 and 50.9% for patients aged ≤14, 15–24, 25–44, 45–64, and ≥65 years, respectively. Students demonstrated greater seasonal amplitude than peasants, migrant workers and workers (115.3% vs. 43.5, 41.6 and 48.1%). Patients with pulmonary TB had lower amplitude compared to patients with pleural and other extra-pulmonary TB (EPTB) (45.9% vs. 52.0 and 56.3%). Relapse cases with sputum smear positive TB (SS+ TB) had significantly higher seasonal amplitude compared to new cases with sputum smear positive TB (52.2% vs. 41.6%). Conclusions TB is a seasonal disease in China. The peak and trough of TB transmission actually are in winter and in autumn respectively after factors of delay are removed. Higher amplitudes of TB seasonality are more likely to happen in temperate continental, plateau and mountain climate regions and regions with lower annual average temperature, and young person, students, patients with EPTB and relapse cases with SS+ TB are more likely to be affected by TB seasonality. PMID:23874512

  2. Tuberculosis Treatment Non-Adherence and Lost to Follow Up among TB Patients with or without HIV in Developing Countries: A Systematic Review.

    PubMed

    Tola, Habteyes Hailu; Tol, Azar; Shojaeizadeh, Davoud; Garmaroudi, Gholamreza

    2015-01-01

    This systematic review intended to combine factors associated with tuberculosis treatment non-adherence and lost to follow up among TB patients with/without HIV in developing countries. Comprehensive remote electronic databases (MEDLINE, (PMC, Pub Med Central), Google scholar and Web of science) search was conducted using the following keywords: Tuberculosis, treatment, compliance, adherence, default, behavioural factors and socioeconomic factors. All types of studies intended to assess TB treatment non-adherence and lost to follow up in developing countries among adult TB patient from 2008 to data extraction date were included. Twenty-six original and one-reviewed articles, which meet inclusion criteria, were reviewed. TB treatment non-adherence and lost to follow up were continued across developing countries. The main factors associated with TB treatment non-adherence and lost to follow up were socioeconomic factors: lack of transportation cost, lack of social support, and patients-health care worker poor communication. Behavioural factors were Feeling better after few weeks of treatments, tobacco and alcohol use, knowledge deficit about duration of treatment and consequences of non-adherence and lost to follow up. TB treatment non-adherence and lost to follow up were continued across developing countries throughout the publication years of reviewed articles. Numerous, socioeconomic and behavioural factors were influencing TB treatment adherence and lost to follow up. Therefore, well understanding and minimizing of the effect of these associated factors is very important to enhance treatment adherence and follow up completion in developing countries.

  3. Evaluation of Interleukin17and Interleukin 23 expression in patients with active and latent tuberculosis infection

    PubMed Central

    Heidarnezhad, Fatemeh; Asnaashari, Amir; Rezaee, Seyed Abdolrahim; Ghezelsofla, Roghayeh; Ghazvini, Kiarash; Valizadeh, Narges; Basiri, Reza; Ziaeemehr, Aghigh; Sobhani, Somayeh; Rafatpanah, Houshang

    2016-01-01

    Objective(s): Tuberculosis is one of the most important infectious diseases with high mortality rates worldwide, especially in developing countries. Interleukin17 (IL-17) is an important acquired immunity cytokine, which is mainly produced by CD4+TH17 cells. It can recruit neutrophils and macrophages to the infected site in the lungs. IL-23 is one of the most important inducers of IL-17. In the present study, the expressions of IL-23 and IL-17 were examined in the pathogenesis of tuberculosis. Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from subjects with latent tuberculosis infection (LTB) and newly diagnosed active tuberculosis patients (ATB). PBMCs were activated with purified protein derivative (PPD) for 72 hr. Activated cells were harvested, RNA was extracted, and cDNA was synthesized. IL-17 and IL-23 mRNA expressions were evaluated by real-time PCR. The frequency of Th17 cells was examined by flowcytometry. Results: The expressions of IL-17 and IL-23 mRNA were lower in patients than subjects with LTB (P<0.05). The frequency of IL-17 producing CD4+ T cells in patients with active TB was lower than LTB subjects (P<0.05). Conclusion: The results of the present study might suggest that IL-17 and IL-23 play critical roles in the immune response against TB. PMID:27746865

  4. 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…

  5. Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

    PubMed Central

    Périssé, André R. S.; Smeaton, Laura; Chen, Yun; La Rosa, Alberto; Walawander, Ann; Nair, Apsara; Grinsztejn, Beatriz; Santos, Breno; Kanyama, Cecilia; Hakim, James; Nyirenda, Mulinda; Kumarasamy, Nagalingeswaran; Lalloo, Umesh G.; Flanigan, Timothy; Campbell, Thomas B.; Hughes, Michael D.

    2013-01-01

    Background Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study. Methods Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results 31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death. Conclusions Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients. PMID:24391801

  6. An urgent need for building technical capacity for rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB) among new cases: A case report from Maharashtra, India.

    PubMed

    Atre, Sachin

    2015-01-01

    Multidrug-resistant tuberculosis (MDR-TB), the prevalence of which has increased across the globe in recent years, is a serious threat to public health. Timely diagnosis of MDR-TB, especially among new TB cases, is essential to facilitate appropriate treatment, which can prevent further emergence of drug resistance and its spread in the population. The present case report from India aims to address some operational challenges in diagnosing MDR-TB among new cases and potential measures to overcome them. It argues that even after seven years of implementing the DOTS-Plus program for controlling MDR-TB, India still lacks the technical capacity for rapid MDR-TB diagnosis. The case report underscores an urgent need to explore the use of WHO-endorsed techniques such as Xpert MTB/Rif and commercial assays such as Genotype MTBDR for rapid diagnosis of MDR-TB among new cases. Suitable applications may be found for other TB high-burden countries where MDR-TB is a major concern.

  7. Perceptions of HIV, AIDS and tuberculosis among patients on antiretroviral therapy in Bulawayo, Zimbabwe: implications for the provision of HIV and TB care services.

    PubMed

    Rödlach, Alexander; Dlodlo, Riitta A; Hwalima, Zanele E

    2012-06-01

    The objectives of the research were to explore perceptions of HIV, AIDS and tuberculosis (TB) among individuals enrolled in antiretroviral therapy (ART) at two municipal clinics in Bulawayo, Zimbabwe, and to assess the implications of these perceptions on the provision of HIV and TB care services. Data were collected using the freelist technique to elicit the elements of a cultural domain as well as open-ended interviews with ART clients, conducted during June and July 2009. Participants were recruited through non-probability convenience sampling. The freelist data were analysed using multidimensional scaling and hierarchical clustering, and the interview data were analysed using the grounded theory method. The results suggest that: 1) the participants had substantial knowledge about HIV, AIDS and TB; 2) the participants' perceptions of HIV, AIDS and TB constituted three distinct, though overlapping, cultural domains; 3) because of the availability of ART and TB treatment, a diagnosis of HIV infection or TB alone was generally perceived with hope that one would be able to live a normal life, while AIDS illness or TB/HIV coinfection were associated with notions of death and despair; and, 4) such perceptions may negatively impact the uptake of testing for HIV and TB, and thereby contribute to delayed start of the respective treatment. Health messages should build on these meanings which have the potential to either enhance or compromise available health programmes and their use by people living with HIV or TB.

  8. Schistosoma mansoni, nematode infections, and progression to active tuberculosis among HIV-1-infected Ugandans.

    PubMed

    Brown, Michael; Miiro, George; Nkurunziza, Peter; Watera, Christine; Quigley, Maria A; Dunne, David W; Whitworth, James A G; Elliott, Alison M

    2006-05-01

    Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66-2.10) or Mansonella perstans (RR, 0.42; CI, 0.13-1.34). A weak association between Schistosoma mansoni infection and TB was found (RR, 1.42; CI, 0.86-2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00-5.33). This analysis suggests an effect of S. mansoni infection on progression to active TB among HIV-1-infected Ugandans. PMID:16687687

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

    PubMed Central

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

    2016-01-01

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

  10. Specificity of the Tuberculin Skin Test and the T-SPOT."TB" Assay among Students in a Low-Tuberculosis Incidence Setting

    ERIC Educational Resources Information Center

    Talbot, Elizabeth A.; Harland, Dawn; Wieland-Alter, Wendy; Burrer, Sherry; Adams, Lisa V.

    2012-01-01

    Objective: Interferon-[gamma] release assays (IGRAs) are an important tool for detecting latent "Mycobacterium tuberculosis" infection (LTBI). Insufficient data exist about IGRA specificity in college health centers, most of which screen students for LTBI using the tuberculin skin test (TST). Participants: Students at a low-TB incidence college…

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

    PubMed

    Advani, Meeta J; Siddiqui, Imran; Sharma, Pawan; Reddy, Hemalatha

    2012-01-01

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

  12. Cytokine Profiles for Peripheral Blood Lymphocytes from Patients with Active Pulmonary Tuberculosis and Healthy Household Contacts in Response to the 30-Kilodalton Antigen of Mycobacterium tuberculosis

    PubMed Central

    Torres, Martha; Herrera, Teresa; Villareal, Hector; Rich, Elizabeth A.; Sada, Eduardo

    1998-01-01

    Patients with active tuberculosis (TB) have a stronger humoral but a poorer cellular immune response to the secreted 30-kDa antigen (Ag) of Mycobacterium tuberculosis than do healthy household contacts (HHC), who presumably are more protected against disease. The basis for this observation was studied by examining the Th1 (interleukin 2 [IL-2] and gamma interferon [IFN-γ])- and Th2 (IL-10 and IL-4)-type cytokines produced in response to the 30-kDa Ag by peripheral blood mononuclear cells (PBMC) from patients with active pulmonary TB (n = 7) and from HHC who were tuberculin (purified protein derivative) skin test positive (n = 12). Thirty-kilodalton-Ag-stimulated PBMC from TB patients produced significantly lower levels of IFN-γ (none detectable) than did those from HHC (212 ± 73 pg/ml, mean ± standard error) (P < 0.001). Likewise, 30-kDa-Ag-stimulated PBMC from TB patients failed to express IFN-γ mRNA by reverse transcription-PCR, whereas cells from HHC expressed the IFN-γ gene. In contrast, 30-kDa-Ag-stimulated PBMC from TB patients produced significantly higher levels of IL-10 (403 ± 80 pg/ml) than did those from HHC (187 ± 66 pg/ml) (P < 0.013), although cells from both groups expressed the IL-10 gene. IL-2 and IL-4 were not consistently produced, and their genes were not expressed by 30-kDa-Ag-stimulated cells from either TB patients or HHC. After treatment with antituberculous drugs, lymphocytes from four of the seven TB patients proliferated and three of them expressed IFN-γ mRNA in response to the 30-kDa Ag and produced decreased levels of IL-10. PMID:9423855

  13. Differences between TB cases infected with M. africanum, West-African type 2, relative to Euro-American M. tuberculosis- an update

    PubMed Central

    de Jong, Bouke C; Adetifa, Ifedayo; Walther, Brigitte; Hill, Philip C; Antonio, Martin; Ota, Martin; Adegbola, Richard A

    2009-01-01

    M. africanum is a common cause of human pulmonary TB in West Africa. We previously described phenotypic differences between M. africanum and M. tuberculosis among 290 patients. In the present analysis we compared 692 TB patients infected with the two most common lineages within the M. tuberculosis complex found in the Gambia, namely M. africanum West African type 2 (39% prevalence) and Euro American M. tuberculosis (55% prevalence). We identified additional phenotypic differences between infections with these two organisms. M. africanum patients were more likely to be of older age and HIV infected. In addition, they had worse disease on chest x-ray, despite complaining of cough for equal duration, and were more likely severely malnourished. In this cohort the prevalence of M. africanum did not change significantly over a seven year period. PMID:20002176

  14. 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

  15. Tuberculosis 2004: Challenges and Opportunities

    PubMed Central

    Glassroth, Jeffrey

    2005-01-01

    Tuberculosis (TB) continues as a major public health challenge worldwide. HIV-TB coinfection is especially concerning as it accelerates progression of infection to active disease and amplifies spread of TB including drug resistant disease. Application of molecular biology and insights from classic microbiology to TB control have resulted in important innovations in diagnosis and treatment. Radiometric assay and, particularly, PCR, with nucleic acid probing, have reduced the time to diagnosis. Moreover, the sensitivity of these techniques is potentially log orders of magnitude more sensitive. Molecular techniques can be adapted to drug susceptibility testing. The differential activity and post-antibiotic effect of various drugs against TB have led to highly effective briefer regimens and to directly observed therapy. Insights into basic host defense against TB and description of the M. tuberculosis genome have created optimism for developing new treatments and effective vaccines in the years to come. PMID:16555622

  16. Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States.

    PubMed

    Ghosh, Smita; Moonan, Patrick K; Cowan, Lauren; Grant, Juliana; Kammerer, Steve; Navin, Thomas R

    2012-06-01

    Molecular characterization of Mycobacterium tuberculosis complex isolates (genotyping) can be used by public health programs to more readily identify tuberculosis (TB) transmission. The Centers for Disease Control and Prevention's National Tuberculosis Genotyping Service has offered M. tuberculosis genotyping for every culture-confirmed case in the United States since 2004. The TB Genotyping Information Management System (TB GIMS), launched in March 2010, is a secure online database containing genotype results linked with case characteristics from the national TB registry for state and local TB programs to access, manage and analyze these data. As of September 2011, TB GIMS contains genotype results for 89% of all culture-positive TB cases for 2010. Over 400 users can generate local and national reports and maps using TB GIMS. Automated alerts on geospatially concentrated cases with matching genotypes that may represent outbreaks are also generated by TB GIMS. TB genotyping results are available to enhance national TB surveillance and apply genotyping results to conduct TB control activities in the United States. PMID:22044522

  17. Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States.

    PubMed

    Ghosh, Smita; Moonan, Patrick K; Cowan, Lauren; Grant, Juliana; Kammerer, Steve; Navin, Thomas R

    2012-06-01

    Molecular characterization of Mycobacterium tuberculosis complex isolates (genotyping) can be used by public health programs to more readily identify tuberculosis (TB) transmission. The Centers for Disease Control and Prevention's National Tuberculosis Genotyping Service has offered M. tuberculosis genotyping for every culture-confirmed case in the United States since 2004. The TB Genotyping Information Management System (TB GIMS), launched in March 2010, is a secure online database containing genotype results linked with case characteristics from the national TB registry for state and local TB programs to access, manage and analyze these data. As of September 2011, TB GIMS contains genotype results for 89% of all culture-positive TB cases for 2010. Over 400 users can generate local and national reports and maps using TB GIMS. Automated alerts on geospatially concentrated cases with matching genotypes that may represent outbreaks are also generated by TB GIMS. TB genotyping results are available to enhance national TB surveillance and apply genotyping results to conduct TB control activities in the United States.

  18. Socio-Demographic Predictors and Distribution of Pulmonary Tuberculosis (TB) in Xinjiang, China: A Spatial Analysis

    PubMed Central

    Wubuli, Atikaimu; Xue, Feng; Jiang, Daobin; Yao, Xuemei; Upur, Halmurat; Wushouer, Qimanguli

    2015-01-01

    Objectives Xinjiang is one of the high TB burden provinces of China. A spatial analysis was conducted using geographical information system (GIS) technology to improve the understanding of geographic variation of the pulmonary TB occurrence in Xinjiang, its predictors, and to search for targeted interventions. Methods Numbers of reported pulmonary TB cases were collected at county/district level from TB surveillance system database. Population data were extracted from Xinjiang Statistical Yearbook (2006~2014). Spatial autocorrelation (or dependency) was assessed using global Moran’s I statistic. Anselin’s local Moran’s I and local Getis-Ord statistics were used to detect local spatial clusters. Ordinary least squares (OLS) regression, spatial lag model (SLM) and geographically-weighted regression (GWR) models were used to explore the socio-demographic predictors of pulmonary TB incidence from global and local perspectives. SPSS17.0, ArcGIS10.2.2, and GeoDA software were used for data analysis. Results Incidence of sputum smear positive (SS+) TB and new SS+TB showed a declining trend from 2005 to 2013. Pulmonary TB incidence showed a declining trend from 2005 to 2010 and a rising trend since 2011 mainly caused by the rising trend of sputum smear negative (SS-) TB incidence (p<0.0001). Spatial autocorrelation analysis showed the presence of positive spatial autocorrelation for pulmonary TB incidence, SS+TB incidence and SS-TB incidence from 2005 to 2013 (P <0.0001). The Anselin’s Local Moran’s I identified the “hotspots” which were consistently located in the southwest regions composed of 20 to 28 districts, and the “coldspots” which were consistently located in the north central regions consisting of 21 to 27 districts. Analysis with the Getis-Ord Gi* statistic expanded the scope of “hotspots” and “coldspots” with different intensity; 30 county/districts clustered as “hotspots”, while 47 county/districts clustered as

  19. Equal sensitivity of the new generation QuantiFERON-TB Gold plus in direct comparison with the previous test version QuantiFERON-TB Gold IT.

    PubMed

    Hoffmann, H; Avsar, K; Göres, R; Mavi, S-C; Hofmann-Thiel, S

    2016-08-01

    QuantiFERON-TB Gold IT analyses interferon-γ release from CD4(+) T cells after stimulation with specific tuberculosis (TB) antigens. Its sensitivity is approximately 80% for active TB. A new test generation (QFTGplus) also analyses the response of CD8(+) T cells. We investigated both test generations in a direct head-to-head comparison in a German pulmonary hospital. Sensitivity rates for active TB were identical, no matter whether diagnosis was bacteriologically confirmed or not.

  20. Tim-3 pathway affects NK cell impairment in patients with active tuberculosis.

    PubMed

    Wang, Feng; Hou, Hongyan; Wu, Shiji; Tang, Qing; Huang, Min; Yin, Botao; Huang, Jing; Liu, Weiyong; Mao, Lie; Lu, Yanfang; Sun, Ziyong

    2015-12-01

    Active tuberculosis (TB) patients show impaired NK cell function, and the underlying mechanism remains largely unknown. In this study, we confirmed the decrease in activation, cytokine secretion, and degranulation potential of NK cells in active TB patients. We further investigated whether coinhibitory receptor Tim-3 was involved with impairment of NK cells. Our results revealed that the expression of Tim-3 on NK cells was increased in active TB patients. Tim-3 expression was inversely correlated with IL-12-stimualted IFN-γ production. Moreover, blocking the Tim-3 pathway restored IFN-γ secretion and degranulation of NK cells. Blocking this pathway also increased NK cell cytotoxicity against K562 target cells, and improved the ability of NK cells to control Mtb growth in monocyte-derived macrophages. The Tim-3 expression on NK cells was also observed to be significantly decreased in TB patients post-treatment. In this study, we have identified that Tim-3 is involved with NK cell impairment in TB patients.

  1. Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response

    PubMed Central

    Nam, Sung-Jin; Jeong, Jee-Yeong; Jang, Tae-Won; Jung, Mann-Hong; Chun, Bong-Kwon; Cha, Hee-Jae; Oak, Chul-Ho

    2016-01-01

    Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions. PMID:27271274

  2. Mycobacterium tuberculosis at the human/wildlife interface in a high TB burden country.

    PubMed

    Michel, A L; Hlokwe, T M; Espie, I W; van Zijll Langhout, M; Koeppel, K; Lane, E

    2013-11-01

    This study reports on an investigation of Mycobacterium tuberculosis cases in mostly captive wild animals using molecular typing tools [Variable Number of Tandem Repeat (VNTR) typing and Restriction Fragment Length Polymorphism typing]. The investigation included cases from (i) the National Zoological Gardens of South Africa (NZG) recorded between 2002 and 2011; (ii) Johannesburg Zoo, where tuberculosis was first diagnosed in 2007 and has since been detected in three antelope species; (iii) a rehabilitation centre for vervet monkeys (Chlorocebus pygerythrus) in which M. tuberculosis was diagnosed in 2008; and (iv) incidental cases in other facilities including a sable antelope (Hippotragus niger), two unrelated cases in chacma baboons (Papio ursinus) (one of which was from a free-ranging troop) and a colony of capuchin monkeys (Cebus capucinus). Identical genetic profiles of the latter three isolates indicate the persistence of a single M. tuberculosis strain in this population since at least 2006. Results of the outbreak investigation in the captive vervet monkey colony indicate that it was caused by two unrelated strains, while all 13 M. tuberculosis isolates from 11 animal species in the NZG showed different VNTR patterns. A substantial increase in tuberculosis cases of 60% was recorded in the NZG, compared with the previous reporting period 1991-2001, and may indicate a countrywide trend of increasing spillover of human tuberculosis to wild animals. South Africa ranks among the countries with the highest-tuberculosis burden worldwide, complicated by an increasing rate of multidrug-resistant strains. Exposure and infection of captive wildlife in this high prevalence setting is therefore a growing concern for wildlife conservation but also for human health through potential spillback.

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

    PubMed Central

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

    2016-01-01

    Objectives Data on the prevalence of tuberculosis (TB) in healthcare workers (HCW) in Oman and the Arabian Gulf is scarce. The aim of this study was to estimate the prevalence of latent tuberculosis (LTB) among HCW exposed to active TB in one of the tertiary care hospitals in Muscat. Methods Exposed HCW were screened for LTB from January to June 2012 using skin tuberculin and serum interferon tests. Candidates were followed-up for a total of nine months. Descriptive statistics were used to summarize the data. Results A total of 371 exposed HCW were involved in the study. The incidence of LTB in exposed HCW was 33.2% (n = 123). Almost 54% (66/123) of the HCW started treatment and only 42.4% (28/66) completed the full nine-month treatment course. Conclusions The high prevalence of LTBI in exposed HCW merits further evaluation of the screening and treatment programs in the country. Future countrywide studies are warranted to provide more precise statistics on the prevalence and management of this public health issue. PMID:27403243

  4. The association between the ratio of monocytes:lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life

    PubMed Central

    2014-01-01

    Background Recent transcriptomic studies revived a hypothesis suggested by historical studies in rabbits that the ratio of peripheral blood monocytes to lymphocytes (ML) is associated with risk of tuberculosis (TB) disease. Recent data confirmed the hypothesis in cattle and in adults infected with HIV. Methods We tested this hypothesis in 1,336 infants (540 HIV-infected, 796 HIV-exposed, uninfected (HEU)) prospectively followed in a randomized controlled trial of isoniazid prophylaxis in Southern Africa, the IMPAACT P1041 study. We modeled the relationship between ML ratio at enrollment (91 to 120 days after birth) and TB disease or death in HIV-infected children and latent Mycobacterium tuberculosis (MTB) infection, TB disease or death in HEU children within 96 weeks (with 12 week window) of randomization. Infants were followed-up prospectively and routinely assessed for MTB exposure and outcomes. Cox proportional hazards models allowing for non-linear associations were used; in all cases linear models were the most parsimonious. Results Increasing ML ratio at baseline was significantly associated with TB disease/death within two years (adjusted hazard ratio (HR) 1.17 per unit increase in ML ratio; 95% confidence interval (CI) 1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocyte counts alone were associated with TB disease. The association was not statistically dissimilar between HIV infected and HEU children. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It was strongest when restricted to probable and definite TB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore, per 0.1 unit increase in the ML ratio at three to four months of age, the hazard of probable or definite TB disease before two years was increased by roughly 4% (95% CI 1.7% to 6.6%). Conclusion Elevated ML ratio at three- to four-months old is associated with increased hazards of TB disease before two years among

  5. Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB).

    PubMed

    Kotila, Saara M; Payne Hallström, Lara; Jansen, Niesje; Helbling, Peter; Abubakar, Ibrahim

    2016-01-01

    As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment. PMID:26848520

  6. Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB).

    PubMed

    Kotila, Saara M; Payne Hallström, Lara; Jansen, Niesje; Helbling, Peter; Abubakar, Ibrahim

    2016-01-01

    As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment.

  7. 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 ...

  8. Increased Risk of Active Tuberculosis following Acute Kidney Injury: A Nationwide, Population-Based Study

    PubMed Central

    Chang, Chia-Hsui; Huang, Hui-Yu; Huang, Tao-Min; Lai, Chun-Fu; Lin, Meng-Chun; Ko, Wen-Je; Wu, Kwan-Dun; Yu, Chong-Jen; Shu, Chin-Chung; Lee, Chih-Hsin; Wang, Jann-Yuan

    2013-01-01

    Background Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited. Methods This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999–2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization. Results Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032). Conclusions AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB. PMID:23936044

  9. Gamma Interferon Assays Used in the Diagnosis of Tuberculosis

    PubMed Central

    2015-01-01

    Tuberculosis (TB) is an ancient disease that has infected humans for thousands of years. However, despite diagnostic tests that detect the disease and effective therapy, there are still millions of people worldwide who are infected with TB. The first TB test used to detect infected patients was a skin test that identifies individuals actively infected with TB. This test used a mix of proteins from culture filtrates of the bacteria Mycobacterium tuberculosis. Recently, two new diagnostic tests have been introduced; these two new tests can detect TB infection in patients by challenging peripheral blood cells with specific TB proteins. These assays measure the cellular immune response to these proteins. This minireview evaluates the new assays and compares them to the use of the TB skin test. The use of these new assays may have some advantages in detecting individuals with active tuberculosis. However, there is still a role for the use of the skin test, especially in young patients. PMID:26018533

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

    PubMed Central

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

    2015-01-01

    Detection of cyclic-di-adenosine monophosphate (c-di-AMP), a bacterial second messenger, by the host cytoplasmic surveillance pathway (CSP) is known to elicit Type I interferon responses critical for antimicrobial defense1–3. However, the mechanisms and role of c-di-AMP signaling in Mycobacterium tuberculosis virulence remain unclear. Here we show that resistance to tuberculosis (TB) requires CSP-mediated detection of c-di-AMP produced by M. tuberculosis and that levels of c-di-AMP modulate the fate of infection. We found that a di-adenylate cyclase (disA or dacA)4 over-expressing M. tuberculosis strain that secretes excess c-di-AMP activates the interferon regulatory factor (IRF) pathway with enhanced levels of IFN-β, elicits increased macrophage autophagy, and exhibits significant attenuation in mice. We show that c-di-AMP-mediated IFN-β induction during M. tuberculosis infection requires stimulator of interferon genes (STING)5-signaling. We observed that c-di-AMP induction of IFN-β is independent of the cytosolic nucleic acid receptor cyclic-GMP-AMP (cGAMP) synthase (cGAS)6–7, but cGAS nevertheless contributes substantially to the overall IFN-β response to M. tuberculosis infection. In sum, our results reveal c-di-AMP to be a key mycobacterial pathogen associated molecular pattern (PAMP) driving host Type I IFN responses and autophagy. These findings suggest that modulating the levels of this small molecule may lead to novel immunotherapeutic strategies against TB. PMID:25730264

  11. The Effect of Garcin® in Preventing AntiTB-Induced Hepatitis in Newly Diagnosed Tuberculosis Patients

    PubMed Central

    Tabarsi, Payam; Fahimi, Fanak; Heidarzadeh, Nader; Haghgoo, Roodabeh; Kazempour, Mehdi; Masjedi, Mohammadreza; Velayati, Ali Akbar

    2014-01-01

    Adverse effects of antituberculosis agents such as hepatotoxicity may reduce treatment effectiveness, because they significantly contribute to nonadherence and eventually result in treatment failure, relapse or the emergence of drug resistance. Garlic is an ancient herbal substance, which its effectiveness on isoniazid and rifampicin-induced hepatic injury in animal models has been demonstrated (1). In the present study a randomized, double blind, placebo-controlled, parallel group clinical trial was designed to assess the effect(s) of garlic tablets (1000 mg daily) administered for two weeks orally. Fifty eight newly diagnosed, smear positive pulmonary tuberculosis patients, with age ranges between 18-65 years old, were randomly allocated into two groups. Each patient received either garlic or placebo tablets for the first two weeks of tuberculosis treatment. Of total 58 patients, 31 received garlic tablets while 27 received placebo. No significant difference was found between the two groups regarding age, sex, nationality, smoking, underlying diseases and opium usage. During 8 weeks of anti-TB (antituberculosis) treatment, 8 (13.0%) patients developed drug-induced hepatotoxicity (DIH). Of them, 6 (75%) occurred in the first two weeks of treatment. Fifty percent of the patients who developed DIH were in garlic group. Results indicated no significant difference between groups in developing DIH (p=1.000). We could not show a significant role in preventing DIH by 1000 mg daily garlic administration. PMID:24711843

  12. The Effect of Garcin® in Preventing AntiTB-Induced Hepatitis in Newly Diagnosed Tuberculosis Patients.

    PubMed

    Tabarsi, Payam; Fahimi, Fanak; Heidarzadeh, Nader; Haghgoo, Roodabeh; Kazempour, Mehdi; Masjedi, Mohammadreza; Velayati, Ali Akbar

    2014-01-01

    Adverse effects of antituberculosis agents such as hepatotoxicity may reduce treatment effectiveness, because they significantly contribute to nonadherence and eventually result in treatment failure, relapse or the emergence of drug resistance. Garlic is an ancient herbal substance, which its effectiveness on isoniazid and rifampicin-induced hepatic injury in animal models has been demonstrated (1). In the present study a randomized, double blind, placebo-controlled, parallel group clinical trial was designed to assess the effect(s) of garlic tablets (1000 mg daily) administered for two weeks orally. Fifty eight newly diagnosed, smear positive pulmonary tuberculosis patients, with age ranges between 18-65 years old, were randomly allocated into two groups. Each patient received either garlic or placebo tablets for the first two weeks of tuberculosis treatment. Of total 58 patients, 31 received garlic tablets while 27 received placebo. No significant difference was found between the two groups regarding age, sex, nationality, smoking, underlying diseases and opium usage. During 8 weeks of anti-TB (antituberculosis) treatment, 8 (13.0%) patients developed drug-induced hepatotoxicity (DIH). Of them, 6 (75%) occurred in the first two weeks of treatment. Fifty percent of the patients who developed DIH were in garlic group. Results indicated no significant difference between groups in developing DIH (p=1.000). We could not show a significant role in preventing DIH by 1000 mg daily garlic administration. PMID:24711843

  13. A novel molecule with notable activity against multi-drug resistant tuberculosis.

    PubMed

    Nair, Vasu; Okello, Maurice O; Mangu, Naveen K; Seo, Byung I; Gund, Machhindra G

    2015-03-15

    Multi-drug resistant tuberculosis (MDR-TB) is emerging as a serious global health problem, which has been elevated through co-infection involving HIV and MDR-Mtb. The discovery of new compounds with anti-MDR TB efficacy and favorable metabolism profiles is an important scientific challenge. Using computational biology and ligand docking data, we have conceived a multifunctional molecule, 2, as a potential anti-MDR TB agent. This compound was produced through a multi-step synthesis. It exhibited significant in vitro activity against MDR-TB (MIC 1.56μg/mL) and its half-life (t1/2) in human liver microsomes was 14.4h. The metabolic profiles of compound 2 with respect to human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes were favorable. Compound 2 also had relatively low in vitro cytotoxicity in uninfected macrophages. It displayed synergistic behavior against MDR-TB in combination with PA-824. Interestingly, compound 2 also displayed in vitro anti-HIV activity. PMID:25677656

  14. Monocyte Signal Transduction Receptors in Active and Latent Tuberculosis

    PubMed Central

    Druszczynska, Magdalena; Wlodarczyk, Marcin; Janiszewska-Drobinska, Beata; Kielnierowski, Grzegorz; Zawadzka, Joanna; Kowalewicz-Kulbat, Magdalena; Fol, Marek; Szpakowski, Piotr; Rudnicka, Karolina; Chmiela, Magdalena; Rudnicka, Wieslawa

    2013-01-01

    The mechanisms that promote either resistance or susceptibility to TB disease remain insufficiently understood. Our aim was to compare the expression of cell signaling transduction receptors, CD14, TLR2, CD206, and β2 integrin LFA-1 on monocytes from patients with active TB or nonmycobacterial lung disease and healthy individuals with M.tb latency and uninfected controls to explain the background of the differences between clinical and subclinical forms of M.tb infection. A simultaneous increase in the expression of the membrane bound mCD14 receptor and LFA-1 integrin in patients with active TB may be considered a prodrome of breaking immune control by M.tb bacilli in subjects with the latent TB and absence of clinical symptoms. PMID:23401703

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

    PubMed

    Maeda, Hideo; Shirai, Chika

    2013-03-01

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

  16. Achievements in and Challenges of Tuberculosis Control in South Korea.

    PubMed

    Kim, Ji Han; Yim, Jae-Joon

    2015-11-01

    After the Korean War (1950-1953), nearly 6.5% of South Korea's population had active tuberculosis (TB). In response, South Korea implemented the National Tuberculosis Program in 1962. From 1965 to 1995, the prevalence of bacteriologically confirmed pulmonary TB in South Korea decreased from 940 to 219 cases per 100,000 population. Astounding economic growth might have contributed to this result; however, TB incidence in South Korea remains the highest among high-income countries. The rate of decrease in TB incidence seems to have slowed over the past 15 years. A demographic shift toward an older population, many of whom have latent TB and various concurrent conditions, is challenging TB control efforts in South Korea. The increasing number of immigrants also plays a part in the prolonged battle against TB. A historical review of TB in South Korea provides an opportunity to understand national TB control efforts that are applicable to other parts of the world.

  17. Comparison of the tuberculin skin test and the QuantiFERON-TB Gold test in detecting latent tuberculosis in health care workers in Iran

    PubMed Central

    2016-01-01

    OBJECTIVES: The tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT) are used to identify latent tuberculosis infections (LTBIs). The aim of this study was to determine the agreement between these two tests among health care workers in Iran. METHODS: This cross-sectional study included 177 tuberculosis (TB) laboratory staff and 67 non-TB staff. TST indurations of 10 mm or more were considered positive. The Student’s t-test and the chi-square test were used to compare the mean score and proportion of variables between the TB laboratory staff and the non-TB laboratory staff. Kappa statistics were used to evaluate the agreement between these tests, and logistic regression was used to assess the risk factors associated with positive results for each test. RESULTS: The prevalence of LTBIs according to both the QFT and the TST was 17% (95% confidence interval [CI], 12% to 21%) and 16% (95% CI, 11% to 21%), respectively. The agreement between the QFT and the TST was 77.46%, with a kappa of 0.19 (95% CI, 0.04 to 0.34). CONCLUSIONS: Although the prevalence of LTBI based on the QFT and the TST was not significantly different, the kappa statistic was low between these two tests for the detection of LTBIs. PMID:27457062

  18. A VSEIR model for transmission of tuberculosis (TB) disease in North Sumatera, Indonesia

    NASA Astrophysics Data System (ADS)

    Rangkuti, Yulita M.; Sinaga, Marlina S.; Marpaung, F.; Side, Syafruddin

    2014-12-01

    In this work, Vaccination (V), Susceptible (S) Infected (I), and Recovered (R) (VSIR) model for transmission of Tuberculosis in North Sumatera is modified. An exposed class is adopted to VSIR model so called VSEIR to determine the probability of people who infectious before infected. This model is written in ordinary differential equation (ODEs) in five classes. Determination the equilibrium point and stability analysis of the model is discussed to determine the dynamic behaviour of systems. A simulation is also discussed to see the suitable model to North Sumatera data. The simulation of VSEIR model indicates Tuberculosis has not endemic in North Sumatera.

  19. Activity of 5-chloro-pyrazinamide in mice infected with Mycobacterium tuberculosis or Mycobacterium bovis

    PubMed Central

    Ahmad, Zahoor; Tyagi, Sandeep; Minkowski, Austin; Almeida, Deepak; Nuermberger, Eric L.; Peck, Kaitlin M.; Welch, John T.; Baughn, Anthony D.; Jacobs, Williams R.; Grosset, Jacques H.

    2012-01-01

    & conclusion: Our findings showed that 5-Cl-PZA at doses up to 150 mg/kg was not active in chronic murine TB model. Further studies need to be done to understand the mechanism and mode of inactivation in murine model of tuberculosis. PMID:23287128

  20. Tuberculosis and the military.

    PubMed

    O'Shea, Matthew K; Wilson, D

    2013-09-01

    Tuberculosis (TB) causes significant morbidity and mortality among the global civilian population. Historically, TB has also been responsible for a considerable burden of disease among military populations during periods of both peace and conflict. TB will continue to be of importance to the military for several reasons. Military units live and work in confined environments, personnel may deploy to areas highly endemic for TB where there is the potential to be exposed to infected local communities, and they undertake physiologically stressful activities during training and operations. These are just a few of the factors that may increase the risk of acquiring, developing and transmitting TB among military personnel. This review examines the military relevance of TB in the modern era within the context of epidemiological, pathological and clinical considerations of this ancient disease.

  1. Comparison of Mycobacterium tuberculosis susceptibility testing performed with BACTEC 460TB (Becton Dickinson) and MB/BacT (Organon Teknika) systems.

    PubMed

    Tortoli, E; Mattei, R; Savarino, A; Bartolini, L; Beer, J

    2000-10-01

    The recently introduced automated culture systems MB/BacT (Organon Teknika, Belgium) was compared with radiometric BACTEC 460TB (Becton Dickinson, USA) to test antimicrobial susceptibility of Mycobacterium tuberculosis to first line drugs. On 113 strains 97.5% agreement was obtained, with the difference being not significant. Concordance was practically complete for the most important drugs, isoniazid and rifampin. The two methods however significantly differed for the time needed to complete the test; in fact MB/BacT required on the average five days more than BACTEC 460TB. Despite the delay in the completion of the test, the excellent reliability along with the elimination of radioactivity and full automation make MB/BacT an attractive alternative for susceptibility testing of M. tuberculosis.

  2. Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    Scherman, Michael S.; Woolhiser, Lisa K.; Madhura, Dora B.; Maddox, Marcus M.; Singh, Aman P.; Lee, Robin B.; Hurdle, Julian G.; McNeil, Michael R.; Lenaerts, Anne J.; Meibohm, Bernd; Lee, Richard E.

    2014-01-01

    The reductively activated nitroaromatic class of antimicrobials, which include nitroimidazole and the more metabolically labile nitrofuran antitubercular agents, have demonstrated some potential for development as therapeutics against dormant TB bacilli. In previous studies, the pharmacokinetic properties of nitrofuranyl isoxazolines were improved by incorporation of the outer ring elements of the antitubercular nitroimidazole OPC-67683. This successfully increased stability of the resulting pentacyclic nitrofuran lead compound Lee1106 (referred to herein as 9a). In the current study, we report the synthesis and antimicrobial properties of 9a and panel of 9a analogs, which were developed to increase oral bioavailability. These hybrid nitrofurans remained potent inhibitors of Mycobacterium tuberculosis with favorable selectivity indices (>150) and a narrow spectrum of activity. In vivo, the pentacyclic nitrofuran compounds showed long half-lives and high volumes of distribution. Based on pharmacokinetic testing and lack of toxicity in vivo, 9a remained the series lead. 9a exerted a lengthy post antibiotic effect and was highly active against nonreplicating M. tuberculosis grown under hypoxia. 9a showed a low potential for cross resistance to current antitubercular agents, and a mechanism of activation distinct from pre-clinical tuberculosis candidates PA-824 and OPC-67683. Together these studies show that 9a is a nanomolar inhibitor of actively growing as well as nonreplicating M. tuberculosis. PMID:24505329

  3. Numerical study for multi-strain tuberculosis (TB) model of variable-order fractional derivatives

    PubMed Central

    Sweilam, Nasser H.; AL-Mekhlafi, Seham M.

    2015-01-01

    In this paper, we presented a novel multi-strain TB model of variable-order fractional derivatives, which incorporates three strains: drug-sensitive, emerging multi-drug resistant (MDR) and extensively drug-resistant (XDR), as an extension for multi-strain TB model of nonlinear ordinary differential equations which developed in 2014 by Arino and Soliman [1]. Numerical simulations for this variable-order fractional model are the main aim of this work, where the variable-order fractional derivative is defined in the sense of Grünwald–Letnikov definition. Two numerical methods are presented for this model, the standard finite difference method (SFDM) and nonstandard finite difference method (NSFDM). Numerical comparison between SFDM and NSFDM is presented. It is concluded that, NSFDM preserves the positivity of the solutions and numerically stable in large regions than SFDM. PMID:26966568

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

    PubMed

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

    2011-07-01

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

  5. The Differential Gene Expression Pattern of Mycobacterium tuberculosis in Response to Capreomycin and PA-824 versus First-Line TB Drugs Reveals Stress- and PE/PPE-Related Drug Targets

    PubMed Central

    Fu, Li M.; Tai, Shu C.

    2009-01-01

    Tuberculosis is a leading infectious disease causing millions of deaths each year. How to eradicate mycobacterial persistence has become a central research focus for developing next-generation TB drugs. Yet, the knowledge in this area is fundamentally limited and only a few drugs, notably capreomycin and PA-824, have been shown to be active against non-replicating persistent TB bacilli. In this study, we performed a new bioinformatics analysis on microarray-based gene expression data obtained from the public domain to explore genes that were differentially induced by drugs between the group of capreomycin and PA-824 and the group of mainly the first-line TB drugs. Our study has identified 42 genes specifically induced by capreomycin and PA-824. Many of these genes are related to stress responses. In terms of the distribution of identified genes in a specific category relative to the whole genome, only the categories of PE/PPE and conserved hypotheticals have statistical significance. Six among the 42 genes identified in this study are on the list of the top 100 persistence targets selected by the TB Structural Genomics Consortium. Further biological elucidation of their roles in mycobacterial persistence is warranted. PMID:20016672

  6. What's new in tuberculosis vaccines?

    PubMed Central

    Ginsberg, Ann M.

    2002-01-01

    Over the past 10 years, tuberculosis (TB) vaccine development has resurged as an active area of investigation. The renewed interest has been stimulated by the recognition that, although BCG is delivered to approximately 90% of all neonates globally through the Expanded Programme on Immunization, Mycobacterium tuberculosis continues to cause over 8 million new cases of TB and over 2 million deaths annually. Over one hundred TB vaccine candidates have been developed, using different approaches to inducing protective immunity. Candidate vaccines are typically screened in small animal models of primary TB disease for their ability to protect against a virulent strain of M. tuberculosis. The most promising are now beginning to enter human safety trials, marking real progress in this field for the first time in 80 years. PMID:12132007

  7. Characteristics of Active Tuberculosis Patients Requiring Intensive Care Monitoring and Factors Affecting Mortality

    PubMed Central

    Levent, Dalar; Emel, Eryüksel; Pelin, Uysal; Turkay, Akbaş; Aybüke, Kekeçoğlu

    2016-01-01

    Background One to three percent of cases of acute tuberculosis (TB) require monitoring in the intensive care unit (ICU). The purpose of this study is to establish and determine the mortality rate and discuss the causes of high mortality in these cases, and to evaluate the clinical and laboratory findings of TB patients admitted to the pulmonary ICU. Methods The data of patients admitted to the ICU of Yedikule Chest Diseases and Chest Surgery Education and Research Hospital due to active TB were retrospectively evaluated. Demographic characteristics, medical history, and clinical and laboratory findings were evaluated. Results Thirty-five TB patients (27 males) with a median age of 47 years were included, of whom 20 died within 30 days (57%). The Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were significantly higher, and albumin and PaO2/FIO2 levels were significantly lower, and shock, multiple organ failure, the need for invasive mechanical ventilation and drug resistance were more common in the patients who died. The mortality risk was 7.58 times higher in the patients requiring invasive mechanical ventilation. The SOFA score alone was a significant risk factor affecting survival. Conclusion The survival rate is low in cases of tuberculosis treated in an ICU. The predictors of mortality include the requirement of invasive mechanical ventilation and multiple organ failure. Another factor specific to TB patients is the presence of drug resistance, which should be taken seriously in countries where there is a high incidence of the disease. Finding new variables that can be established with new prospective studies may help to decrease the high mortality rate. PMID:27433176

  8. Development and Evaluation of a Pilot Nurse Case Management Model to Address Multidrug-Resistant Tuberculosis (MDR-TB) and HIV in South Africa

    PubMed Central

    Farley, Jason E.; Kelly, Ana M.; Reiser, Katrina; Brown, Maria; Kub, Joan; Davis, Jeane G.; Walshe, Louise; Van der Walt, Martie

    2014-01-01

    Setting Multidrug-resistant tuberculosis (MDR-TB) unit in KwaZulu-Natal, South Africa. Objective To develop and evaluate a nurse case management model and intervention using the tenets of the Chronic Care Model to manage treatment for MDR-TB patients with a high prevalence of human immunodeficiency virus (HIV) co-infection. Design A quasi-experimental pilot programme utilizing a nurse case manager to manage care for 40 hospitalized MDR-TB patients, 70% HIV co-infected, during the intensive phase of MDR-TB treatment. Patients were followed for six months to compare proximal outcomes identified in the model between the pre- and post-intervention period. Results The greatest percent differences between baseline and six-month MDR-TB proximal outcomes were seen in the following three areas: baseline symptom evaluation on treatment initiation (95% improvement), baseline and monthly laboratory evaluations completed per guidelines (75% improvement), and adverse drug reactions acted upon by medical and/or nursing intervention (75% improvement). Conclusion Improvements were identified in guideline-based treatment and monitoring of adverse drug reactions following implementation of the nurse case management intervention. Further study is required to determine if the intervention introduced in this model will ultimately result in improvements in final MDR-TB treatment outcomes. PMID:25405988

  9. Tuberculosis in HIV-positive patients: cellular response and immune activation in the lung.

    PubMed

    Law, K F; Jagirdar, J; Weiden, M D; Bodkin, M; Rom, W N

    1996-04-01

    The host response to Mycobacterium tuberculosis is dependent on the accumulation and activation of cytotoxic and memory CD4+ T cells, resulting in granuloma formation and delayed type hypersensitivity. We characterized the cellular response of radiographically involved lung segments from 17 HIV-positive and 11 HIV-negative patients with acute tuberculosis (TB) using bronchoalveolar lavage (BAL) and compared the response to uninvolved segments, normal control subjects and peripheral blood. In both HIV-positive and HIV-negative patients, radiographically involved segments had significantly increased numbers of total cells per milliliter, percent of neutrophils recovered, and percent of lymphocytes recovered compared with uninvolved segments or normal control subjects, but HIV-positive patients had a lower proportion of lymphocytes in the involved segments than HIV-negative patients with tuberculosis (19 +/- 5% versus 33 +/- 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentages of CD4+ lymphocytes (CD4+ lymphocytes in HIV-positive TB involved site 25 +/- 6%; HIV-negative TB involved site 73 +/- 2%; p < 0.01) and an increase in the percentage of CD8+ lymphocytes (HIV positive involved site 61 +/- 6% versus HIV negative involved site 19 +/- 3%; p < 0.01). Immunohistochemistry of lung biopsy tissue in five HIV-negative patients showed similar lymphocyte subset profiles as BAL, indicating that BAL reflects cell populations in tissue granulomas. BAL lymphocytes from four HIV-positive and four HIV-negative tuberculosis patients demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apoptosis (HIV positive 48 +/- 6%, HIV negative 31 +/- 7%, normals 11 +/- 5%). Steady state mRNA for gamma-interferon was decreased in four HIV-positive patients when compared with four HIV-negative patients. IL-8 production was comparable in HIV-negative and

  10. Factors Associated with Prevalent Tuberculosis Among Patients Receiving Highly Active Antiretroviral Therapy in a Nigerian Tertiary Hospital

    PubMed Central

    Iroezindu, MO; Ofondu, EO; Mbata, GC; van Wyk, B; Hausler, HP; DH, Au; Lynen, L; Hopewell, PC

    2016-01-01

    Background: Tuberculosis (TB) causes significant morbidity/mortality among human immunodeficiency virus-infected individuals in Africa. Reducing TB burden in the era of highly active antiretroviral therapy (HAART) is a public health priority. Aim: We determined the factors associated with prevalent TB among patients receiving HAART. Subjects and Methods: We conducted a cross-sectional study of adult patients who had received HAART for ≥12 weeks in a Nigerian tertiary hospital. Patients whose TB diagnosis predated HAART were excluded from the study. Pre-HAART data were collected from the clinic records, whereas post-HAART data were obtained through medical history, physical examination, and laboratory investigations. Standard TB screening/diagnostic algorithms as applicable in Nigeria were used. Logistic regression analysis was used to determine factors independently associated with prevalent TB. Results: about 65.8% (222/339) were women. The mean age was 41.1 (10.0) years and 23.6% (73/339) had past history of TB. The prevalence of active TB was 7.7% (26/339). Among these patients, 42.3% (11/26) had pulmonary TB, 34.6% (9/26) had disseminated TB, whereas 23.1% (6/26) had only extra-pulmonary disease. Only 45% (9/20) of patients with pulmonary involvement had positive sputum smear. Factors independently associated with prevalent TB were lower social class (adjusted odds ratio [aOR]: 31.7; 95% confidence interval [CI]: 1.1–1417.3), HAART non-adherence (aOR125.5; 95% CI: 9.6–1636.3), baseline CD4 <200cells/μl (aOR31.0; 95%CI: 1.6–590.6), previous TB (aOR13.8; 95% CI: 2.0–94.1), and current hemoglobin <10 g/dl (aOR10.3; 95% CI: 1.1–99.2). Conclusion: Factors associated with prevalent TB were a lower social class, HAART non-adherence, severe immunosuppression before HAART initiation, previous TB, and anemia post-HAART. TB case finding should be intensified in these high-risk groups. PMID:27213096

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

    PubMed Central

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

    2015-01-01

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

  12. Impaired NK cells' activity and increased numbers of CD4 + CD25+ regulatory T cells in multidrug-resistant Mycobacterium tuberculosis patients.

    PubMed

    Fan, Renhua; Xiang, Yangen; Yang, Li; Liu, Yanke; Chen, Pingsheng; Wang, Lei; Feng, Wenjun; Yin, Ke; Fu, Manjiao; Xu, Yixin; Wu, Jialin

    2016-05-01

    Multidrug-resistant tuberculosis (MDR-TB) often causes persistent infection and chemotherapy failure, which brings heavy burden of society and family. Many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. The presence of regulatory T cells (Tregs) is thought to be an important mechanism that TB successfully evades the immune system. Tregs play a central role in the prevention of autoimmunity and in the control of immune responses. The role of Tregs in MDR-TB infection and persistence is inadequately documented. The current study was designed to determine whether CD4 + CD25+ regulatory T cells may modulate innate immunity (such as NK cells) against human tuberculosis. Our results indicated that the numbers of CD4 + CD25+ Treg cells increased in MDR-TB patients' blood, and the cytokine production of IL-10 increased from MDR-patients compared with healthy subjects, along with the lower activity and low CD69 expression of NK cells in patients. These results suggested that immunity to MDR-TB patients induced circulating CD4 + CD25+ T regulatory cells expansion, which may be related to the persistence of Mycobacterium tuberculosis (M. tb) infection, and to the balance between effectors immune responses and suppression immune responses. PMID:27156613

  13. Application of Elephant TB STAT-PAK assay and MAPIA (multi-antigen print immunoassay) for detection of tuberculosis and monitoring of treatment in black rhinoceros (Diceros bicornis).

    PubMed

    Duncan, Ann E; Lyashchenko, Konstantin; Greenwald, Rena; Miller, Michelle; Ball, Ray

    2009-12-01

    Many wildlife species including rhinos are susceptible to infection with Mycobacterium tuberculosis or M. bovis. Antemortem diagnostic testing in large exotic hoof stock species has been limited by challenges associated with test administration, sample collection, and interpretation. Hence, a simple, rapid, blood-based test is needed. Two confirmed M. tuberculosis-infected black rhinoceros and one exposed suspect were evaluated for antibody responses using a lateral-flow rapid test (ElephantTB STAT-PAK) and multi-antigen print immunoassay (MAPIA). All three animals were seropositive by both tests. MAPIA detected antibodies to ESAT-6, CFP10, and MPB83 antigens. When the rhinos were treated with antitubercular therapeutics, their antibody responses gradually declined. One rhinoceros died approximately 9 mo after initiation of treatment and showed an increase in antibody titer shortly before death. The other two rhinoceros, which were treated for 1 and 2 yr, respectively, had no clinical signs or positive culture for M. tuberculosis at the time of necropsy performed 2 or 6 yr later for unrelated reasons. The antibody levels in these rhinos continued to be significantly decreased. The findings suggest that the ElephantTB STAT-PAK and MAPIA may be useful tools to detect M. tuberculosis infection and monitor treatment in black rhinoceros. PMID:20063826

  14. Active case finding for tuberculosis among people who inject drugs on methadone treatment in Dar es Salaam, Tanzania

    PubMed Central

    Gupta, A.; Mbwambo, J.; Mteza, I.; Shenoi, S.; Lambdin, B.; Nyandindi, C.; Doula, B. I.; Mfaume, S.; Bruce, R. D.

    2015-01-01

    SUMMARY SETTING Active case finding is a World Health Organization (WHO) endorsed strategy for improving tuberculosis (TB) case detection. Despite WHO recommendations for active case finding among people who inject drugs (PWID), few studies have been published. The historical focus of case finding has been in populations that are human immunodeficiency virus-positive, incarcerated or at higher occupational risk. OBJECTIVE We sought to examine the yield of active case finding among PWID newly started on methadone in Tanzania. DESIGN Of 222 methadone clients, 156 (70%) met with study administrators; 150 consented to participate, 139 (93%) of whom were male. The median age was 34 years. A symptom-based questionnaire was developed by the investigators and administered to every consenting patient by a native Swahili speaker. RESULTS Of the 150 patients surveyed, 16 (11%) had one or more TB symptoms and were referred for laboratory testing. Six new TB cases were identified in this active case finding program, with a prevalence of 4%. CONCLUSION This study presents the first data on TB prevalence in a population of PWID in Tanzania. This prevalence is 23 times that of the general Tanzanian TB prevalence of 0.2%. These results have significant implications for TB control. PMID:24902554

  15. In vitro Anti-mycobacterial activity of selected medicinal plants against Mycobacterium tuberculosis and Mycobacterium bovis Strains

    PubMed Central

    2013-01-01

    Background Tuberculosis (TB) is a global burden with one –third of the world’s population infected with the pathogen Mycobacterium tuberculosis complex and annually 1.4 million deaths occur due to the disease. This high incidence of infection and the increased rate of multi-drug resistant and extensively-drug resistant strains of the organism further complicated the problem of TB control and have called for an urgent need to develop new anti-TB drugs from plants. In this study, the in vitro activity of root of Calpurnia aurea, seeds of Ocimum basilicum, leaves of Artemisia abyssinica, Croton macrostachyus, and Eucalyptus camaldulensis were evaluated against M. tuberculosis and M. bovis strains. Methods Five Ethiopian medicinal plants, root of Calpurnia aurea, seeds of Ocimum basilicum, leaves of Artemisia abyssinica, Croton macrostachyus, and Eucalyptus camaldulensis used locally for the management of TB. They were investigated for in vitro antimycobacterial activity against M. tuberculosis and M. bovis strains. 80% methanolic extracts of the plant materials were obtained by maceration. The antimycobacterial activity was determined using 96 wells of microplate with the help of visual Resazurin Microtiter Assay. Results The crude 80% methanolic extracts of the root of C. aurea, seeds of O. basilicum, and leaves of A. abyssinica, C. macrostachyus, and E. camaldulensis had anti-mycobacterial activity with minimum inhibitory concentration (MIC) ranging from 6.25–100 μg/mL. The MIC of 80% methanol extracts in the order mentioned above ranged 25-100 μg/ml and 12.5-75 μg/mL, 25–100 μg/mL and 25–50 μg/mL, 6.25-50 μg/mL and 12.5-50 μg/mL, 12.5-100 μg/mL and 18.25-50 μg/mL and 6.25-50 μg/mL and 12.5-50 μg/mL, respectively for M. tuberculosis and M. bovis strains. Conclusions The results support the local use of these plants in the treatment of TB and it is suggested that these plants may have therapeutic value in the treatment of TB. However

  16. Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB)

    PubMed Central

    Dlugovitzky, D; Bay, M L; Rateni, L; Fiorenza, G; Vietti, L; Farroni, M A; Bottasso, O A

    2000-01-01

    Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-β), nitric oxide and tumour necrosis factor-alpha (TNF-α) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-γ), IL-4, IL-12, TGF-β, TNF-α and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 ± 13 years (mean ±s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-γ, TGF-β and TNF-α production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-γ were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-β and TNF-α concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease. PMID:11122239

  17. Serological markers of hepatitis B and C in patients with HIV/AIDS and active tuberculosis.

    PubMed

    Araújo-Mariz, Carolline; Lopes, Edmundo Pessoa; Ximenes, Ricardo A A; Lacerda, Heloísa R; Miranda-Filho, Demócrito B; Montarroyos, Ulisses R; Barreto, Silvana; Salustiano, Daniela Medeiros; Albuquerque, Maria Fátima Pessoa Militão

    2016-06-01

    Infection with hepatitis B virus (HBV) and C virus (HCV) are common in patients with HIV/AIDS and tuberculosis (TB). This is a cross-sectional study with patients infected with HIV/AIDS and active TB in Recife, Brazil, aiming to verify the prevalence of markers for HBV: antibody to hepatitis B core antigen (anti-HBc); and HCV: antibody to hepatitis C virus (anti-HCV) by chemiluminescence, and to identify the frequency of associated factors. Data were collected through questionnaires, and blood was drawn from patients for analysis. We used the chi-square test and the Fisher exact test when necessary. We conducted a bivariate logistic regression analysis and the magnitude of the associations was expressed as odds ratio (OR) with a confidence interval of 95%. Among 166 patients studied with HIV/AIDS and active TB, anti-HBc was positive in 61 patients [36.7%; 95%CI (29.4-44.6%)] and anti-HCV in 11[6.6%; 95%CI (3.4-11.5%)]. In the logistic regression analysis, male sex, and age ≥40 years were independent factors associated with the occurrence of anti-HBc. In conclusion, we verified a high frequency of HBV contact marker and a low frequency of HCV markers in patients with HIV/AIDS and TB in Recife.

  18. Evaluating the anti Mycobacterium tuberculosis activity of Alpinia galanga (L.) Willd. axenically under reducing oxygen conditions and in intracellular assays

    PubMed Central

    2014-01-01

    Background In tuberculosis (TB), the steadily increasing bacterial resistance to existing drugs and latent TB continue to be major concerns. A combination of conventional drugs and plant derived therapeutics can serve to expand the antimicrobial spectrum, prevent the emergence of drug resistant mutants and minimize toxicity. Alpinia galanga, used in various traditional medicines, possesses broad spectrum antibacterial properties. The study was undertaken to assess the antimycobacterial potential of A. galanga in axenic (under aerobic and anaerobic conditions) and intracellular assays. Methods Phytochemical analysis was done using HPTLC. The acetone, aqueous and ethanolic extracts (1, 10, 25, 50 and 100 μg/ml) of A. galanga were tested axenically using Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis (M.tb) H37Rv and three drug sensitive and three multi drug resistant clinical isolates. The activity of the extracts was also evaluated intracellularly in A549 cell line against these strains. The extracts active under intracellular conditions were further tested in an axenic setup under reducing oxygen concentrations using only H37Rv. Results 1´ acetoxychavicol acetate, the reference standard used, was present in all the three extracts. The acetone and ethanolic extracts were active in axenic (aerobic and anaerobic) and intracellular assays. The aqueous extract did not demonstrate activity under the defined assay parameters. Conclusion A. galanga exhibits anti M.tb activity with multiple modes of action. Since the activity of the extracts was observed under reducing oxygen concentrations, it may be effective in treating the dormant and non-replicating bacteria of latent TB. Though the hypothesis needs further testing, A. galanga being a regular dietary component may be utilized in combination with the conventional TB therapy for enhanced efficacy. PMID:24592852

  19. Seasonality of Tuberculosis

    PubMed Central

    Fares, Auda

    2011-01-01

    Objectives: This study was designed to review previous studies and analyse the current knowledge and controversies related to seasonal variability of tuberculosis (TB) to examine whether TB has an annual seasonal pattern. Study Design and Methods: Systematic review of peer reviewed studies identified through literature searches using online databases belonging to PubMed and the Cochrane library with key words “Tuberculosis, Seasonal influence” and “Tuberculosis, Seasonal variation”. The search was restricted to articles published in English. The references of the identified papers for further relevant publications were also reviewed. Results: Twelve studies conducted between the period 1971 and 2006 from 11 countries/regions around the world (South Western Cameroon, South Africa, India, Hong Kong, Japan, Kuwait, Spain, UK, Ireland, Russia, and Mongolia) were reviewed. A seasonal pattern of tuberculosis with a mostly predominant peak is seen during the spring and summer seasons in all of the countries (except South Western Cameroon and Russia). Conclusions: The observation of seasonality leads to assume that the risk of transmission of M. tuberculosis does appear to be the greatest during winter months. Vitamin D level variability, indoor activities, seasonal change in immune function, and delays in the diagnosis and treatment of tuberculosis are potential stimuli of seasonal tuberculosis disease. Additionally, seasonal variation in food availability and food intake, age, and sex are important factors which can play a role in the tuberculosis notification variability. Prospective studies regarding this topic and other related subjects are highly recommended. PMID:21572609

  20. [ANTI-TUBERCULOSIS THERAPY AND PARADOXICAL RESPONSE WHEN TUBERCULOSIS DEVELOPS UNDER THE INFLUENCE OF BIOLOGICS FOR RHEUMATOID ARTHRITIS].

    PubMed

    Matsumoto, Tomoshige

    2015-01-01

    A paradoxical response is designated as the clinical or radiological worsening of pre-existing TB lesions or the development of new lesions during appropriate anti-TB treatment. Tuberculosis bacilli have no toxin and the organism apparently does not produce any toxins, so the virulence depends on a response to the host immune reaction. According to our report, the annual reported numbers of tuberculosis cases and death did not decrease during biologics treatment in Japan. We have been monitoring and analyzing all the TB cases activated during adalimumab treatments in Japan. According to the analysis, there was no TB related death and severe sequelae in patients with lung tuberculosis without extra pulmonary TB; TB related deaths were caused not by delays of diagnosis and therapy but by the paradoxical response following miliary TB. Paradoxical response after abrupt cessation of anti-TB treatment is caused by immune activation to cell components despite TB bacilli are alive or dead. So, we concluded that the abrupt cessation of anti-TNF agents after TB development could activate immune response causing paradoxical response, which lead to severe sequelae and death, and that continuation of anti-TNF therapy for rheumatoid arthritis in patients with active tuberculosis reactivated during anti-TNF medication is more beneficial than its cessation concerning not only clinical and radiological but also bacteriological outcomes.

  1. 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)

  2. Bovine Tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. 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.

  4. Cytokine and chemokine expression profiles in response to Mycobacterium tuberculosis stimulation are altered in HIV-infected compared to HIV-uninfected subjects with active tuberculosis.

    PubMed

    Waruk, Jillian L M; Machuki, Zipporah; Mesa, Christine; Juno, Jennifer A; Anzala, Omu; Sharma, Meenu; Ball, T Blake; Oyugi, Julius; Kiazyk, Sandra

    2015-09-01

    Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.

  5. Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

    PubMed

    Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

    2016-01-01

    India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. PMID:27235937

  6. Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

    PubMed

    Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

    2016-01-01

    India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes.

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

    PubMed

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

    2008-03-18

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

  8. [Tuberculosis prevention measure in medical and correlated facilities].

    PubMed

    Nagao, Keiichi

    2011-08-01

    Tuberculosis (TB) infection of healthcare workers in medical and correlated facilities is serious issue. For the prevention of TB transmission in the facilities, there are five important matters which are management of work environment, self protection manner, TB infection screening, a system for infection control, and TB education. The air containing TB nuclei must be exhausted from the work space mechanically, the workers should wear N95 mask at high risk places, regular chest X-ray examination and periodically QuantiFERON test for healthcare workers should undergo, the infection control committee must be active and TB education course for healthcare workers must be held annually. PMID:21838052

  9. 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.

  10. Drug Resistance Mechanisms in Mycobacterium tuberculosis

    PubMed Central

    Palomino, Juan Carlos; Martin, Anandi

    2014-01-01

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis. PMID:27025748

  11. Drug Resistance Mechanisms in Mycobacterium tuberculosis.

    PubMed

    Palomino, Juan Carlos; Martin, Anandi

    2014-01-01

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis. PMID:27025748

  12. Diagnosis and Treatment of Latent Tuberculosis Infection in Healthcare Workers

    PubMed Central

    2016-01-01

    Tuberculosis (TB) is one of the most important occupational risks for healthcare workers (HCWs) in South Korea. Many policies regarding the control and prevention of TB in healthcare settings recommend that HCWs are tested for latent tuberculosis infection (LTBI) in addition to active TB. Moreover, the Korean Tuberculosis Prevention Act also recommends that HCWs receive regular testing for LTBI. However, there are no specific or detailed guidelines for dealing with LTBI in HCWs. Herein, we discuss the diagnosis and treatment of LTBI in HCWs and focus particularly on the baseline screening of hired HCWs, routine follow-up, and contact investigation. PMID:27433172

  13. Cost-Effectiveness Analysis of Community Active Case Finding and Household Contact Investigation for Tuberculosis Case Detection in Urban Africa

    PubMed Central

    Sekandi, Juliet N.; Dobbin, Kevin; Oloya, James; Okwera, Alphonse; Whalen, Christopher C.; Corso, Phaedra S.

    2015-01-01

    Introduction Case detection by passive case finding (PCF) strategy alone is inadequate for detecting all tuberculosis (TB) cases in high burden settings especially Sub-Saharan Africa. Alternative case detection strategies such as community Active Case Finding (ACF) and Household Contact Investigations (HCI) are effective but empirical evidence of their cost-effectiveness is sparse. The objective of this study was to determine whether adding ACF or HCI compared with standard PCF alone represent cost-effective alternative TB case detection strategies in urban Africa. Methods A static decision modeling framework was used to examine the costs and effectiveness of three TB case detection strategies: PCF alone, PCF+ACF, and PCF+HCI. Probability and cost estimates were obtained from National TB program data, primary studies conducted in Uganda, published literature and expert opinions. The analysis was performed from the societal and provider perspectives over a 1.5 year time-frame. The main effectiveness measure was the number of true TB cases detected and the outcome was incremental cost-effectiveness ratios (ICERs) expressed as cost in 2013 US$ per additional true TB case detected. Results Compared to PCF alone, the PCF+HCI strategy was cost-effective at US$443.62 per additional TB case detected. However, PCF+ACF was not cost-effective at US$1492.95 per additional TB case detected. Sensitivity analyses showed that PCF+ACF would be cost-effective if the prevalence of chronic cough in the population screened by ACF increased 10-fold from 4% to 40% and if the program costs for ACF were reduced by 50%. Conclusions Under our baseline assumptions, the addition of HCI to an existing PCF program presented a more cost-effective strategy than the addition of ACF in the context of an African city. Therefore, implementation of household contact investigations as a part of the recommended TB control strategy should be prioritized. PMID:25658592

  14. 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.

  15. [Tuberculosis: actual problems with diagnosis and treatment].

    PubMed

    Korzeniewska-Koseła, Maria

    2016-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex. It remains health problem also in developed countries. Most common form of tuberculosis is pulmonary disease but other sites of the body can be affected (extrapulmonary TB). As TB incidence falls, the probability of developing active diseases in people infected with M. tuberculosis is higher among imunocompromised people and in people from risk groups. People who present with unexplained cough lasting two or more weeks or with findings suggestive of tuberculosis on chest radiographs should be evaluated for tuberculosis. For patients suspected of having pulmonary or extrapulmonary tuberculosis specimens from the sites of involvement should be obtained for microbiological tests. Bronchoscopy and BAL should be performed in patients that do not produce sputum and with negative sputum smears. Ct scan may also play an important role in the evaluation of patients suspected of having TB but with negative sputum smears. The standard therapy for TB should consist of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol in the initial phase and of isoniazid and rifampicin given for 4 months (the continuation phase). PMID:27421129

  16. 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.

  17. Latent Tuberculosis Infection in an Urban Cohort: Screening and Treatment for Latent TB in an Urban Setting

    PubMed Central

    Morano, Jamie P.; Walton, Mary R.; Zelenev, Alexei; Bruce, R. Douglas; Altice, Frederick L.

    2013-01-01

    Background Despite its benefit for treating active tuberculosis, directly observed therapy (DOT) for latent tuberculosis infection (LTBI) has been largely understudied among challenging inner city populations. Methods Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2523 completed tuberculin skin tests (TST’s) resulted in 357 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes 1) initiation of isoniazid preventative therapy (IPT) and 2) completion of 9-months IPT. Results Of 357 new LTBIs, 86.3% (n=308) completed screening CXRs: 90.3% (n=278) were normal and 0.3% (n=1) with active tuberculosis. Of those completing CXR screening, 44.0% (n=135) agreed to IPT: 69.6% (n=94) selected DOT, and 30.4% (n=41) selected SAT. Initiating IPT was correlated with undocumented status (AOR=3.43; p<0.001) and being born in a country of highest and third highest tuberculosis prevalence (AOR=14.09; p=0.017 and AOR=2.25; p=0.005, respectively). Those selecting DOT were more likely to be Hispanic (83.0% vs 53.7%; p<0.0001), undocumented (57.4% vs 41.5%; p=0.012), have stable housing (p=0.002), employed (p<0.0001), uninsured (p=0.014), no prior cocaine or crack use (p=0.013) and no recent incarceration (p=0.001). Completing 9-months of IPT was correlated with no recent incarceration (AOR 5.95; p=0.036) and younger age (AOR 1.03; p=0.031). SAT and DOT participants did not significantly differ for IPT duration (6.54 vs 5.68 months; p=0.216) nor 9-month completion (59.8% vs 46.3%; p=0.155). Conclusions In an urban mobile healthcare sample, screening completion for LTBI was high with nearly half initiating IPT. Undocumented, Hispanic immigrants from high prevalence tuberculosis countries were more likely to self-select DOT at the mobile outreach clinic, potentially because of more culturally, linguistically, and logistically accessible services and self-selection optimization

  18. Intensified tuberculosis case finding amongst vulnerable communities in southern India.

    PubMed

    Reddy, K K; Ananthakrishnan, R; Jacob, A G; Das, M; Isaakidis, P; Kumar, A M V

    2015-12-21

    India mainly uses passive case finding to detect tuberculosis (TB) patients through the Revised National Tuberculosis Control Programme (RNTCP). An intensified case finding (ICF) intervention was conducted among vulnerable communities in two districts of Karnataka during July-December 2013; 658 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 8.8% relative to the pre-intervention period (July-December 2012) in intervention communities as compared to an 8.6% decrease in communities without the ICF intervention. ICF activities brought TB services closer to vulnerable communities, moderately increasing TB case detection rates.

  19. Influence of HLA-DRB1 Alleles on the Variations of Antibody Response to Tuberculosis Serodiagnostic Antigens in Active Tuberculosis Patients

    PubMed Central

    Zhou, Fangbin; Xu, Xindong; Wu, Sijia; Cui, Xiaobing; Fan, Lin; Pan, Weiqing

    2016-01-01

    Serology-based tests for tuberculosis (TB) diagnosis, though rapid, efficient and easily implemented, have so far shown unsatisfactory levels of sensitivity and specificity, probably due to variations of the antibody response in TB patients. The number and types of seropositive antigens vary from individual to individual. The person-to-person variations of antigen recognition may be linked to genetic polymorphisms of the human leukocyte antigen (HLA) class II alleles. In the present study, we find that there is a significant increase in the frequency of HLA-DRB1*14 (P = 2.5×10−4) among subjects with high antibody response levels compared to those with low antibody levels. HLA-DRB1*15, the most frequent allelic group in the studied active TB population, positively correlates with subjects with low antibody response levels rather than subjects with high antibody response levels (P = 0.005), which indicates the loss of relevant antigens for screening of patients with this allelic group. The potential association between HLA-DRB1 allelic group and individual antigens implies that TB diagnostic yield could be improved by the addition of antigens screened at the proteome scale in infected subjects from the HLA-DRB1*15 allelic group. PMID:27788190

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

    PubMed Central

    Burger, Divan Aristo; Schall, Robert

    2015-01-01

    Trials of the early bactericidal activity (EBA) of tuberculosis (TB) treatments assess the decline, during the first few days to weeks of treatment, in colony forming unit (CFU) count of Mycobacterium tuberculosis in the sputum of patients with smear-microscopy-positive pulmonary TB. Profiles over time of CFU data have conventionally been modeled using linear, bilinear, or bi-exponential regression. We propose a new biphasic nonlinear regression model for CFU data that comprises linear and bilinear regression models as special cases and is more flexible than bi-exponential regression models. A Bayesian nonlinear mixed-effects (NLME) regression model is fitted jointly to the data of all patients from a trial, and statistical inference about the mean EBA of TB treatments is based on the Bayesian NLME regression model. The posterior predictive distribution of relevant slope parameters of the Bayesian NLME regression model provides insight into the nature of the EBA of TB treatments; specifically, the posterior predictive distribution allows one to judge whether treatments are associated with monolinear or bilinear decline of log(CFU) count, and whether CFU count initially decreases fast, followed by a slower rate of decrease, or vice versa. PMID:25322214

  1. The Pregnane X Receptor in Tuberculosis Therapeutics

    PubMed Central

    Shehu, Amina I.; Li, Guangming; Xie, Wen; Ma, Xiaochao

    2016-01-01

    Introduction Among the infectious diseases, tuberculosis (TB) remains the second cause of death after HIV. TB treatment requires the combination of multiple drugs including the rifamycin class. However, rifamycins are activators of human pregnane X receptor (PXR), a transcription factor that regulates drug metabolism, drug resistance, energy metabolism, and immune response. Rifamycin-mediated PXR activation may affect the outcome of TB therapy. Areas covered This review describes the role of PXR in modulating metabolism, efficacy, toxicity, and resistance to anti-TB drugs; as well as polymorphisms of PXR that potentially affect TB susceptibility. Expert opinion The wide range of PXR functions aside mediating drug metabolism and toxicity in TB therapy is underappreciated and thus understudied. Further studies are needed to determine the overall impact of PXR activation on the outcome of TB therapy. PMID:26592418

  2. Special computer-aided computed tomography (CT) volume measurement and comparison method for pulmonary tuberculosis (TB)

    PubMed Central

    Liu, Jingming; Sun, Zhaogang; Xie, Ruming; Gao, Mengqiu; Li, Chuanyou

    2015-01-01

    The computed tomography (CT) manifestations in pulmonary tuberculosis (PTB) patients are complex and could not be quantitatively evaluated. We aimed to establish a new method to objectively measure the lung injury level in PTB by thoracic CT and make quantitative comparisons. In the retrospective study, a total of 360 adults were selected and divided into four groups according to their CT manifestations and medical history: Normal group, PTB group, PTB with diabetes mellitus (DM) group and Death caused by PTB group. Five additional patients who had continuous CT scans were chosen for preliminary longitudinal analysis. We established a new computer-aided CT volume measurement and comparison method for PTB patients (CACTV-PTB) which measured lung volume (LV) and thoracic volume (TV). RLT was calculated as the ratio of LV to TV and comparisons were performed among different groups. Standardized RLT (SRLT) was used in the longitudinal analysis among different patients. In the Normal group, LV and TV were positively correlated in linear regression (Ŷ=-0.5+0.46X, R2=0.796, P<0.01). RLT values were significantly different among four groups (Normal: 0.40±0.05, PTB: 0.37±0.08, PTB+DM: 0.34±0.06, Death: 0.23±0.04). The curves of SRLT value from different patients shared a same start point and could be compared directly. Utilizing the novel objective method CACTV-PTB makes it possible to compare the severity and dynamic change among different PTB patients. Our early experience also suggested that the lung injury is severer in the PTB+DM group than in the PTB group. PMID:26628995

  3. Kinetics of purified protein derivative (PPD) proliferation reflects underlying suppressor mechanisms revealed by limiting dilution analysis (LDA) in patients with extrapulmonary tuberculosis (TB)

    PubMed Central

    Lukey, P T; Latouf, S E; Ress, S R

    1998-01-01

    Mononuclear leucocytes from the blood (PBML) and effusion (EML) of patients undergoing pericardiocentesis were assayed for proliferative response to purified protein derivative of Mycobacterium tuberculosis (PPD). Of the 23 patients tested, 10 had culture-positive tuberculous effusions, while 13 had non-tuberculous aetiologies. Three different kinetic responses were identified: (i) accelerated responses (found in 70% of EML from patients with culture-positive tuberculous effusions); (ii) ‘flat’ responses (found in 10% of EML from patients with culture-positive tuberculous effusions); and (iii) normal kinetic responses. These differences in kinetic response may reflect underlying immune mechanisms important in the immunopathogenesis of TB. In order to address this possibility we performed LDA on a selection of patients with culture-positive extrapulmonary TB: three patients with accelerated responses, two with normal responses, and one with a ‘flat’ response. The results confirm the previously reported accumulation of PPD-specific responder cells in the effusion of patients with TB. Cell-mediated suppressor mechanisms (as shown by ‘V’-shaped LDA curves) were found in the blood of one patient and the effusion of another. In both cases ‘flat’ PPD-proliferative responses were observed. However, the LDA data also suggested the presence of in vivo mechanisms limiting the clonal burst size. Thus it appears that immune responses in extrapulmonary TB are influenced by an array of inhibitory mechanisms, modulation of which may influence the outcome of infection. PMID:9486395

  4. Interferon-Gamma Release Assays for the Diagnosis of Active Tuberculosis in HIV-Infected Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Jun; Zhang, Renfang; Wang, Jiangrong; Liu, Li; Zheng, Yufang; Shen, Yinzhong; Qi, Tangkai; Lu, Hongzhou

    2011-01-01

    Background Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear. Methods We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001–July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients. Results The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6–80.5%) and 77.4% (95%CI, 71.4–82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0–78.0%) and 63.1% (95%CI, 57.6–68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8–11.3%) and 13.2% (95%CI, 10.6–16.0%) for QFT-GIT and T-SPOT, respectively. Conclusion IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy. PMID:22069472

  5. Optimal intervention strategies for tuberculosis

    NASA Astrophysics Data System (ADS)

    Bowong, Samuel; Aziz Alaoui, A. M.

    2013-06-01

    This paper deals with the problem of optimal control of a deterministic model of tuberculosis (abbreviated as TB for tubercle bacillus). We first present and analyze an uncontrolled tuberculosis model which incorporates the essential biological and epidemiological features of the disease. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium co-exists with one or more stable endemic equilibria when the associated basic reproduction number is less than the unity. Based on this continuous model, the tuberculosis control is formulated and solved as an optimal control problem, indicating how control terms on the chemoprophylaxis and detection should be introduced in the population to reduce the number of individuals with active TB. Results provide a framework for designing the cost-effective strategies for TB with two intervention methods.

  6. Discordance across Phenotypic and Molecular Methods for Drug Susceptibility Testing of Drug-Resistant Mycobacterium tuberculosis Isolates in a Low TB Incidence Country.

    PubMed

    Ahmad, Suhail; Mokaddas, Eiman; Al-Mutairi, Noura; Eldeen, Hanaa S; Mohammadi, Shirin

    2016-01-01

    With increasing incidence of multidrug-resistant tuberculosis (MDR-TB), accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis to first-line drugs has become crucial for proper patient management. We evaluated concordance of DST results for 70 M. tuberculosis isolates across two phenotypic and two molecular methods: BACTEC 460TB, MGIT 960 system, GenoType MTBDRplus and DNA sequencing of gene segments most commonly implicated in conferring resistance to anti-TB drugs. Most (84%) M. tuberculosis isolates were multidrug-resistant. Twenty-four isolates yielded discrepant DST results. For rifampicin, isoniazid and streptomycin, 96%, 97% and 93% of isolates, respectively, were susceptible or resistant by all four methods, whereas for ethambutol, this agreement was observed for only 76% of isolates (P<0.05 for rifampicin or isoniazid or streptomycin versus ethambutol). Occurrence of rare mutations in three isolates that confer low-level resistance caused lower agreement for rifampicin among the four methods (kappa coefficient (κ) range, 0.84 to 0.95). For isoniazid, there was perfect agreement among phenotypic methods and molecular methods (κ, 1.00) but lower agreement between phenotypic and molecular methods. Three isolates were detected as polydrug-resistant by MGIT 960 system but as multidrug-resistant by DNA sequence-based method. The agreement was higher for streptomycin among the two phenotypic methods (κ, 0.97) while targeted sequencing yielded lower agreement (κ range, 0.86 to 0.89). The discrepancy for ethambutol resulted largely due to lower concordance of MGIT 960 results (κ range, 0.53 to 0.64). The MGIT 960 system is an accurate method for DST of M. tuberculosis against isoniazid and streptomycin while the results of rifampicin susceptibility should be complemented with DNA sequencing-based method when the suspicion for resistance is high. The possibility of false susceptibility to ethambutol with MGIT 960 system suggests that molecular

  7. Discordance across Phenotypic and Molecular Methods for Drug Susceptibility Testing of Drug-Resistant Mycobacterium tuberculosis Isolates in a Low TB Incidence Country

    PubMed Central

    Ahmad, Suhail; Mokaddas, Eiman; Al-Mutairi, Noura; Eldeen, Hanaa S.; Mohammadi, Shirin

    2016-01-01

    With increasing incidence of multidrug-resistant tuberculosis (MDR-TB), accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis to first-line drugs has become crucial for proper patient management. We evaluated concordance of DST results for 70 M. tuberculosis isolates across two phenotypic and two molecular methods: BACTEC 460TB, MGIT 960 system, GenoType MTBDRplus and DNA sequencing of gene segments most commonly implicated in conferring resistance to anti-TB drugs. Most (84%) M. tuberculosis isolates were multidrug-resistant. Twenty-four isolates yielded discrepant DST results. For rifampicin, isoniazid and streptomycin, 96%, 97% and 93% of isolates, respectively, were susceptible or resistant by all four methods, whereas for ethambutol, this agreement was observed for only 76% of isolates (P <0.05 for rifampicin or isoniazid or streptomycin versus ethambutol). Occurrence of rare mutations in three isolates that confer low-level resistance caused lower agreement for rifampicin among the four methods (kappa coefficient (κ) range, 0.84 to 0.95). For isoniazid, there was perfect agreement among phenotypic methods and molecular methods (κ, 1.00) but lower agreement between phenotypic and molecular methods. Three isolates were detected as polydrug-resistant by MGIT 960 system but as multidrug-resistant by DNA sequence-based method. The agreement was higher for streptomycin among the two phenotypic methods (κ, 0.97) while targeted sequencing yielded lower agreement (κ range, 0.86 to 0.89). The discrepancy for ethambutol resulted largely due to lower concordance of MGIT 960 results (κ range, 0.53 to 0.64). The MGIT 960 system is an accurate method for DST of M. tuberculosis against isoniazid and streptomycin while the results of rifampicin susceptibility should be complemented with DNA sequencing-based method when the suspicion for resistance is high. The possibility of false susceptibility to ethambutol with MGIT 960 system suggests that

  8. Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis

    PubMed Central

    Galli, Luisa; Lancella, Laura; Tersigni, Chiara; Venturini, Elisabetta; Chiappini, Elena; Bergamini, Barbara Maria; Codifava, Margherita; Venturelli, Cristina; Tosetti, Giulia; Marabotto, Caterina; Cursi, Laura; Boccuzzi, Elena; Garazzino, Silvia; Tovo, Pier Angelo; Pinon, Michele; Le Serre, Daniele; Castiglioni, Laura; Lo Vecchio, Andrea; Guarino, Alfredo; Bruzzese, Eugenia; Losurdo, Giuseppe; Castagnola, Elio; Bossi, Grazia; Marseglia, Gian Luigi; Esposito, Susanna; Bosis, Samantha; Grandolfo, Rita; Fiorito, Valentina; Valentini, Piero; Buonsenso, Danilo; Domenici, Raffaele; Montesanti, Marco; Salvini, Filippo Maria; Riva, Enrica; Dodi, Icilio; Maschio, Francesca; Abbagnato, Luisa; Fiumana, Elisa; Fornabaio, Chiara; Ballista, Patrizia; Portelli, Vincenzo; Bottone, Gabriella; Palladino, Nicola; Valenzise, Mariella; Vecchi, Barbara; Di Gangi, Maria; Lupi, Carla; Villani, Alberto; de Martino, Maurizio

    2016-01-01

    Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries. PMID:27322255

  9. Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis.

    PubMed

    Galli, Luisa; Lancella, Laura; Tersigni, Chiara; Venturini, Elisabetta; Chiappini, Elena; Bergamini, Barbara Maria; Codifava, Margherita; Venturelli, Cristina; Tosetti, Giulia; Marabotto, Caterina; Cursi, Laura; Boccuzzi, Elena; Garazzino, Silvia; Tovo, Pier Angelo; Pinon, Michele; Le Serre, Daniele; Castiglioni, Laura; Lo Vecchio, Andrea; Guarino, Alfredo; Bruzzese, Eugenia; Losurdo, Giuseppe; Castagnola, Elio; Bossi, Grazia; Marseglia, Gian Luigi; Esposito, Susanna; Bosis, Samantha; Grandolfo, Rita; Fiorito, Valentina; Valentini, Piero; Buonsenso, Danilo; Domenici, Raffaele; Montesanti, Marco; Salvini, Filippo Maria; Riva, Enrica; Dodi, Icilio; Maschio, Francesca; Abbagnato, Luisa; Fiumana, Elisa; Fornabaio, Chiara; Ballista, Patrizia; Portelli, Vincenzo; Bottone, Gabriella; Palladino, Nicola; Valenzise, Mariella; Vecchi, Barbara; Di Gangi, Maria; Lupi, Carla; Villani, Alberto; de Martino, Maurizio

    2016-01-01

    Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries. PMID:27322255

  10. [Tuberculosis in the Czech Republic in 1999].

    PubMed

    Trnka, L; Danková, D; Krejbich, F; Svandová, E

    2000-11-01

    Report is given on the tuberculosis (TB) prevalence and the new diseases monitoring in Czech Republic (CR) in 1999 using the register of notifiable TB diseases. 1631 new TB cases and relapse were notified (15.9/100,000 citizens). Majority TB cases, 1369 (13.3/100,000 citizens) were of the respiratory system and 262 TB cases were in other locations. 63% of the respiratory system diseases were bacteriologically verified. In comparison with the year 1998, the number of newly notified TB patients was 9.6% lower, number of TB cases of the respiratory system which were bacteriologically verified was 12.3% lower, cases of microscopically positive TB were 17.4% less frequent. Among the notified TB patients there were 91 foreigners. TB relapse was identified in 61 patients. Among the notified TB cases, 987 (60.5%) were males and 644 (39.5%) were females. In both sexes patients over 65 predominated. Prevalence of TB cases higher than the average for the whole state was found in Prague, northern and western Bohemia. Groups with TB prevalence higher than 50/100,000 citizens were identified (the risk groups). They include homeless people, drug addicts, asylum applicants, and prisoners. Due to subjective troubles of patients TB was diagnosed in 70.2% cases, by active investigation in 13.9% patients. Late TB diagnosis at autopsy came in 6.8% cases. Decease due to TB was notified in 79 patients. In 77 of them TB had not been diagnosed premortally. 106 new cases and relapses of non-TB mycobacterial disease were notified in 1999. The case of tuberculosis in CR was in 1999 restrainable. In comparison with 1998 significant decrease of TB prevalence in individual subgroups of TB disease was described (10 to 17%). Also the decrease of the long-term trend (10 years) of newly notified TB patients and TB of the respiratory system was depicted. It is necessary to maintain the quality and extend of the TB control program in order to prevent the new outbreak of TB disease.

  11. Integrating tuberculosis and HIV care in rural Rwanda

    PubMed Central

    Gasana, M.; Vandebriel, G.; Kabanda, G.; Tsiouris, S. J.; Justman, J.; Sahabo, R.; Kamugundu, D.; El-Sadr, W. M.

    2016-01-01

    SETTING Rwanda has generalised human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics. The Rwandan Ministry of Health approved a policy on TB-HIV collaborative activities in 2005. The present study is a report on the results of the integrated TB and HIV activities at a rural health care site between July 2005 and June 2006. METHODS Activities included provider-initiated HIV testing and counselling (PITC) of TB patients and the implementation of a standardised TB screening questionnaire for in-patients on medical wards and HIV-infected out-patients. RESULTS Of a total 259 TB patients registered, 87% with unknown HIV status or who were HIV-negative accepted PITC. Overall, 48% (125/259) of TB patients were HIV-infected. The proportion of TB patients ever tested for HIV increased from 82% (138/169) in 2004–2005 to 93% (240/259) in 2005–2006 (P < 0.001). Of the 770 in-patients screened for TB, 162 (21%) tested positive, of whom 53 (33%) were diagnosed with TB; 39 (76%) of these were HIV co-infected. Three hundred out-patients with HIV were screened for TB; 80 (27%) tested positive, of whom 11 (14%) were diagnosed with TB. DISCUSSION Activities integrating TB and HIV were feasible in a rural health care setting. PITC was successful in TB patients and unrecognised TB was common, particularly among HIV-infected in-patients. PMID:18302821

  12. Mycobacterial Protein Tyrosine Phosphatases A and B Inhibitors Augment the Bactericidal Activity of the Standard Anti-tuberculosis Regimen

    PubMed Central

    Dutta, Noton K.; He, Rongjun; Pinn, Michael L.; He, Yantao; Burrows, Francis; Zhang, Zhong-Yin; Karakousis, Petros C.

    2016-01-01

    Novel drugs are required to shorten the duration of treatment for tuberculosis (TB) and to combat the emergence of drug resistance. One approach has been to identify and target Mycobacterium tuberculosis (Mtb) virulence factors, which promote the establishment of TB infection and pathogenesis. Mtb produces a number of virulence factors, including two protein tyrosine phosphatases (PTPs), mPTPA and mPTPB, to evade the antimicrobial functions of host macrophages. To assess the therapeutic potential of targeting the virulent Mtb PTPs, we developed highly potent and selective inhibitors of mPTPA (L335-M34) and mPTPB (L01-Z08) with drug-like properties. We tested the bactericidal activity of L335-M34 and L01-Z08 alone or together in combination with the standard antitubercular regimen of isoniazid-rifampicin-pyrazinamide (HRZ) in the guinea pig model of chronic TB infection, which faithfully recapitulates some of the key histological features of human TB lesions. Following a single dose of L335-M34 50mg/kg and L01-Z08 20 mg/kg, plasma levels were maintained at levels 10-fold greater than the biochemical IC50 for 12–24 hours. Although neither PTP inhibitor alone significantly enhanced the antibacterial activity of HRZ, dual inhibition of mPTPA and mPTPB in combination with HRZ showed modest synergy, even after 2 weeks of treatment. After 6 weeks of treatment, the degree of lung inflammation correlated with the bactericidal activity of each drug regimen. This study highlights the potential utility of targeting Mtb virulence factors, and specifically the Mtb PTPs, as a strategy for enhancing the activity of standard anti-TB treatment. PMID:27478867

  13. 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…

  14. Development of vaccines to control the worldwide tuberculosis pandemic.

    PubMed

    Hoft, Daniel F

    2014-01-01

    Mycobacterium tuberculosis (Mtb) infection and tuberculosis (TB) disease are major public health problems. Available BCG vaccines are partially effective against severe disease, but have not reduced the overall prevalence of TB infection and disease. A third of the world's population is latently infected with Mtb, and therefore more effective prophylactic and therapeutic vaccines are urgently needed. The Hoft laboratory and the Saint Louis University Center for Vaccine Development (SLUCVD) are actively pursuing these important goals.

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

    PubMed Central

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

    2016-01-01

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

  16. Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

    PubMed Central

    2013-01-01

    Background A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras. PMID:23497342

  17. Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4+CD25+ T cells in patients with active tuberculosis

    PubMed Central

    Kong, Bin; Liu, Gan-Bin; Zhang, Jun-Ai; Fu, Xiao-Xia; Xiang, Wen-Yu; Gao, Yu-Chi; Lu, Yuan-Bin; Wu, Xian-Jing; Qiu, Feng; Wang, Wan-Dang; Yi, Lai-Long; Zhong, Ji-Xin; Chen, Zheng W; Xu, Jun-Fa

    2016-01-01

    Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4+ but not CD8+ T cells. Most p35+CD4+ T cells and EBI3+CD4+ T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB. PMID:27158354

  18. Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4(+)CD25(+) T cells in patients with active tuberculosis.

    PubMed

    Kong, Bin; Liu, Gan-Bin; Zhang, Jun-Ai; Fu, Xiao-Xia; Xiang, Wen-Yu; Gao, Yu-Chi; Lu, Yuan-Bin; Wu, Xian-Jing; Qiu, Feng; Wang, Wan-Dang; Yi, Lai-Long; Zhong, Ji-Xin; Chen, Zheng W; Xu, Jun-Fa

    2016-01-01

    Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4(+) but not CD8(+) T cells. Most p35(+)CD4(+) T cells and EBI3(+)CD4(+) T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB.

  19. Affordable TB treatments. South.

    PubMed

    1998-07-01

    This short article reports the proceedings of a session of the World Health Organization (WHO) on tuberculosis (TB) prevention and management. 15 million persons are infected with both TB and HIV; 11 million of these people are in sub-Saharan Africa. Current TB management relies on finding cases and treating them. According to Paul Nunn of WHO, the role of preventive therapy is unclear. Jensa Bell, of Mt. Sinai Hospital in New York, reported on the cost effectiveness of prevention with isoniazid (INH) in sub-Saharan Africa. Direct medical costs of the drug for 6 months are CHF171/year of life saved. When social costs of TB and prevention of secondary cases are included, INH prophylaxis saves money; initial investment is CHF34.50/person treated, while cost averted is CHF36.24/person treated. Mary Mulindwa, of the Joint Clinical Research Centre in Kampala, Uganda, studied reasons for nonadherence to TB preventive regimens in a clinical trial. Major reasons included the following: 1) transport difficulties; 2) caring for a sick family member; 3) change of address without informing the home visitor; and 4) stigma of being seen with a health worker. Richard Chaisson, of the CP-CRA004/ACTG177 study group, reported results from a trial comparing prevention with INH for 12 months to rifampin plus pyrazinamide (R/P) for 2 months in 1600 tuberculin-positive, HIV-positive people without active disease in the US, Mexico, Brazil, and Haiti. "Effective therapy" with INH was equal to at least 6 months of continuous adherence; 67% of patients met this standard. 80% of R/P patients were adherent. Over 3 years, there were 26 confirmed cases of TB in the INH group and 19 in the R/P group; these results are equivalent. However, Chaisson noted that the cost and feasibility of R/P treatment in resource-poor settings should be considered.

  20. Affordable TB treatments. South.

    PubMed

    1998-07-01

    This short article reports the proceedings of a session of the World Health Organization (WHO) on tuberculosis (TB) prevention and management. 15 million persons are infected with both TB and HIV; 11 million of these people are in sub-Saharan Africa. Current TB management relies on finding cases and treating them. According to Paul Nunn of WHO, the role of preventive therapy is unclear. Jensa Bell, of Mt. Sinai Hospital in New York, reported on the cost effectiveness of prevention with isoniazid (INH) in sub-Saharan Africa. Direct medical costs of the drug for 6 months are CHF171/year of life saved. When social costs of TB and prevention of secondary cases are included, INH prophylaxis saves money; initial investment is CHF34.50/person treated, while cost averted is CHF36.24/person treated. Mary Mulindwa, of the Joint Clinical Research Centre in Kampala, Uganda, studied reasons for nonadherence to TB preventive regimens in a clinical trial. Major reasons included the following: 1) transport difficulties; 2) caring for a sick family member; 3) change of address without informing the home visitor; and 4) stigma of being seen with a health worker. Richard Chaisson, of the CP-CRA004/ACTG177 study group, reported results from a trial comparing prevention with INH for 12 months to rifampin plus pyrazinamide (R/P) for 2 months in 1600 tuberculin-positive, HIV-positive people without active disease in the US, Mexico, Brazil, and Haiti. "Effective therapy" with INH was equal to at least 6 months of continuous adherence; 67% of patients met this standard. 80% of R/P patients were adherent. Over 3 years, there were 26 confirmed cases of TB in the INH group and 19 in the R/P group; these results are equivalent. However, Chaisson noted that the cost and feasibility of R/P treatment in resource-poor settings should be considered. PMID:12222196

  1. Current Concepts in the Management of Tuberculosis

    PubMed Central

    Sia, Irene G.; Wieland, Mark L.

    2011-01-01

    Tuberculosis (TB) poses a serious threat to public health throughout the world but disproportionately afflicts low-income nations. Persons in close contact with a patient with active pulmonary TB and those from endemic regions of the world are at highest risk of primary infection, whereas patients with compromised immune systems are at highest risk of reactivation of latent TB infection (LTBI). Tuberculosis can affect any organ system. Clinical manifestations vary accordingly but often include fever, night sweats, and weight loss. Positive results on either a tuberculin skin test or an interferon-γ release assay in the absence of active TB establish a diagnosis of LTBI. A combination of epidemiological, clinical, radiographic, microbiological, and histopathologic features is used to establish the diagnosis of active TB. Patients with suspected active pulmonary TB should submit 3 sputum specimens for acid-fast bacilli smears and culture, with nucleic acid amplification testing performed on at least 1 specimen. For patients with LTBI, treatment with isoniazid for 9 months is preferred. Patients with active TB should be treated with multiple agents to achieve bacterial clearance, to reduce the risk of transmission, and to prevent the emergence of drug resistance. Directly observed therapy is recommended for the treatment of active TB. Health care professionals should collaborate, when possible, with local and state public health departments to care for patients with TB. Patients with drug-resistant TB or coinfection with human immunodeficiency virus should be treated in collaboration with TB specialists. Public health measures to prevent the spread of TB include appropriate respiratory isolation of patients with active pulmonary TB, contact investigation, and reduction of the LTBI burden. PMID:21454737

  2. Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment.

    PubMed

    Sánchez, María D; García, Yoenis; Montes, Carlos; París, Sara C; Rojas, Mauricio; Barrera, Luis F; Arias, Mauricio A; García, Luis F

    2006-08-01

    Alterations of monocyte/macrophages have been reported in patients with tuberculosis (TB), but their significance is poorly understood. Blood mononuclear cells from patients with different clinical forms of TB, at various times of anti-TB treatment, and healthy tuberculin positive individuals, were double-stained for CD14 plus CD206, TLR-2, IFN-gammaR1, CD40, HLA-DR, CD36 and CD163, and analyzed by flow cytometry. Monocytes were infected with Mycobacterium tuberculosis H37Rv and 24h later the phenotype, induction of necrosis and apoptosis and production of tumor necrosis factor TNFalpha, interleukin (IL)-10 and IL-12p40 were determined. TB patients presented higher percentage of CD14+ cells but lower percentage of CD14+DR+ and CD14+CD36+ cells. Expression of CD14, HLA-DR and CD36 was decreased in TB patients. Normal percentages and expression were restored during anti-TB treatment. Monocytes from TB patients underwent necrosis and apoptosis after M. tuberculosis infection, whereas monocytes from healthy controls exhibited only apoptosis. Anti-TB treatment reverted necrosis. There were no differences between the various clinical forms of TB. In vitro M. tuberculosis infection decreased expression of the membrane molecules studied. HLA-DR and CD36 inhibition correlated with induction of apoptosis. Restoration of monocyte alterations during anti-TB treatment suggests that such alterations may be caused by the high M. tuberculosis load present during active disease.

  3. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    2016-01-01

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells. PMID:27144688

  4. Perspectives on tuberculosis in pregnancy.

    PubMed

    Bates, Matthew; Ahmed, Yusuf; Kapata, Nathan; Maeurer, Markus; Mwaba, Peter; Zumla, Alimuddin

    2015-03-01

    Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations. PMID:25809768

  5. 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.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar. PMID:24842853

  8. Targeting Dormant Bacilli to Fight Tuberculosis

    PubMed Central

    Fattorini, Lanfranco; Piccaro, Giovanni; Mustazzolu, Alessandro; Giannoni, Federico

    2013-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which kills about 2 million people annually. Furthermore, 2 billion people worldwide are latently infected with this organism, with 10% of them reactivating to active TB due to re-growth of nonreplicating (dormant) Mtb residing in their tissues. Because of the huge reservoir of latent TB it is important to find novel drugs/drug combinations killing dormant bacilli (microaerophiles, anaerobes and drug-tolerant persisters) surviving for decades in a wide spectrum of granulomatous lesions in the lungs of TB patients. Antibiotic treatment of drug-susceptible TB requires administration of isoniazid, rifampin, pyrazinamide, ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. To avoid reactivation of dormant Mtb to active pulmonary TB, up to 9 months of treatment with isoniazid is required. Therefore, a strategy to eliminate dormant bacilli needs to be developed to shorten therapy of active and latent TB and reduce the reservoir of people with latent TB. Finding drugs with high rate of penetration into the caseous granulomas and understanding the biology of dormant bacilli and in particular of persister cells, phenotypically resistant to antibiotics, will be essential to eradicate Mtb from humans. In recent years unprecedented efforts have been done in TB drug discovery, aimed at identifying novel drugs and drug combinations killing both actively replicating and nonreplicating Mtb in vitro, in animal models and in clinical trials in humans. PMID:24363887

  9. Targeting dormant bacilli to fight tuberculosis.

    PubMed

    Fattorini, Lanfranco; Piccaro, Giovanni; Mustazzolu, Alessandro; Giannoni, Federico

    2013-11-19

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which kills about 2 million people annually. Furthermore, 2 billion people worldwide are latently infected with this organism, with 10% of them reactivating to active TB due to re-growth of nonreplicating (dormant) Mtb residing in their tissues. Because of the huge reservoir of latent TB it is important to find novel drugs/drug combinations killing dormant bacilli (microaerophiles, anaerobes and drug-tolerant persisters) surviving for decades in a wide spectrum of granulomatous lesions in the lungs of TB patients. Antibiotic treatment of drug-susceptible TB requires administration of isoniazid, rifampin, pyrazinamide, ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. To avoid reactivation of dormant Mtb to active pulmonary TB, up to 9 months of treatment with isoniazid is required. Therefore, a strategy to eliminate dormant bacilli needs to be developed to shorten therapy of active and latent TB and reduce the reservoir of people with latent TB. Finding drugs with high rate of penetration into the caseous granulomas and understanding the biology of dormant bacilli and in particular of persister cells, phenotypically resistant to antibiotics, will be essential to eradicate Mtb from humans. In recent years unprecedented efforts have been done in TB drug discovery, aimed at identifying novel drugs and drug combinations killing both actively replicating and nonreplicating Mtb in vitro, in animal models and in clinical trials in humans.

  10. Differential expression of antimicrobial peptides in active and latent tuberculosis and its relationship with diabetes mellitus.

    PubMed

    Gonzalez-Curiel, Irma; Castañeda-Delgado, Julio; Lopez-Lopez, Nallely; Araujo, Zaida; Hernandez-Pando, Rogelio; Gandara-Jasso, Benjamin; Macias-Segura, Noe; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

    2011-08-01

    Tuberculosis (TB) is one of the most important infectious diseases, causing 1.8 million deaths annually worldwide. This problem has increased because of the association with human immmunodeficiency virus and diabetes mellitus type 2, mainly in developing countries. In the past few years it has been highlighted the significance of antimicrobial peptides in the immunopathogenesis of TB ex vivo and in experimental models studies. In this study we analyzed the expression of CAMP, DEFA1, DEFB4, and DEFB103A in patients with latent TB and progressive TB with and without comorbidity with diabetes mellitus type 2. Antimicrobial peptide gene expression increased during progressive TB, which could be used as a biomarker for reactivation. By contrast, patients with diabetes mellitus type 2 have lower antimicrobial peptides gene expression, suggesting that the lack of its proper production in these patients contribute to enhance the risk for TB reactivation.

  11. Tuberculosis Data and Statistics

    MedlinePlus

    ... Organization Chart Advisory Groups Federal TB Task Force Data and Statistics Language: English Español (Spanish) Recommend on ... United States publication. PDF [6 MB] Interactive TB Data Tool Online Tuberculosis Information System (OTIS) OTIS is ...

  12. Active tuberculosis in a psoriasis patient treated with tumor necrosis factor inhibitors despite an initial negative tuberculin skin test and no known risk factors.

    PubMed

    Gilbert, Kathleen E Gilbert E; Manalo, Iviesan F; Wu, Jashin J

    2016-01-01

    Tumor necrosis factor (TNF) inhibitors are becoming more common in the treatment of moderate-to-severe chronic plaque psoriasis. These medications have a low incidence of serious adverse events and are generally considered safe; however, they do make patients more susceptible to tuberculosis (TB) infection both through latent reactivation and primary infection. We describe a case of a patient who had an initial negative tuberculin skin test (TST), began TNF inhibitor therapy, and then 11 years later was diagnosed with active TB. After the initial screening, the patient did not have any subsequent screenings for TB and no apparent change to his TB risk status. TB is still common in many areas of the United States and travel is not necessary to be exposed. Patients on TNF inhibitors that develop active TB have increased morbidity and mortality than those who are not. It is necessary that dermatologists limit the risk of TB to patients by screening them before initiation and annually when they are on the TNF inhibitor. PMID:27617949

  13. Antimycobacterial activity of pyrazinoate prodrugs in replicating and non-replicating Mycobacterium tuberculosis.

    PubMed

    Segretti, Natanael Dante; Simões, Cristina Kortstee; Corrêa, Michelle Fidelis; Felli, Veni Maria Andres; Miyata, Marcelo; Cho, Sang Hyun; Franzblau, Scott Gary; Fernandes, João Paulo Dos Santos

    2016-07-01

    Tuberculosis (TB) is an important infectious disease caused by Mycobacterium tuberculosis (Mtb) and responsible for thousands of deaths every year. Although there are antimycobacterial drugs available in therapeutics, just few new chemical entities have reached clinical trials, and in fact, since introduction of rifampin only two important drugs had reached the market. Pyrazinoic acid (POA), the active agent of pyrazinamide, has been explored through prodrug approach to achieve novel molecules with anti-Mtb activity, however, there is no activity evaluation of these molecules against non-replicating Mtb until the present. Additionally, pharmacokinetic must be preliminary evaluated to avoid future problems during clinical trials. In this paper, we have presented six POA esters as prodrugs in order to evaluate their anti-Mtb activity in replicating and non-replicating Mtb, and these showed activity highly influenced by medium composition (especially by albumin). Lipophilicity seems to play the main role in the activity, possibly due to controlling membrane passage. Novel duplicated prodrugs of POA were also described, presenting interesting activity. Cytotoxicity of these prodrugs set was also evaluated, and these showed no important cytotoxic profile. PMID:27449999

  14. Accuracy of the QuantiFERON-TB Gold in Tube for diagnosing tuberculosis in a young pediatric population previously vaccinated with Bacille Calmette-Guérin

    PubMed Central

    Vallada, Marcelo Genofre; Okay, Thelma Suely; Del Negro, Gilda Maria B.; Antonio, Claudio Amaral; Yamamoto, Lidia; Ramos, Sonia Regina T. S.

    2014-01-01

    Objective: To evaluate the accuracy of an interferongamma release assay (QuantiFERON-TB Gold in Tube) for diagnosing Mycobacterium tuberculosis infection in a young pediatric population. Methods: 195 children previously vaccinated with BCG were evaluated, being 184 healthy individuals with no clinical or epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium tuberculosis infection, according to clinical, radiological, and laboratory parameters. A blood sample was obtained from each child and processed according to the manufacturer's instructions. The assay performance was evaluated by a Receiver Operating Characteristic (ROC) curve. Results: In the group of 184 non-infected children, 130 (70.6%) were under the age of four years (mean age of 35 months). In this group, 177 children (96.2%) had negative test results, six (3.2%) had indeterminate results, and one (0.5%) had a positive result. In the group of 11 infected children, the mean age was 58.5 months, and two of them (18%) had negative results. The ROC curve had an area under the curve of 0.88 (95%CI 0.82-0.92; p<0.001), disclosing a predictive positive value of 81.8% for the test (95%CI 46.3-97.4). The assay sensitivity was 81.8% (95%CI 48.2-97.2) and the specificity was 98.8% (95%CI 96-99.8). Conclusions: In the present study, the QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection was appropriate in a young pediatric population. PMID:24676183

  15. Micrococcin P1 - A bactericidal thiopeptide active against Mycobacterium tuberculosis.

    PubMed

    Degiacomi, Giulia; Personne, Yoann; Mondésert, Guillaume; Ge, Xueliang; Mandava, Chandra Sekhar; Hartkoorn, Ruben C; Boldrin, Francesca; Goel, Pavitra; Peisker, Kristin; Benjak, Andrej; Barrio, Maria Belén; Ventura, Marcello; Brown, Amanda C; Leblanc, Véronique; Bauer, Armin; Sanyal, Suparna; Cole, Stewart T; Lagrange, Sophie; Parish, Tanya; Manganelli, Riccardo

    2016-09-01

    The lack of proper treatment for serious infectious diseases due to the emergence of multidrug resistance reinforces the need for the discovery of novel antibiotics. This is particularly true for tuberculosis (TB) for which 3.7% of new cases and 20% of previously treated cases are estimated to be caused by multi-drug resistant strains. In addition, in the case of TB, which claimed 1.5 million lives in 2014, the treatment of the least complicated, drug sensitive cases is lengthy and disagreeable. Therefore, new drugs with novel targets are urgently needed to control resistant Mycobacterium tuberculosis strains. In this manuscript we report the characterization of the thiopeptide micrococcin P1 as an anti-tubercular agent. Our biochemical experiments show that this antibiotic inhibits the elongation step of protein synthesis in mycobacteria. We have further identified micrococcin resistant mutations in the ribosomal protein L11 (RplK); the mutations were located in the proline loop at the N-terminus. Reintroduction of the mutations into a clean genetic background, confirmed that they conferred resistance, while introduction of the wild type RplK allele into resistant strains re-established sensitivity. We also identified a mutation in the 23S rRNA gene. These data, in good agreement with previous structural studies suggest that also in M. tuberculosis micrococcin P1 functions by binding to the cleft between the 23S rRNA and the L11 protein loop, thus interfering with the binding of elongation factors Tu and G (EF-Tu and EF-G) and inhibiting protein translocation. PMID:27553416

  16. Tuberculosis and Pregnancy

    MedlinePlus

    ... Contacts of Persons with Infectious TB Epidemiology of Pediatric Tuberculosis in the United States Targeted Tuberculosis Testing ... and unknown risks of second-line antituberculosis drugs. Breastfeeding Breastfeeding should not be discouraged for women being ...

  17. The MprB Extracytoplasmic Domain Negatively Regulates Activation of the Mycobacterium tuberculosis MprAB Two-Component System

    PubMed Central

    Bretl, Daniel J.; Bigley, Tarin M.; Terhune, Scott S.

    2014-01-01

    Mycobacterium tuberculosis is an acid-fast pathogen of humans and the etiological agent of tuberculosis (TB). It is estimated that one-third of the world's population is latently (persistently) infected with M. tuberculosis. M. tuberculosis persistence is regulated, in part, by the MprAB two-component signal transduction system, which is activated by and mediates resistance to cell envelope stress. Here we identify MprAB as part of an evolutionarily conserved cell envelope stress response network and demonstrate that MprAB-mediated signal transduction is negatively regulated by the MprB extracytoplasmic domain (ECD). In particular, we report that deregulated production of the MprB sensor kinase, or of derivatives of this protein, negatively impacts M. tuberculosis growth. The observed growth attenuation is dependent on MprAB-mediated signal transduction and is exacerbated in strains of M. tuberculosis producing an MprB variant lacking its ECD. Interestingly, full-length MprB, and the ECD of MprB specifically, immunoprecipitates the Hsp70 chaperone DnaK in vivo, while overexpression of dnaK inhibits MprAB-mediated signal transduction in M. tuberculosis grown in the absence or presence of cell envelope stress. We propose that under nonstress conditions, or under conditions in which proteins present in the extracytoplasmic space are properly folded, signaling through the MprAB system is inhibited by the MprB ECD. Following exposure to cell envelope stress, proteins present in the extracytoplasmic space become unfolded or misfolded, leading to removal of the ECD-mediated negative regulation of MprB and subsequent activation of MprAB. PMID:24187094

  18. Risk of Tuberculosis Among Patients on Dialysis

    PubMed Central

    Shu, Chin-Chung; Hsu, Chia-Lin; Wei, Yu-Feng; Lee, Chih-Yuan; Liou, Hung-Hsiang; Wu, Vin-Cent; Yang, Feng-Jung; Lin, Hsien-Ho; Wang, Jann-Yuan; Chen, Jin-Shing; Yu, Chong-Jen; Lee, Li-Na

    2016-01-01

    Abstract Patients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis. Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6-month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed. The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT-GIT. In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs. PMID:27258523

  19. Microwave synthesis and photocatalytic activity of Tb(3+) doped BiVO4 microcrystals.

    PubMed

    Wang, Ying; Liu, Fuyang; Hua, Yingjie; Wang, Chongtai; Zhao, Xudong; Liu, Xiaoyang; Li, Hongdong

    2016-12-01

    Tb(3+) doped BiVO4 has been successfully synthesized by a simple microwave-assisted hydrothermal method at 140°C for 30min. The structure, morphology and optical property of the Tb(3+) doped BiVO4 products have been systematically investigated. This study indicates that the incorporation of Tb(3+) could induce the conversion of structure from monoclinic to tetragonal for BiVO4. Furthermore, the as-obtained Tb(3+) doped BiVO4 samples showed an obvious morphological change: the hollow square rod-like BiVO4 crystal gradually changed to spindle-like crystal. The Tb(3+) doped BiVO4 products exhibited extraordinary photocatalytic activity for Methylene Blue (MB) degradation under visible light irradiation. The doped BiVO4 at a molar ratio of 2at% (Tb and Bi) with a mixture of monoclinic and tetragonal phases showed and prominent photocatalytic degradation rate, which reached 99.9% in 120min. The results suggest that the differences in the photocatalytic activity of these BiVO4 crystals with different Tb(3+) doping concentrations can be attributed to the change of crystalline phases, and the coexistence of the monoclinic/tetragonal phases in BiVO4 products, which improve the efficient charge separation and transportation. PMID:27565962

  20. Multidrug-Resistant Tuberculosis Treatment Outcomes in Karakalpakstan, Uzbekistan: Treatment Complexity and XDR-TB among Treatment Failures

    PubMed Central

    Cox, Helen S.; Kalon, Stobdan; Allamuratova, Sholpan; Sizaire, Vinciane; Tigay, Zinaida N.; Rüsch-Gerdes, Sabine; Karimovich, Hamraev A.; Kebede, Yared; Mills, Clair

    2007-01-01

    Background A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. Methodology This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. Principal Findings Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. Conclusions While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment. PMID:17987113

  1. Tuberculosis in children.

    PubMed

    Marais, Ben J; Schaaf, H Simon

    2014-09-01

    Many clinicians regard tuberculosis as an adult pulmonary disease, but tuberculosis (TB) is a major cause of disease, both pulmonary and extrapulmonary, and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children. PMID:25037105

  2. Standardization of natural mycolic acid antigen composition and production for use in biomarker antibody detection to diagnose active tuberculosis.

    PubMed

    Ndlandla, F L; Ejoh, V; Stoltz, A C; Naicker, B; Cromarty, A D; van Wyngaardt, S; Khati, M; Rotherham, L S; Lemmer, Y; Niebuhr, J; Baumeister, C R; Al Dulayymi, J R; Swai, H; Baird, M S; Verschoor, J A

    2016-08-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, is characterized by the abundance of species specific, antigenic cell wall lipids called mycolic acids. These wax-like molecules all share an identical, amphiphilic mycolic motif, but have different functional groups in a long hydrophobic hydrocarbon mero-chain that divide them into three main classes: alpha-, keto- and methoxy-mycolic acids. Whereas alpha-mycolic acids constitutively maintain an abundance of around 50%, the ratio of methoxy- to keto-mycolic acid types may vary depending on, among other things, the growth stage of M. tuberculosis. In human patients, antibodies to mycolic acids have shown potential as diagnostic serum biomarkers for active TB. Variations in mycolic acid composition affect the antigenic properties and can potentially compromise the precision of detection of anti-mycolic acids antibodies in patient sera to natural mixtures. We demonstrate this here with combinations of synthetic mycolic acid antigens, tested against TB patient and control sera. Combinations of methoxy- and α-mycolic acids are more antigenic than combinations of keto- and α-mycolic acids, showing the former to give a more sensitive test for TB biomarker antibodies. Natural mixtures of mycolic acids isolated from mature cultures of M. tuberculosis H37Rv give the same sensitivity as that with synthetic methoxy- and α-mycolic acids in combination, in a surface plasmon resonance inhibition biosensor test. To ensure that the antigenic activity of isolates of natural mycolic acids is reproducible, we cultured M. tuberculosis H37Rv on Middlebrook 7H10 solid agar plates to stationary growth phase in a standardized, optimal way. The proportions of mycolic acid classes in various batches of the isolates prepared from these cultures were compared to a commercially available natural mycolic acid isolate. LC-MS/MS and NMR data for quantitation of mycolic acids class compositions show that the variation in batches

  3. 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.

  4. Tuberculosis (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Tuberculosis KidsHealth > For Parents > Tuberculosis Print A A A Text Size What's in ... When to You Call the Doctor en español Tuberculosis Tuberculosis (popularly known as "TB") is a disease ...

  5. Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis.

    PubMed

    1995-09-01

    Tuberculosis (TB) rates declined steadily for decades in the United States, but several complex social and medical factors caused TB morbidity to increase 14% from 1985 through 1993. The recent increases in TB morbidity have placed additional demands on state and local TB control programs, which already had been substantially weakened by inadequate staffing and funding support. TB programs throughout the nation must be revitalized if they are to provide core TB control activities that enable effective responses to this public health challenge. This report describes a model for TB control programs and the essential components of a successful TB control program, including three priority strategies for TB prevention and control: a) identifying and treating persons who have active TB, b) finding and screening persons who have had contact with TB patients to determine whether they are infected with Mycobacterium tuberculosis or have active TB and providing appropriate treatment, and c) screening populations at high risk for TB infection and the development of TB disease to detect infected persons and providing therapy to prevent progression to active TB. State and local health departments have primary responsibility for preventing and controlling TB. To meet this challenge successfully, TB control programs should be able to administer activities that include the following core components: conducting overall planning and development of policy, identifying persons who have clinically active TB, managing persons who have or who are suspected of having disease, identifying and managing persons infected with M. tuberculosis, providing laboratory and diagnostic services, collecting and analyzing data, and providing training and education. The Advisory Council for the Elimination of Tuberculosis has prepared this report to provide a national standard by which policymakers, TB control program managers, and others evaluating TB programs can assess individual TB control programs

  6. Mycobacterium tuberculosis Peptidyl-Prolyl Isomerases Also Exhibit Chaperone like Activity In-Vitro and In-Vivo

    PubMed Central

    Pandey, Saurabh; Sharma, Ashish; Tripathi, Deeksha; Kumar, Ashutosh; Khubaib, Mohd; Bhuwan, Manish; Chaudhuri, Tapan Kumar; Hasnain, Seyed Ehtesham; Ehtesham, Nasreen Zafar

    2016-01-01

    Peptidyl-prolyl cis-trans isomerases (Ppiases), also known as cyclophilins, are ubiquitously expressed enzymes that assist in protein folding by isomerization of peptide bonds preceding prolyl residues. Mycobacterium tuberculosis (M.tb) is known to possess two Ppiases, PpiA and PpiB. However, our understanding about the biological significance of mycobacterial Ppiases with respect to their pleiotropic roles in responding to stress conditions inside the macrophages is restricted. This study describes chaperone-like activity of mycobacterial Ppiases. We show that recombinant rPpiA and rPpiB can bind to non-native proteins in vitro and can prevent their aggregation. Purified rPpiA and rPpiB exist in oligomeric form as evident from gel filtration chromatography.E. coli cells overexpressing PpiA and PpiB of M.tb could survive thermal stress as compared to plasmid vector control. HEK293T cells transiently expressing M.tb PpiA and PpiB proteins show increased survival as compared to control cells in response to oxidative stress and hypoxic conditions generated after treatment with H2O2 and CoCl2 thereby pointing to their likely role in adaption under host generated oxidative stress and conditions of hypoxia. The chaperone-like function of these M.tuberculosis cyclophilins may possibly function as a stress responder and consequently contribute to virulence. PMID:26981873

  7. 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

  8. Cross-matching TB and AIDS registries: TB patients with HIV co-infection, United States, 1993-1994.

    PubMed Central

    Moore, M; McCray, E; Onorato, I M

    1999-01-01

    OBJECTIVES: Because of limited reporting of HIV status in case reports to the national tuberculosis (TB) surveillance system, the authors conducted this study to estimate the proportion of US TB cases with HIV co-infection and to describe demographic and clinical characteristics of co-infected patients. METHODS: The 50 states, New York City, and Puerto Rico submitted the results of cross-matches of TB registries and HIV-AIDS registries. The authors determined the number of TB cases reported for 1993-1994 that were listed in HIV-AIDS registries and analyzed data on demographic and clinical characteristics by match status. RESULTS: Of 49,938 TB cases reported for 1993-1994, 6863 (14%) were listed in AIDS or HIV registries. The proportions of TB-AIDS cases among TB cases varied by reporting area, from 0% to 31%. Anti-TB drug resistance was higher among TB-AIDS cases, particularly resistance to isoniazid and rifampin (multidrug resistance) and rifampin alone, In some areas with low proportions of multidrug-resistant TB cases, however, the difference in multidrug resistance between TB-AIDS patients and non-AIDS TB patients was not found. CONCLUSIONS: The proportion of TB cases with HIV co-infection, particularly in some areas, underscores the importance of the HIV-AIDS epidemic for the epidemiology of TB. Efforts to improve HIV testing as well as reporting of HIV status for TB patients should continue to ensure optimum management of coinfected patients, enhance surveillance activities, and promote judicious resource allocation and targeted prevention and control activities. PMID:10476997

  9. Rifampicin Mono-Resistance in Mycobacterium tuberculosis in KwaZulu-Natal, South Africa: A Significant Phenomenon in a High Prevalence TB-HIV Region

    PubMed Central

    Coovadia, Yacoob Mahomed; Mahomed, Sharana; Pillay, Melendhran; Werner, Lise; Mlisana, Koleka

    2013-01-01

    Setting The dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH. Increasing proportions of rifampicin mono-resistance resistance (RMR) have recently been reported from South Africa and other countries. Objective This laboratory based study was conducted at NHLS TB Laboratory, Durban, which is the reference laboratory for culture and susceptibility testing in KwaZulu-Natal. We retrospectively determined, for the period 2007 to 2009, the proportion of RMR amongst Mycobacterium tuberculosis (MTB) isolates, that were tested for both RIF and INH, using the gold standard of culture based phenotypic drug susceptibility testing (DST). Gender and age were also analysed to identify possible risk factors for RMR. Design MTB culture positive sputum samples from 16,748 patients were analysed for susceptibility to RIF and INH during the period 2007 to 2009. RMR was defined as MTB resistant to RIF and susceptible to INH. For the purposes of this study, only the first specimen from each patient was included in the analysis. Results RMR was observed throughout the study period. The proportion of RMR varied from a low of 7.3% to a high of 10.0% [overall 8.8%]. Overall, males had a 42% increased odds of being RMR as compared to females. In comparison to the 50 plus age group, RMR was 37% more likely to occur in the 25–29 year age category. Conclusion We report higher proportions of RMR ranging from 7.3% to 10% [overall 8.8%] than previously reported in the literature. To avoid misclassification of RMR, detected by the GeneXpert, as MDR-TB, culture based phenotypic DST must be performed on a second specimen, as

  10. Composition of three essential oils, and their mammalian cell toxicity and antimycobacterial activity against drug resistant-tuberculosis and nontuberculous mycobacteria strains.

    PubMed

    Bueno, Juan; Escobar, Patricia; Martínez, Jairo René; Leal, Sandra Milena; Stashenko, Elena E

    2011-11-01

    Tuberculosis (TB) is the most ancient epidemic disease in the world and a serious opportunistic disease in HIV/AIDS patients. The increase in multidrug resistant Mycobacterium tuberculosis (MDR-TB, XDR-TB) demands the search for novel antimycobacterial drugs. Essential oils (EOs) have been widely used in medicine and some EOs and their major components have been shown to be active against M. tuberculosis. The aim of this work was to evaluate the antimycobacterial and cell toxicity activities of three EOs derived from Salvia aratocensis, Turnera diffusa and Lippia americana, aromatics plants collected in Colombia. The EOs were isolated by hydrodistillation and analyzed by GC/MS techniques. The EOs were tested against 15 Mycobacterium spp using a colorimetric macrodilution method and against mammalian Vero and THP-1 cells by MTT. The activity was expressed as minimal concentration in microg/mL that inhibits growth, and the concentration that is cytotoxic for 50 or 90% of the cells (CC50 and CC90). The major components were epi-alpha-cadinol (20.1%) and 1,10-di-epi-cubenol (14.2%) for Salvia aratocensis; drima-7,9(11)-diene (22.9%) and viridiflorene (6.6%) for Turnera diffusa; and germacrene D (15.4%) and trans-beta- caryophyllene (11.3%) for Lippia americana. The most active EO was obtained from S. aratocensis, with MIC values below 125 microg mL(-1) for M. tuberculosis Beijing genotype strains, and 200 to 500 microg mL(-1) for nontuberculous mycobacterial strains. The EOs were either partially or non toxic to Vero and THP-1 mammalian cells with CC50 values from 30 to > 100 microg mL(-1), and a CC90 > 100 microg mL(-1). The EOs obtained from the three aromatic Colombian plants are an important source of potential compounds against TB. Future studies using the major EO components are recommended. PMID:22224302

  11. New insights toward the discovery of antibacterial agents: multi-tasking QSBER model for the simultaneous prediction of anti-tuberculosis activity and toxicological profiles of drugs.

    PubMed

    Speck-Planche, Alejandro; Kleandrova, Valeria V; Cordeiro, M Natália D S

    2013-03-12

    Tuberculosis (TB) constitutes one of the most dangerous and serious health problems around the world. It is a very lethal disease caused by microorganisms of the genus mycobacterium, principally Mycobacterium tuberculosis (MTB) which affects humans. A very active field for the search of more efficient anti-TB chemotherapies is the use in silico methodologies for the discovery of potent anti-TB agents. The battle against MTB by using antimicrobial chemotherapies will depend on the design of new chemicals with high anti-TB activity and low toxicity as possible. Multi-target methodologies focused on quantitative-structure activity relationships (mt-QSAR) have played a very important role for the rationalization of drug design, providing a better understanding about the molecular patterns related with diverse pharmacological profiles including antimicrobial activity. Nowadays, almost all mt-QSAR models have considered the study of biological activity or toxicity separately. In the present study, we develop by the first time, a unified multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for the simultaneous prediction of anti-TB activity and toxicity against Mus musculus and Rattus norvegicus. The mtk-QSBER model was created by using linear discriminant analysis (LDA) for the classification of compounds as positive (high biological activity and/or low toxicity) or negative (otherwise) under many experimental conditions. Our mtk-QSBER model, correctly classified more than 90% of the case in the whole database (more than 12,000 cases), serving as a powerful tool for the computer-assisted screening of potent and safe anti-TB drugs.

  12. 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.

  13. [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.

  14. Mean Platelet Volume in Mycobacterium tuberculosis Infection

    PubMed Central

    Lee, Min Young; Kim, Young Jin; Lee, Hee Joo; Park, Tae Sung

    2016-01-01

    Introduction. Mean platelet volume (MPV) has been thought as a useful index of platelet activation. It is supposed that MPV is also associated with several inflammatory and infectious diseases. Korea still has a high incidence of tuberculosis (TB). The aim of this study was to investigate MPV as an inflammatory marker in TB patients. Materials and Methods. MPV were determined in 221 patients with TB and 143 individuals for control group. MPV was estimated by an Advia 2120 (Siemens Healthcare Diagnostics, Tarrytown, NY, USA). Results. In the TB patient group, a positive correlation was found between CRP and MPV. Age and MPV had a positive correlation in TB patient group. Conclusions. We conclude that there is a significant relation between MPV and inflammatory conditions. MPV can be an inflammatory marker to determine the disease activity in TB patients. PMID:27419136

  15. Tuberculosis.

    PubMed

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

    2016-03-19

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

  16. Tuberculosis.

    PubMed

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

    2016-03-19

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

  17. In Vitro Antimicrobial Activity of Extracts from Plants Used Traditionally in South Africa to Treat Tuberculosis and Related Symptoms

    PubMed Central

    Madikizela, Balungile; Ndhlala, Ashwell Rungano; Finnie, Jeffrey Franklin; Staden, Johannes Van

    2013-01-01

    Respiratory ailments are major human killers, especially in developing countries. Tuberculosis (TB) is an infectious disease causing a threat to human healthcare. Many South African plants are used in the traditional treatment of TB and related symptoms, but there has not been a sufficient focus on evaluating their antimicrobial properties. The aim of this study was to evaluate the antimicrobial properties of plants used traditionally to treat TB and related symptoms against microorganisms (Klebsiella pneumoniae, Staphylococcus aureus, and Mycobacterium aurum A+) associated with respiratory infections using the microdilution assay. Ten plants were selected based on a survey of available literature of medicinal plants used in South Africa for the treatment of TB and related symptoms. The petroleum ether, dichloromethane, 80% ethanol, and water extracts of the selected plants were evaluated for antibacterial activity. Out of 68 extracts tested from different parts of the 10 plant species, 17 showed good antimicrobial activities against at least one or more of the microbial strains tested, with minimum inhibitory concentration ranging from 0.195 to 12.5 mg/mL. The good antimicrobial properties of Abrus precatorius, Terminalia phanerophlebia, Indigofera arrecta, and Pentanisia prunelloides authenticate their traditional use in the treatment of respiratory diseases. Thus, further pharmacological and phytochemical analysis is required. PMID:23533527

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

    PubMed Central

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

    2016-01-01

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

  19. A Focused Screen Identifies Antifolates with Activity on Mycobacterium tuberculosis.

    PubMed

    Kumar, Anuradha; Guardia, Ana; Colmenarejo, Gonzalo; Pérez, Esther; Gonzalez, Ruben R; Torres, Pedro; Calvo, David; Gómez, Ruben M; Ortega, Fátima; Jiménez, Elena; Gabarro, Raquel C; Rullás, Joaquín; Ballell, Lluis; Sherman, David R

    2015-12-11

    Antifolates are widely used to treat several diseases but are not currently used in the first-line treatment of tuberculosis, despite evidence that some of these molecules can target Mycobacterium tuberculosis (Mtb) bacilli in vitro. To identify new antifolate candidates for animal-model efficacy studies of tuberculosis, we paired knowledge and tools developed in academia with the infrastructure and chemistry resources of a large pharmaceutical company. Together we curated a focused library of 2508 potential antifolates, which were then tested for activity against live Mtb. We identified 210 primary hits, confirmed the on-target activity of potent compounds, and now report the identification and characterization of 5 hit compounds, representative of 5 different chemical scaffolds. These antifolates have potent activity against Mtb and represent good starting points for improvement that could lead to in vivo efficacy studies. PMID:26771003

  20. 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.

  1. [TUBERCULOSIS ANNUAL REPORT 2014--(1) Summary of Statistics on Tuberculosis Notification and Foreign-born Tuberculosis Patients].

    PubMed

    2016-02-01

    This brief is the first of a series of documents based on the Tuberculosis Annual Report 2014. It includes a summary of tuberculosis (TB) statistics, including data on foreign-born TB patients notified and registered in Japan in 2014. For the first time, the number of newly notified cases (all forms of TB) fell below 20,000. In 2014, a total of 19,615 patients were notified, a rate of 15.4 per 100,000 population The number of sputum-smear positive pulmonary. TB patients notified was 7,651, a rate of 6.0 per 100,000 population. The number of patients with latent TB infections increased slightly from 7,147 in 2013 to 7,562 in 2014. The proportion of miliary TB cases has constantly increased over the past 10 years, especially among women aged 80 years and older. The number of foreign-born TB patients continued to increase from 1,064 in 2013 to 1,101 in 2014. In 2014, new foreign-born TB patients aged 20-29 years accounted for 44.1% of all new TB patients in that age group. Among foreign-born TB patients, half were from the Philippines (26.5%) and China (23.5%). However, the number of patients from Vietnam and Nepal is increasing. Among foreign-born TB patients, 28% were regular employees, 26% were students, and 20% were unemployed. The changing trend in the nationality of foreign students entering Japan may at least partially explain the differences in TB burden among foreign-born patients, by country of birth. As we expect to see the proportion of foreign-born TB patients continue to rise, more tailored case identification and treatment support activities are needed.

  2. [TUBERCULOSIS ANNUAL REPORT 2014--(1) Summary of Statistics on Tuberculosis Notification and Foreign-born Tuberculosis Patients].

    PubMed

    2016-02-01

    This brief is the first of a series of documents based on the Tuberculosis Annual Report 2014. It includes a summary of tuberculosis (TB) statistics, including data on foreign-born TB patients notified and registered in Japan in 2014. For the first time, the number of newly notified cases (all forms of TB) fell below 20,000. In 2014, a total of 19,615 patients were notified, a rate of 15.4 per 100,000 population The number of sputum-smear positive pulmonary. TB patients notified was 7,651, a rate of 6.0 per 100,000 population. The number of patients with latent TB infections increased slightly from 7,147 in 2013 to 7,562 in 2014. The proportion of miliary TB cases has constantly increased over the past 10 years, especially among women aged 80 years and older. The number of foreign-born TB patients continued to increase from 1,064 in 2013 to 1,101 in 2014. In 2014, new foreign-born TB patients aged 20-29 years accounted for 44.1% of all new TB patients in that age group. Among foreign-born TB patients, half were from the Philippines (26.5%) and China (23.5%). However, the number of patients from Vietnam and Nepal is increasing. Among foreign-born TB patients, 28% were regular employees, 26% were students, and 20% were unemployed. The changing trend in the nationality of foreign students entering Japan may at least partially explain the differences in TB burden among foreign-born patients, by country of birth. As we expect to see the proportion of foreign-born TB patients continue to rise, more tailored case identification and treatment support activities are needed. PMID:27263231

  3. To control and beyond: moving towards eliminating the global tuberculosis threat

    PubMed Central

    Brewer, T.; Heymann, S

    2004-01-01

    For 10 years the World Health Organisation has had a single answer to the deadly threat of tuberculosis (TB)—provide treatment to smear positive patients and watch them take it. In contrast with confident statements about how global TB would be brought under control when directly observed therapy, short course (DOTS) was introduced, TB continues to rise worldwide. The introduction of selected multiple drug resistant TB treatment programmes, "DOTS-Plus", although important, also focuses on therapy for active TB. HIV endemic countries in particular have experienced tremendous increases in TB despite having DOTS programmes. A critical review of recent epidemiological data and computer models shows that the present international strategy of concentrating on providing treatment for smear positive TB, DOTS and DOTS-Plus, is likely to have only a modest impact on population based TB control. Effective global TB control will require strategies that go beyond relying on treatment of people with active disease. PMID:15365106

  4. Comparison of AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR for Detection of Mycobacterium tuberculosis Complex in Routine Clinical Practice.

    PubMed

    Cho, Won-Hyung; Won, Eun-Jeong; Choi, Hyun-Jung; Kee, Seung-Jung; Shin, Jong-Hee; Ryang, Dong-Wook; Suh, Soon-Pal

    2015-05-01

    The AdvanSure tuberculosis/non-tuberculous mycobacterium (TB/NTM) PCR (LG Life Science, Korea) and COBAS TaqMan Mycobacterium tuberculosis (MTB) PCR (Roche Diagnostics, USA) are commonly used in clinical microbiology laboratories. We aimed to evaluate these two commercial real-time PCR assays for detection of MTB in a large set of clinical samples over a two-year period. AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR were performed on 9,119 (75.2%) and 3,010 (24.8%) of 12,129 (9,728 respiratory and 2,401 non-respiratory) MTB specimens, with 361 (4.0%) and 102 (3.4%) acid-fast bacilli (AFB)-positive results, respectively. In MTB culture, 788 (6.5%) MTB and 514 (4.2%) NTM were identified. The total sensitivity and specificity of the AdvanSure assay were 67.8% (95% confidence interval [CI], 63.9-71.6) and 98.3% (95% CI, 98.0-98.6), while those of the COBAS TaqMan assay were 67.2% (95% CI, 60.0-73.8) and 98.4% (95% CI, 97.9-98.9), respectively. The sensitivities and specificities of the AdvanSure and COBAS TaqMan assays for AFB-positive and AFB-negative samples were comparable. Furthermore, the AdvanSure assay showed fewer invalid results compared with the COBAS TaqMan assay (5.0 vs. 20.4 invalid results/1,000 tests, P<0.001). AdvanSure assay represents a comparable yet more reliable method than COBAS TaqMan for the identification of mycobacteria in routine clinical microbiology.

  5. Mycobacterium tuberculosis PPE protein Rv0256c induces strong B cell response in tuberculosis patients.

    PubMed

    Abraham, Philip Raj; Latha, Gaddam Suman; Valluri, Vijaya Lakshmi; Mukhopadhyay, Sangita

    2014-03-01

    Tuberculosis (TB) is one of the most important diseases of humans and major public health problem worldwide. Early and accurate diagnosis of TB is necessary for the treatment, prevention, and control of TB. Therefore, it is important to identify suitable antigens that can differentiate active tuberculosis patients from BCG-vaccinated individuals. In the present study, we have used Rv0256c (PPE2) protein of Mycobacterium tuberculosis to screen the sera of infected patients belonging to different clinical TB presentations, and BCG-vaccinated clinically healthy individuals by enzyme immunoassay. Our results demonstrated that Rv0256c displayed stronger and specific immunoreactivity against the sera obtained from clinically active tuberculosis patients compared to PPD and ESAT-6 and could differentiate the TB-patients from the BCG-vaccinated controls. Importantly, Rv0256c was also found to detect even the extrapulmonary and smear-negative pulmonary cases which often are tedious and difficult to detect using conventional diagnostic methods. This study suggests that Rv0256c can be used as a potential marker for the serodiagnosis of tuberculosis patients. PMID:23827809

  6. 38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  7. 38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  8. 38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  9. 38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  10. Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan

    PubMed Central

    Pan, Sung-Ching; Chen, Yee-Chun; Wang, Jann-Yuan; Sheng, Wang-Huei; Lin, Hsien-Ho; Fang, Chi-Tai; Chang, Shan-Chwen

    2015-01-01

    Background Proportional mortality ratio data indicate that healthcare workers (HCWs) have an elevated tuberculosis (TB) mortality. Whether this is caused by an increased TB incidence, a worse TB treatment outcome, or a combination of effects, remains unclear. To elucidate the hazard components of occupational TB, we assessed TB incidence and TB treatment outcome among HCWs in Taiwan. Methods We compared the incidence of active TB among HCWs at a major medical center in Taiwan with that of Taiwan general population in 2004–2012. We also compared the TB treatment outcome of HCWs with that of age/sex-matched non-HCW patients treated at the same hospital, as well as that of nationally registered TB patients. Results The standardized TB incidence ratio of the HCWs was 1.9 (95% confidence interval [CI]: 1.2–2.9), compared with the general population. HCWs with pulmonary TB (n = 30) were less likely to have underlying diseases, delay in diagnosis, delay in treatment, or side effects of treatment, compared with age/sex-matched non-HCW TB patients (n = 120) (all Ps<0.05). The TB treatment outcome of HCWs was significantly better than that of non-HCW patients (TB-related mortality: 0.0% vs. 5.8%, P = 0.008, Mantel-Haenszel test). The standardized TB-related mortality rate was 1.08% [95% CI: 0.96% - 1.20%] for all of the nationally registered TB patients in Taiwan. Conclusions HCWs are at increased risk of active TB, compared with general population. To mitigate this occupational hazard, more efforts need to be directed towards the prevention of nosocomial TB transmission. Healthy worker effect, more rapid diagnosis, and less delay in treatment contribute to a lower TB-related mortality in HCWs. PMID:26679188

  11. A Missed Tuberculosis Diagnosis Resulting in Hospital Transmission

    PubMed Central

    Medrano, Belinda A.; Salinas, Gloria; Sanchez, Connie; Miramontes, Roque; Restrepo, Blanca I.; Haddad, Maryam B.; Lambert, Lauren A.

    2016-01-01

    OBJECTIVE To find the source of tuberculin skin test conversions among 38 hospital employees on 1 floor during routine testing January–February 2010. METHODS Record review of patients at a private hospital during September–December 2009 and interviews with hospital employees. Names of patients from the state tuberculosis (TB) registry were cross-referenced with hospital records for admissions. Mycobacterium tuberculosis genotype results in the county and adjacent counties were examined, and contacts were evaluated for TB infection and disease. RESULTS One of the 38 employees, a nurse, was diagnosed with pulmonary TB with a matching M. tuberculosis genotype and drug resistance pattern (isoniazid monoresistant) to those of a county jail inmate also recently diagnosed with pulmonary TB. The nurse had no known contact with that inmate; however, another inmate in his 20’s from the same jail had been hospitalized under that nurse’s care in October 2009. That young man died, and a postmortem examination result subsequently confirmed TB, which had not been suspected. Exposure to this man with undiagnosed TB could explain the transmission: 87 (27%) of the 318 hospital-based contacts without previous positive tuberculin skin test results were infected, and 9 contacts had active TB. CONCLUSIONS This investigation demonstrated M. tuberculosis transmission in a hospital due to a missed diagnosis and nonadherence to national TB infection control guidelines. Routine TB screening of employees allowed early detection of this missed TB diagnosis, facilitating prompt evaluation of contacts. Healthcare providers should suspect TB in symptomatic persons and adhere to TB control policies. PMID:24709722

  12. Tuberculosis-resistant transgenic cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis is a devastating disease that affects humans and many animal species. In humans, tuberculosis (TB) is mainly caused by Mycobacterium tuberculosis, while most cases in cattle are caused by Mycobacterium bovis. However, Mb can also cause, albeit rarely, human TB. In this issue, Wu et al. ...

  13. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (TB) to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the burden of TB is now difficult to manage. Therefore, new antimycobacterial agents are being sought from natural sources. This review focuses on natural antimycobacterial agents from endophytes and medicinal plants of Africa, Europe, Asia, South America and Canada. In the countries mentioned in this review, numerous plant species display putative anti-TB activity. Several antimycobacterial chemical compounds have also been isolated, including: ellagitannin punicalagin, allicin, anthraquinone glycosides, iridoids, phenylpropanoids, beta-sitosterol, galanthimine, crinine, friedelin, gallic acid, ellagic acids, anthocyanidin, taraxerol, termilignan B, arjunic acid, glucopyranosides, 1-epicatechol, leucopelargonidol, hydroxybenzoic acids, benzophenanthridine alkaloids, neolignans, and decarine. These compounds may provide leads to novel and more efficacious drugs to lessen the global burden of TB and drug-resistant M. tuberculosis strains. If there is a long-term remedy for TB, it must lie in nature's pharmacy of putative antimycobacterial agents.

  14. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (TB) to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the burden of TB is now difficult to manage. Therefore, new antimycobacterial agents are being sought from natural sources. This review focuses on natural antimycobacterial agents from endophytes and medicinal plants of Africa, Europe, Asia, South America and Canada. In the countries mentioned in this review, numerous plant species display putative anti-TB activity. Several antimycobacterial chemical compounds have also been isolated, including: ellagitannin punicalagin, allicin, anthraquinone glycosides, iridoids, phenylpropanoids, beta-sitosterol, galanthimine, crinine, friedelin, gallic acid, ellagic acids, anthocyanidin, taraxerol, termilignan B, arjunic acid, glucopyranosides, 1-epicatechol, leucopelargonidol, hydroxybenzoic acids, benzophenanthridine alkaloids, neolignans, and decarine. These compounds may provide leads to novel and more efficacious drugs to lessen the global burden of TB and drug-resistant M. tuberculosis strains. If there is a long-term remedy for TB, it must lie in nature's pharmacy of putative antimycobacterial agents. PMID:26464047

  15. Diagnostics for pulmonary tuberculosis

    PubMed Central

    Cudahy, Patrick

    2016-01-01

    Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID:27005271

  16. Tuberculin Skin Test and QuantiFERON(®)-TB Gold In-Tube Test for Diagnosing Latent Tuberculosis Infection among Thai Healthcare Workers.

    PubMed

    Khawcharoenporn, Thana; Apisarnthanarak, Anucha; Sangkitporn, Somchai; Rudeeaneksin, Janisara; Srisungngam, Sopa; Bunchoo, Supranee; Phetsuksiri, Benjawan

    2016-05-20

    A cross-sectional study was conducted on the performance of the tuberculin skin test (TST) and QuantiFERON(®)-TB Gold In-Tube test (QFT-IT) for detecting latent tuberculosis infection among Thai healthcare workers (HCWs). Each HCW underwent both the TST and QFT-IT during the annual health screening. Among the 260 HCWs enrolled, the median age was 30 years (range 19-60 years), 92% were women, 64% were nurses and nurse assistants, 78% were Bacillus Calmette Guérin vaccinated, and 37% had previously taken the TST. Correlation between TST reaction size and the interferon-γ level was weak (r = 0.29; P < 0.001). Of the HCWs, 38% and 20% had a reactive TST and a positive QFT-IT, respectively. Using QFT-IT positivity as a standard for latent tuberculosis diagnosis, the cut-off for TST reactivity with the best performance was ≥13 mm with a sensitivity, specificity, false positivity, and false negativity of 71%, 70%, 30%, and 29%, respectively (area under the curve 0.73; P < 0.001). The independent factor associated with a false reactive TST was a previous TST (adjusted odds ratio 1.83; P = 0.04). Our findings suggest that the QFT-IT may be the preferred test among HCWs with previous TST. In settings where the QFT-IT is not available, appropriate cut-offs for TST reactivity should be evaluated for use among HCWs.

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

    PubMed Central

    2010-01-01

    Background Plants have long been investigated as a source of antibiotics and other bioactives for the treatment of human disease. New Zealand contains a diverse and unique flora, however, few of its endemic plants have been used to treat tuberculosis. One plant, Laurelia novae-zelandiae, was reportedly used by indigenous Maori for the treatment of tubercular lesions. Methods Laurelia novae-zelandiae and 44 other native plants were tested for direct anti-bacterial activity. Plants were extracted with different solvents and extracts screened for inhibition of the surrogate species, Mycobacterium smegmatis. Active plant samples were then tested for bacteriostatic activity towards M. tuberculosis and other clinically-important species. Results Extracts of six native plants were active against M. smegmatis. Many of these were also inhibitory towards M. tuberculosis including Laurelia novae-zelandiae (Pukatea). M. excelsa (Pohutukawa) was the only plant extract tested that was active against Staphylococcus aureus. Conclusions Our data provide support for the traditional use of Pukatea in treating tuberculosis. In addition, our analyses indicate that other native plant species possess antibiotic activity. PMID:20537175

  18. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens.

    PubMed

    Sali, Michela; De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Delogu, Giovanni; Giagulli, Cinzia

    2016-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance.

  19. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens

    PubMed Central

    De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Giagulli, Cinzia

    2015-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance. PMID:26491178

  20. Implementing a successful tuberculosis programme within primary care services in a conflict area using the stop TB strategy: Afghanistan case study

    PubMed Central

    2014-01-01

    Introduction Afghanistan has faced health consequences of war including those due to displacement of populations, breakdown of health and social services, and increased risks of disease transmission for over three decades. Yet it was able to restructure its National Tuberculosis Control Programme (NTP), integrate tuberculosis treatment into primary health care and achieve most of its targets by the year 2011. What were the processes that enabled the programme to achieve its targets? More importantly, what were the underpinning factors that made this success possible? We addressed these important questions through a case study. Case description We adopted a processes and outcomes framework for this study, which began with examining the change in key programme indicators, followed by backwards tracing of the processes and underlying factors, responsible for this change. Methods included review of the published and grey literature along with in-depth interviews of 15 key informants involved with the care of tuberculosis patients in Afghanistan. Discussion and evaluation TB incidence and mortality per 100,000 decreased from 325 and 92 to 189 and 39 respectively, while case notification and treatment success improved during the decade under study. Efficient programme structures were enabled through high political commitment from the Government, strong leadership from the programme, effective partnership and coordination among stakeholders, and adequate technical and financial support from the development partners. Conclusions The NTP Afghanistan is an example that public health programmes can be effectively implemented in fragile states. High political commitment and strong local leadership are essential factors for such programmes. To ensure long-term effectiveness of the NTP, the international support should be withdrawn in a phased manner, coupled with a sequential increase in resources allocated to the NTP by the Government of Afghanistan. PMID:24507446

  1. Nutritional supplements for people being treated for active tuberculosis

    PubMed Central

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

    2016-01-01

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

  2. Nutritional supplements for people being treated for active tuberculosis

    PubMed Central

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

    2016-01-01

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

  3. Interferon-γ release assay in HIV-infected patients with active tuberculosis: impact of antituberculous drugs on host immune response.

    PubMed

    Sauzullo, Ilaria; Mengoni, Fabio; Ermocida, Angela; Massetti, Anna P; D'Agostino, Claudia; Russo, Gianluca; Salotti, Alessandra; Falciano, Mario; Vullo, Vincenzo; Mastroianni, Claudio M

    2014-04-01

    The objective of the study was to: 1) investigate the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) in HIV-infected patients with active tuberculosis (TB); 2) evaluate the sequential changes in QFT-GIT assay during the treatment response; 3) investigate the direct in vitro effects of antituberculous drugs on both secretion of IFN-g and apoptosis of T cells. Forty-four HIV-patients with active TB were enrolled and tested with QFT-GIT. Thirteen of them were followed longitudinally by QFT-GIT, performed at baseline and six and nine months after TB-treatment onset. For in vitro experiments, cells from healthy donors and HIV-naive subjects were pretreated with four antituberculous-drugs, and then examined for IFN-g secretion and apoptosis of T-cells. The QFT-GIT was positive in 66%, negative in 11.3% and indeterminate in 22.7%. Longitudinal analysis in 13 HIV-TB subjects showed that at therapy completion a reversion to negative response was found only in 38.4% of patients, but in 30.7% the QFT-GIT remained positive. Overall, during the anti-TB treatment no significant decrease in average IFN-g response was observed in these patients (p<0.001). In vitro experiments showed that the four antituberculous- drugs, within the range of therapeutically achievable concentrations, did not exert any down-regulatory effect on IFN-g production and did not have any effect on apoptosis of T cells from HIV naïve subjects. Despite the high rate of indeterminate results, QFT-GIT assay may represent a good tool in the diagnostic workup for active TB in HIV-patients. Although the antituberculous drugs do not have any direct effect on host immune response to mycobacterial antigen, changes in longitudinal IGRA response have been found during in vivo anti-TB treatment.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  6. Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia.

    PubMed

    Guan, Yi-Fu; Song, Xun; Qiu, Ming-Hua; Luo, Shi-Hong; Wang, Bao-Jie; Van Hung, Nguyen; Cuong, Nguyen M; Soejarto, Djaja Doel; Fong, Harry H S; Franzblau, Scott G; Li, Sheng-Hong; He, Zhen-Dan; Zhang, Hong-Jie

    2016-08-01

    Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 μm in MABA assay, respectively, and 91.7 and 168.3 μm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 μm in MABA assay and 100.2 μm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives.

  7. Blood Transcriptional Biomarkers for Active Tuberculosis among Patients in the United States: a Case-Control Study with Systematic Cross-Classifier Evaluation

    PubMed Central

    Miller, Mikaela A.; Vasquez, Joshua; Weiner, Marc; Chapman, Adam; Engle, Melissa; Higgins, Michael; Quinones, Amy M.; Rosselli, Vanessa; Canono, Elizabeth; Yoon, Christina; Cattamanchi, Adithya; Davis, J. Lucian; Phang, Tzu; Stearman, Robert S.; Datta, Gargi; Garcia, Benjamin J.; Daley, Charles L.; Strong, Michael; Kechris, Katerina; Fingerlin, Tasha E.; Reves, Randall; Geraci, Mark W.

    2015-01-01

    Blood transcriptional signatures are promising for tuberculosis (TB) diagnosis but have not been evaluated among U.S. patients. To be used clinically, transcriptional classifiers need reproducible accuracy in diverse populations that vary in genetic composition, disease spectrum and severity, and comorbidities. In a prospective case-control study, we identified novel transcriptional classifiers for active TB among U.S. patients and systematically compared their accuracy to classifiers from published studies. Blood samples from HIV-uninfected U.S. adults with active TB, pneumonia, or latent TB infection underwent whole-transcriptome microarray. We used support vector machines to classify disease state based on transcriptional patterns. We externally validated our classifiers using data from sub-Saharan African cohorts and evaluated previously published transcriptional classifiers in our population. Our classifier distinguishing active TB from pneumonia had an area under the concentration-time curve (AUC) of 96.5% (95.4% to 97.6%) among U.S. patients, but the AUC was lower (90.6% [89.6% to 91.7%]) in HIV-uninfected Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 90.0% (87.7% to 92.3%) and 82.9% (80.8% to 85.1%) when tested in U.S. patients. Our classifier distinguishing active TB from latent TB had AUC values of 95.9% (95.2% to 96.6%) among U.S. patients and 95.3% (94.7% to 96.0%) among Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 98.0% (97.4% to 98.7%) and 94.8% (92.9% to 96.8%) when tested in U.S. patients. Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable

  8. [Tuberculosis in Asia].

    PubMed

    2002-10-01

    1. Philippines: The development, expansion and maintenance of pilot area activities: Cristina B. Giango (Technical Division, Cebu Provincial Health Office, the Philippines) In 1994, the Department of Health developed the new NTP policies based on WHO recommendations and started a pilot project in Cebu Province in collaboration with the Japan International Cooperation Agency. To test its feasibility and effectiveness, the new NTP policies were pre-tested in one city and one Rural Health Unit. The test showed a high rate of three sputum collection (90%), high positive rate (10%), and high cure rate (80%). Before the new guidelines were introduced, the new policy was briefed, a baseline survey of the facility was conducted, equipment was provided, and intensive training was given. Recording/Reporting forms and procedures were also developed to ensure accurate reporting. Supervision, an important activity to ensure effective performance, was institutionalized. Laboratory services were strengthened, and a quality-control system was introduced in 1995 to ensure the quality of the laboratory services. With the implementation of DOTS strategy, barangay health workers were trained as treatment partners. In partnership with the private sector, the TB Diagnostic Committee was organized to deliberate and assess sputum negative but X-ray positive cases. The implementation of the new NTP guidelines in Cebe Province has reached a satisfactory level, the cure rate and positive rate have increased, and laboratory services have improved. Because of its successful implementation, the new NTP guidelines are now being used nationwide. 2. Nepal: The DOTS Strategy in the area with hard geographic situation: Dirgh Singh Bam (National Tuberculosis Center, Nepal) Three groups of factors characterize the population of Nepal: 1) Socio-cultural factors, e.g. migration, poverty, language; 2) Environmental factors, e.g. geography and climate; and 3) Political factors, prisoners and refugee

  9. Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions

    PubMed Central

    Savolainen, Laura E.; Kantele, Anu; Knuuttila, Aija; Pusa, Liana; Karttunen, Riitta; Valleala, Heikki; Tuuminen, Tamara

    2016-01-01

    New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette–Guérin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-γ, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential. PMID:27379100

  10. Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions.

    PubMed

    Savolainen, Laura E; Kantele, Anu; Knuuttila, Aija; Pusa, Liana; Karttunen, Riitta; Valleala, Heikki; Tuuminen, Tamara

    2016-01-01

    New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette-Guérin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-γ, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential. PMID:27379100

  11. How human immunodeficiency virus voluntary testing can contribute to tuberculosis control.

    PubMed Central

    Godfrey-Faussett, Peter; Maher, Dermot; Mukadi, Ya Diul; Nunn, Paul; Perriëns, Joseph; Raviglione, Mario

    2002-01-01

    Human immunodeficiency virus (HIV) is fueling the tuberculosis (TB) epidemic, particularly in sub-Saharan Africa. However, despite their close epidemiological links, the public health responses have largely been separate. WHO has set out a strategy to decrease the burden of HIV-related TB, comprising interventions against both TB and HIV. Voluntary counselling and testing (VCT) for HIV can link TB and HIV programme activities. The benefits of VCT for HIV to TB patients include referral for appropriate clinical care and support for those testing HIV-positive. Likewise, people attending a centre for VCT can benefit from TB screening: those found to be both HIV-positive and with active TB need referral for TB treatment; those without active TB should be offered TB preventive treatment with isoniazid. To explore how VCT for HIV can contribute to a more coherent response to TB, WHO is coordinating the ProTEST Initiative. The name "ProTEST" is derived from the Promotion of voluntary testing as an entry point for access to the core interventions of intensified TB case-finding and isoniazid preventive treatment. Other interventions may be added to provide finally a comprehensive range of HIV and TB prevention and care interventions. Under the ProTEST Initiative, pilot districts are establishing links between centres for VCT for HIV and TB prevention and care. This will pave the way for large-scale operationalization of the comprehensive range of interventions needed to control TB in settings with high HIV prevalence. PMID:12571721

  12. LL-37 immunomodulatory activity during Mycobacterium tuberculosis infection in macrophages.

    PubMed

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

    2015-12-01

    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.

  13. 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

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

    PubMed Central

    Malhotra, Shelly; Koeut, Pichenda; Thai, Sopheak; Khun, Kim Eam; Colebunders, Robert; Lynen, Lut

    2015-01-01

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

  15. Tuberculosis Contact Investigations--United States, 2003-2012.

    PubMed

    Young, Kai H; Ehman, Melissa; Reves, Randall; Peterson Maddox, Brandy L; Khan, Awal; Chorba, Terence L; Jereb, John

    2016-01-01

    Mycobacterium tuberculosis is transmitted through the air from an infectious patient (index patient) to other persons (contacts) who share space. Exposure to M. tuberculosis can result in tuberculosis (TB) disease or latent TB infection (LTBI), which has no clinical symptoms or radiologic evidence of disease. The cycle of transmission can be ended by isolating and treating patients with TB disease, examining contacts, and treating LTBI to prevent progression to TB disease. CDC systematically collects aggregate data on contact investigations from the 50 states, the District of Columbia (DC), and Puerto Rico. Data from 2003-2012 were analyzed for trends in yields from contact investigations, in terms of numbers of contacts elicited and examined and the estimated number of TB cases averted through treatment of LTBI among contacts in 2012. During 2003-2012, the number of TB cases decreased, while the number of contacts listed per index patient with contacts elicited increased. In 2012, U.S. public health authorities reported 9,945 cases of TB disease (1) and 105,100 contacts. Among these contacts, 84,998 (80.9%) were examined; TB was diagnosed in 532 (0.6%) and LTBI in 15,411 (18.1%). Among contacts with LTBI, 10,137 (65.8%) started treatment, and 6,689 (43.4% of all contacts with LTBI) completed treatment. By investigating contacts in 2012, an estimated 128 TB cases (34% of all potential cases) over the initial 5 years were averted, but an additional 248 cases (66%) might have been averted if all potentially contagious TB patients had contacts elicited, all contacts were examined, and all infected contacts completed treatment. Enhancing contact investigation activities, particularly by ensuring completion of treatment by contacts recently infected with M. tuberculosis, is essential to achieve the goal of TB elimination.

  16. Drug-Resistant Tuberculosis: A Genetic Analysis Using Online Bioinformatics Tools

    ERIC Educational Resources Information Center

    Taylor, Jessica M.; Davidson, Rebecca M.; Strong, Michael

    2014-01-01

    Tuberculosis (TB) continues to be a serious global health problem, resulting in >1.4 million deaths each year. Of increasing concern is the evolution of antibiotic resistant strains of the bacterium that causes TB. Using this real-world scenario, we created a 90-minute activity for high school or undergraduate students to use online…

  17. Cytokine and Antibody Based Diagnostic Algorithms for Sputum Culture-Positive Pulmonary Tuberculosis

    PubMed Central

    Fleming, Joy; Chen, Liang; Wang, Yunxia; Li, Haicheng; Guo, Huixin; Zhou, Jie; Chen, Xunxun; Chen, Yuhui; Liao, Qinghua; Shu, Yang; Tan, Yaoju; Yu, Meiling; Li, Guozhou; Zhou, Lin; Zhong, Qiu; Bi, Lijun; Guo, Lina; Zhao, Meigui

    2015-01-01

    Background Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples. Methods TB-related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods. Results Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%). Conclusions Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical

  18. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; Del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death. PMID:25754313

  19. Time-series analysis of monthly age-specific numbers of newly registered cases of active tuberculosis in Japan from 1998 to 2013.

    PubMed

    Kohei, Y; Sumi, A; Kobayashi, N

    2016-08-01

    We investigated the seasonality of age-specific tuberculosis (TB) in Japan. To allow the development of TB control strategies for different age groups we used a time-series analysis, including a spectral analysis and least squares method, to analyse the monthly age-specific numbers of newly registered cases of all forms of active TB in Japan from January 1998 to December 2013. The time-series data are reported in 10-year age groups: 0-9, 10-19, …, 70-79, and ⩾80 years. We defined the contribution ratio of the 1-year cycle, Q 1, as the contribution of the amplitude of a 1-year cycle to the whole amplitude of the time-series data. The Q 1 values in the age groups corresponding to adolescence and middle life (10-39 years) and old age (⩾70 years) were high. The peaks in the active TB epidemics for the ⩾70 years age group occurred in August and September, 1-2 months behind the peaks for the 10-39 years age group (June and July). An active TB epidemic might be attributable to travel by public transport and irregular employment in the 10-39 years age group and immune system suppression by low winter temperatures in the ⩾70 years age group.

  20. Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH): protocol for a multicentric prospective observational study

    PubMed Central

    Gupte, Akshay; Padmapriyadarsini, Chandrasekaran; Mave, Vidya; Kadam, Dileep; Suryavanshi, Nishi; Shivakumar, Shri Vijay Bala Yogendra; Kohli, Rewa; Gupte, Nikhil; Thiruvengadam, Kannan; Kagal, Anju; Meshram, Sushant; Bharadwaj, Renu; Khadse, Sandhya; Ramachandran, Geetha; Hanna, Luke Elizabeth; Pradhan, Neeta; Gomathy, N S; DeLuca, Andrea; Gupta, Amita; Swaminathan, Soumya

    2016-01-01

    Introduction Tuberculosis disease (TB) remains an important global health threat. An evidence-based response, tailored to local disease epidemiology in high-burden countries, is key to controlling the global TB epidemic. Reliable surrogate biomarkers that predict key active disease and latent TB infection outcomes are vital to advancing clinical research necessary to ‘End TB’. Well executed longitudinal studies strengthening local research capacity for addressing TB research priorities and advancing biomarker discovery are urgently needed. Methods and analysis The Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH) study conducted in Byramjee Jeejeebhoy Government Medical College (BJGMC), Pune and National Institute for Research in Tuberculosis (NIRT), Chennai, India, will establish and maintain three prospective cohorts: (1) an Active TB Cohort comprising 800 adults with pulmonary TB, 200 adults with extrapulmonary TB and 200 children with TB; (2) a Household Contact Cohort of 3200 adults and children at risk of developing active disease; and (3) a Control Cohort consisting of 300 adults and 200 children with no known exposure to TB. Relevant clinical, sociodemographic and psychosocial data will be collected and a strategic specimen repository established at multiple time points over 24 months of follow-up to measure host and microbial factors associated with (1) TB treatment outcomes; (2) progression from infection to active TB disease; and (3) Mycobacterium tuberculosis transmission among Indian adults and children. We anticipate CTRIUMPH to serve as a research platform necessary to characterise some relevant aspects of the TB epidemic in India, generate evidence to inform local and global TB control strategies and support novel TB biomarker discovery. Ethics and dissemination This study is approved by the Institutional Review Boards of NIRT, BJGMC and Johns Hopkins University, USA. Study results will be disseminated through peer

  1. Pyrimidine salvage pathway in Mycobacterium tuberculosis.

    PubMed

    Villela, A D; Sánchez-Quitian, Z A; Ducati, R G; Santos, D S; Basso, L A

    2011-01-01

    The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, infects one-third of the world population. TB remains the leading cause of mortality due to a single bacterial pathogen. The worldwide increase in incidence of M. tuberculosis has been attributed to the high proliferation rates of multi and extensively drug-resistant strains, and to co-infection with the human immunodeficiency virus. There is thus a continuous requirement for studies on mycobacterial metabolism to identify promising targets for the development of new agents to combat TB. Singular characteristics of this pathogen, such as functional and structural features of enzymes involved in fundamental metabolic pathways, can be evaluated to identify possible targets for drug development. Enzymes involved in the pyrimidine salvage pathway might be attractive targets for rational drug design against TB, since this pathway is vital for all bacterial cells, and is composed of enzymes considerably different from those present in humans. Moreover, the enzymes of the pyrimidine salvage pathway might have an important role in the mycobacterial latent state, since M. tuberculosis has to recycle bases and/or nucleosides to survive in the hostile environment imposed by the host. The present review describes the enzymes of M. tuberculosis pyrimidine salvage pathway as attractive targets for the development of new antimycobacterial agents. Enzyme functional and structural data have been included to provide a broader knowledge on which to base the search for compounds with selective biological activity.

  2. Autophagy in the fight against tuberculosis.

    PubMed

    Bento, Carla F; Empadinhas, Nuno; Mendes, Vítor

    2015-04-01

    Tuberculosis (TB), a chronic infectious disease mainly caused by the tubercle bacillus Mycobacterium tuberculosis, is one of the world's deadliest diseases that has afflicted humanity since ancient times. Although the number of people falling ill with TB each year is declining, its incidence in many developing countries is still a major cause of concern. Upon invading host cells by phagocytosis, M. tuberculosis can replicate within infected cells by arresting the maturation of the phagosome whose function is to target the pathogen for elimination. Host cells have mechanisms of controlling this evasion by inducing autophagy, an elaborate cellular process that targets bacteria for progressive elimination, decreasing bacterial loads within infected cells. In addition, autophagy activation also aids in the control of inflammation, contributing to a more efficient innate immune response against M. tuberculosis. Several innovative TB therapies have been envisaged based on autophagy manipulation, with some of them revealing high potential for future clinical trials and eventual implementation in healthcare systems. Thus, this review highlights the recent advances on the innate immune response regulation by autophagy upon M. tuberculosis infection and the promising new autophagy-based therapies for TB.

  3. Combined use of Mycobacterium tuberculosis-specific CD4 and CD8 T-cell responses is a powerful diagnostic tool of active tuberculosis.

    PubMed

    Rozot, Virginie; Patrizia, Amelio; Vigano, Selena; Mazza-Stalder, Jesica; Idrizi, Elita; Day, Cheryl L; Perreau, Matthieu; Lazor-Blanchet, Catherine; Ohmiti, Khalid; Goletti, Delia; Bart, Pierre-Alexandre; Hanekom, Willem; Scriba, Thomas J; Nicod, Laurent; Pantaleo, Giuseppe; Harari, Alexandre

    2015-02-01

    Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infection.

  4. Treatment outcome among cases of multidrug-resistant tuberculosis (MDR TB) in Western India: A prospective study.

    PubMed

    Patel, Sangita V; Nimavat, Kapil B; Alpesh, Patel B; Shukla, Lipy K; Shringarpure, Kalpita S; Mehta, Kedar G; Joshi, Chakshu C

    2016-01-01

    Multidrug-resistant TB has become a significant public health problem in a number of countries and an obstacle to effective TB control. Therefore, the present study sought to determine the treatment outcome in patients with MDR TB in seven districts and to examine the factors affecting the treatment outcome. A prospective cohort study was carried out by enrolling all the registered patients in DOTs Plus center of Vadodara district from February 2010 to December 2010. A total of 142 patients were interviewed using a pre-tested semi-structured questionnaire at the DOTS centers of seven districts of Gujarat or at their homes in cases of defaulters/death. After 24 months, of those 145 patients, 48 (33.10%) were declared cured, 8 (5.50%) had completed their treatment, 43 (29.70%) patients died during the treatment, and 32 (21.10%) patients defaulted during treatment. Factors associated with a significant difference in the outcomes were income, marital status, and education. Only education significantly affected treatment outcome upon applying logistic regression. Therefore, proper counseling on drug adherence should be applied at the programmatic level.

  5. [Recommendations for the diagnosis and treatment of latent and active tuberculosis in patients with inflammatory joint diseases treated with tumour necrosis factor alpha inhibitors].

    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-alpha) 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-alpha therapy. When TB (LTBI orAT) treatment is indicated, it should be performed before the beginning of anti-TNF-alpha therapy. If the IJD activity requires urgent anti-TNF-alpha 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. IfTST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test.

  6. Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors: March 2008 update.

    PubMed

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

    2008-01-01

    The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn s complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment.

  7. Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors - March 2008 update.

    PubMed

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

    2008-01-01

    The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFα) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFα therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFα therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFα therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn's complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-α therapy, even in the presence of a negative test, after risk / benefit assessment. Rev Port Pneumol 2007; XIV (2): 271-283.

  8. Cytotoxic response persists in subjects treated for tuberculosis decades ago

    PubMed Central

    2013-01-01

    Background Data exploring the potential use of effector molecules produced by cytotoxic T lymphocytes (CTLs) in the immunodiagnostics of tuberculosis (TB) are scarce. The present study focused a) to gain an insight into the discriminatory power of CTLs in patients with acute pulmonary or extra-pulmonary TB, or latent tuberculosis infection (LTBI); and b) to evaluate the influence of various anti-TB therapeutic schemes on the immunological profiles of residual CTLs. Methods Immunological signatures of antigen-specific CTLs were explored in patients with active pulmonary and extra-pulmonary TB, LTBI and in those treated for TB decades ago by using ELISPOT, intracellular flow cytometry and extracellular CD107a detection. Results No difference was seen between active TB, LTBI or any of those treated for TB in the ELISPOT analysis of antigen-specific Granzyme B (GrB), Perforin (Prf) and interferon-gamma (IFN-γ) producing lymphocytes, the FACS analysis of the intracellular expression of IFN-γ, or the surface expression of CD107a degranulation factor of both CD8+ and CD4+ antigen-specific T cell subsets. The effector memory (TEM) phenotype proved predominant in the surface marker profiling both in active TB and LTBI. The proportion of the CD107a degranulation factor proved higher in the central memory (TCM) than in the other cell subsets in all the study groups. Interestingly, functionally and phenotypically similar CTLs profiles were observed in active TB, LTBI and in all the three groups treated for TB. Conclusion The phenotypic and functional profiling of CTLs has a limited potential in the immunodiagnostics of active TB. Antigen-specific CTLs persist in patients treated for TB decades ago regardless of the efficacy of implemented and completed anti-TB therapy. PMID:24308801

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

    PubMed

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

    2016-01-08

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

  10. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis.

    PubMed

    Coppola, Mariateresa; van den Eeden, Susan J F; Wilson, Louis; Franken, Kees L M C; Ottenhoff, Tom H M; Geluk, Annemieke

    2015-09-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by "dormant" M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ(+)/TNF(+)) and IFN-γ(+) CD4(+) T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting.

  11. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

    PubMed Central

    Coppola, Mariateresa; van den Eeden, Susan J. F.; Wilson, Louis; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.

    2015-01-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by “dormant” M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ+/TNF+) and IFN-γ+ CD4+ T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting. PMID:26202436

  12. Novel approaches to tuberculosis prevention: DNA vaccines.

    PubMed

    Rivas-Santiago, Bruno; Cervantes-Villagrana, Alberto R

    2014-03-01

    It is estimated that there are approximately eight million new cases of active tuberculosis (TB) worldwide annually. There is only 1 vaccine available for prevention: bacillus Calmette-Guérin (BCG). This has variable efficacy and is only protective for certain extrapulmonary TB cases in children, therefore new strategies for the creation of novel vaccines have emerged. One of the promising approaches is the DNA vaccine, used as a direct vaccination or as a prime-boost vaccine. This review describes the experimental data obtained during the design of DNA vaccines for TB.

  13. LAG3 Expression in Active Mycobacterium tuberculosis Infections

    PubMed Central

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

    2016-01-01

    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. PMID:25549835

  14. 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.

  15. TB drug development: immunology at the table

    PubMed Central

    Nathan, Carl; Barry, Clifton E.

    2014-01-01

    Summary Our understanding of the host-pathogen relationship in tuberculosis can help guide tuberculosis (TB) drug discovery in at least two ways. First, the recognition that host immunopathology affects lesional TB drug distribution means that pharmacokinetic evaluation of drug candidates needs to move beyond measurements of drug levels in blood, whole lungs or alveolar epithelial lining fluid to include measurements in specific types of lesions. Second, by restricting the replication of M. tuberculosis (Mtb) subpopulations in latent TB infection and in active disease, the host immune response puts Mtb into a state associated with phenotypic tolerance to TB drugs selected for their activity against replicating Mtb. This has spurred a major effort to conduct high throughput screens in vitro for compounds that can kill Mtb when it is replicating slowly if at all. Each condition used in vitro to slow Mtb’s replication and thereby model the phenotypically drug-tolerant state has advantages and disadvantages. Lead candidates emerging from such in vitro studies face daunting challenges in the design of proof-of-concept studies in animal models. Moreover, some non-replicating subpopulations of Mtb fail to resume replication when plated on agar, although their viability is demonstrable by other means. There is as yet no widely replicated assay in which to screen compounds for their ability to kill this ‘viable but non-culturable’ subpopulation. Despite these hurdles, drugs that can kill slowly replicating or non-replicating Mtb may offer our best hope for treatment-shortening combination chemotherapy of TB. PMID:25703568

  16. 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

  17. HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide.

    PubMed

    Montales, Maria Theresa; Chaudhury, Arun; Beebe, Alexandria; Patil, Sowmya; Patil, Naveen

    2015-01-01

    The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV-Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority. PMID:26779470

  18. HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide

    PubMed Central

    Montales, Maria Theresa; Chaudhury, Arun; Beebe, Alexandria; Patil, Sowmya; Patil, Naveen

    2015-01-01

    The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV–Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority. PMID:26779470

  19. Recent advances in the diagnosis and treatment of childhood tuberculosis

    PubMed Central

    Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali

    2015-01-01

    Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-γ IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge. PMID:26283820

  20. Recent advances in the diagnosis and treatment of childhood tuberculosis.

    PubMed

    Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali

    2015-01-01

    Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-γ IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. A comparative examination of tuberculosis immigration medical screening programs from selected countries with high immigration and low tuberculosis incidence rates

    PubMed Central

    2011-01-01

    Background Tuberculosis (TB) in migrants is an ongoing challenge in several low TB incidence countries since a large proportion of TB in these countries occurs in migrants from high incidence countries. To meet these challenges, several countries utilize TB screening programs. The programs attempt to identify and treat those with active and/or infectious stages of the disease. In addition, screening is used to identify and manage those with latent or inactive disease after arrival. Between nations, considerable variation exists in the methods used in migration-associated TB screening. The present study aimed to compare the TB immigration medical examination requirements in selected countries of high immigration and low TB incidence rates. Methods Descriptive study of immigration TB screening programs Results 16 out of 18 eligible countries responded to the written standardized survey and phone interview. Comparisons in specific areas of TB immigration screening programs included authorities responsible for TB screening, the primary objectives of the TB screening program, the yield of detection of active TB disease, screening details and aspects of follow up for inactive pulmonary TB. No two countries had the same approach to TB screening among migrants. Important differences, common practices, common problems, evidence or lack of evidence for program specifics were noted. Conclusions In spite of common goals, there is great diversity in the processes and practices designed to mitigate the impact of migration-associated TB among nations that screen migrants for the disease. The long-term goal in decreasing migration-related introduction of TB from high to low incidence countries remains diminishing the prevalence of the disease in those high incidence locations. In the meantime, existing or planned migration screening programs for TB can be made more efficient and evidenced based. Cooperation among countries doing research in the areas outlined in this study should

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

    PubMed Central

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

    2016-01-01

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

  7. Tuberculosis control activities before and after Hurricane Sandy--northeast and mid-Atlantic states, 2012.

    PubMed

    2013-03-22

    On October 29, 2012, Hurricane Sandy struck the U.S. northeast and mid-Atlantic seaboard; the effects of the storm extended to southeastern and midwestern states and to eastern Canada. At the time, 1,899 residents in the most affected areas were undergoing treatment for tuberculosis (TB) disease or infection. To ascertain the operational abilities of state and local TB programs during and after the storm and to determine whether lessons learned from a previous hurricane were effective in ensuring continuity of TB patient care, CDC interviewed staff members at all of the affected state and city TB control programs, including those in areas with power outages and flooded streets, tunnels, and subway lines. The interviews determined that continuity of care for TB patients in programs affected by Hurricane Sandy was better preserved than it had been during and after Hurricane Katrina in August 2005. This improvement might be attributed to 1) preparedness measures learned from Hurricane Katrina (e.g., preparing line lists of patients, providing patients with as-needed medications, and making back-up copies of patient records in advance of the storm) and 2) less widespread displacement of persons after Hurricane Sandy than occurred after Hurricane Katrina. Maintaining readiness among clinicians and TB control programs to respond to natural disasters remains essential to protecting public health and preserving TB patients' continuity of care.

  8. Tuberculosis control activities before and after Hurricane Sandy--northeast and mid-Atlantic states, 2012.

    PubMed

    2013-03-22

    On October 29, 2012, Hurricane Sandy struck the U.S. northeast and mid-Atlantic seaboard; the effects of the storm extended to southeastern and midwestern states and to eastern Canada. At the time, 1,899 residents in the most affected areas were undergoing treatment for tuberculosis (TB) disease or infection. To ascertain the operational abilities of state and local TB programs during and after the storm and to determine whether lessons learned from a previous hurricane were effective in ensuring continuity of TB patient care, CDC interviewed staff members at all of the affected state and city TB control programs, including those in areas with power outages and flooded streets, tunnels, and subway lines. The interviews determined that continuity of care for TB patients in programs affected by Hurricane Sandy was better preserved than it had been during and after Hurricane Katrina in August 2005. This improvement might be attributed to 1) preparedness measures learned from Hurricane Katrina (e.g., preparing line lists of patients, providing patients with as-needed medications, and making back-up copies of patient records in advance of the storm) and 2) less widespread displacement of persons after Hurricane Sandy than occurred after Hurricane Katrina. Maintaining readiness among clinicians and TB control programs to respond to natural disasters remains essential to protecting public health and preserving TB patients' continuity of care. PMID:23515057

  9. Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

    PubMed

    Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

    2016-10-01

    The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy.

  10. Engaging informal providers in TB control: what is the potential in the implementation of the WHO Stop TB Strategy? A discussion paper.

    PubMed

    Kaboru, Berthollet Bwira; Uplekar, Mukund; Lönnroth, Knut

    2011-01-01

    The World Health Organization (WHO) Stop TB Strategy calls for involvement of all healthcare providers in tuberculosis (TB) control. There is evidence that many people with TB seek care from informal providers before or after diagnosis, but very little has been done to engage these informal providers. Their involvement is often discussed with regard to DOTS (directly observed treatment - short course), rather than to the implementation of the comprehensive Stop TB Strategy. This paper discusses the potential contribution of informal providers to all components of the WHO Stop TB Strategy, including DOTS, programmatic management of multi-drug-resistant TB (MDR-TB), TB/HIV collaborative activities, health systems strengthening, engaging people with TB and their communities, and enabling research.The conclusion is that with increased stewardship by the national TB program (NTP), informal providers might contribute to implementation of the Stop TB Strategy. NTPs need practical guidelines to set up and scale up initiatives, including tools to assess the implications of these initiatives on complex dimensions like health systems strengthening.

  11. Turning off the tap: stopping tuberculosis transmission through active case-finding and prompt effective treatment.

    PubMed

    Yuen, Courtney M; Amanullah, Farhana; Dharmadhikari, Ashwin; Nardell, Edward A; Seddon, James A; Vasilyeva, Irina; Zhao, Yanlin; Keshavjee, Salmaan; Becerra, Mercedes C

    2015-12-01

    To halt the global tuberculosis epidemic, transmission must be stopped to prevent new infections and new cases. Identification of individuals with tuberculosis and prompt initiation of effective treatment to rapidly render them non-infectious is crucial to this task. However, in settings of high tuberculosis burden, active case-finding is often not implemented, resulting in long delays in diagnosis and treatment. A range of strategies to find cases and ensure prompt and correct treatment have been shown to be effective in high tuberculosis-burden settings. The population-level effect of targeted active case-finding on reducing tuberculosis incidence has been shown by studies and projected by mathematical modelling. The inclusion of targeted active case-finding in a comprehensive epidemic-control strategy for tuberculosis should contribute substantially to a decrease in tuberculosis incidence. PMID:26515675

  12. 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. PMID:26405286

  13. 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.

  14. 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

  15. Predominance of modern Mycobacterium tuberculosis strains and active transmission of Beijing sublineage in Jayapura, Indonesia Papua.

    PubMed

    Chaidir, Lidya; Sengstake, Sarah; de Beer, Jessica; Oktavian, Antonius; Krismawati, Hana; Muhapril, Erfin; Kusumadewi, Inri; Annisa, Jessi; Anthony, Richard; van Soolingen, Dick; Achmad, Tri Hanggono; Marzuki, Sangkot; Alisjahbana, Bachti; van Crevel, Reinout

    2016-04-01

    Mycobacterium tuberculosis genotype distribution is different between West and Central Indonesia, but there are no data on the most Eastern part, Papua. We aimed to identify the predominant genotypes of M. tuberculosis responsible for tuberculosis in coastal Papua, their transmission, and the association with patient characteristics. A total of 199 M. tuberculosis isolates were collected. Spoligotyping was applied to describe the population structure of M. tuberculosis, lineage identification was performed using a combination of lineage-specific markers, and genotypic clusters were identified using a combination of 24-locus-MIRU-VNTR and spoligotyping. A high degree of genetic diversity was observed among isolates based on their spoligopatterns. Strains from modern lineage 4 made up almost half of strains (46.9%), being more abundant than the ancient lineage 1 (33.7%), and modern lineage 2 (19.4%). Thirty-five percent of strains belonged to genotypic clusters, especially strains in the Beijing genotype. Previous TB treatment and mutations associated with drug resistance were more common in patients infected with strains of the Beijing genotype. Papua shows a different distribution of M. tuberculosis genotypes compared to other parts of Indonesia. Clustering and drug resistance of modern strains recently introduced to Papua may contribute to the high tuberculosis burden in this region.

  16. Activity of levofloxacin in a murine model of tuberculosis.

    PubMed Central

    Klemens, S P; Sharpe, C A; Rogge, M C; Cynamon, M H

    1994-01-01

    The activity of levofloxacin (LEV) was evaluated in a murine model of tuberculosis. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 were given intravenously to 4-week-old female outbred mice. In a dose-response study, treatment with LEV at 100, 200, and 400 mg/kg of body weight was started 1 day after infection and was given daily for 28 days. Viable cell counts were determined from homogenates of spleens and lungs. A dose-related reduction in organism cell counts in organs was noted for LEV. The activities of LEV at 100, 200, and 300 mg/kg were compared with those of first-line antituberculosis agents. Both isoniazid and rifampin were more active than LEV. There was no difference in activity between LEV and either ethambutol or pyrazinamide against splenic organisms. The activities of ethambutol and LEV at the two higher doses were comparable against lung organisms. LEV at 300 mg/kg was more active than pyrazinamide against lung organisms. The activity of LEV was compared with those of two other quinolones, ofloxacin and sparfloxacin. LEV at 200 mg/kg had more than twofold greater activity than ofloxacin at the same dose. Sparfloxacin at 100 mg/kg was more active than LEV at 200 mg/kg; however, the activities of sparfloxacin at 50 mg/kg and LEV at 200 mg/kg were comparable. The promising activity of LEV in M. tuberculosis-infected mice suggests that it is a good candidate for clinical development as a new antituberculosis agent. PMID:7979275

  17. [Evaluation of the tuberculosis control program through tuberculosis surveillance].

    PubMed

    Ohmori, Masako

    2008-12-01

    Tuberculosis (TB) surveillance has involved three main functions: (1) data collection, (2) data analysis, and (3) feedback. There is now one more important function: (4) a new action plan based on the results of feedback. If all four functions are operating smoothly, the result will be effective so-called "program surveillance". In Japan, the first nationwide computerized TB surveillance system was established in 1987 and it was revised in 1992, 1998 and 2007. Treatment outcomes have been decided automatically in this system since 1998, based on data concerning treatment status, bacteriological test results and so on. Two optional systems, the recording of DOTS and managing of contact tracing, were added to this system in 2007. Since we can thus obtain and use a large amount of surveillance data, we have developed assessment indicators and methods of evaluating the national or regional TB control programs (Fig. 1). However, the accuracy of surveillance data entered into computers at public health centers has been inadequate. Therefore, one of the objectives of evaluating regional TB control program activities is to improve the quality of surveillance data. As regional governments have responsibility for TB control programs in Japan, TB control is generally evaluated at the regional level; i.e. prefecture and designated city. This evaluation process should be done in the cycle of "Plan-Do-See" (planning, execution, evaluation). However, the priority of "See" in this cycle seems to be low, because of the heavy workload of TB control activities. Nevertheless, the evaluation of TB control is very important, so I have introduced some examples of evaluation methods in WHO and Osaka city, and propose the optimum approach to evaluating TB control programs at the regional level. This approach is: (1) to observe the correct epidemiological situation, (2) to set a clear goal, (3) to announce the strategy, and (4) to carry out an annual evaluation. It might also be possible to

  18. The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.

    PubMed

    Pareek, Manish; Greenaway, Christina; Noori, Teymur; Munoz, Jose; Zenner, Dominik

    2016-01-01

    Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy. PMID:27004556

  19. The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.

    PubMed

    Pareek, Manish; Greenaway, Christina; Noori, Teymur; Munoz, Jose; Zenner, Dominik

    2016-01-01

    Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy.

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

    PubMed Central

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

    2016-01-01

    Background In Afghanistan, improving TB case detection remains challenging. In 2014, only half of the estimated incident TB cases were notified, and notifications have decreased since peaking in 2007. Active case finding has been increasingly considered to improve TB case notifications. While access to health services has improved in Afghanistan, it remains poor and many people seeking health services won’t receive proper care. Methods From October 2011 through December 2012 we conducted three separate case finding strategies in six provinces of Afghanistan and measured impact on TB case notification. Systematically screening cough among attendees at 47 health facilities, active household contact investigation of smear-positive index TB patients, and active screening at 15 camps for internally displaced people were conducted. We collected both intervention yield and official quarterly notification data. Additional TB notifications were calculated by comparing numbers of cases notified during the intervention with those notified before the intervention, then adjusting for secular trends in notification. Results We screened 2,022,127 people for TB symptoms during the intervention, tested 59,838 with smear microscopy and detected 5,046 people with smear-positive TB. Most cases (81.7%, 4,125) were identified in health facilities while nearly 20% were found through active case finding. A 56% increase in smear-positive TB notifications was observed between the baseline and intervention periods among the 47 health facilities, where cases detected by all three strategies were notified. Discussion While most people with TB are likely to be identified through health facility screening, there are many people who remain without a proper diagnosis if outreach is not attempted. This is especially true in places like Afghanistan where access to general services is poor. Targeted active case finding can improve the number of people who are detected and treated for TB and can

  1. The Human Antibody Response to the Surface of Mycobacterium tuberculosis

    PubMed Central

    Perley, Casey C.; Frahm, Marc; Click, Eva M.; Dobos, Karen M.; Ferrari, Guido; Stout, Jason E.; Frothingham, Richard

    2014-01-01

    Background Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis. Methods Plasma from humans with latent tuberculosis (TB) infection (n = 23), active TB disease (n = 40), and uninfected controls (n = 9) were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins). Results When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (Δ = 0.72 log10), whole cell lysate (Δ = 0.82 log10), and secreted proteins (Δ = 0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (Δ = 1.4 to 2.6) to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (Δ = –1.53, p = 0.004). Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (Δ = 0.55 log10, p = 0.008), foreign-born (Δ = 0.61 log10, p = 0.004), or HIV-seronegative (Δ = 0.60 log10, p = 0.04). Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (Δ = 1.12, p<0.001) and foreign-born (Δ = 0.87, p = 0.01). Conclusions/Significance Humans

  2. Population-Level Impact of Active Tuberculosis Case Finding in an Asian Megacity

    PubMed Central

    Dowdy, David W.; Lotia, Ismat; Azman, Andrew S.; Creswell, Jacob; Sahu, Suvanand; Khan, Aamir J.

    2013-01-01

    Background The potential population-level impact of private-sector initiatives for tuberculosis (TB) case finding in Southeast Asia remains uncertain. In 2011, the Indus Hospital TB Control Program in Karachi, Pakistan, undertook an aggressive case-finding campaign that doubled notification rates, providing an opportunity to investigate potential population-level effects. Methods We constructed an age-structured compartmental model of TB in the intervention area. We fit the model using field and literature data, assuming that TB incidence equaled the estimated nationwide incidence in Pakistan (primary analysis), or 1.5 times greater (high-incidence scenario). We modeled the intervention as an increase in the rate of formal-sector TB diagnosis and evaluated the potential impact of sustaining this rate for five years. Results In the primary analysis, the five-year intervention averted 24% (95% uncertainty range, UR: 18-30%) of five-year cumulative TB cases and 52% (95% UR: 45-57%) of cumulative TB deaths. Corresponding reductions in the high-incidence scenario were 12% (95% UR: 8-17%) and 27% (95% UR: 21-34%), although the absolute number of lives saved was higher. At the end of five years, TB notification rates in the primary analysis were below their 2010 baseline, incidence had dropped by 45%, and annual mortality had fallen by 72%. About half of the cumulative impact on incidence and mortality could be achieved with a one-year intervention. Conclusions Sustained, multifaceted, and innovative approaches to TB case-finding in Asian megacities can have substantial community-wide epidemiological impact. PMID:24147015

  3. Vitamin d and tuberculosis status in refugee children.

    PubMed

    Gray, Kara; Wood, Nicholas; Gunasekera, Hasantha; Sheikh, Mohammad; Hazelton, Briony; Barzi, Federica; Isaacs, David

    2012-05-01

    Vitamin D deficiency and tuberculosis (TB) are associated in adults, but data in children are scarce. We screened refugee children routinely for vitamin D status and TB. Vitamin D values were significantly lower in latent TB (n = 81) and TB infection (n = 11) than in children without TB (n = 236). We conclude that refugee children with TB have reduced vitamin D levels.

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

    PubMed Central

    Kateete, David P.; Wajja, Anne; Bugumirwa, Eric; Mboowa, Gerald; Namaganda, Carolyn; Nakayita, Germine; Nassolo, Maria; Mumbowa, Francis; Asiimwe, Benon B.; Waako, James; Verver, Suzanne; Musoke, Philippa; Mayanja-Kizza, Harriet; Joloba, Moses L.

    2012-01-01

    The World Health Organization (WHO) recommends collection of two sputum samples for tuberculosis (TB) diagnosis, with at least one being an early morning (EM) using smear microscopy. It remains unclear whether this is necessary even when sputum culture is employed. Here, we determined the diagnostic yield from spot and the incremental yield from the EM sputum sample cultures among TB-suspected adolescents from rural Uganda. Sputum samples (both spot and early-morning) from 1862 adolescents were cultured by the Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT) methods. For spot samples, the diagnostic yields for TB were 19.0% and 57.1% with LJ and MGIT, respectively, whereas the incremental yields (not totals) of the early-morning sample were 9.5% and 42.9% (P < 0.001) with LJ and MGIT, respectively. Among TB-suspected adolescents in rural Uganda, the EM sputum culture has a high incremental diagnostic yield. Therefore, EM sputum in addition to spot sample culture is necessary for improved TB case detection. PMID:23304491

  5. STUDY OF THE STATUS OF TUBERCULOSIS CONTROL PROGRAM BASED ON THE IMPLEMENTATION OF THE DIRECTLY OBSERVED TREATMENT SHORT-COURSE STRATEGY (DOTS)

    PubMed Central

    Farzianpour, Fereshteh; Kooshad, Mahdokht Afarin

    2016-01-01

    Introduction: Ascendant trend of tuberculosis in the world introduces this disease to be one of the most important infectious diseases in the world. So that every year, 9 million people are afflicted to active TB and about 5.1 million people die of the disease. As the HIV contaminated cases are increased, emergence and spread field of Multidrug-resistant tuberculosis (MDR-TB) bacilli has been provided. Objective: This study aimed to assess the Tuberculosis Control Program from 2005 to 2012 to determine the overall situation of disease epidemiology and prioritized strategies in disease control program within the south of Tehran. Materials and Methods: This cross-sectional study was extracted and analyzed retrospectively on the basis of records of all TB patients in TB health center and TB software in south Tehran in 2005-2012 years. Results: From the total population under protection of health center of south Tehran, 99% are urban and 1% are rural. During 2005-2012, 1242 TB cases have been registered and they were treated by DOTS method. There were 553 cases of new smear-positive pulmonary TB (44%), 222 cases of smear-negative pulmonary TB (18%) and 336 cases of extra-pulmonary tuberculosis (27%), 26 cases of recurrence (2%) and 11 cases of MDR (0.9%). Smear-positive pulmonary tuberculosis has included 67.4% of all tuberculosis patients. Conclusions: The results showed that, in accordance with TB worldwide statistics, at the health center of south Tehran, pulmonary TB is the most common form of the disease (67.4%). The incidence of smear-positive tuberculosis and all forms of TB cases has been an ascending trend over the period between 2005 and 2012. PMID:27698595

  6. STUDY OF THE STATUS OF TUBERCULOSIS CONTROL PROGRAM BASED ON THE IMPLEMENTATION OF THE DIRECTLY OBSERVED TREATMENT SHORT-COURSE STRATEGY (DOTS)

    PubMed Central

    Farzianpour, Fereshteh; Kooshad, Mahdokht Afarin

    2016-01-01

    Introduction: Ascendant trend of tuberculosis in the world introduces this disease to be one of the most important infectious diseases in the world. So that every year, 9 million people are afflicted to active TB and about 5.1 million people die of the disease. As the HIV contaminated cases are increased, emergence and spread field of Multidrug-resistant tuberculosis (MDR-TB) bacilli has been provided. Objective: This study aimed to assess the Tuberculosis Control Program from 2005 to 2012 to determine the overall situation of disease epidemiology and prioritized strategies in disease control program within the south of Tehran. Materials and Methods: This cross-sectional study was extracted and analyzed retrospectively on the basis of records of all TB patients in TB health center and TB software in south Tehran in 2005-2012 years. Results: From the total population under protection of health center of south Tehran, 99% are urban and 1% are rural. During 2005-2012, 1242 TB cases have been registered and they were treated by DOTS method. There were 553 cases of new smear-positive pulmonary TB (44%), 222 cases of smear-negative pulmonary TB (18%) and 336 cases of extra-pulmonary tuberculosis (27%), 26 cases of recurrence (2%) and 11 cases of MDR (0.9%). Smear-positive pulmonary tuberculosis has included 67.4% of all tuberculosis patients. Conclusions: The results showed that, in accordance with TB worldwide statistics, at the health center of south Tehran, pulmonary TB is the most common form of the disease (67.4%). The incidence of smear-positive tuberculosis and all forms of TB cases has been an ascending trend over the period between 2005 and 2012.

  7. Achievements in and Challenges of Tuberculosis Control in South Korea

    PubMed Central

    Kim, Ji Han

    2015-01-01

    After the Korean War (1950–1953), nearly 6.5% of South Korea’s population had active tuberculosis (TB). In response, South Korea implemented the National Tuberculosis Program in 1962. From 1965 to 1995, the prevalence of bacteriologically confirmed pulmonary TB in South Korea decreased from 940 to 219 cases per 100,000 population. Astounding economic growth might have contributed to this result; however, TB incidence in South Korea remains the highest among high-income countries. The rate of decrease in TB incidence seems to have slowed over the past 15 years. A demographic shift toward an older population, many of whom have latent TB and various concurrent conditions, is challenging TB control efforts in South Korea. The increasing number of immigrants also plays a part in the prolonged battle against TB. A historical review of TB in South Korea provides an opportunity to understand national TB control efforts that are applicable to other parts of the world. PMID:26485188

  8. Screening for tuberculosis and LTBI in diabetes patients, Pohnpei, Federated States of Micronesia.

    PubMed

    Defang, R R; Brostrom, R; Ram, S; Johnson, E; Perman, P S

    2014-06-21

    A retrospective cohort study was performed in Pohnpei, a small Pacific Island, to evaluate the feasibility and results of screening adult diabetes (DM) patients for tuberculosis (TB) and latent tuberculous infection (LTBI) using a symptom screen, tuberculin skin testing and chest radiography. Of 79 patients, 65 (82%) completed screening. Two (3%) patients with active TB and 16 (25%) with LTBI were referred for anti-tuberculosis treatment and isoniazid preventive therapy, respectively. It is feasible and worthwhile to screen diabetes patients for TB, but a number of changes are needed to improve both the screening process and the diagnostic yield.

  9. Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model.

    PubMed

    Moses, Mark W; Zwerling, Alice; Cattamanchi, Adithya; Denkinger, Claudia M; Banaei, Niaz; Kik, Sandra V; Metcalfe, John; Pai, Madhukar; Dowdy, David

    2016-01-01

    Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8-25.5) of the entire population testing false-positive over ten years. Raising the cutoff to >1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95%UR: 2.0-2.6%) or 4.1% (95%UR: 3.7-4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95%UR: 66.3-84.6%) to 54.8% (95%UR: 44.6-64.5%) or 61.5% (95%UR: 51.6-70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections. PMID:27469388

  10. Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model

    PubMed Central

    Moses, Mark W.; Zwerling, Alice; Cattamanchi, Adithya; Denkinger, Claudia M.; Banaei, Niaz; Kik, Sandra V.; Metcalfe, John; Pai, Madhukar; Dowdy, David

    2016-01-01

    Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8–25.5) of the entire population testing false-positive over ten years. Raising the cutoff to >1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95%UR: 2.0–2.6%) or 4.1% (95%UR: 3.7–4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95%UR: 66.3–84.6%) to 54.8% (95%UR: 44.6–64.5%) or 61.5% (95%UR: 51.6–70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections. PMID:27469388

  11. Musculosceletal tuberculosis with involvement of tendon sheaths and formation of synovial cyst.

    PubMed

    Zieliński, Michał; Mazur-Zielińska, Henryka; Kozielski, Jerzy

    2016-01-01

    Due to an increasing amount of patients on immunosuppressive treatment, the number of tuberculosis (TB) of atypical course and extrapulmonary tuberculosis cases increase. Locomotor system is a place of every fifth case of extrapulmonary TB. Because of lack of characteristic symptoms, as well as rare co-occurrence of active lung lesions in radiological imaging, proper diagnosis is hard to establish. We present a case of patient on immunosuppressive therapy due to myositis, in whom we diagnosed musculoskeletal tuberculosis in form of involvement of tendon sheath and formation of synovial cyst. PMID:27672070

  12. Tuberculosis in Tropical Areas and Immigrants

    PubMed Central

    Zammarchi, Lorenzo; Bartalesi, Filippo; Bartoloni, Alessandro

    2014-01-01

    About 95% of cases and 98% of deaths due to tuberculosis (TB) occur in tropical countries while, in temperate low incidence countries, a disproportionate portion of TB cases is diagnosed in immigrants. Urbanization, poverty, poor housing conditions and ventilation, poor nutritional status, low education level, the HIV co-epidemic, the growing impact of chronic conditions such as diabetes are the main determinants of the current TB epidemiology in tropical areas. TB care in these contests is complicated by several barriers such as geographical accessibility, educational, cultural, sociopsychological and gender issues. High quality microbiological and radiological facilities are not widely available, and erratic supply of anti-TB drugs may affect tropical areas from time to time. Nevertheless in recent years, TB control programs reached major achievements in tropical countries as demonstrated by several indicators. Migrants have a high risk of acquire TB before migration. Moreover, after migration, they are exposed to additional risk factors for acquiring or reactivating TB infection, such as poverty, stressful living conditions, social inequalities, overcrowded housing, malnutrition, substance abuse, and limited access to health care. TB mass screening programs for migrants have been implemented in low endemic countries but present several limitations. Screening programs should not represent a stand-alone intervention, but a component of a wider approach integrated with other healthcare activities to ensure the health of migrants. PMID:24959340

  13. Tuberculosis pharmacotherapy: strategies to optimize patient care

    PubMed Central

    Mitnick, Carole D.; McGee, Bryan; Peloquin, Charles A.

    2009-01-01

    The treatment of tuberculosis (TB) is a mature discipline, with over 60 years of clinical experience accrued across the globe. The requisite multidrug treatment of drug-susceptible TB, however, lasts six months and has never been optimized according to current standards. Multi-drug resistant tuberculosis and tuberculosis in individuals coinfected with HIV present additional treatment challenges. This article reviews the role that existing drugs and new compounds could have in shortening or improving treatment for tuberculosis. The key to treatment shortening appears to be sterilizing activity, or the ability of drugs to kill mycobacteria that persist after the initial days of multidrug treatment. Among existing anti-TB drugs, the rifamycins hold the greatest potential for shortening treatment and improving outcomes, in both HIV-infected and HIV-uninfected populations, without dramatic increases in toxicity. Clinical studies underway or being planned, are supported by in vitro, animal, and human evidence of increased sterilizing activity–without significant increases in toxicity–at elevated daily doses. Fluoroquinolones also appear to have significant sterilizing activity. At least two class members are currently under evaluation for treatment shortening with different combinations of first-line drugs. However, in light of apparent rapid selection for fluoroquinolone-resistant mutants, relative frequency of serious adverse events, and a perceived need to ‘reserve’ fluoroquinolones for the treatment of drug-resistant TB, their exact role in TB treatment remains to be determined. Other possible improvements may come from inhaled delivery or split dosing (linezolid) of anti-TB drugs for which toxicity (ethionamide) or lack of absorption (aminoglycosides and polypeptides) precludes delivery of maximally effective, oral doses, once daily. New classes of drugs with novel mechanisms of action, nitroimidazopyrans and a diarylquinoline, among others, may soon provide

  14. High IFN-γ Release and Impaired Capacity of Multi-Cytokine Secretion in IGRA Supernatants Are Associated with Active Tuberculosis

    PubMed Central

    Pisoni, Amandine; Bendriss, Sophie; Marin, Grégory; Peries, Marianne; Bolloré, Karine; Terru, Dominique; Godreuil, Sylvain; Bourdin, Arnaud; Van de Perre, Philippe; Tuaillon, Edouard

    2016-01-01

    Interferon gamma (IFN-γ) release assays (IGRAs) detect Mycobacterium tuberculosis (Mtb) infection regardless of the active (ATB) or latent (LTBI) forms of tuberculosis (TB). In this study, Mtb-specific T cell response against region of deletion 1 (RD1) antigens were explored by a microbead multiplex assay performed in T-SPOT TB assay (T-SPOT) supernatants from 35 patients with ATB and 115 patients with LTBI. T-SPOT is positive when over 7 IFN-γ secreting cells (SC)/250 000 peripheral blood mononuclear cells (PBMC) are enumerated. However, over 100 IFN-γ SC /250 000 PBMC were more frequently observed in the ATB group compared to the LTBI group. By contrast, lower cytokine concentrations and lower cytokine productions relative to IFN-γ secretion were observed for IL 4, IL-12, TNF-α, GM-CSF, Eotaxin and IFN-α when compared to LTBI. Thus, high IFN-γ release and low cytokine secretions in relation with IFN-γ production appeared as signatures of ATB, corroborating that multicytokine Mtb-specific response against RD1 antigens reflects host capacity to contain TB reactivation. In this way, testing cytokine profile in IGRA supernatants would be helpful to improve ATB screening strategy including immunologic tests. PMID:27603919

  15. High IFN-γ Release and Impaired Capacity of Multi-Cytokine Secretion in IGRA Supernatants Are Associated with Active Tuberculosis.

    PubMed

    Carrère-Kremer, Séverine; Rubbo, Pierre-Alain; Pisoni, Amandine; Bendriss, Sophie; Marin, Grégory; Peries, Marianne; Bolloré, Karine; Terru, Dominique; Godreuil, Sylvain; Bourdin, Arnaud; Van de Perre, Philippe; Tuaillon, Edouard

    2016-01-01

    Interferon gamma (IFN-γ) release assays (IGRAs) detect Mycobacterium tuberculosis (Mtb) infection regardless of the active (ATB) or latent (LTBI) forms of tuberculosis (TB). In this study, Mtb-specific T cell response against region of deletion 1 (RD1) antigens were explored by a microbead multiplex assay performed in T-SPOT TB assay (T-SPOT) supernatants from 35 patients with ATB and 115 patients with LTBI. T-SPOT is positive when over 7 IFN-γ secreting cells (SC)/250 000 peripheral blood mononuclear cells (PBMC) are enumerated. However, over 100 IFN-γ SC /250 000 PBMC were more frequently observed in the ATB group compared to the LTBI group. By contrast, lower cytokine concentrations and lower cytokine productions relative to IFN-γ secretion were observed for IL 4, IL-12, TNF-α, GM-CSF, Eotaxin and IFN-α when compared to LTBI. Thus, high IFN-γ release and low cytokine secretions in relation with IFN-γ production appeared as signatures of ATB, corroborating that multicytokine Mtb-specific response against RD1 antigens reflects host capacity to contain TB reactivation. In this way, testing cytokine profile in IGRA supernatants would be helpful to improve ATB screening strategy including immunologic tests. PMID:27603919

  16. Complement component 3: a new paradigm in tuberculosis vaccine.

    PubMed

    De La Fuente, José; Gortázar, Christian; Juste, Ramón

    2016-01-01

    Vaccines are critical for the control of tuberculosis (TB) affecting humans and animals worldwide. First-generation vaccines protect from active TB but new vaccines are required to protect against pulmonary disease and infection. Recent advances in post-genomics technologies have allowed the characterization of host-pathogen interactions to discover new protective antigens and mechanisms to develop more effective vaccines against TB. Studies in the wild boar model resulted in the identification of complement component 3 (C3) as a natural correlate of protection against TB. Oral immunization with heat-inactivated mycobacteria protected wild boar against TB and showed that C3 plays a central role in protection. These results point at C3 as a target to develop novel vaccine formulations for more effective protection against TB in humans and animals. PMID:26605515

  17. 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.

  18. Natural Killer cell activation distinguishes M. tuberculosis-mediated Immune reconstitution syndrome (IRIS) from chronic HIV and HIV-MTB co-infection

    PubMed Central

    Conradie, F.; Foulkes, A.S.; Ive, P.; Yin, X.; Roussos, K.; Glencross, D.K.; Lawrie, D.; Stevens, W.; Montaner, L.J.; Sanne; Azzoni, L.

    2011-01-01

    Background With increased access to antiretroviral treatment (ART), Immune Reconstitution Inflammatory Syndrome (IRIS) in Mycobacterium tuberculosis (MTB)-infected populations remains a clinical challenge. We studied a cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to help define the immune correlates that best distinguish IRIS from ongoing MTB cases. Methods We studied HIV+ subjects developing MTB-related unmasking IRIS (u-TB-IRIS) after ART initiation; control groups were HIV subjects and HIV-TB co-infected subjects with comparable ART treatment. Testing was conducted with whole blood-based 4-color flow cytometry and plasma-based Luminex cytokine assessment. Results NK cell activation, C-reactive protein and IL-8 serum concentration were significantly higher in u-TB-IRIS subjects as compared to both control groups. In addition, all MTB co-infected subjects, independent of clinical presentation, had higher neutrophils and T cell activation, together with lower lymphocytes, CD4+ T cell and myeloid DC counts. Using conditional inference tree analysis we show that elevated NK cell activation in combination with lymphocyte count characterizes the immunological profile of u-TB-IRIS. Conclusions Our results support a role for innate immune effectors in the immunopathogenesis of unmasking MTB-related IRIS, and identify new immune parameters defining this pathology. PMID:21826013

  19. Prisons as reservoir for community transmission of tuberculosis, Brazil.

    PubMed

    Sacchi, Flávia P C; Praça, Renata M; Tatara, Mariana B; Simonsen, Vera; Ferrazoli, Lucilaine; Croda, Mariana G; Suffys, Philip N; Ko, Albert I; Andrews, Jason R; Croda, Julio

    2015-03-01

    We conducted a population-based study of tuberculosis (TB) cases in Dourados, Brazil, to assess the relationship between incarceration and TB in the general population. Incarceration was associated with TB in an urban population; 54% of Mycobacterium tuberculosis strains were related to strains from persons in prisons. TB control in prisons is critical for reducing disease prevalence.

  20. Prisons as reservoir for community transmission of tuberculosis, Brazil.

    PubMed

    Sacchi, Flávia P C; Praça, Renata M; Tatara, Mariana B; Simonsen, Vera; Ferrazoli, Lucilaine; Croda, Mariana G; Suffys, Philip N; Ko, Albert I; Andrews, Jason R; Croda, Julio

    2015-03-01

    We conducted a population-based study of tuberculosis (TB) cases in Dourados, Brazil, to assess the relationship between incarceration and TB in the general population. Incarceration was associated with TB in an urban population; 54% of Mycobacterium tuberculosis strains were related to strains from persons in prisons. TB control in prisons is critical for reducing disease prevalence. PMID:25642998

  1. Prisons as Reservoir for Community Transmission of Tuberculosis, Brazil

    PubMed Central

    Sacchi, Flávia P.C.; Praça, Renata M.; Tatara, Mariana B.; Simonsen, Vera; Ferrazoli, Lucilaine; Croda, Mariana G.; Suffys, Philip N.; Ko, Albert I.; Andrews, Jason R.

    2015-01-01

    We conducted a population-based study of tuberculosis (TB) cases in Dourados, Brazil, to assess the relationship between incarceration and TB in the general population. Incarceration was associated with TB in an urban population; 54% of Mycobacterium tuberculosis strains were related to strains from persons in prisons. TB control in prisons is critical for reducing disease prevalence. PMID:25642998

  2. Thiolates Chemically Induce Redox Activation of BTZ043 and Related Potent Nitro Aromatic Anti-Tuberculosis Agents

    PubMed Central

    Tiwari, Rohit; Moraski, Garrett C.; Krchňák, Viktor; Miller, Patricia A.; Colon-Martinez, Mariangelli; Herrero, Eliza; Oliver, Allen G.; Miller, Marvin J.

    2013-01-01

    The development of multidrug resistant (MDR) and extensively drug resistant (XDR) forms of tuberculosis (TB) has stimulated research efforts globally to expand the new drug pipeline. Nitro aromatic compounds, including 1, 3-Benzothiazin-4-ones (BTZs) and related agents, are a promising new class for the treatment of TB. Research has shown that the nitroso intermediates of BTZs that are generated in vivo cause suicide inhibition of decaprenylphosphoryl-β-D-ribose 2′ oxidase (DprE1), which is responsible for cell wall arabinogalactan biosynthesis. We have designed and synthesized novel anti-TB agents inspired from BTZs and other nitroaromatic compounds. Computational studies indicated that the unsubstituted aromatic carbons of BTZ043 and related nitroaromatic compounds are the most electron deficient and might be prone to nucleophilic attack. Our chemical studies on BTZ043 and the additional nitro aromatic compounds synthesized by us and the others confirmed the postulated reactivity. The results indicate that nucleophiles such as thiolates, cyanide and hydride induce non-enzymatic reduction of the nitro groups present in these compounds to the corresponding nitroso intermediates by addition at the unsubstituted electron deficient aromatic carbon present in these compounds. Furthermore we demonstrate here that these compounds are good candidates for the classical von Richter reaction. These chemical studies offer an alternate hypotheses for the mechanism of action of nitro aromatic anti-TB agents in that the cysteine thiol(ate) or a hydride source at the active site of DprE1 may trigger the reduction of the nitro groups in a manner similar to the von Richter reaction to the nitroso intermediates, to initiate the inhibition of DprE1. PMID:23402278

  3. Repurposing clinically approved cephalosporins for tuberculosis therapy

    PubMed Central

    Ramón-García, Santiago; González del Río, Rubén; Villarejo, Angel Santos; Sweet, Gaye D.; Cunningham, Fraser; Barros, David; Ballell, Lluís; Mendoza-Losana, Alfonso; Ferrer-Bazaga, Santiago; Thompson, Charles J.

    2016-01-01

    While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug. Synergy was observed even under intracellular growth conditions where beta-lactams typically have limited activities. Cephalosporins and rifampicin were 4- to 64-fold more active in combination than either drug alone; however, limited synergy was observed with rifapentine or rifabutin. Clavulanate was a key synergistic partner in triple combinations. Cephalosporins (and other beta-lactams) together with clavulanate rescued the activity of rifampicin against a rifampicin resistant strain. Synergy was not due exclusively to increased rifampicin accumulation within the mycobacterial cells. Cephalosporins were also synergistic with new anti-TB drugs such as bedaquiline and delamanid. Studies will be needed to validate their in vivo activities. However, the fact that cephalosporins are orally bioavailable with good safety profiles, together with their anti-mycobacterial activities reported here, suggest that they could be repurposed within new combinatorial TB therapies. PMID:27678056

  4. Oral Administration of Heat-Killed Mycobacterium manresensis Delays Progression toward Active Tuberculosis in C3HeB/FeJ Mice.

    PubMed

    Cardona, Paula; Marzo-Escartín, Elena; Tapia, Gustavo; Díaz, Jorge; García, Vanessa; Varela, Ismael; Vilaplana, Cristina; Cardona, Pere-Joan

    2015-01-01

    Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression toward active tuberculosis (TB) lesions in a human-like murine model using C3HeB/FeJ mice. In the present study, we studied the effect of different treatment schedules with heat-killed non-tuberculous-mycobacteria (NTM) species when given orally, based on the hypothesis of generating oral tolerance. This study included M. manresensis, a new species belonging to the fortuitum group, present in drinking water. Oral treatment with M. manresensis for 2 weeks was able to induce a PPD-specific Tregs population, which has been related to a decrease in the neutrophilic infiltration found in TB lesions. Further mechanistic analysis using PPD-stimulated splenocytes links this 2-week treatment with heat-killed M. manresensis to IL-10 production and memory PPD-specific Tregs, and also to a weak PPD-specific global immune response stimulation, increasing IL-6, TNF, and IFN-γ production. In lungs, this treatment decreased the bacillary load, granulomatous infiltration and pro-inflammatory cytokines (TNF, IFN-γ, IL-6, and IL-17). Oral administration of M. manresensis during standard treatment for TB also significantly reduced the relapse of active TB after ending the treatment. Overall the data suggest that the use of heat-killed M. manresensis could be a new and promising tool for avoiding active TB induction and as adjunctive to TB</