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.

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

PubMed

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

2017-08-10

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

[Multidrug-resistant tuberculosis (MDR-TB) in a black African carceral area: Experience of Mali].

PubMed

Toloba, Y; Ouattara, K; Soumaré, D; Kanouté, T; Berthé, G; Baya, B; Konaté, B; Keita, M; Diarra, B; Cissé, A; Camara, F S; Diallo, S

2018-02-01

Prison constitutes a risk factor for the emergence of multi-drug resistance of tuberculosis (MDR-TB). The aim of this work was to study MDR-TB in a black African carceral center. Prospective study from January to December 2016 at the central house of arrest for men, Bamako. The study population was composed of tuberculous detainee. The suspicion of MDR-TB was done in any tuberculosis case remained positive in the second month of first-line treatment or in contact with an MDR-TB case. Among 1622 detainee, 21 cases of pulmonary tuberculosis were notified (1.29%), with an annual incidence of 13 cases/1000 detainee, they were 16 cases of SP-PTB (microscopy smear positive tuberculosis) and five cases of microscopy smear negative tuberculosis. The mean age was 28±7 years, extremes of 18 and 46 years. A negative association was found between the notion of smoking and occupation in the occurrence of tuberculosis (OR=0.036, [95% CI: 0.03-0.04], P=0.03. Among the 21 tuberculosis cases notified, one confirmed case of MDR-TB was detected (4.7%). In the first semester of 2016 cohort, we notified a cure rate of 87.5% (7/8 SP-PTB cases), and the confirmed MDR-TB case on treatment (21-month regimen), evolution enameled of pulmonary and hearing sequelae at seven months treatment. It was the first case of MDR-TB detected in a prison in Mali. Late diagnosis, evolution is enameled of sequelae and side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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 ...

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

PubMed

Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro

2018-03-01

The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The prevalence and determinants of active tuberculosis among diabetes patients in Cape Town, South Africa, a high HIV/TB burden setting.

PubMed

Berkowitz, Natacha; Okorie, Adaeze; Goliath, Rene; Levitt, Naomi; Wilkinson, Robert J; Oni, Tolu

2018-04-01

Studies addressing the association between diabetes mellitus (DM) and tuberculosis (TB) in sub-Saharan Africa are limited. We assessed the prevalence of active TB among DM patients at a primary care clinic, and identified risk factors for prevalent TB. A cross-sectional study was conducted in adult DM patients attending a clinic in Khayelitsha, Cape Town. Participants were screened for active TB (symptom screening and microbiological diagnosis) and HIV. Among 440 DM patients screened, the active TB prevalence was 3.0% (95% CI 1.72-5.03). Of the 13 prevalent TB cases, 53.9% (n = 7; 95% CI 27.20-78.50) had no TB symptoms, and 61.5% (n = 8; 95% CI 33.30-83.70) were HIV-1 co-infected. There were no significant differences in either fasting plasma glucose or HbA 1c levels between TB and non-TB participants. On multivariate analysis, HIV-1 infection (OR 11.3, 95% CI 3.26-39.42) and hemoptysis (OR 31.4, 95% CI 3.62-273.35) were strongly associated with prevalent active TB, with no differences in this association by age or gender. The prevalence of active TB among DM patients was 4-fold higher than the national prevalence; suggesting the need for active TB screening, particularly if hemoptysis is reported. Our results highlight the importance of HIV screening in this older population group. The high prevalence of sub-clinical TB among those diagnosed with TB highlights the need for further research to determine how best to screen for active TB in high-risk TB/HIV population groups and settings. Copyright © 2018. Published by Elsevier B.V.

High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

PubMed Central

Bai, Fengmin; Zhang, Shu; Jiang, Ting; Shen, Jie; Zhu, Qi; Yue, Tao; Shao, Lingyun; Gao, Yan; Feng, Yun; Weng, Xinhua; Zou, Hejian; Zhang, Ying

2013-01-01

We conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TST-positive (induration, ≥10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P = 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for ≥12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy. PMID:23554465

Extensively Drug-resistant Tuberculosis (XDR-TB): A daunting challenge to the current End TB Strategy and policy recommendations.

PubMed

Rahman, Md Arifur; Sarkar, Atanu

2017-07-01

Extensively Drug-resistant Tuberculosis (XDR-TB) has emerged as one of the most formidable challenges to the End TB Strategy that has targeted a 95% reduction in TB deaths and 90% reduction in cases by 2035. Globally, there were an estimated 55,100 new XDR-TB cases in 2015 in 117 countries. However, only one in 30 XDR-TB cases had been reported so far. Drug susceptibility test (DST) is the mainstay for diagnosing XDR-TB, but the lack of laboratory facilities in the resource-limited endemic countries limit its uses. A few new drugs including bedaquiline and delamanid, have the potential to improve the efficiency of XDR-TB treatment, but the drugs have been included in 39 countries only. The costs of XDR-TB treatment are several folds higher than that of the MDR-TB. Despite the financing from the donors, there is an urgent need to fill the current funding gap of US$ 2 billion to ensure effective treatment and robust surveillance. In the review article we have addressed current update on XDR-TB, including surveillance, diagnosis and the interventions needed to treat and limit its spread, emphasis on extensive financial support for implementing of current recommendations to meet the goals of End TB Strategy. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

PubMed Central

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ≥90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID:22301692

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.

PubMed

Caccamo, Nadia; Pietra, Gabriella; Sullivan, Lucy C; Brooks, Andrew G; Prezzemolo, Teresa; La Manna, Marco P; Di Liberto, Diana; Joosten, Simone A; van Meijgaarden, Krista E; Di Carlo, Paola; Titone, Lucina; Moretta, Lorenzo; Mingari, Maria C; Ottenhoff, Tom H M; Dieli, Francesco

2015-04-01

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multidrug-resistant tuberculosis (MDR-TB) in India: an attempt to link biosocial determinants.

PubMed

Atre, Sachin R; Mistry, Nerges F

2005-04-01

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a possible threat to global tuberculosis control efforts in recent years. It is a challenge not only from a public health point of view but also in the context of global economy, especially in the absence of treatment for MDR-TB at national-level programs in developing countries. Biological accounts are insufficient to understand the emergence and dynamics of drug resistance. This article focuses essentially on the need for a holistic perspective, linking biosocial determinants that would probably lead to better insights into MDR-TB control strategies.

PolyTB: A genomic variation map for Mycobacterium tuberculosis

PubMed Central

Coll, Francesc; Preston, Mark; Guerra-Assunção, José Afonso; Hill-Cawthorn, Grant; Harris, David; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Drobniewski, Francis; Gagneux, Sebastien; Glynn, Judith R.; Pain, Arnab; Parkhill, Julian; McNerney, Ruth; Martin, Nigel; Clark, Taane G.

2014-01-01

Summary Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to the ability to generate whole genome information in clinical isolates of M. tuberculosis complex (MTBC). The identification of informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb in the context of epidemiological, diagnostic and clinical studies. Mtb genomic datasets are increasingly available as raw sequences, which are potentially difficult and computer intensive to process, and compare across studies. Here we have processed the raw sequence data (>1500 isolates, eight studies) to compile a catalogue of SNPs (n = 74,039, 63% non-synonymous, 51.1% in more than one isolate, i.e. non-private), small indels (n = 4810) and larger structural variants (n = 800). We have developed the PolyTB web-based tool (http://pathogenseq.lshtm.ac.uk/polytb) to visualise the resulting variation and important meta-data (e.g. in silico inferred strain-types, location) within geographical map and phylogenetic views. This resource will allow researchers to identify polymorphisms within candidate genes of interest, as well as examine the genomic diversity and distribution of strains. PolyTB source code is freely available to researchers wishing to develop similar tools for their pathogen of interest. PMID:24637013

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

Treatment: Latent TB Infection (LTBI) and TB Disease

MedlinePlus

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

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

PubMed

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

2009-08-01

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. 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. 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. In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective.

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

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. ...

TB Terms

MedlinePlus

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

PolyTB: a genomic variation map for Mycobacterium tuberculosis.

PubMed

Coll, Francesc; Preston, Mark; Guerra-Assunção, José Afonso; Hill-Cawthorn, Grant; Harris, David; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Drobniewski, Francis; Gagneux, Sebastien; Glynn, Judith R; Pain, Arnab; Parkhill, Julian; McNerney, Ruth; Martin, Nigel; Clark, Taane G

2014-05-01

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to the ability to generate whole genome information in clinical isolates of M. tuberculosis complex (MTBC). The identification of informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb in the context of epidemiological, diagnostic and clinical studies. Mtb genomic datasets are increasingly available as raw sequences, which are potentially difficult and computer intensive to process, and compare across studies. Here we have processed the raw sequence data (>1500 isolates, eight studies) to compile a catalogue of SNPs (n = 74,039, 63% non-synonymous, 51.1% in more than one isolate, i.e. non-private), small indels (n = 4810) and larger structural variants (n = 800). We have developed the PolyTB web-based tool (http://pathogenseq.lshtm.ac.uk/polytb) to visualise the resulting variation and important meta-data (e.g. in silico inferred strain-types, location) within geographical map and phylogenetic views. This resource will allow researchers to identify polymorphisms within candidate genes of interest, as well as examine the genomic diversity and distribution of strains. PolyTB source code is freely available to researchers wishing to develop similar tools for their pathogen of interest. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Outbreak column 21: Tuberculosis (TB): Still a nosocomial threat.

PubMed

Curran, Evonne T

2018-05-01

This outbreak column explores the epidemiology and infection prevention guidance on tuberculosis (TB) in the UK. The column finds that, at present, national guidance leaves UK hospitals ill-prepared to prevent nosocomial TB transmission. Reasons for this conclusion are as follows: (1) while TB is predominantly a disease that affects people with 'social ills', it has the potential to infect anyone who is sufficiently exposed; (2) nosocomial transmission is documented throughout history; (3) future nosocomial exposures may involve less treatable disease; and (4) current UK guidance is insufficient to prevent nosocomial transmission and is less than that advocated by the World Health Organization and the Centers for Disease Control and Prevention.

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

[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

Extensively Drug-Resistant Tuberculosis (XDR-TB) - A Potential Threat in Ireland

PubMed Central

Mc Laughlin, Anne Marie; O’Donnell, Rory A; Gibbons, Noel; Scully, Mary; O’Flangan, Darina; Keane, Joseph

2007-01-01

We describe a case of a 25 year old female from Lithuania who presented with a productive cough. Chest radiograph demonstrated an infiltrate in the left upper lobe and a cavitating lesion in the right middle lobe. Sensitivity testing of her sputum led to a diagnosis of extensively drug-resistant tuberculosis (XDR-TB). This is the first case in Ireland and highlights the need for physicians to be aware of the possibility of XDR-TB. Moreover it underlines the need for improvement in service provision in terms of a TB reference laboratory and TB clinics. PMID:19340317

Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis

PubMed Central

Petruccioli, Elisa; Scriba, Thomas J.; Petrone, Linda; Hatherill, Mark; Cirillo, Daniela M.; Joosten, Simone A.; Ottenhoff, Tom H.; Denkinger, Claudia M.; Goletti, Delia

2016-01-01

New approaches to control the spread of tuberculosis (TB) are needed, including tools to predict development of active TB from latent TB infection (LTBI). Recent studies have described potential correlates of risk, in order to inform the development of prognostic tests for TB disease progression. These efforts have included unbiased approaches employing “omics” technologies, as well as more directed, hypothesis-driven approaches assessing a small set or even individual selected markers as candidate correlates of TB risk. Unbiased high-throughput screening of blood RNAseq profiles identified signatures of active TB risk in individuals with LTBI, ≥1 year before diagnosis. A recent infant vaccination study identified enhanced expression of T-cell activation markers as a correlate of risk prior to developing TB; conversely, high levels of Ag85A antibodies and high frequencies of interferon (IFN)-γ specific T-cells were associated with reduced risk of disease. Others have described CD27−IFN-γ+CD4+ T-cells as possibly predictive markers of TB disease. T-cell responses to TB latency antigens, including heparin-binding haemagglutinin and DosR-regulon-encoded antigens have also been correlated with protection. Further studies are needed to determine whether correlates of risk can be used to prevent active TB through targeted prophylactic treatment, or to allow targeted enrolment into efficacy trials of new TB vaccines and therapeutic drugs. PMID:27836953

Technology and tuberculosis control: the OUT-TB Web experience.

PubMed

Guthrie, Jennifer L; Alexander, David C; Marchand-Austin, Alex; Lam, Karen; Whelan, Michael; Lee, Brenda; Furness, Colin; Rea, Elizabeth; Stuart, Rebecca; Lechner, Julia; Varia, Monali; McLean, Jennifer; Jamieson, Frances B

2017-04-01

Develop a tool to disseminate integrated laboratory, clinical, and demographic case data necessary for improved contact tracing and outbreak detection of tuberculosis (TB). In 2007, the Public Health Ontario Laboratories implemented a universal genotyping program to monitor the spread of TB strains within Ontario. Ontario Universal Typing of TB (OUT-TB) Web utilizes geographic information system (GIS) technology with a relational database platform, allowing TB control staff to visualize genotyping matches and microbiological data within the context of relevant epidemiological and demographic data. OUT-TB Web is currently available to the 8 health units responsible for >85% of Ontario's TB cases and is a valuable tool for TB case investigation. Users identified key features to implement for application enhancements, including an e-mail alert function, customizable heat maps for visualizing TB and drug-resistant cases, socioeconomic map layers, a dashboard providing TB surveillance metrics, and a feature for animating the geographic spread of strains over time. OUT-TB Web has proven to be an award-winning application and a useful tool. Developed and enhanced using regular user feedback, future versions will include additional data sources, enhanced map and line-list filter capabilities, and development of a mobile app. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Epidemiological Characteristics and Clinical Outcome of HIV-Related Tuberculosis in a Population of TB Patients in South-western Nigeria.

PubMed

Olowe, Olugbenga A; Makanjuola, Olufunmilola B; Adekanmi, Adeniyi S; Adefioye, Olusola J; Olowe, Rita A

2017-06-01

Tuberculosis (TB) is the second leading cause of death from infectious disease globally with its impact more dramatic in resource limited settings. Individuals with human immunodeficiency virus (HIV) infection who also develop tuberculosis represent a significant challenge to TB control. This study was carried out to determine the prevalence of TB-HIV coinfection and pattern of infection among TB patients. We also compared treatment outcome among coinfected patients with those not coinfected. A six-year retrospective review of records of patients managed at the Tuberculosis Treatment Center of the LAUTECH Teaching Hospital, South-Western Nigeria from January 2009 to December 2014 was carried out. One hundred and five (26.3%) of the 399 TB patients seen in the study period were coinfected with HIV. About 10% of the subjects had extrapulmonary tuberculosis. Treatment failure was significantly worse among patients who had both HIV and TB compared with those who had TB only (49.5% vs. 32%, p = 0.001). Death rate was also higher in the coinfected individuals implying a poorer clinical outcome. High prevalence of TB-HIV coinfection and poor treatment outcome in this group of individuals, though predictable, calls for a more concerted effort in the management of TB-HIV coinfection.

Factors influencing quality of life in patients with active tuberculosis.

PubMed

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

2004-10-20

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

Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.

PubMed

Zhou, Yu; Du, Juan; Hou, Hong-Yan; Lu, Yan-Fang; Yu, Jing; Mao, Li-Yan; Wang, Feng; Sun, Zi-Yong

2017-01-01

Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.

Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB)

PubMed Central

Ekins, Sean; Spektor, Anna Coulon; Clark, Alex M.; Dole, Krishna; Bunin, Barry A.

2016-01-01

Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project. PMID:27884746

TB Mobile: a mobile app for anti-tuberculosis molecules with known targets

PubMed Central

2013-01-01

Background An increasing number of researchers are focused on strategies for developing inhibitors of Mycobacterium tuberculosis (Mtb) as tuberculosis (TB) drugs. Results In order to learn from prior work we have collated information on molecules screened versus Mtb and their targets which has been made available in the Collaborative Drug Discovery (CDD) database. This dataset contains published data on target, essentiality, links to PubMed, TBDB, TBCyc (which provides a pathway-based visualization of the entire cellular biochemical network) and human homolog information. The development of mobile cheminformatics apps could lower the barrier to drug discovery and promote collaboration. Therefore we have used this set of over 700 molecules screened versus Mtb and their targets to create a free mobile app (TB Mobile) that displays molecule structures and links to the bioinformatics data. By input of a molecular structures and performing a similarity search within the app we can infer potential targets or search by targets to retrieve compounds known to be active. Conclusions TB Mobile may assist researchers as part of their workflow in identifying potential targets for hits generated from phenotypic screening and in prioritizing them for further follow-up. The app is designed to lower the barriers to accessing this information, so that all researchers with an interest in combatting this deadly disease can use it freely to the benefit of their own efforts. PMID:23497706

Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection.

PubMed

Kim, Ji Yeun; Park, Joung Ha; Kim, Min-Chul; Cha, Hye Hee; Jeon, Na-Young; Park, Seong Yeon; Kim, Min-Jae; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-08

The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Combining the IGRA and TARA appears to be useful for diagnosing active TB. Copyright © 2018. Published by Elsevier Ltd.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.

PubMed

Domínguez, J; Boettger, E C; Cirillo, D; Cobelens, F; Eisenach, K D; Gagneux, S; Hillemann, D; Horsburgh, R; Molina-Moya, B; Niemann, S; Tortoli, E; Whitelaw, A; Lange, C

2016-01-01

The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

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. Published by Elsevier B.V.

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

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.

PubMed

Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug

[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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Tuberculosis after liver transplantation in a large center in New York City: QuantiFERON® -TB Gold-based pre-transplant screening performance and active tuberculosis post-transplant.

PubMed

Hand, Jonathan; Sigel, Keith; Huprikar, Shirish; Hamula, Camille; Rana, Meena

2018-04-01

Pre-transplant screening for latent tuberculosis infection (LTBI) is a complex consideration that varies by institution. Inconsistent performance of interferon-gamma release assay (IGRA) further complicates screening. Data regarding LTBI screening outcomes and test characteristics in a large, foreign-born pre-transplant population within the United States are limited. In this retrospective study, patients who received QuantiFERON ® -TB Gold (QFT) prior to liver transplantation (LT) were included. Characteristics of patients were compared by QFT result, and predictors of indeterminate results were evaluated. Similar comparisons were performed between patients who developed active TB and those who did not. Of 148 patients screened, the rate of positive, indeterminate, and negative testing was 13.5% (20/148), 27% (40/148), and 59% (88/148), respectively. An indeterminate QFT result was more than 16 times more likely in patients with a Model for End-stage Liver Disease score >25 (odds ratio [OR] 16.7; 95% confidence interval [CI], 2.1-132.0; P = .008) and more than 4 times when performed in our institution's lab compared with commercial lab (OR 4.1; 95% CI, 1.34-12.44; P = .013). The overall TB incidence was 1102/100 000 transplant cases. No patient who developed active TB had a positive QFT. All were born outside of the United States (P = .06) and had pre-transplantation chest imaging demonstrating granulomatous disease (P = .006). Our experience further highlights the challenges of LTBI screening prior to LT and suggests that QFT may be a poor predictor of active TB in higher risk pre-transplant populations. Candidates should be screened as early as possible to optimize QFT performance, and local epidemiological data should be used to create institution-specific screening protocols in areas with large populations from TB-endemic regions. Management should consider TB risk factors, QFT, and imaging instead of reliance on QFT testing alone. © 2018 John Wiley

Tuberculosis

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Testing for TB Infection

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

PubMed

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

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

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

PubMed Central

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity. PMID:29320502

Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB.

PubMed

Martins, Marta

2011-05-01

The emergence of resistance in tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca(2+) and K(+) flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).

[CLINICAL UTILITY OF T-SPOT.TB ASSAY WITH T-Cell Xtend REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS IN THE FIELD TEST AT OUR HOSPITAL].

PubMed

Nemoto, Kenji; Oh-ishi, Shuji; Taguchi, Masato; Hyodo, Kentaro; Kanazawa, Jun; Miura, Yukiko; Takaku, Takio; Usui, Shingo; Hayashihara, Kenji; Saito, Takefumi

2016-04-01

T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.

Knowledge and perceptions of national and provincial tuberculosis control programme managers in Pakistan about the WHO Stop TB strategy: a qualitative study.

PubMed

Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz; Hassounah, Sondus

2016-01-01

To understand how national and provincial tuberculosis programme managers in Pakistan perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. National and provincial tuberculosis programme managers play an important role in effective implementation of the Stop TB strategy. A qualitative interview study was conducted with 10 national and provincial tuberculosis programme managers to understand how they perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). National and provincial tuberculosis programme managers in Pakistan. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). National and provincial tuberculosis programmes in Pakistan. 1. Knowledge and perceptions of national and provincial tuberculosis programme managers about the Stop TB strategy 2. Progress in implementing the strategy in Pakistan 3. Significant success factors 4. Significant implementation challenges 5. Lessons learnt to scale up successful implementation. The managers reported that most progress had been made in extending DOTS, health systems strengthening, public -private mixed interventions, MDR-TB care and TB/HIV care. The four factors that contributed significantly to progress were the availability of DOTS services, the public-private partnership approach, comprehensive guidance for TB control and government and donor commitment to TB control. This study identified three main challenges as perceived by national and provincial tuberculosis programme managers in terms of implementing the Stop TB strategy: 1. Inadequate political commitment, 2. Issue pertaining to prioritisation of certain components in the TB strategy over others due to external influences and 3. Limitations in the overall

Knowledge and perceptions of national and provincial tuberculosis control programme managers in Pakistan about the WHO Stop TB strategy: a qualitative study

PubMed Central

Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz

2016-01-01

Objective To understand how national and provincial tuberculosis programme managers in Pakistan perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. National and provincial tuberculosis programme managers play an important role in effective implementation of the Stop TB strategy. Design A qualitative interview study was conducted with 10 national and provincial tuberculosis programme managers to understand how they perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). Participants National and provincial tuberculosis programme managers in Pakistan. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). Setting National and provincial tuberculosis programmes in Pakistan Main outcome measures 1. Knowledge and perceptions of national and provincial tuberculosis programme managers about the Stop TB strategy 2. Progress in implementing the strategy in Pakistan 3. Significant success factors 4. Significant implementation challenges 5. Lessons learnt to scale up successful implementation. Results The managers reported that most progress had been made in extending DOTS, health systems strengthening, public -private mixed interventions, MDR-TB care and TB/HIV care. The four factors that contributed significantly to progress were the availability of DOTS services, the public-private partnership approach, comprehensive guidance for TB control and government and donor commitment to TB control. Conclusion This study identified three main challenges as perceived by national and provincial tuberculosis programme managers in terms of implementing the Stop TB strategy: 1. Inadequate political commitment, 2. Issue pertaining to prioritisation of certain components in the TB

TB epidemiology: where are the young women? Know your tuberculosis epidemic, know your response.

PubMed

Perumal, Rubeshan; Naidoo, Kogieleum; Padayatchi, Nesri

2018-03-27

The global predominance of tuberculosis in men has received significant attention. However, epidemiological studies now demonstrate that there is an increased representation of young women with tuberculosis, especially in high HIV burden settings where young women bear a disproportionate burden of HIV. The role of the HIV epidemic, as well as changes in behavioural, biological, and structural risk factors are explored as potential explanations for the increasing burden of tuberculosis in young women. As young women are particularly vulnerable to HIV infection in sub-Saharan Africa, it is unsurprising that the TB epidemic in this setting has become increasingly feminised. This age-sex trend of TB in South Africa is similar to WHO estimates for other countries with a high HIV prevalence where there are more female than male cases notified up to the age of 25 years. The high prevalence of anaemia of chronic disease in young women with HIV is an additional potential reason for their increased TB risk. The widespread use of injectable medroxyprogesterone acetate contraception, which has been shown to possess selective glucocorticoid effect and oestrogen suppression, in young women may be an important emerging biological risk factor for tuberculosis in young women. Behavioural factors such as alcohol use and tobacco smoking patterns are further factors which may be responsible for the narrowing of the sex gap in TB epidemiology. In comparison to the significantly higher alcohol consumption rates in men globally, there is a narrowing gap in alcohol consumption between the sexes in South Africa with alarming rates of alcohol abuse in young women. There is a similar narrowing of the tobacco smoking gap between the sexes in South Africa, with increasing smoking prevalence in young women. With nearly 70% of all TB patients being co-infected with HIV in our setting, it is not surprising that the age and sex distribution of TB is increasingly resembling the distribution of HIV

PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates▿

PubMed Central

Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Greenwald, David; Nacy, Carol A.; Gibson, Susan; Didier, Peter J.; Washington, Marc; Szczerba, Peter; Motzel, Sherri; Handt, Larry; Pollock, John M.; McNair, James; Andersen, Peter; Langermans, Jan A. M.; Verreck, Frank; Ervin, Sean; Ervin, Frank; McCombs, Candace

2007-01-01

Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP. PMID:17652522

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

PubMed

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

2017-01-01

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

Mycobacterium tuberculosis thymidylate kinase antigen assays for designating incipient, high-risk latent M.tb infection.

PubMed

Wayengera, Misaki; Kateete, David P; Asiimwe, Benon; Joloba, Moses L

2018-03-16

Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI. TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD®); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays. IgM levels were found to be equally low across QuantiFERON-TB GOLD® prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 ± 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 ± 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 ± 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI). TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.

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

PubMed

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

2017-01-01

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

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

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

PubMed

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

2017-04-01

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2006-01-01

Background Rapid and accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of infectious cases and thus to reduce its spread. To improve the diagnosis of TB, more rapid diagnostic techniques such as antibody detection methods including enzyme-linked immunosorbent assay (ELISA)-based serological tests and immunochromatographic methods were developed. This study was designed to evaluate the validity of an immunochromatographic assay, ICT Tuberculosis test for the serologic diagnosis of TB in Antalya, Turkey. Methods Sera from 72 patients with active pulmonary (53 smear-positive and 19 smear-negative cases) and eight extrapulmonary (6 smear-positive and 2 smear-negative cases) TB, and 54 controls from different outpatient clinics with similar demographic characteristics as patients were tested by ICT Tuberculosis test. Results The sensitivity, specificity, and negative predictive value of the ICT Tuberculosis test for pulmonary TB were 33.3%, 100%, and 52.9%, respectively. Smear-positive pulmonary TB patients showed a higher positivity rate for antibodies than smear-negative patients, but the difference was not statistically significant. Of the eight patients with extrapulmonary TB, antibody was detected in four patients. Conclusion Our results suggest that ICT Tuberculosis test can be used to aid TB diagnosis in smear-positive patients until the culture results are available. PMID:16504161

Gene mutations in Mycobacterium tuberculosis: multidrug-resistant TB as an emerging global public health crisis.

PubMed

Mishra, Rahul; Shukla, Priyanka; Huang, Wei; Hu, Ning

2015-01-01

Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. TB poses formidable challenges to the global health at the public health and scientific level by acquiring gene mutation into anti TB drugs specially rifampin and isoniazid which leads resistant to drug regime and treatment forms. Our tools to combat MDR (multidrug resistant) TB are dangerously out of date and ineffective. Besides new tools (TB drugs, vaccines, diagnostics), we also need new strategies to identify key Mycobacterium tuberculosis and human host interaction. It is all equally important that we build up high quality clinical trial capacity and bio banks for TB biomarkers identification. But most important is global commitment at all levels to roll back TB before it expose us again. Rapid development of drug resistance caused by M. tuberculosis has lead to measure resistance accurately and easily. This knowledge will certainly help us to understand how to prevent the occurrence of drug resistance as well as identifying genes associated with new drug resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing

PubMed Central

Nkurunungi, Gyaviira; Lutangira, Jimreeves E.; Lule, Swaib A.; Akurut, Hellen; Kizindo, Robert; Fitchett, Joseph R.; Kizito, Dennison; Sebina, Ismail; Muhangi, Lawrence; Webb, Emily L.; Cose, Stephen; Elliott, Alison M.

2012-01-01

Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of

A comparative study of tuberculosis patients initiated on ART and receiving different models of TB-HIV care.

PubMed

Schulz, S A; Draper, H R; Naidoo, P

2013-12-01

Although health policy in South Africa calls for the integration of services, the effectiveness of different models of integration on patient outcomes has not been well demonstrated. To evaluate the outcomes of coinfected patients starting antiretroviral treatment (ART) in a tuberculosis (TB) hospital who received different models of ongoing care. This cohort study compared outcomes for 271 coinfected patients who started ART in a TB hospital in the Western Cape. After discharge, one group of patients received anti-tuberculosis treatment and ART from different providers, in the same or in different clinics (vertical care). The other group received anti-tuberculosis treatment and ART at the same visit from the same service provider (integrated care). Demographic and clinical data and TB and ART outcomes were compared. The vertical care model had more unfavourable outcomes for anti-tuberculosis treatment (28.7% vs. 5.9%, P < 0.001) and ART (30.1% vs. 7.4%, P < 0.001) than the integrated care model. The vertical care model showed no difference whether services were provided by two service providers in the same or in geographically separate primary health care clinics. Patient outcomes were better when TB and HIV care was received from the same service provider at the same visit.

Whole blood bactericidal activity during treatment of pulmonary tuberculosis.

PubMed

Wallis, Robert S; Vinhas, Solange A; Johnson, John L; Ribeiro, Fabíola C; Palaci, Moisés; Peres, Renata L; Sá, Ricardo T; Dietze, Reynaldo; Chiunda, Allan; Eisenach, Kathleen; Ellner, Jerrold J

2003-01-15

The timely evaluation of new drugs that can be used to shorten tuberculosis (TB) treatment will require surrogate markers for relapse. This study examined bactericidal activity against intracellular Mycobacterium tuberculosis in whole blood culture (whole blood bactericidal activity; WBA) during TB treatment. In the absence of chemotherapy, immune mechanisms in patient blood resulted in bacteriostasis, whereas administration of oral chemotherapy resulted in bacillary killing. Total WBA per dose was greater during the intensive phase of treatment than during the continuation phase (mean, -2.32 vs. -1.67 log(10) cfu-days, respectively; P<.001). Cumulative WBA throughout treatment was greater in subjects whose sputum cultures converted to negative by the eighth week of treatment than in those for whom conversion was delayed (mean, -365 vs. -250 log(10) cfu-days; P=.04) and correlated with the rate of decrease of sputum colony-forming unit counts during the first 4 weeks of treatment (P=.018), both of which are indicative of prognosis. These findings indicate that measurement of WBA may have a role in assessing the sterilizing activity of new anti-TB drugs.

Questions and Answers about TB

MedlinePlus

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

Effect of Active Case Finding on Prevalence and Transmission of Pulmonary Tuberculosis in Dhaka Central Jail, Bangladesh

PubMed Central

Banu, Sayera; Rahman, Md. Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md. Siddiqur Rahman; Rahman, Md. Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D.

2015-01-01

Background Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh

Effect of active case finding on prevalence and transmission of pulmonary tuberculosis in Dhaka Central Jail, Bangladesh.

PubMed

Banu, Sayera; Rahman, Md Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md Siddiqur Rahman; Rahman, Md Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D

2015-01-01

Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh.

Pulmonary tuberculosis

MedlinePlus

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

Active Site Flexibility of Mycobacterium tuberculosis Isocitrate Lyase in Dimer Form.

PubMed

Lee, Yie-Vern; Choi, Sy Bing; Wahab, Habibah A; Choong, Yee Siew

2017-09-25

Tuberculosis (TB) still remains a global threat due to the emergence of a drug-resistant strain. Instead of focusing on the drug target of active stage TB, we are highlighting the isocitrate lyase (ICL) at the dormant stage TB. ICL is one of the persistent factors for Mycobacterium tuberculosis (MTB) to survive during the dormant phase. In addition, the absence of ICL in human has made ICL a potential drug target for TB therapy. However, the dynamic details of ICL which could give insights to the ICL-ligand interaction have yet to be solved. Therefore, a series of ICL dimer dynamics studies through molecular dynamics simulation were performed in this work. The ICL active site entrance gate closure is contributed to by hydrogen bonding and electrostatic interactions with the C-terminal. Analysis suggested that the open-closed behavior of the ICL active site entrance depends on the type of ligand present in the active site. We also observed four residues (Ser91, Asp108, Asp153, and Cys191) which could possibly be the nucleophiles for nucleophilic attack on the cleavage of isocitrate at the C 2 -C 3 bond. We hope that the elucidation of ICL dynamics can benefit future works such as lead identification or antibody design against ICL for TB therapeutics.

More significance of TB-IGRA except for the diagnose of tuberculosis.

PubMed

Xu, Jun-Chi; Li, Ze-Yi; Chen, Xin-Nian; Shi, Cui-Lin; Wu, Mei-Ying; Chen, Hui; Zhu, Xiao-Yan; Song, Hua-Feng; Wu, Min-Juan; Xu, Ping

2018-01-01

Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015. The TB-IGRA, routine blood test, T-cell subgroup data were collected for statistical analysis. TB-IGRA results were in positive proportion to the lymphocytes, CD4 + T cells and CD4 + CD28 + T cells, whereas negative to the Treg cells. Patient with unilateral pulmonary lesion had higher TB-IGRA than those with bilateral pulmonary lesions. After the stimulation of TB-specific antigen, the proportion of CD4 + IFN-γ + and CD8 + IFN-γ + T Tcells were both increased and the CD4 + IFN-γ + T had positive correlation with the value of TB-IGRA. IFN-γ was tested with TB-IGRA in patients with TB by the specific TB T cells and correlated with the lymphocytes, while the lymphocytes also closely related to the host's anti-TB immunity and disease outcome. Hence the result of TB-IGRA could reflect the specific anti-TB immunity ability of the host, disease progression and prognosis. This study further expands the application scope of TB-IGRA technology in the diagnosis of TB and lays a foundation for clinical practice to understand the immunity state of the patients with TB and the application of auxiliary clinical immunity regulators. © 2017 Wiley Periodicals, Inc.

Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are higher in healthy household contacts of TB: a novel immunodominant antigen from M. tuberculosis.

PubMed

Devasundaram, Santhi; Raja, Alamelu

2017-07-01

The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates. Multicolor flow cytometry analysis of whole-blood cultures showed higher Lpd-specific Th1 recall response (IFN-γ, TNF-α, and IL-2; P = 0.0006) and memory CD4 + and CD8 + T cells (CCR7 + CD45RA - and CCR7 - CD45RA - ) in healthy household contacts (HHC) of TB ( P < 0.0001), which is comparable with or higher than the standard antigens, ESAT-6 and CFP-10. The frequency of Lpd-specific multifunctional T cells was higher in HHC compared with PTB patients. However, there is no significant statistical correlation. Regulatory T cell (T reg ) analysis of HHCs and active TB patients demonstrated very low Lpd-specific CD4 + T regs relative to ESAT-6 and CFP-10. Our study demonstrates that the Lpd antigen induces a strong cellular immune response in healthy mycobacteria-infected individuals. In consideration of this population having demonstrated immunologic protection against active TB disease development, our data are encouraging about the possible use of Lpd as a target for further TB subunit vaccine development. © Society for Leukocyte Biology.

"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

PubMed

Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

2017-06-14

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

The Activity of a Hexameric M17 Metallo-Aminopeptidase Is Associated With Survival of Mycobacterium tuberculosis

PubMed Central

Correa, Andre F.; Bastos, Izabela M. D.; Neves, David; Kipnis, Andre; Junqueira-Kipnis, Ana P.; de Santana, Jaime M.

2017-01-01

Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied. Aminopeptidases constitute a set of proteases that selectively remove amino acids from the N-terminus of proteins and peptides and may act as virulence factors, essential for survival and maintenance of many microbial pathogens. Here, we characterized a leucine aminopeptidase of M. tuberculosis (MtLAP) as a cytosolic oligomeric metallo-aminopeptidase. Molecular and enzymatic properties lead us to classify MtLAP as a typical member of the peptidase family M17. Furthermore, the aminopeptidase inhibitor bestatin strongly inhibited MtLAP activity, in vitro M. tuberculosis growth and macrophage infection. In murine model of TB, bestatin treatment reduced bacterial burden and lesion in the lungs of infected mice. Thus, our data suggest that MtLAP participates in important metabolic pathways of M. tuberculosis necessary for its survival and virulence and consequently may be a promising target for new anti-TB drugs. PMID:28396657

TB Summit 2014

PubMed Central

Maitra, Arundhati; Bhakta, Sanjib

2014-01-01

World TB Day commemorates Dr Robert Koch’s first announcement on March 24, 1882, that the bacterium Mycobacterium tuberculosis is the causative agent of tuberculosis. Currently, the event comprises of several conferences, meetings and activities held all over the world with the singular intention of raising public awareness about the global health emergency. In spite of having discovered the etiological agent of tuberculosis more than a century ago, a sizeable population still contract the disease every year and fall prey to it. In 2012, an estimated 8.6 million people developed the disease with 1.3 million succumbing to it. The number of TB deaths in children is unacceptably large, given that most are preventable. However, the challenge appears to be shifting toward attempts to control the rise and spread of the drug resistant variants of the microbe. To achieve this, a concerted effort from academia, clinical practice, and industry has been put forth. The TB Summit 2014 attempted to raise awareness as well as bring together experts involved in different aspects of tuberculosis research to help establish a more collective approach to battle this age-old disease. PMID:25003368

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

PubMed

Çakar, Beyhan; Çiledağ, Aydın

2018-01-01

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

A tuberculosis biomarker database: the key to novel TB diagnostics.

PubMed

Yerlikaya, Seda; Broger, Tobias; MacLean, Emily; Pai, Madhukar; Denkinger, Claudia M

2017-03-01

New diagnostic innovations for tuberculosis (TB), including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this 'biomarker pipeline problem', FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs) for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

PubMed

Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

2017-10-03

Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

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 ...

Primary lung cancer coexisting with active pulmonary tuberculosis.

PubMed

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

2014-09-01

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

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

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

Recent transmission of Mycobacterium tuberculosis in China: the implication of molecular epidemiology for tuberculosis control.

PubMed

Yang, Chongguang; Gao, Qian

2018-02-01

Tuberculosis (TB) has remained an ongoing concern in China. The national scale-up of the Directly Observed Treatment, Short Course (DOTS) program has accelerated the fight against TB in China. Nevertheless, many challenges still remain, including the spread of drug-resistant strains, high disease burden in rural areas, and enormous rural-to-urban migrations. Whether incident active TB represents recent transmission or endogenous reactivation has helped to prioritize the strategies for TB control. Evidence from molecular epidemiology studies has delineated the recent transmission of Mycobacterium tuberculosis (M. tuberculosis) strains in many settings. However, the transmission patterns of TB in most areas of China are still not clear. Studies carried out to date could not capture the real burden of recent transmission of the disease in China because of the retrospective study design, incomplete sampling, and use of low-resolution genotyping methods. We reviewed the implementations of molecular epidemiology of TB in China, the estimated disease burden due to recent transmission of M. tuberculosis strains, the primary transmission of drug-resistant TB, and the evaluation of a feasible genotyping method of M. tuberculosis strains in circulation.

Prevalence and Factors Associated with Tuberculosis Treatment Success among TB/HIV Co-Infection in North-East Malaysia.

PubMed

Jalal, Tengku Mardhiah Tengku; Abdullah, Sarimah; Wahab, Farhanah Abd; Dir, Sharina; Naing, Nyi Nyi

2017-12-01

One of the six strategies developed by WHO, in order to stop Tuberculosis (TB) is addressing TB/HIV high-risk groups. This study aimed to determine the prevalence of successful TB treatment and factors associated with TB treatment success among TB/HIV co-infection patients in North-East Malaysia. A cross-sectional study was carried out in the a-year period from 2003 to 2012 by reviewing TB/HIV records in all hospitals and health clinics. The outcome of interest was treatment success as defined by Ministry of Health (MOH) when the patients was cured or completed TB treatment. Out of 1510 total TB/HIV co-infection cases, 27.9% (95% CI: 25.2, 30.6) of the patients were having treatment success. A majority of TB/HIV co-infection cases were male (91.1%). Fifty-eight percent the patients were drug addicts and 6% were having positive tuberculin tests. The multiple logistic regression revealed that male (OR: 0.39, 95% CI: 0.22, 0.71) and positive tuberculin test result (OR: 2.61, 95% CI: 1.63, 4.19) were significantly associated with the treatment success of TB/HIV co-infection patients. Other factors such as age, comorbid, sputum smear and x-ray findings were not significantly factors in this study. Female patients and those with negative tuberculin test should be emphasised for successful tuberculosis treatment.

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

PubMed

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

2017-02-27

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

Tuberculosis Reports - UDOH-EPI

Science.gov Websites

Tuberculosis Tuberculosis Reports Tuberculosis Reports Tuberculosis Utah Reports Tuberculosis in Utah - Five (IBIS-PH) Tuberculosis 2015 Monthy Reports January February March April May June Tuberculosis National Reports National TB Data and Statistics Tuberculosis Global Reports TB Incidence Map by country TB

Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment▿

PubMed Central

Sahiratmadja, Edhyana; Alisjahbana, Bachti; de Boer, Tjitske; Adnan, Iskandar; Maya, Anugrah; Danusantoso, Halim; Nelwan, Ronald H. H.; Marzuki, Sangkot; van der Meer, Jos W. M.; van Crevel, Reinout; van de Vosse, Esther; Ottenhoff, Tom H. M.

2007-01-01

Pro- and anti-inflammatory cytokines and their signaling pathways play key roles in protection from and pathogenesis of mycobacterial infection, and their balance and dynamic changes may control or predict clinical outcome. Peripheral blood cells' capacity to produce proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin-12/23p40 [IL-12/23p40], and gamma interferon [IFN-γ]) and anti-inflammatory (IL-10) cytokines in response to Mycobacterium tuberculosis or unrelated stimuli (lipopolysaccharide, phytohemagglutinin) was studied in 93 pulmonary tuberculosis (TB) patients and 127 healthy controls from Indonesia. Their cells' ability to respond to IFN-γ was examined to investigate whether M. tuberculosis infection can also inhibit IFN-γ receptor (IFN-γR) signaling. Although there was interindividual variability in the observed responses, the overall results revealed that M. tuberculosis-induced TNF-α and IFN-γ levels showed opposite trends. Whereas TNF-α production was higher in active-TB patients than in controls, IFN-γ production was strongly depressed during active TB, correlated inversely with TB disease severity, and increased during therapy. By contrast, mitogen-induced IFN-γ production, although lower in patients than in controls, did not change during treatment, suggesting an M. tuberculosis-specific and reversible component in the depression of IFN-γ. Depressed IFN-γ production was not due to decreased IL-12/IL-23 production. Importantly, IFN-γ-inducible responses were also significantly depressed during active TB and normalized during treatment, revealing disease activity-related and reversible impairment in IFN-γR signaling in TB. Finally, IFN-γ/IL-10 ratios significantly correlated with TB cure. Taken together, these results show that M. tuberculosis-specific stimulation of IFN-γ (but not TNF-α) production and IFN-γR signaling are significantly depressed in active TB, correlate with TB disease severity and activity, and

T7 Phage Display Library a Promising Strategy to Detect Tuberculosis Specific Biomarkers.

PubMed

Talwar, Harvinder; Talreja, Jaya; Samavati, Lobelia

2016-06-01

One-third of the world's population is infected with tuberculosis, only 10% will develop active disease and the remaining 90% is considered to have latent TB (LTB). While active TB is contagious and can be lethal, the LTB can evolve to active TB. The diagnosis of TB can be challenging, especially in the early stages, due to the variability in presentation and nonspecific signs and symptoms. Currently, we have limited tools available to diagnose active TB, predict treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses through vaccination. Therefore, the identification of robust and accurate tuberculosis-specific biomarkers is crucial for the successful eradication of TB. In this commentary, we summarized the available methods for diagnosis and differentiation of active TB from LTB and their limitations. Additionally, we present a novel peptide microarray platform as promising strategy to identify TB biomarkers.

Risk factors for latent tuberculosis infection in close contacts of active tuberculosis patients in South Korea: a prospective cohort study.

PubMed

Lee, Seung Jun; Lee, Seung Hun; Kim, You Eun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Jang Rak; Hwang, Young Sil; Kim, Hee Jin; Menzies, Dick

2014-11-18

The diagnosis and treatment of latent tuberculosis infection (LTBI) have become mandatory to reduce the burden of tuberculosis worldwide. Close contacts of active TB patients are at high risk of both active and LTBI. The aim of this study is to identify the predominant risk factors of contracting LTBI, persons in close contact with TB patients were recruited. This study also aimed to compare the efficacy of the tuberculin skin test (TST) and QuantiFERON(®)-TB GOLD (QFT-G) to diagnose LTBI. Close contacts of active pulmonary TB patients visiting a hospital in South Korea were diagnosed for LTBI using TST and/or QFT-G. The association of positive TST and/or QFT-G with the following factors was estimated: age, gender, history of Bacillius Calmette-Guerin (BCG) vaccination, history of pulmonary TB, cohabitation status, the acid-fast bacilli smear status, and presence of cough in source cases. Of 308 subjects, 38.0% (116/305) were TST positive and 28.6% (59/206) were QFT-G positive. TST positivity was significantly associated with male gender (OR: 1.734; 95% CI: 1.001-3.003, p =0.049), history of pulmonary TB (OR: 4.130; 95% CI: 1.441-11.835, p =0.008) and household contact (OR: 2.130; 95% CI: 1.198-3.786, p =0.01) after adjustment for confounding variables. The degree of concordance between TST and QFT-G was fair (70.4%, κ =0.392). A prevalence of LTBI among close contacts of active pulmonary TB patients was high, and prior TB history and being a household contact were risk factors of LTBI in the study population.

Scale-up of collaborative TB/HIV activities in Guyana.

PubMed

Baker, Brian J; Peterson, Brandy; Mohanlall, Jeetendra; Singh, Shanti; Hicks, Collene; Jacobs, Ruth; Ramos, Ruth; Allen, Barbara; Pevzner, Eric

2017-04-20

To assess scale-up of recommended tuberculosis (TB)/HIV activities in Guyana and to identify specific strategies for further expansion. Medical records and clinic registers were reviewed at nine TB clinics and 10 HIV clinics. At TB clinics, data were collected on HIV testing and antiretroviral therapy (ART) for patients with TB/HIV; at HIV clinics, data were collected on intensified case finding (ICF), tuberculin skin test (TST) results, and provision of isoniazid preventive therapy (IPT). At TB clinics, among 461 patients newly diagnosed with TB, 419 (90.9%) had a known HIV status and 121 (28.9%) were HIV-infected. Among the 63 patients with TB/HIV, 33 (52.4%) received ART. Among the 45 patients with TB/HIV for whom dates of HIV diagnosis were available, 38 (84.4%) individuals knew their HIV status prior to TB diagnosis. At HIV clinics, among 127 patients eligible to receive a TST, 87 (68.5%) received a TST, 66 (75.9%) had a TST result, seven (10.6%) had a newly positive result, two had a previously positive result, and six of nine patients with positive results (66.7%) received IPT. ICF could not be assessed because of incomplete or discrepant documentation. An in-depth evaluation of TB/HIV activities successfully identified areas of success and remaining challenges. At TB clinics, HIV testing rates are high; further scale-up of ART for persons with TB/HIV is needed. At HIV clinics, use of TST to focus IPT is a feasible and efficient strategy; improving rates of annual TST screening will allow for further expansion of IPT.

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

PubMed

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

2017-10-01

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

Collaboration between the national tuberculosis programme and a non governmental organisation in TB/HIV care at a district level: experience from Tanzania.

PubMed

Wandwalo, Eliud; Kapalata, Neema; Tarimo, Edith; Corrigan, C Brigid; Morkve, Odd

2004-08-01

The increase in tuberculosis and HIV/AIDS patients in many countries in Africa including Tanzania, is outstripping the ability of public health services to cope. This calls for a closer collaboration between tuberculosis programmes and other stakeholders involved in HIV/AIDS care. To determine the feasibility of establishing collaboration between the tuberculosis programme and an NGO in TB/ HIV care at a district level in Tanzania. Quantitative and qualitative study designs involving TB as well as HIV suspects and patients together with health workers, were conducted between December, 2001 and September, 2002. A total of 72 patients and 28 key informants were involved. The collaboration was in the following areas; voluntary counselling and testing for HIV, diagnosis and treatment of TB, referral and follow up of patients and suspects, home based care, psychological support and training. Both the tuberculosis programme and NGO benefited from the collaboration. TB case detection among PLWA increased more than three folds and TB treatment was integrated in home based care of NGO. The main barriers identified in this study were; poor communication, poor referral system and lack of knowledge and skills among health staff. The study has shown that it is possible for a tuberculosis programme and a non governmental organisation to collaborate in TB/HIV care. The study has also identified potential areas of collaboration and barriers that needed to be overcome in order to provide such comprehensive services at a district level.

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

[Evaluation of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups].

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Gao, Mengqiu; Sun, Huishan; Du, Boping; Sun, Qi; Xing, Aiying; Wei, Rongrong; Zhang, Zongde

2015-12-01

To evaluate the value of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups. We analyzed 1 518 suspected pulmonary tuberculosis (PTB) patients who were admitted to the Beijing Chest Hospital from November 2012 to February 2014 and had valid T-SPOT.TB tests before anti-tuberculosis therapy. The 599 microbiologically and/or histopathologically-confirmed PTB patients (16-89 years old, 388 males and 211 females) and 235 non-TB patients (14-85 years old, 144 males and 91 females) were enrolled for the analysis of diagnostic performance of T-SPOT.TB, while patients with uncertain diagnosis or diagnosis based on clinical impression (n=684) were excluded from the analysis. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB were analyzed according to the final diagnosis. Furthermore, the diagnostic performance of T-SPOT.TB assay in the younger patients (14-59 years old) and elderly patients (60-89 years old) were also analyzed respectively. Categorical variables were compared by Pearson's Chi-square test, while continuous variables were compared by the Mann-Whitney U-test. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB in diagnosis of PTB were 90.1% (540/599), 65.5% (154/235), 86.9% (540/621), 72.3% (154/213), 2.61, and 0.15, respectively. The sensitivity and specificity of T-SPOT.TB assay were 92.6% (375/405) and 75.6% (99/131), respectively in the younger patients, and 85.0% (165/194), 52.9% (55/104) respectively in the elderly patients. The sensitivity and specificity of T-SPOT.TB assay in the younger patients were significantly higher than those in the elderly patients (P<0.01), and the spot forming cells in the younger PTB patients were significantly higher than in the elderly PTB patients [300 (126, 666)/10(6) PBMCs vs

The Prevalence of Tuberculosis in Zambia: Results from the First National TB Prevalence Survey, 2013-2014.

PubMed

Kapata, Nathan; Chanda-Kapata, Pascalina; Ngosa, William; Metitiri, Mine; Klinkenberg, Eveline; Kalisvaart, Nico; Sunkutu, Veronica; Shibemba, Aaron; Chabala, Chishala; Chongwe, Gershom; Tembo, Mathias; Mulenga, Lutinala; Mbulo, Grace; Katemangwe, Patrick; Sakala, Sandra; Chizema-Kawesha, Elizabeth; Masiye, Felix; Sinyangwe, George; Onozaki, Ikushi; Mwaba, Peter; Chikamata, Davy; Zumla, Alimuddin; Grobusch, Martin P

2016-01-01

Tuberculosis in Zambia is a major public health problem, however the country does not have reliable baseline data on the TB prevalence for impact measurement; therefore it was among the priority countries identified by the World Health Organization to conduct a national TB prevalence survey. To estimate the prevalence of tuberculosis among the adult Zambian population aged 15 years and above, in 2013-2014. A cross-sectional population-based survey was conducted in 66 clusters across all the 10 provinces of Zambia. Eligible participants aged 15 years and above were screened for TB symptoms, had a chest x-ray (CXR) performed and were offered an HIV test. Participants with TB symptoms and/or CXR abnormality underwent an in-depth interview and submitted one spot- and one morning sputum sample for smear microscopy and liquid culture. Digital data collection methods were used throughout the process. Of the 98,458 individuals who were enumerated, 54,830 (55.7%) were eligible to participate, and 46,099 (84.1%) participated. Of those who participated, 45,633/46,099 (99%) were screened by both symptom assessment and chest x-ray, while 466/46,099 (1.01%) were screened by interview only. 6,708 (14.6%) were eligible to submit sputum and 6,154/6,708 (91.7%) of them submitted at least one specimen for examination. MTB cases identified were 265/6,123 (4.3%). The estimated national adult prevalence of smear, culture and bacteriologically confirmed TB was 319/100,000 (232-406/100,000); 568/100,000 (440-697/100,000); and 638/100,000 (502-774/100,000) population, respectively. The risk of having TB was five times higher in the HIV positive than HIV negative individuals. The TB prevalence for all forms was estimated to be 455 /100,000 population for all age groups. The prevalence of tuberculosis in Zambia was higher than previously estimated. Innovative approaches are required to accelerate the control of TB.

The Association Between Lung Carcinoma and Tuberculosis

PubMed Central

Cukic, Vesna

2017-01-01

Introduction: The association between lung tuberculosis and lung carcinoma is still controversial. Objective: to describe the characteristics of patients with associated lung tuberculosis (TB) and lung carcinoma (LC) in patients treated in Clinic for pulmonary diseases and TB “Podhrastovi”. Material and Methods: This is the retrospective study of patients with LC associated with TB treated in Clinic for pulmonary diseases and TB “Podhrastovi” in five-year period -from 2012 to 2016. We analyzed sex and age of patients, whether TB preceded LC or LC preceded TB, a time period between the developments of these two diseases, activity of TB, the histopathological type of LC, localization of LC in lungs (bronchial, peripheral, cavern) according to histopathological type. Results: In this period there were 2608 patients treated for LC. Among them there were 34 patients with diagnosed TB or 1.3%. All of them were smokers. No one had active TB. TB was the first diagnosis in all these patients. Each patient was previously treated for TB in hospital and had regular anti TB treatment. TB preceded LC in median time of 5 years (interquartile range 2 to 25 years). In 21 cases it was carcinoma of the drainage bronchus, in 11 cases it was peripheral lung carcinoma and 2 cases it was cavern carcinoma. Conlusion: patients with cured pulmonary tuberculosis represent a group at risk for developing lung carcinoma. Changes in the bronchial and alveolar mucosa which tuberculosis leaves behind in the lungs must be taken as a possible place of later malignant alteration. Patients with any form of pulmonary tuberculosis have to be controlled continuously. PMID:28974836

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

PubMed Central

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

2017-01-01

In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired. PMID:28367796

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

PubMed

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

2018-04-24

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

Multidrug-resistant tuberculosis.

PubMed

Zager, Ellen M; McNerney, Ruth

2008-01-25

With almost 9 million new cases each year, tuberculosis remains one of the most feared diseases on the planet. Led by the STOP-TB Partnership and WHO, recent efforts to combat the disease have made considerable progress in a number of countries. However, the emergence of mutated strains of Mycobacterium tuberculosis that are resistant to the major anti-tuberculosis drugs poses a deadly threat to control efforts. Multidrug-resistant tuberculosis (MDR-TB) has been reported in all regions of the world. More recently, extensively drug resistant-tuberculosis (XDR-TB) that is also resistant to second line drugs has emerged in a number of countries. To ensure that adequate resources are allocated to prevent the emergence and spread of drug resistance it is important to understand the scale of the problem. In this article we propose that current methods of describing the epidemiology of drug resistant tuberculosis are not adequate for this purpose and argue for the inclusion of population based statistics in global surveillance data. Whereas the prevalence of tuberculosis is presented as the proportion of individuals within a defined population having disease, the prevalence of drug resistant tuberculosis is usually presented as the proportion of tuberculosis cases exhibiting resistance to anti-tuberculosis drugs. Global surveillance activities have identified countries in Eastern Europe, the former Soviet Union and regions of China as having a high proportion of MDR-TB cases and international commentary has focused primarily on the urgent need to improve control in these settings. Other regions, such as sub-Saharan Africa have been observed as having a low proportion of drug resistant cases. However, if one considers the incidence of new tuberculosis cases with drug resistant disease in terms of the population then countries of sub-Saharan Africa have amongst the highest rates of transmitted MDR-TB in the world. We propose that inclusion of population based statistics in

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

PubMed

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

2015-01-01

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

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

PubMed

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

2015-06-26

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

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2018-01-01

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

TB in Children in the United States

MedlinePlus

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

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. Copyright © 2016. Published by Elsevier Ltd.

Tuberculosis Screening by Tuberculosis Skin Test or QuantiFERON®-TB Gold In-Tube Assay among an Immigrant Population with a High Prevalence of Tuberculosis and BCG Vaccination

PubMed Central

Painter, John A.; Graviss, Edward A.; Hai, Hoang Hoa; Nhung, Duong Thi Cam; Nga, Tran Thi Thanh; Ha, Ngan P.; Wall, Kirsten; Loan, Le Thien Huong; Parker, Matt; Manangan, Lilia; O’Brien, Rick; Maloney, Susan A.; Hoekstra, R. M.; Reves, Randall

2013-01-01

Rationale Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth. Objectives 1. Compare the sensitivity of QuantiFERON ®-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR. Methods We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR. Results The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15–19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants. Conclusions During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population.  PMID:24367546

Cellular immune response in MDR-TB patients to different protein expression of MDR and susceptible Mycobacterium tuberculosis: Rv0147, a novel MDR-TB biomarker.

PubMed

Hadizadeh Tasbiti, Alireza; Yari, Shamsi; Siadat, Seyed Davar; Tabarsi, Payam; Saeedfar, Kayvan; Yari, Fatemeh

2018-02-01

Tuberculosis (TB) is a crucial public health problem with prevalence of multidrug resistant (MDR) rising. An accurate TB biomarker is urgently needed to monitor the response to treatment in patients with MDR tuberculosis. To analyze interaction between selected MDR-TB purified protein and immune cells, dendritic cells from MDR-TB patients and healthy subjects were stimulated by 55KDa protein fractions (Rv0147). The purified proteins identified by proteomic techniques (two-dimensional gel electrophoresis, mass spectrometry) and peptide sequences are known to bind a MHC class I alleles which are extracted from the Immune Epitope Database and Analysis Resource database ( www.iedb.org ). T cells were isolated from PBMC by negative selection and cells were cultured in RPMI-1640 at 37 °C and 5% CO 2 . Cell culture was assayed for cytokine IL-10 and INF-γ by ELISA. We found that INF-γ production was significantly (335 ± 35.5 pg/ml, P ˂ 0.05) upregulated after protein candidate (Rv0147) stimulation by dendritic cells from MDR-TB patients, whereas IL-10 production was greatly reduced compared with production in healthy subjects (212 ± 9.94 pg/ml, P ˂ 0.05). In fact, the purified protein, Rv0147, stimulated dendritic cells from MDR-TB patients, failed to produce IL-10 and directly stimulates INF-γ production by T cells. These results suggest that the purified protein, Rv0147, may stimulate Th1 type protective cytokine response in MDR-TB patients but not in normal subjects. The production of INF-γ but not IL-10 in the presence of purified protein, Rv0147, may be shifted to Th1 responses in MDR-TB patients and supports its potential as protein vaccine candidates against TB.

Latent tuberculosis infection among close contacts of multidrug-resistant tuberculosis patients in central Taiwan.

PubMed

Huang, Y-W; Shen, G-H; Lee, J-J; Yang, W-T

2010-11-01

Both the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) may be used to detect Mycobacterium tuberculosis infection. A positive reaction to either test can indicate latent tuberculosis infection (LTBI). These tests can be used to study the rate of infection in contacts of multidrug-resistant tuberculosis (MDR-TB) patients. To evaluate the transmission status of MDR-TB patients in Taiwan by examining their close contacts and to compare the efficiency of TST and QFT-GIT. Chest radiographs, TST and QFT-GIT were performed in household contacts of confirmed MDR-TB patients to determine their infection status. A total of 78 close contacts of confirmed MDR-TB patients were included in the study. The majority of the MDR-TB patients were parents of the close contacts and lived in the same building; 46% of the subjects were TST-positive and 19% were QFT-GIT-positive, indicating LTBI that was likely to develop into active MDR-TB. There was a lack of consistency between TST and QFT-GIT results in subjects with previous bacille Calmette-Guérin vaccination. Household contacts of MDR-TB patients are likely to develop LTBI; thus, follow-up and monitoring are mandatory to provide treatment and reduce the occurrence of active infection.

Drug permeation and metabolism in Mycobacterium tuberculosis: Prioritising local exposure as essential criterion in new TB drug development.

PubMed

Tanner, Lloyd; Denti, Paolo; Wiesner, Lubbe; Warner, Digby F

2018-06-22

Anti-tuberculosis (TB) drugs possess diverse abilities to penetrate the different host tissues and cell types in which infecting Mycobacterium tuberculosis bacilli are located during active disease. This is important since there is increasing evidence that the respective "lesion-penetrating" properties of the front-line TB drugs appear to correlate well with their specific activity in standard combination therapy. In turn, these observations suggest that rational efforts to discover novel treatment-shortening drugs and drug combinations should incorporate knowledge about the comparative abilities of both existing and experimental anti-TB agents to access bacilli in defined physiological states at different sites of infection, as well as avoid elimination by efflux or inactivation by host or bacterial metabolism. However, while there is a fundamental requirement to understand the mode of action and pharmacological properties of any current or experimental anti-TB agent within the context of the obligate human host, this is complex and, until recently, has been severely limited by the available methodologies and models. Here, we discuss advances in analytical models and technologies which have enabled investigations of drug metabolism and pharmacokinetics (DMPK) for new TB drug development. In particular, we consider the potential to shift the focus of traditional pharmacokinetic-pharmacodynamic analyses away from plasma to a more specific "site of action" drug exposure as an essential criterion for drug development and the design of dosing strategies. Moreover, in summarising approaches to determine DMPK data for the "unit of infection" comprising host macrophage and intracellular bacillus, we evaluate the potential benefits of including these analyses at an early stage in the preclinical drug development algorithm. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Assessment of the influence of direct tobacco smoke on infection and active TB management

PubMed Central

Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A.

2017-01-01

Background Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). Objective In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. Methods A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer’s instructions. Results In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs’ false-negative results (aOR: 3.35; 95%CI:1.47–7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02–3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97–22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Conclusions Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke. PMID:28837570

Assessment of the influence of direct tobacco smoke on infection and active TB management.

PubMed

Altet, Neus; Latorre, Irene; Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A; Domínguez, Jose

2017-01-01

Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer's instructions. In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs' false-negative results (aOR: 3.35; 95%CI:1.47-7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02-3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97-22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke.

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

Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study.

PubMed

Walker, Naomi F; Wilkinson, Katalin A; Meintjes, Graeme; Tezera, Liku B; Goliath, Rene; Peyper, Janique M; Tadokera, Rebecca; Opondo, Charles; Coussens, Anna K; Wilkinson, Robert J; Friedland, Jon S; Elkington, Paul T

2017-07-01

Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. MMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS. © The Author 2017. Published by Oxford

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

PubMed

Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

2013-02-02

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

Optimal treatment interruptions control of TB transmission model

NASA Astrophysics Data System (ADS)

Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

2018-03-01

A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

Utility of Th1-cell immune responses for distinguishing active tuberculosis from non-active tuberculosis: A case-control study

PubMed Central

Zhang, Lifan; Cheng, Xinhe; Bian, Sainan; Song, Yanhua; Li, Qiang; Gao, Mengqiu; Zhang, Yueqiu; Shi, Xiaochun

2017-01-01

Currently available Interferon-γ release assay (IGRA) cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). A study was performed to evaluate the value of Mycobacterium tuberculosis (MTB) specific Th1 cell immune responses which test IFN-γ and IL-2 simultaneous for differentiating ATB from non-ATB. Forty-nine newly diagnosed inpatients with ATB (26 pulmonary TB and 23 extrapulmonary TB) were enrolled as the ATB group. Forty-five volunteers with latent tuberculosis infection (LTBI) and twenty with evidence of previous TB were enrolled during the same period as the non-ATB group. Clinical examination and MTB specific Th1 cell immune responses were performed for all participants. After being stimulated with ESAT-6 and CFP-10, the median frequencies of single IL-2-, single IFN-γ-, and dual IFN-γ/IL-2-secreting T-cells were all higher in the ATB group than in the non-ATB group (20(8–45) vs. 7(3–13), P<0.001;131(44–308) vs. 10(6–27), P<0.001;25(9–74) vs. 7(3–23), P = 0.001, respectively). Evaluation of the diagnostic performance of detecting single IFN-γ-secreting T cells for pulmonary TB employed a cutoff value of 35 iSFCs/250,000 PBMC. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 92.3%, 80.0%, 64.9%, 96.3%, 4.62, and 0.10, respectively. For extrapulmonary TB, using a cutoff value of 23 iSFCs/ 250,000 PBMC, the sensitivity, specificity, PPV, NPV, PLR, and NLR were 91.3%, 76.9%, 58.3%, 96.2%, 3.96, and 0.11, respectively. When combining frequencies and proportion of single IFN-γ-secreting T cells, the test sensitivity was 100% in parallel tests and the specificity was 87.7% in serial tests for pulmonary TB. MTB specific Th1 cell immune responses (FluoroSpot) had value for the differentiation of ATB and non-ATB. Further confirmatory studies are indicated. PMID:28531231

Fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of Mycobacterium tuberculosis.

PubMed

Tiwari, Dileep; Haque, Shafiul; Tiwari, Ram P; Jawed, Arshad; Govender, Thavendran; Kruger, Hendrik G

2017-04-01

A rapid and efficient diagnostic test was developed for the detection of Mycobacterium tuberculosis antigens in serum samples of active tuberculosis (TB) and extrapulmonary TB patients via a liposomal agglutination-based method. A rapid card test has been developed to facilitate the recognition of high-affinity binding rabbit raised purified culture filtrate protein antibodies coupled on the surface of activated liposomal preparation. In the presence of TB antigens, the polyclonal antibodies bound to the liposomal particles demonstrate a visible agglutination reaction. The developed assay was simple, rapid, reliable, sensitive, and specific as a diagnostic test for the detection of antigens in serum samples of clinically confirmed cases of TB within 4-5 minutes' duration. The test was evaluated at different hospitals, medical colleges, and pathology centers, and involved 1483 participants. This investigation was conducted to detect the presence of these antigens during the period of active growth of the microorganism in serum samples for pulmonary TB and processed tissue biopsy for other extrapulmonary TB. Results obtained using this test were compared with acid-fast bacilli smear and culture results. Our study demonstrated that the newly developed liposome tuberculosis antigen card test detected antigens in our study population with approximately 97.48% sensitivity and 95.79% specificity. This is the first study to report the liposomal encapsulation of culture filtrate proteins from M. tuberculosis for diagnostic application. Copyright © 2015. Published by Elsevier B.V.

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

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…

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.

Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model

PubMed Central

Harrington-Kandt, Rachel; Stylianou, Elena; Eddowes, Lucy A.; Lim, Pei Jin; Stockdale, Lisa; Pinpathomrat, Nawamin; Bull, Naomi; Pasricha, Janet; Ulaszewska, Marta; Beglov, Yulia; Vaulont, Sophie

2018-01-01

Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. PMID:29324800

Understanding Latent Tuberculosis: A Moving Target

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2012-01-01

Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be ~2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease. PMID:20562268

Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis.

PubMed

Bagchi, S; Sachdev, S S; Nalwa, A; Das, C J; Sinha, S; Suri, V; Mahajan, S; Bhowmik, D; Agarwal, S

2014-10-01

Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Evaluation of risk factors for false-negative results with an antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT®. TB) in the diagnosis of active tuberculosis: A large-scale retrospective study in China.

PubMed

Yang, Chi; Zhang, Shaojun; Yao, Lan; Fan, Lin

2018-05-01

Objective To investigate the diagnostic efficacy of an interferon-γ release assay, T-SPOT ® . TB, for diagnosing active tuberculosis (TB) and to identify risk factors for false-negative results. Methods This retrospective study enrolled consecutive patients with active TB and with non-TB respiratory diseases to evaluate the risk factors for false-negative results when using the T-SPOT ® . TB assay for the diagnosis of active TB. Patients with active TB were categorized as having confirmed pulmonary TB, clinically diagnosed pulmonary TB or extrapulmonary TB (EPTB). Results This study analysed 4964 consecutive patients; 2425 with active TB and 2539 with non-TB respiratory diseases. Multivariate logistic regression analyses identified the following five factors that were all associated with an increased false-negative rate with the T-SPOT ® . TB assay: increased age (odds ratio [OR] 1.018; 95% confidence interval [CI] 1.013, 1.024); decreased CD8+ count (OR 0.307; 95% CI 0.117, 0.803); negative sputum acid-fast bacilli (AFB) smear staining (OR 1.821; 95% CI 1.338, 2.477); negative mycobacterial cultures (OR 1.379; 95% CI 1.043, 1.824); and absence of EPTB (OR 1.291; 95% CI 1.026, 1.623). Conclusions Increased age, decreased CD8+ count, negative sputum AFB smear results, negative sputum mycobacterial cultures and absence of EPTB might lead to an increased false-negative rate when using the T-SPOT ® . TB assay.

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

PubMed

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

2017-03-23

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

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

Risk factors associated with multidrug-resistant tuberculosis (MDR-TB) in a tertiary armed force referral and teaching hospital, Ethiopia.

PubMed

Demile, Biresaw; Zenebu, Amare; Shewaye, Haile; Xia, Siqing; Guadie, Awoke

2018-05-31

Ethiopia is one of the world health organization defined higher tuberculosis (TB) burden countries where the disease remains a massive public health threat. This study aimed to identify the prevalence and associated factors of multidrug-resistant tuberculosis (MDR-TB) using all armed force and civilian TB attendants in a tertiary level armed force hospital, where data for MDR-TB are previously unpublished. Cross-sectional study was conducted from September 2014 to August 2015 in a tertiary level Armed Force Referral and Teaching Hospital (AFRTH), Ethiopia. Armed force members (n = 251) and civilians (n = 130) which has been undergone TB diagnosis at AFRTH were included. All the specimens collected were subjected to microscopic smear observation, culture growth and drug susceptibility testing. Data were analyzed using statistical package for social sciences following binary logistic regression and Chi-square. P-values < 0.05 were considered statistically significant. Among 381 TB patients, 355 (93.2%) new and 26 (6.8%) retreatment cases were identified. Culture and smear positive TB cases were identified in 297 (77.9%) and 252 (66.1%) patients, respectively. The overall prevalence of MDR-TB in AFRTH was found 1.8% (1.3% for armed force members and 0.5% for civilian patients) all of which were previously TB treated cases. The entire treatment success rates were 92.6% achieved highest in the armed force (active and pension) than the civilian patients. The failure and dead cases were also found 2.5 and 4.6%, respectively. Using bivariate analysis, category of attendants and TB contact history were strong predictors of MDR-TB in armed force and civilian patients. Moreover, human immunodeficiency virus (HIV) infection also identified a significant (OR = 14.6; 95% CI = 2.3-92.1; p = 0.004) predicting factor for MDR-TB in armed force members. However, sex, age and body mass index were not associated factor for MDR-TB. In AFRTH, lower prevalence of

Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants.

PubMed

Yao, Xiangyang; Liu, Yongliang; Liu, Yang; Liu, Wei; Ye, Zhizhong; Zheng, Chao; Ge, Shengxiang

2017-12-01

Interferon gamma release assays (IGRAs) have been widely used to diagnose Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate between active TB patients and latent TB infection (LTBI), and the sensitivity of IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in MTB antigen-stimulated and -unstimulated plasma samples to identify host biomarkers that are associated with active TB and MTB infection. Active TB patients, subjects with LTBI and healthy participants were recruited. Seventy-one soluble cytokines and chemokines were tested using Luminex liquid array-based multiplexed immunoassays. For the 71 examined factors, our results indicated that the unstimulated levels of IL-8 Nil , IP-10 Nil , MIP-1a Nil , and sIL-2Ra Nil and the antigen stimulated levels of IL-8 (Ag-Nil) , VEGF (Ag-Nil) , and MCP-3 (Ag-Nil) were potential biomarkers for differentiating between active TB and LTBI, with AUCs of 0.8, 0.86, 0.755, 0.845, 0.825, 0.812 and 0.75, respectively. The G-CSF (Ag-Nil) , GM-CSF (Ag-Nil) , IL-1a (Ag-Nil) , IL-2 (Ag-Nil) , IP-10 (Ag-Nil) , BCA-1 (Ag-Nil) and Eotaxin-1 (Ag-Nil) responses were significantly higher in patients with active TB and LTBI compared with healthy participants (p < 0.05), with AUCs of 0.922, 0.902, 0.908, 1.0, 0.937, 0.919 and 0.935, respectively. Our preliminary data suggest that unstimulated or stimulated levels of cytokines and chemokines could be used as host biomarkers for diagnosing active TB as well as additional biomarkers, except IFN-γ, for MTB infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

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. Copyright ©ERS 2015.

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

Performance evaluation of Xpert MTB/RIF in a moderate tuberculosis incidence compared with TaqMan MTB and TRCRapid M.TB.

PubMed

Tsuyuguchi, Kazunari; Nagai, Hideaki; Ogawa, Kenji; Matsumoto, Tomoshige; Morimoto, Kozo; Takaki, Akiko; Mitarai, Satoshi

2017-02-01

Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources. A total of 427 sputum specimens were obtained from 237 suspected TB cases. Of these, 159 were identified as active TB, while the other 78 were non-TB diseases. The overall sensitivity and specificity of MTC detection by Xpert MTB/RIF using culture results as a reference were 86.8% [95% confidence interval (CI): 81.8%-90.6%] and 96.8% (95% CI: 93.1%-98.5%), respectively. Among MTC-positive culture specimens, Xpert MTB/RIF positivity was 95.2% (95% CI: 91.2%-97.5%) in smear-positive and 44.7% (95% CI 30.1-60.3) in smear-negative specimens. Xpert MTB/RIF was similar to other NATs (TaqMan MTB and TRCRapid M.TB) in terms of performance. Xpert MTB/RIF detected 25 RIF-resistant isolates as compared to 22 with the mycobacterial growth indicator tube antimicrobial susceptibility testing system, yielding a sensitivity of 100% (95% CI: 85.1%-100%) and specificity of 98.3% (95% CI: 95.1%-99.4%). These results indicate that although sensitivity in smear-negative/culture-positive specimens was relatively low, Xpert MTB/RIF is a useful diagnostic tool for detecting TB and RIF resistance even in settings of moderate TB burden. Copyright © 2016. Published by Elsevier Ltd.

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

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…

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 ...

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

Tuberculosis Treatment and Pregnancy

MedlinePlus

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

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.

PEPFAR Support for the Scaling Up of Collaborative TB/HIV Activities

PubMed Central

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

2014-01-01

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 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 (IPT), intensified case finding and infection control. Issues to be addressed by future programming include accelerating implementation of IPT, 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. PMID:22797735

Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits.

PubMed

Lempp, Jason M; Zajdowicz, Margan J; Hankinson, Arlene L; Toney, Sean R; Keep, Lisa W; Mancuso, James D; Mazurek, Gerald H

2017-01-01

Immunologic tests such as the tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infection, both latent M. tuberculosis infection (LTBI) and infection manifesting as active tuberculosis disease (TB). These tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of TB. Estimate QFT-GIT specificity, compare QFT-GIT and TST results, and assess factor associations with test discordance among U.S. Navy recruits. Among 792 subjects with completed TST and QFT-GIT, 42(5.3%) had TST indurations ≥10mm, 23(2.9%) had indurations ≥15mm, 14(1.8%) had positive QFT-GIT results, and 5(0.6%) had indeterminate QFT-GITs. Of 787 subjects with completed TST and determinate QFT-GIT, 510(64.8%) were at low-risk for infection, 277(35.2%) were at increased risk, and none had TB. Among 510 subjects at low-risk (presumed not infected), estimated TST specificity using a 15mm cutoff, 99.0% (95%CI: 98.2-99.9%), and QFT-GIT specificity, 98.8% (95%CI: 97.9-99.8%), were not significantly different (p>0.99). Most discordance was among recruits at increased risk of infection, and most was TST-positive but QFT-GIT-negative discordance. Of 18 recruits with TST ≥15mm but QFT-GIT negative discordance, 14(78%) were at increased risk. TB prevalence in country of birth was the strongest predictor of positive TST results, positive QFT-GIT results, and TST-positive but QFT-GIT-negative discordance. Reactivity to M. avium purified protein derivative (PPD) was associated with positive TST results and with TST-positive but QFT-GIT-negative discordance using a 10 mm cutoff, but not using a 15 mm cutoff or with QFT-GIT results. M. tuberculosis infection prevalence was low, with the vast majority of infection occurring in recruits with recognizable risks. QFT-GIT and TST specificities were high and not significantly different. Negative QFT-GIT results among subjects

[The Enhanceing effect of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils in tuberculosis patients].

PubMed

Jiang, Li-na; Yao, Chun-yan; Jin, Qi-li; He, Wen-xin; Li, Bai-qing

2011-11-01

To explore the effects of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils or polymorphonuclear cells (PMNs) in tuberculosis patients. The fresh peripheral blood samples from TB patients and healthy adults were incubated with M.tb labeled with FITC, and the percentages of phagocytosis of M.tb by PMNs was measured by flow cytometry (FCM). The fresh peripheral blood samples were incubated with DCFH-DA, and with or without M.tb for different times, the percentage of activation and the ROS production of PMNs were measured by FCM. Whole blood samples were pretreated with IL-12, the changes of phagocytosis, activation and ROS production of PMNs were measured by FCM. The percentages of phagocytosis by PMNs, activation and ROS production of PMNs in both TB patients and healthy adults increased dependent on the time of incubation with M.tb. Only the phagocytosis of M.tb by PMNs at 5 min in TB patients of tuberculosis patients (51.82±6.93)% was obviously higher than that in healthy adults (47.20±4.26)%, (P<0.05). Pretreatment of whole blood with IL-12 before incubation with M.tb, the percentages of phagocytosis, activation and ROS production of PMNs in both TB patients and healthy adults increased in dose dependent manner, but no significant difference was found between both groups. The results indicated that the phagocytosis of M.tb and ROS production by PMNs in TB patients were almost the same as that in healthy controls, except for phagocytosis is higher at early stage. Furthermore, IL-12 can enhance the responsiveness to the phagocytosis and ROS production of PMNs.

The dormant cells of Mycobacterium tuberculosis may be resuscitated by targeting-expression system of recombinant mycobacteriophage-Rpf: implication of shorter course of TB chemotherapy in the future.

PubMed

Gan, Yiling; Yao, Yiyong; Guo, Shuliang

2015-05-01

Here we hypothesized that dormant cells of Mycobacterium tuberculosis (M. tuberculosis) may be resuscitated by a new expression system of recombinant mycobacteriophage-resuscitation-promoting factor (Rpf). In this system, gene of targeted Rpf was cloned into mycobacteriophage genome, since mycobacteriophages possess several characteristics, including automatic identification and specific infection of M. tuberculosis. Thus the targeted delivery and endogenous expression of Rpf to the infected area of M. tuberculosis can be realized, followed by resuscitating the dormant cells of M. tuberculosis. Finally, these resuscitated M. tuberculosis can be thoroughly killed by a strong short-term subsequent chemotherapy, which makes the course of TB chemotherapy much shorter in the future compared to simple chemotherapy. Early studies have confirmed that dormant cells of M. tuberculosis can be resuscitated by Rpf in vitro, but so far, there is no report that Rpf can succeed in resuscitating dormant cells of M. tuberculosis in vivo, the reason may be that it is difficult for purified Rpf to remain active in vivo, especially to achieve targeted delivery of exogenous Rpf to the infected area of dormant cells of M. tuberculosis. Mycobacteriophage is a virus, capable of specifically identifying and infecting mycobacterium, such as M. tuberculosis. Several studies show that motif 3-containing proteins have peptidoglycan-hydrolysing activity and that while this activity is not required for mycobacteriophage viability, it facilitates efficient infection and DNA injection of mycobacteriophage (including motif 3 protein) into stationary phase cells. Thus this expression system can achieve targeted delivery and endogenous expression of Rpf to infected area of dormant cells of M. tuberculosis. Finally, we discuss the implication of this recombinant expression system for shortening the course of TB chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Active case-finding for tuberculosis by mobile teams in Myanmar: yield and treatment outcomes.

PubMed

Myint, Ohnmar; Saw, Saw; Isaakidis, Petros; Khogali, Mohammed; Reid, Anthony; Hoa, Nguyen Binh; Kyaw, Thi Thi; Zaw, Ko Ko; Khaing, Tin Mi Mi; Aung, Si Thu

2017-06-02

Since 2005, the Myanmar National Tuberculosis Programme (NTP) has been implementing active case finding (ACF) activities involving mobile teams in hard-to-reach areas. This study revealed the contribution of mobile team activities to total tuberculosis (TB) case detection, characteristics of TB patients detected by mobile teams and their treatment outcomes. This was a descriptive study using routine programme data between October 2014 and December 2014. Mobile team activities were a one-stop service and included portable digital chest radiography (CXR) and microscopy of two sputum samples. The algorithm of the case detection included screening patients by symptoms, then by CXR followed by sputum microscopy for confirmation. Diagnosed patients were started on treatment and followed until a final outcome was ascertained. A total of 9 349 people with symptoms suggestive of TB were screened by CXR, with an uptake of 96.6%. Of those who were meant to undergo sputum smear microscopy, 51.4% had sputum examinations. Finally, 504 TB patients were identified by the mobile teams and the overall contribution to total TB case detection in the respective townships was 25.3%. Among total cases examined by microscopy, 6.4% were sputum smear positive TB. Treatment success rate was high as 91.8% in study townships compared to national rate 85% (2014 cohort). This study confirmed the feasibility and acceptability of ACF by mobile teams in hard-to-reach contexts, especially when equipped with portable, digital CXR machines that provided immediate results. However, the follow-up process of sputum examination created a significant barrier to confirmation of the diagnosis. In order to optimize the ACF through mobile team activity, future ACF activities were needed to be strengthened one stop service including molecular diagnostics or provision of sputum cups to all presumptive TB cases prior to CXR and testing if CXR suggestive of TB.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis.

PubMed

Rosenthal, Alex; Gabrielian, Andrei; Engle, Eric; Hurt, Darrell E; Alexandru, Sofia; Crudu, Valeriu; Sergueev, Eugene; Kirichenko, Valery; Lapitskii, Vladzimir; Snezhko, Eduard; Kovalev, Vassili; Astrovko, Andrei; Skrahina, Alena; Taaffe, Jessica; Harris, Michael; Long, Alyssa; Wollenberg, Kurt; Akhundova, Irada; Ismayilova, Sharafat; Skrahin, Aliaksandr; Mammadbayov, Elcan; Gadirova, Hagigat; Abuzarov, Rafik; Seyfaddinova, Mehriban; Avaliani, Zaza; Strambu, Irina; Zaharia, Dragos; Muntean, Alexandru; Ghita, Eugenia; Bogdan, Miron; Mindru, Roxana; Spinu, Victor; Sora, Alexandra; Ene, Catalina; Vashakidze, Sergo; Shubladze, Natalia; Nanava, Ucha; Tuzikov, Alexander; Tartakovsky, Michael

2017-11-01

The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis

PubMed Central

Gabrielian, Andrei; Engle, Eric; Hurt, Darrell E.; Alexandru, Sofia; Crudu, Valeriu; Sergueev, Eugene; Kirichenko, Valery; Lapitskii, Vladzimir; Snezhko, Eduard; Kovalev, Vassili; Astrovko, Andrei; Skrahina, Alena; Harris, Michael; Long, Alyssa; Wollenberg, Kurt; Akhundova, Irada; Ismayilova, Sharafat; Skrahin, Aliaksandr; Mammadbayov, Elcan; Gadirova, Hagigat; Abuzarov, Rafik; Seyfaddinova, Mehriban; Avaliani, Zaza; Strambu, Irina; Zaharia, Dragos; Muntean, Alexandru; Ghita, Eugenia; Bogdan, Miron; Mindru, Roxana; Spinu, Victor; Sora, Alexandra; Ene, Catalina; Vashakidze, Sergo; Shubladze, Natalia; Nanava, Ucha; Tuzikov, Alexander; Tartakovsky, Michael

2017-01-01

ABSTRACT The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/. PMID:28904183

TB & HIV: the deadly intersection.

PubMed

MacDougall, D S

1999-05-01

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

HIV and Tuberculosis (TB)

MedlinePlus

... or brain. If not treated, TB disease can cause death. HIV weakens the immune system , increasing the risk ... spine, or brain. If not treated, TB can cause death. How does TB spread from person to person? ...

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

PubMed

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

2014-05-01

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

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

Drug resistance of Mycobacterium tuberculosis isolates from tuberculosis lymphadenitis patients in Ethiopia

PubMed Central

Biadglegne, Fantahun; Tessema, Belay; Sack, Ulrich; Rodloff, Arne C.

2014-01-01

Background & objectives: The emergence of drug resistance tuberculosis (TB) is a significant challenge for TB control and prevention programmes, and the major problem is multidrug resistant tuberculosis (MDR-TB). The present study was carried out to determine the frequency of drug resistant Mycobacterium tuberculosis isolates among newly and retreated TB lymphadenitis patients and risk factors for acquiring this infection. Methods: Two hundred twenty five M. tuberculosis isolates from TB lymphadenitis patients who were diagnosed as new and retreated tuberculosis cases between April 2012 and May 2012 were included in this study. Isolates were tested for susceptibility to isoniazed (INH), rifampicin (RMP), streptomycin (SM), ethambutol (EMB) and pyrazinamide (PZA) using the BacT/AlerT 3D system protocol. Results: Among 225 isolates, 15 (6.7%) were resistant to at least one first line anti-TB drug. Three (1.3%) were MDR-TB. Resistance to INH, RMP, SM, and EMB was found in 8 (3.6%), 4 (1.8%), 10 (4.4%), and 4 (1.8%) isolates, respectively. Of the 212 new TB lymphadenitis cases three (1.4%) were MDR-TB. A rifampicin resistant M. tuberculosis isolate was diagnosed from smear and culture negative newly treated cases. All isolates were susceptible to PZA. Matted cervical lymph nodes were the prominent sites involved. Newly treated TB lymphadenitis patients had a greater risk for presenting resistance to anti-TB drugs (P=0.046). Interpretation & conclusions: Our study showed that TB lymphadenitis patients harboured drug resistant TB and MDR-TB, although at a low rate. Resistance was not associated with age, sex, patients’ education and contact history. Further research is required to determine transmission dynamics of drug resistant strains. PMID:25222786

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

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

PubMed

Soares, Patrícia; Alves, Renato J; Abecasis, Ana B; Penha-Gonçalves, Carlos; Gomes, M Gabriela M; Pereira-Leal, José B

2013-08-30

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. 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 laboratories, hospitals or

The association between sterilizing activity and drug distribution into tuberculosis lesions

PubMed Central

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, TaeSun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N.; Barry, Clifton E.; Dartois, Véronique

2015-01-01

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 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 reside1. In contrast, moxifloxacin which is active in vitro against persisters, a sub-population of Mycobacterium tuberculosis that persists in specific niches under drug pressure, and achieved treatment shortening in mice2, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We also 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 contributes to treatment outcome has wide implications for TB. PMID:26343800

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. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis.

PubMed

Flandrois, Jean-Pierre; Lina, Gérard; Dumitrescu, Oana

2014-04-14

Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis. It remains a major health threat, killing over one million people every year worldwide. An early antibiotic therapy is the basis of the treatment, and the emergence and spread of multidrug and extensively drug-resistant mutant strains raise significant challenges. As these bacteria grow very slowly, drug resistance mutations are currently detected using molecular biology techniques. Resistance mutations are identified by sequencing the resistance-linked genes followed by a comparison with the literature data. The only online database is the TB Drug Resistance Mutation database (TBDReaM database); however, it requires mutation detection before use, and its interrogation is complex due to its loose syntax and grammar. The MUBII-TB-DB database is a simple, highly structured text-based database that contains a set of Mycobacterium tuberculosis mutations (DNA and proteins) occurring at seven loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs. Resistance mutation data were extracted after the systematic review of MEDLINE referenced publications before March 2013. MUBII analyzes the query sequence obtained by PCR-sequencing using two parallel strategies: i) a BLAST search against a set of previously reconstructed mutated sequences and ii) the alignment of the query sequences (DNA and its protein translation) with the wild-type sequences. The post-treatment includes the extraction of the aligned sequences together with their descriptors (position and nature of mutations). The whole procedure is performed using the internet. The results are graphs (alignments) and text (description of the mutation, therapeutic significance). The system is quick and easy to use, even for technicians without bioinformatics training. MUBII-TB-DB is a structured database of the mutations occurring at seven loci of major therapeutic value in tuberculosis management. Moreover, the system provides

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

PubMed Central

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

2013-01-01

SUMMARY Active tuberculosis (TB) among HIV-infected patients, even when successfully treated, may be associated with excess mortality. We conducted a prospective cohort study nested in a randomized TB vaccine trial to compare mortality between HIV-infected patients diagnosed and treated for TB (TB, n=77) and HIV-infected patients within the same CD4 range, who were not diagnosed with or treated for active TB (non-TB, n=308) in the period 2001–2008. Only twenty four subjects (6%) were on antiretroviral therapy at the beginning of this study. After accounting for covariate effects including use of antiretroviral therapy, isoniazid preventive therapy, and receipt of vaccine, we found a four-fold increase in mortality in TB patients compared with non-TB patients (adjusted Hazard Ratio 4.61; 95% Confidence Interval (CI): 1.63, 13.05). These findings suggest that treatment for TB alone is not sufficient to avert the excess mortality associated with HIV-related TB and that prevention of TB may provide a mortality benefit. PMID:23523641

Evaluating clinicians' user experience and acceptability of LearnTB, a smartphone application for tuberculosis in India.

PubMed

Pande, Tripti; Saravu, Kavitha; Temesgen, Zelalem; Seyoum, Al; Rai, Shipra; Rao, Raghavendra; Mahadev, Deekshith; Pai, Madhukar; Gagnon, Marie-Pierre

2017-01-01

Tuberculosis (TB) is the leading infectious killer, and India accounts for 2.8 of the 10.4 million TB cases that occur each year, making it the highest TB burden country worldwide. Poor quality of TB care is a major driver of the epidemic in India. India's large private, unregulated sector manages over 50% of the TB patients, with studies showing suboptimal diagnosis and treatment in the private sector. Better education of doctors using mobile applications (apps) is a possible solution. While India has seen an explosion of mobile phone services, and while the use of mobile health interventions has been gaining interest, little is known about mHealth around tuberculosis in India. Our study aimed to understand the user experience and acceptability of a smartphone application, LearnTB , amongst private sector academic clinicians in India. This study was conducted amongst 101 clinicians at Kasturba Hospital, Manipal, India. The user experience of participants (part 1) and acceptability (part 2) were evaluated with the use of two valid, English, paper-based questionnaires. The first questionnaire was based on the System Usability Scale (SUS); the second questionnaire was based on the Technology Acceptance Model (TAM). Data were collected during February and March 2017 and were analyzed using descriptive statistics, multiple linear regression as well as logistic regression analysis. A response rate of 99% was achieved; 100 participants responded to the second questionnaire and 100% of the participants responded to the first questionnaire. User experience was very high [mean SUS score =94.4 (92.07-96.76)]. Perceived usefulness (PU) was significantly correlated to intention to use (IU) (r=0.707, P<0.0001), and perceived ease of use (PEU) was significantly correlated to PU (r=0.466, P<0.0001). Path analysis confirmed the direct relationship between PU and IU (0.936, P<0.0001), and the indirect relationship between PEU and IU (0.5102, P<0.0001). Logistic regression analysis

Evaluating clinicians’ user experience and acceptability of LearnTB, a smartphone application for tuberculosis in India

PubMed Central

Pande, Tripti; Saravu, Kavitha; Temesgen, Zelalem; Seyoum, Al; Rai, Shipra; Rao, Raghavendra; Mahadev, Deekshith; Pai, Madhukar

2017-01-01

Background Tuberculosis (TB) is the leading infectious killer, and India accounts for 2.8 of the 10.4 million TB cases that occur each year, making it the highest TB burden country worldwide. Poor quality of TB care is a major driver of the epidemic in India. India’s large private, unregulated sector manages over 50% of the TB patients, with studies showing suboptimal diagnosis and treatment in the private sector. Better education of doctors using mobile applications (apps) is a possible solution. While India has seen an explosion of mobile phone services, and while the use of mobile health interventions has been gaining interest, little is known about mHealth around tuberculosis in India. Methods Our study aimed to understand the user experience and acceptability of a smartphone application, LearnTB, amongst private sector academic clinicians in India. This study was conducted amongst 101 clinicians at Kasturba Hospital, Manipal, India. The user experience of participants (part 1) and acceptability (part 2) were evaluated with the use of two valid, English, paper-based questionnaires. The first questionnaire was based on the System Usability Scale (SUS); the second questionnaire was based on the Technology Acceptance Model (TAM). Data were collected during February and March 2017 and were analyzed using descriptive statistics, multiple linear regression as well as logistic regression analysis. Results A response rate of 99% was achieved; 100 participants responded to the second questionnaire and 100% of the participants responded to the first questionnaire. User experience was very high [mean SUS score =94.4 (92.07–96.76)]. Perceived usefulness (PU) was significantly correlated to intention to use (IU) (r=0.707, P<0.0001), and perceived ease of use (PEU) was significantly correlated to PU (r=0.466, P<0.0001). Path analysis confirmed the direct relationship between PU and IU (0.936, P<0.0001), and the indirect relationship between PEU and IU (0.5102, P<0

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Index-TB Guidelines: Guidelines on extrapulmonary tuberculosis for India

PubMed Central

Sharma, Surendra K.; Ryan, H.; Khaparde, Sunil; Sachdeva, K. S.; Singh, Achintya D.; Mohan, Alladi; Sarin, Rohit; Paramasivan, C N; Kumar, Prahlad; Nischal, Neeraj; Khatiwada, Saurav; Garner, Paul; Tharyan, Prathap

2017-01-01

Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research. PMID:28862176

Opportunities and challenges for HIV care in overlapping HIV and TB epidemics.

PubMed

Havlir, Diane V; Getahun, Haileyesus; Sanne, Ian; Nunn, Paul

2008-07-23

Tuberculosis (TB) and the emerging multidrug-resistant TB epidemic represent major challenges to human immunodeficiency virus (HIV) care and treatment programs in resource-limited settings. Tuberculosis is a major cause of mortality among patients with HIV and poses a risk throughout the course of HIV disease, even after successful initiation of antiretroviral therapy (ART). Progress in the implementation of activities directed at reducing TB burden in the HIV population lags far behind global targets. HIV programs designed for longitudinal care are ideally suited to implement TB control measures and have no option but to address TB vigorously to save patient lives, to safeguard the massive investment in HIV treatment, and to curb the global TB burden. We propose a framework of strategic actions for HIV care programs to optimally integrate TB into their services. The core activities of this framework include intensified TB case finding, treatment of TB, isoniazid preventive treatment, infection control, administration of ART, TB recording and reporting, and joint efforts of HIV and TB programs at the national and local levels.

Global Tuberculosis Report 2016

MedlinePlus

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

Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia.

PubMed

Bojang, Adama L; Mendy, Francis S; Tientcheu, Leopold D; Otu, Jacob; Antonio, Martin; Kampmann, Beate; Agbla, Schadrac; Sutherland, Jayne S

2016-03-01

Diagnosis of tuberculosis (TB) remains difficult, particularly in resource-limited settings. The development of nucleic acid-based tests for detection of Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity compared to conventional smear microscopy and provides results within a matter of hours compared to weeks for the current gold-standard, liquid culture. In this study we performed side-by-side comparison of mycobacterial detection assays on sputum samples from 285 subjects presenting with symptoms suggestive of TB in The Gambia and a cross-sectional cohort of 156 confirmed TB patients with a median of 2 months of treatment. A novel assay, Loop-Mediated Amplification test for TB (TB-LAMP), was compared to smear microscopy, MGIT culture and GeneXpert MTB/RIF for all samples. When culture was used as the reference standard, we found an overall sensitivity for TB-LAMP of 99% (95% CI: 94.5-99.8) and specificity of 94% (95% CI: 89.3-96.7). When latent class analysis was performed, TB-LAMP had 98.6% (95% CI: 95.9-100) sensitivity and 99% (95% CI: 98.2-100) specificity compared to 91.1% (95% CI: 86.1-96) sensitivity and 100% (95% CI: 98.2-100) specificity for MGIT culture. GeneXpert had the highest sensitivity 99.1% (95% CI: 97.1-100) but the lowest specificity 96% (95% CI: 92.6-98.3). Both TB-LAMP and GeneXpert showed high sensitivity and specificity regardless of age or strain of infection. Our findings show the diagnostic utility of both GeneXpert and TB-LAMP in The Gambia. Whilst TB-LAMP requires less infrastructure, it is unable to detect drug-resistant patterns and therefore would be most suitable as a screening test for new TB cases in peripheral health clinics. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

A Beneficial Effect of Low-Dose Aspirin in a Murine Model of Active Tuberculosis

PubMed Central

Kroesen, Vera Marie; Rodríguez-Martínez, Paula; García, Eric; Rosales, Yaiza; Díaz, Jorge; Martín-Céspedes, Montse; Tapia, Gustavo; Sarrias, Maria Rosa; Cardona, Pere-Joan; Vilaplana, Cristina

2018-01-01

An excessive, non-productive host-immune response is detrimental in active, chronic tuberculosis (TB) disease as it typically leads to tissue damage. Given their anti-inflammatory effect, non-steroidal anti-inflammatory drugs can potentially attenuate excessive inflammation in active TB disease. As such, we investigated the prophylactic and therapeutic effect of low-dose aspirin (LDA) (3 mg/kg/day), either alone or in combination with common anti-TB treatment or BCG vaccination, on disease outcome in an experimental murine model of active TB. Survival rate, bacillary load (BL) in lungs, and lung pathology were measured. The possible mechanism of action of LDA on the host’s immune response was also evaluated by measuring levels of CD5L/AIM, selected cytokines/chemokines and other inflammatory markers in serum and lung tissue. LDA increased survival, had anti-inflammatory effects, reduced lung pathology, and decreased bacillary load in late-stage TB disease. Moreover, in combination with common anti-TB treatment, LDA enhanced survival and reduced lung pathology. Results from the immunological studies suggest the anti-inflammatory action of LDA at both a local and a systemic level. Our results showed a systemic decrease in neutrophilic recruitment, decreased levels of acute-phase reaction cytokines (IL-6, IL-1β, and TNF-α) at late stage and a delay in the decrease in T cell response (in terms of IFN-γ, IL-2, and IL-10 serum levels) that occurs during the course of Mycobacterium tuberculosis infection. An anti-inflammatory milieu was detected in the lung, with less neutrophil recruitment and lower levels of tissue factor. In conclusion, LDA may be beneficial as an adjunct to standard anti-TB treatment in the later stage of active TB by reducing excess, non-productive inflammation, while enhancing Th1-cell responses for elimination of the bacilli. PMID:29740435

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

Development of a POC Test for TB Based on Multiple Immunodominant Epitopes of M. tuberculosis Specific Cell-Wall Proteins

PubMed Central

Gonzalez, Jesus M.; Francis, Bryan; Burda, Sherri; Hess, Kaitlyn; Behera, Digamber; Gupta, Dheeraj; Agarwal, Ashutosh Nath; Verma, Indu; Verma, Ajoy; Myneedu, Vithal Prasad; Niedbala, Sam; Laal, Suman

2014-01-01

The need for an accurate, rapid, simple and affordable point-of-care (POC) test for Tuberculosis (TB) that can be implemented in microscopy centers and other peripheral health-care settings in the TB-endemic countries remains unmet. This manuscript describes preliminary results of a new prototype rapid lateral flow TB test based on detection of antibodies to immunodominant epitopes (peptides) derived from carefully selected, highly immunogenic M. tuberculosis cell-wall proteins. Peptide selection was initially based on recognition by antibodies in sera from TB patients but not in PPD-/PPD+/BCG-vaccinated individuals from TB-endemic settings. The peptides were conjugated to BSA; the purified peptide-BSA conjugates striped onto nitrocellulose membrane and adsorbed onto colloidal gold particles to devise the prototype test, and evaluated for reactivity with sera from 3 PPD-, 29 PPD+, 15 PPD-unknown healthy subjects, 10 patients with non-TB lung disease and 124 smear-positive TB patients. The assay parameters were adjusted to determine positive/negative status within 15 minutes via visual or instrumented assessment. There was minimal or no reactivity of sera from non-TB subjects with the striped BSA-peptides demonstrating the lack of anti-peptide antibodies in subjects with latent TB and/or BCG vaccination. Sera from most TB patients demonstrated reactivity with one or more peptides. The sensitivity of antibody detection ranged from 28–85% with the 9 BSA-peptides. Three peptides were further evaluated with sera from 400 subjects, including additional PPD-/PPD+/PPD-unknown healthy contacts, close hospital contacts and household contacts of untreated TB patients, patients with non-TB lung disease, and HIV+TB- patients. Combination of the 3 peptides provided sensitivity and specificity>90%. While the final fully optimized lateral flow POC test for TB is under development, these preliminary results demonstrate that an antibody-detection based rapid POC lateral flow test

Plan to combat extensively drug-resistant tuberculosis: recommendations of the Federal Tuberculosis Task Force.

PubMed

2009-02-13

An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year. Although tuberculosis (TB) occurs predominantly in resource-limited countries, it also occurs in the United States. During 1985-1992, the United States was confronted with an unprecedented TB resurgence. This resurgence was accompanied by a rise in multidrug-resistant TB (MDR TB), which is defined as TB that is resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin. In addition, virtually untreatable strains of M. tuberculosis are emerging globally. Extensively drug-resistant (XDR) TB is defined as MDR TB that also is resistant to the most effective second-line therapeutic drugs used commonly to treat MDR TB: fluoroquinolones and at least one of three injectable second-line drugs used to treat TB (amikacin, kanamycin, or capreomycin). XDR TB has been identified in all regions of the world, including the United States. In the United States, the cost of hospitalization for one XDR TB patient is estimated to average $483,000, approximately twice the cost for MDR TB patients. Because of the limited responsiveness of XDR TB to available antibiotics, mortality rates among patients with XDR TB are similar to those of TB patients in the preantibiotic era. In January 1992, CDC convened a Federal TB Task Force to draft an action plan to improve prevention and control of drug-resistant TB in the United States (CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992;41([No. RR-11]). In November 2006, CDC reconvened the Task Force to draft an updated action plan to address the issue of MDR TB and XDR TB. Task Force members were divided into nine response areas and charged with articulating the most pressing problems, identifying barriers to improvement, and recommending specific action steps to improve prevention and control of XDR TB within their

Comparison of the socio-demographic and clinical features of pulmonary TB patients infected with sub-lineages within the W-Beijing and non-Beijing Mycobacterium tuberculosis.

PubMed

Hu, Yi; Mathema, Barun; Zhao, Qi; Zheng, Xubin; Li, Dange; Jiang, Weili; Wang, Weibing; Xu, Biao

2016-03-01

Highly lethal outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are increasing. Mycobacterium tuberculosis variant Beijing family and its members is regarded as a successful clone of M. tuberculosis that is associated with drug resistance in China. Understanding the genetic characteristics and molecular mechanism of drug resistant tuberculosis within Beijing family may help to clarify its origin and evolutionary history and the driving forces behind its emergence and current dissemination. Totally of 1222 Mycobacterium tuberculosis isolates were recovered from patients in six counties of two provinces in eastern China within 2010/2012. Strain lineage and its major subgroups were studied respectively by using Spoligotyping and MIRU-VNTR. The 1st-line drug susceptibility was analyzed by proportional method and 2nd-line drug susceptibility was determined by the HAINs MTBDRsl test. The genetic characterization of drug resistance was analyzed by sequencing the previously reported genes and loci associated with drug resistance together with the multiple genotyping including MIRU-VNTR, Spoligotyping and LSP genotyping. Of the 1222 Mtb isolates, 298 (24.4%) were resistant to 1st-line drug and 73 (5.9%) were simultaneously resistant to INH and RIF namely MDR-TB. Respectively 23.8% of 1st-line drug resistant TB and 12.0% of the drug susceptible TB contained the mutation associated with 2nd-line drugs by HAINs test. The Spoligotyping of 1222 Mtb isolates revealed the 967 (79.1%) of the isolates belonged to the W-Beijing family. Within W-Beijing family, 78.8% MDR-TB were observed in the isolates with simultaneous deletion of RD105 and RD207, with sub-lineage 181 accounting for 75% of MDR-TB. Analysis of 24 MIRU-VNTR loci revealed that 88.2% (15/17) of MDR and extensively drug resistant (XDR) clustered isolates were sub-lineage 181. Sublineage 181 might have the capacity to spread throughout the general community in rural China. This is

Application of the Capilia TB assay for culture confirmation of Mycobacterium tuberculosis complex isolates.

PubMed

Hillemann, D; Rüsch-Gerdes, S; Richter, E

2005-12-01

The usefulness of a low-tech rapid test for culture confirmation of Mycobacterium tuberculosis complex, Capilia TB, was tested on 172 mycobacteria-positive clinical samples. The overall sensitivity and specificity were 92.4% and 100%, respectively. In three of nine false-negative isolates a mutation in the mpb64 gene could be detected.

[Follow-up with the assistance of TB-info software of 208 tuberculosis patients who were treated in 2004].

PubMed

Bourgarit, A; Mallet, H-P; Keshtmand, H; De Castro, N; Rambeloarisoa, J; Fain, O; Antoun, F; Picard, C; Rocher, G; Che, D; Farge, D

2009-10-01

The impact of the TB-info software was assessed on the care of patients treated with antituberculosis regimen (ATT). Cohort study of patients with tuberculosis who received an ATT in 2004 in two hospitals and five medical centres in Paris. Follow-up was implemented with the TB-info software. Data were compared to those of the 1999-2003 cohort. Two hundred and nine ATT were initiated in 2004, with a mean duration of 7.2 months. Demographic and clinical data reflected this population precariousness: 79% were foreign-born, 25% lived in institutions and half of them had no or unusual health insurance. Compared to the previous cohort, viral co-infections were tested in more than 80% cases and showed association with HIV, HBV or HCV in 11, 10 and 5% of the patients, respectively. Twenty-one patients were lost for follow-up (11%) and 76% of the smear-positive pulmonary tuberculosis therapies were declared successful but only 34% were declared cured with the WHO criteria. Analysis of the data obtained with TB-info software showed an improvement of tuberculosis patients care with more co-infection tested and less lost for follow-up. These results confirm the usefulness of this software for patients care and assessment of physicians practice in France.

The Risk of Depressive Disorder Among Contacts of Tuberculosis Patients in a TB-endemic Area

PubMed Central

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

2015-01-01

Abstract 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

Mycobacterial lipolytic enzymes: a gold mine for tuberculosis research.

PubMed

Dedieu, L; Serveau-Avesque, C; Kremer, L; Canaan, S

2013-01-01

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide with a strong impact in developing countries. Mycobacterium tuberculosis, the etiological agent of TB, has a high capacity to evade the host immune system and establish a chronic, asymptomatic and latent infection. In a latent TB infection, persistent bacilli are present in a non-replicating dormant state within host granulomas. During reactivation, bacilli start replicating again leading to an active TB infection that can be highly contagious. Mycobacterial lipids and lipolytic enzymes are thought to play important physiological roles during dormancy and reactivation. The role of lipolytic enzymes in the physiology of M. tuberculosis and physiopathology of the disease will be discussed in this review, with an emphasis on the secreted or cell wall-associated, surface exposed lipolytic enzymes characterized to date. Studies on the localization, enzymatic activity and immunological properties of these enzymes highlighted their possible usefulness as new diagnostic markers in the fight against TB. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Field evaluation of a blood based test for active tuberculosis in endemic settings

PubMed Central

Hussainy, Syed Fahadulla; Krishnan, Viwanathan V.; Ambreen, Atiqa; Yusuf, Noshin Wasim; Irum, Shagufta; Rashid, Abdul; Jamil, Muhammad; Zaffar, Fareed; Chaudhry, Muhammad Nawaz; Gupta, Puneet K.; Akhtar, Muhammad Waheed; Khan, Imran H.

2017-01-01

Over 9 million new active tuberculosis (TB) cases emerge each year from an enormous pool of 2 billion individuals latently infected with Mycobacterium tuberculosis (M. tb.) worldwide. About 3 million new TB cases per year are unaccounted for, and 1.5 million die. TB, however, is generally curable if diagnosed correctly and in a timely manner. The current diagnostic methods for TB, including state-of-the-art molecular tests, have failed in delivering the capacity needed in endemic countries to curtail this ongoing pandemic. Efficient, cost effective and scalable diagnostic approaches are critically needed. We report a multiplex TB serology panel using microbead suspension array containing a combination of 11 M.tb. antigens that demonstrated overall sensitivity of 91% in serum/plasma samples from TB patients confirmed by culture. Group wise sensitivities for sputum smear positive and negative patients were 95%, and 88%, respectively. Specificity of the test was 96% in untreated COPD patients and 91% in general healthy population. The sensitivity of this test is superior to that of the frontline sputum smear test with a comparable specificity (30–70%, and 93–99%, respectively). The multiplex serology test can be performed with scalability from 1 to 360 patients per day, and is amenable to automation for higher (1000s per day) throughput, thus enabling a scalable clinical work flow model for TB endemic countries. Taken together, the above results suggest that well defined antibody profiles in blood, analyzed by an appropriate technology platform, offer a valuable approach to TB diagnostics in endemic countries. PMID:28380055

Tuberculosis in Poland in 2012.

PubMed

Korzeniewska-Koseła, Maria

2014-01-01

To evaluate the main features of TB epidemiology in 2012 in Poland and to compare with the corresponding EU data. Analysis of case- based clinical and demographic data on TB patients from Central TB Register, of data submitted by laboratories on anti-TB drug susceptibility testing results in cases notified in 2012, data from National Institute of Public Health - National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report "Tuberculosis Surveillance in Europe, 2014 (situation in 2012). 7 542 TB cases were reported in Poland in 2012. The incidence rate was 19.6 cases per 100 000, with large variability between voivodships from 10.6 to 30.2. The mean annual decrease of TB incidence in 2008-2012 was 2.4%. 6 665 cases had no history of previous treatment; 17.3 per 100 000. The number of all notified pulmonary tuberculosis cases was 7 018; 18.2 per 100 000. The proportion of extrapulmonary tuberculosis among all registered cases was 6.9% (524 cases). In 2012, 36 patients had fibrous-cavernous pulmonary tuberculosis (0.5% of all cases of pulmonary tuberculosis). TB was diagnosed in 95 children (1.3% of all cases, incidence 1.6). The incidence of tuberculosis increased progressively with age to 34.8 among patients 65 years old and older. The mean age of new TB cases was 53.1 years. The incidence among men (27.4) was more than two times higher than among women (12.2). The incidence rate in rural population was lower than in urban; 20.2 vs. 18.6. Bacteriologically confirmed pulmonary cases (4870) constituted 69,4% of all pulmonary TB cases. The number of smear positive pulmonary TB cases was 2 778 (39.6% of all pulmonary cases). In 2012 in the all group of TB patients in Poland there were 276 (3.7%) of homeless and 1 905 (25.3%) of unemployed. There were 48 foreigners registered among all cases of tuberculosis in Poland (0.6%) and 243 cases

2-Thiophenecarboxylic acid hydrazide Derivatives: Synthesis and Anti-Tuberculosis Studies

NASA Astrophysics Data System (ADS)

Fahmi, M. R. G.; Khumaidah, L.; Ilmiah, T. K.; Fadlan, A.; Santoso, M.

2018-04-01

One of the most frequent and widespread infectious diseases especially in developing countries is tuberculosis (TB). The number of TB drug resistant tend to increase, and there has been no new TB drug introduce since the 1960s. Six 2-Thiophenecarboxylic acid hydrazide derivatives were synthesized in 90-97% yields, and 2-thiophenecarbonylhydrazone-5, 7-dibromoisatin showed the highest activity in inhibiting M. tuberculosis H37Rv.

Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.

PubMed

Ruhwald, Morten; Aggerbeck, Henrik; Gallardo, Rafael Vázquez; Hoff, Søren T; Villate, José I; Borregaard, Bettine; Martinez, José A; Kromann, Ingrid; Penas, Antón; Anibarro, Luis L; de Souza-Galvão, Maria Luiza; Sánchez, Francisca; Rodrigo-Pendás, Jose Ángel; Noguera-Julian, Antoni; Martínez-Lacasa, Xavier; Tuñez, Maria Victoria; Fernández, Virginia Leiro; Millet, Joan P; Moreno, Antonio; Cobos, Nazaret; Miró, José M; Roldan, Llanos; Orcau, Angels; Andersen, Peter; Caylá, Joan A

2017-04-01

Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36. From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older

Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains.

PubMed

Uc-Cachón, Andrés Humberto; Borges-Argáez, Rocío; Said-Fernández, Salvador; Vargas-Villarreal, Javier; González-Salazar, Francisco; Méndez-González, Martha; Cáceres-Farfán, Mirbella; Molina-Salinas, Gloria María

2014-02-01

The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid-liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. Plumbagin and its dimers maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56-3.33 μg/mL). The bioactivity of maritinone and 3,3'-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194

Smear plus Detect-TB for a sensitive diagnosis of pulmonary tuberculosis: a cost-effectiveness analysis in an incarcerated population.

PubMed

Schmid, Karen Barros; Scherer, Luciene; Barcellos, Regina Bones; Kuhleis, Daniele; Prestes, Isaías Valente; Steffen, Ricardo Ewbank; Dalla Costa, Elis Regina; Rossetti, Maria Lucia Rosa

2014-12-16

Prison conditions can favor the spread of tuberculosis (TB). This study aimed to evaluate in a Brazilian prison: the performance and accuracy of smear, culture and Detect-TB; performance of smear plus culture and smear plus Detect-TB, according to different TB prevalence rates; and the cost-effectiveness of these procedures for pulmonary tuberculosis (PTB) diagnosis. This paper describes a cost-effectiveness study. A decision analytic model was developed to estimate the costs and cost-effectiveness of five routine diagnostic procedures for diagnosis of PTB using sputum specimens: a) Smear alone, b) Culture alone, c) Detect-TB alone, d) Smear plus culture and e) Smear plus Detect-TB. The cost-effectiveness ratio of costs were evaluated per correctly diagnosed TB case and all procedures costs were attributed based on the procedure costs adopted by the Brazilian Public Health System. A total of 294 spontaneous sputum specimens from patients suspected of having TB were analyzed. The sensibility and specificity were calculated to be 47% and 100% for smear; 93% and 100%, for culture; 74% and 95%, for Detect-TB; 96% and 100%, for smear plus culture; and 86% and 95%, for smear plus Detect-TB. The negative and positive predictive values for smear plus Detect-TB, according to different TB prevalence rates, ranged from 83 to 99% and 48 to 96%, respectively. In a cost-effectiveness analysis, smear was both less costly and less effective than the other strategies. Culture and smear plus culture were more effective but more costly than the other strategies. Smear plus Detect-TB was the most cost-effective method. The Detect-TB evinced to be sensitive and effective for the PTB diagnosis when applied with smear microscopy. Diagnostic methods should be improved to increase TB case detection. To support rational decisions about the implementation of such techniques, cost-effectiveness studies are essential, including in prisons, which are known for health care assessment problems.

The Prevalence Rate of Tuberculin Skin Test Positive by Contacts Group to Predict the Development of Active Tuberculosis After School Outbreaks.

PubMed

Kim, Hee Jin; Chun, Byung Chul; Kwon, AmyM; Lee, Gyeong-Ho; Ryu, Sungweon; Oh, Soo Yeon; Lee, Jin Beom; Yoo, Se Hwa; Kim, Eui Sook; Kim, Je Hyeong; Shin, Chol; Lee, Seung Heon

2015-10-01

The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. The mean duration of follow-up was 3.9±0.9 years. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ ≥ 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.

Vitamin D: Immuno-modulation and tuberculosis treatment.

PubMed

Selvaraj, Paramasivam; Harishankar, Murugesan; Afsal, Kolloli

2015-05-01

Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis.

[Thoracic manifestation of tuberculosis].

PubMed

Kienzl-Palma, D; Prosch, H

2016-10-01

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

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

PubMed Central

Walker, Naomi F.; Clark, Simon O.; Oni, Tolu; Andreu, Nuria; Tezera, Liku; Singh, Shivani; Saraiva, Luísa; Pedersen, Bernadette; Kelly, Dominic L.; Tree, Julia A.; D'Armiento, Jeanine M.; Meintjes, Graeme; Mauri, Francesco A.; Williams, Ann; Wilkinson, Robert J.; Friedland, Jon S.

2012-01-01

Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB. PMID:22345579

User experience analysis of e-TB Manager, a nationwide electronic tuberculosis recording and reporting system in Ukraine.

PubMed

Konduri, Niranjan; Sawyer, Kelly; Nizova, Nataliya

2017-04-01

Ukraine has successfully implemented e-TB Manager nationwide as its mandatory national tuberculosis registry after first introducing it in 2009. Our objective was to perform an end-of-programme evaluation after formal handover of the registry administration to Ukraine's Centre for Disease Control in 2015. We conducted a nationwide, cross-sectional, anonymous, 18-point user experience survey, and stratified the registry's transaction statistics to demonstrate usability. Contrary to initial implementation experience, older users (aged >50 years), often with limited or no computer proficiency prior to using the registry, had significantly better user experience scores for at least six of the 12 measures compared to younger users (aged 18-29 years). Using the registry for >3 years was associated with significantly higher scores for having capacity, adequacy of training received and satisfaction with the registry. Of the 5.9 million transactions over a 4-year period, nine out of 24 oblasts (regions) and Kiev city accounted for 62.5% of all transactions, and corresponded to 59% of Ukraine's tuberculosis burden. There were 437 unique active users in 486 rayons (districts) of Ukraine, demonstrating extensive reach. Our key findings complement the World Health Organization and European Respiratory Society's agenda for action on digital health to help implement the End TB Strategy.

[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

Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases

PubMed Central

Bates, Matthew; Marais, Ben J.; Zumla, Alimuddin

2015-01-01

The 18th WHO Global Tuberculosis Annual Report indicates that there were an estimated 8.6 million incident cases of tuberculosis (TB) in 2012, which included 2.9 million women and 530,000 children. TB caused 1.3 million deaths including 320,000 human immunodeficiency virus (HIV)-infected people; three-quarters of deaths occurred in Africa and Southeast Asia. With one-third of the world’s population latently infected with Mycobacterium tuberculosis (Mtb), active TB disease is primarily associated with a break down in immune surveillance. This explains the strong link between active TB disease and other communicable diseases (CDs) or noncommunicable diseases (NCDs) that exert a toll on the immune system. Comorbid NCD risk factors include diabetes, smoking, malnutrition, and chronic lung disease, all of which have increased relentlessly over the past decade in developing countries. The huge overlap between killer infections such as TB, HIV, malaria, and severe viral infections with NCDs, results in a “double burden of disease” in developing countries. The current focus on vertical disease programs fails to recognize comorbidities or to encourage joint management approaches. This review highlights major disease overlaps and discusses the rationale for better integration of tuberculosis care with services for NCDs and other infectious diseases to enhance the overall efficiency of the public health responses. PMID:25659380

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

PubMed

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

2017-08-01

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

Infection caused by Mycobacterium tuberculosis.

PubMed

Peloquin, C A; Berning, S E

1994-01-01

To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future. The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts. Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis. Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented. The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug-resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control

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

PubMed

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

1996-04-01

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

Tuberculosis in recipients of solid-organ transplants during 1995-2015 in Cali, Colombia.

PubMed

García-Goez, J F; Munera, G A; Rojas, V; Pacheco, R; Caylá, J A; Miro, J M

2017-11-01

Tuberculosis (TB) in solid-organ transplants (SOTs) is an important opportunistic infection associated with mortality and graft loss. SOT recipients carry a higher risk of contracting active TB than the general population. Clinical and radiographic presentations are non-specific, and sputum smear and culture have low yields. TB patients with SOTs require standard anti-tuberculosis treatment. However, rifampicin (RMP) use is associated with a 30% rate of acute graft rejection (AGR) and a 20% rate of transplant loss. To determine treatment outcomes in SOT recipients with active TB. A retrospective study of clinical and microbiological data and TB treatment outcomes. Among the 2349 transplants assessed, active TB was detected in 31 recipients; 55% had pulmonary TB and 40% were sputum smear-positive. In 32% of the patients, TB was diagnosed 30 days after symptom onset, 77% of the patients were cured and 10% died. AGR occurred in 13%. TB was diagnosed in <30 days. Anti-tuberculosis treatment without RMP (80% vs. 67%; P = 0.48, OR 0.5, 95%CI 0.07-3.55) and with moxifloxacin yielded higher treatment success rates and a lower risk of AGR.

Treatment of Latent Tuberculosis Infection.

PubMed

Tang, Patrick; Johnston, James

2017-01-01

The treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) elimination in regions that have a low incidence of TB. However, the decision to treat individuals with LTBI must consider the limitations of current diagnostic tests for LTBI, the risk of developing active TB disease, the potential adverse effects from chemoprophylactic therapy, and the importance of treatment adherence. When an individual has been diagnosed with LTBI and active TB has been ruled out, this is followed by an evaluation of the risks and benefits of LTBI treatment within the context of the regional epidemiology of TB and public health priorities. Once the decision to treat LTBI has been reached, and the infection is not suspected to be due to drug-resistant TB, the recommended regimens include isoniazid and/or rifamycin-derivatives, and the choice of regimen will depend upon the clinical considerations for that individual, such as patient preference, concomitant medications, hepatic disease, pregnancy, or immunodeficiency. As the duration of treatment of LTBI therapy is many months, therapy must be offered within a plan that monitors for adverse drug reactions and emphasizes adherence. For latent multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB) infection, the management is more complicated as there are few options for chemoprophylactic therapy and little evidence regarding the efficacy or risks of these regimens.

Tuberculosis-resistant transgenic cattle

USDA-ARS?s Scientific Manuscript database

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. ...

Presumed latent ocular tuberculosis diagnosed with the positive quantiFERON-TB Gold In-Tube Test in a HLA-A29-positive patient.

PubMed

Rangel, Carlos Mario; Atencia, Cesar; Merayo-Lloves, Jesus; Fernandez-Vega Sanz, Alvaro

2015-06-04

A 59-year-old Hispanic woman presented with a 3-year history of floaters associated with bilateral reduced visual acuity. Her best-corrected visual acuity (BCVA) was 20/40. Both anterior segments were without inflammation, but fundoscopy showed mild vitreous inflammation and multiple inflammatory choroidal lesions. Tests for inflammatory and infectious diseases were negative except for human leucocyte antigen A29. The patient was diagnosed with birdshot choroidoretinopathy, and treatment was initiated with cyclosporine A 2.5 mg/kg/day. One year after treatment, the patient reported systemic symptoms with no improvement in visual acuity. Fundus findings remained with vitreal inflammation. QuantiFERON-TB Gold In-Tube Test was positive, and a diagnosis of presumed latent ocular tuberculosis (TB) was made. We initiated anti-TB treatment for 9 months. At 6 months of anti-TB therapy, there was no active inflammation. The patient was followed for 2 years with no medications and no active inflammation. Her final BCVA was 20/25. 2015 BMJ Publishing Group Ltd.

Validation of the BrockTB Stat-Pak Assay for Detection of Tuberculosis in Eurasian Badgers (Meles meles) and Influence of Disease Severity on Diagnostic Accuracy▿

PubMed Central

Chambers, Mark A.; Crawshaw, Tim; Waterhouse, Sue; Delahay, Richard; Hewinson, R. Glyn; Lyashchenko, Konstantin P.

2008-01-01

A lateral-flow immunoassay (BrockTB Stat-Pak) for detecting tuberculosis in Eurasian badgers was 49% sensitive and 93% specific against culture for M. bovis (n = 1,464) at necropsy. However, the sensitivity was significantly higher (66 to 78%) in animals with more severe tuberculosis, indicating that the BrockTB Stat-Pak may be useful for the detection of badgers with the greatest risk of transmitting disease. PMID:18272706

Exploratory Study on Plasma Immunomodulator and Antibody Profiles in Tuberculosis Patients

PubMed Central

Ravindran, Resmi; Krishnan, Viswanathan V.; Khanum, Azra; Luciw, Paul A.

2013-01-01

Host immune responses to Mycobacterium tuberculosis are generally able to contain infection and maintain a delicate balance between protection and immunopathology. A shift in this balance appears to underlie active disease observed in about 10% of infected individuals. Effects of local inflammation, combined with anti-M. tuberculosis systemic immune responses, are directly detectable in peripheral circulation, without ex vivo stimulation of blood cells or biopsy of the affected organs. We studied plasma immunomodulator and antibody biomarkers in patients with active pulmonary tuberculosis (TB) by a combination of multiplex microbead immunoassays and computational tools for data analysis. Plasma profiles of 10 immunomodulators and antibodies against eight M. tuberculosis antigens (previously reported by us) were examined in active pulmonary TB patients in a country where TB is endemic, Pakistan. Multiplex analyses were performed on samples from apparently healthy individuals without active TB from the same community as the TB patients to establish the assay baselines for all analytes. Over 3,000 data points were collected from patients (n = 135) and controls (n = 37). The data were analyzed by multivariate and computer-assisted cluster analyses to reveal patterns of plasma immunomodulators and antibodies. This study shows plasma profiles that in most patients represented either strong antibody or strong immunomodulator biomarkers. Profiling of a combination of both immunomodulators and antibodies described here may be valuable for the analysis of host immune responses in active TB in countries where the disease is endemic. PMID:23761664

Tuberculosis outbreak investigation of a U.S. Navy amphibious ship crew and the Marine expeditionary unit aboard, 1998.

PubMed

Lamar, James E; Malakooti, Mark A

2003-07-01

A Marine deployed aboard a U.S. Navy amphibious ship had smear-positive, cavitary pulmonary tuberculosis (TB). Contact investigation ultimately found 21 active cases of TB among sailors and Marines who were aboard the affected ship. Approximately 3 months lapsed between onset of the source patient's illness and appropriate diagnosis and treatment. During the contact investigation, 3,338 persons received tuberculin skin tests and 712 were identified as new latent tuberculosis infection cases. Four persons diagnosed with latent tuberculosis infection developed active TB because of poor compliance with treatment. After personnel disembarked from the ship, persistent efforts to identify persons with active disease and latent infections were successful in controlling further spread of tuberculosis in military units and local communities. The Mycobacterium tuberculosis bacteria isolated from the source patient and 16 of the other active cases were susceptible to all drugs commonly used to treat TB.

Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents.

PubMed

Hall, Leslie; Jude, Kurt P; Clark, Shirley L; Dionne, Kim; Merson, Ryan; Boyer, Ana; Parrish, Nicole M; Wengenack, Nancy L

2012-11-01

The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.

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

PubMed

Nasehi, Mahshid; Hashemi-Shahraki, Abdolrazagh; Doosti-Irani, Amin; Sharafi, Saeed; Mostafavi, Ehsan

2017-01-01

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

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

Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

PubMed

Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

2017-06-01

To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Some Nigerian Anti-Tuberculosis Ethnomedicines: A Preliminary Efficacy Assessment

PubMed Central

Ibekwe, Nneka N.; Nvau, John B.; Oladosu, Peters O.; Usman, Auwal M.; Ibrahim, Kolo; Boshoff, Helena I.; Dowd, Cynthia S.; Orisadipe, Abayomi T.; Aiyelaagbe, Olapeju; Adesomoju, Akinbo A.; Barry, Clifton E.; Okogun, Joseph I.

2014-01-01

Ethnopharmacological significance Nigerian herbalists possess indigenous ethnomedicinal recipes for the management of tuberculosis and related ailments. Aim of the study To carry out a collaborative preliminary modern scientific evaluation of the efficacy of some Nigerian ethnomedicines used by traditional medicine practitioners (TMPs) in the management of tuberculosis and related ailments Materials and methods Ethnomedicinal recipes (ETMs) were collected from TMPs from locations in various ecological zones of Nigeria under a collaborative understanding. The aqueous methanolic extracts of the ETMs were screened against Mycobacterium bovis, BCG and Mycobacterium tuberculosis (M. tb.) strain H37Rv using the broth microdilution method. Results Extracts of ETMs screened against BCG showed 69% activity against the organism. The activities varied from weak, ≤ 2500μg /mL to highly active, 33μg /mL 64% of the extracts were active against M. tb. The activities of the extracts against M.tb. varied from weak, ≤ 2500μg /mL to highly active, 128μg/mL. There was 77% agreement in results obtained using BCG or M. tb. as test organisms Conclusion The results show clear evidence for the efficacy of the majority of indigenous Nigerian herbal recipes in the ethnomedicinal management of tuberculosis and related ailments. BCG may be effectively used, to a great extent, as the organism for screening for potential anti-M. tb. agents. A set of prioritization criteria for the selection of plants for initial further studies for the purpose of antituberculsis drug discovery research is proposed. PMID:24911338

Identification of new benzamide inhibitor against α-subunit of tryptophan synthase from Mycobacterium tuberculosis through structure-based virtual screening, anti-tuberculosis activity and molecular dynamics simulations.

PubMed

Naz, Sadia; Farooq, Umar; Ali, Sajid; Sarwar, Rizwana; Khan, Sara; Abagyan, Ruben

2018-03-13

Multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis has emerged as global health threat, causing millions of deaths worldwide. Identification of new drug candidates for tuberculosis (TB) by targeting novel and less explored protein targets will be invaluable for antituberculosis drug discovery. We performed structure-based virtual screening of eMolecules database against a homology model of relatively unexplored protein target: the α-subunit of tryptophan synthase (α-TRPS) from Mycobacterium tuberculosis essential for bacterial survival. Based on physiochemical properties analysis and molecular docking, the seven candidate compounds were selected and evaluated through whole cell-based activity against the H37Rv strain of M. tuberculosis. A new Benzamide inhibitor against α-subunit of tryptophan synthase (α-TRPS) from M. tuberculosis has been identified causing 100% growth inhibition at 25 μg/ml and visible bactericidal activity at 6 μg/ml. This benzamide inhibitor displayed a good predicted binding score (-48.24 kcal/mol) with the α-TRPS binding pocket and has logP value (2.95) comparable to Rifampicin. Further refinement of docking results and evaluation of inhibitor-protein complex stability were investigated through Molecular dynamic (MD) simulations studies. Following MD simulations, Root mean square deviation, Root mean square fluctuation and secondary structure analysis confirmed that protein did not unfold and ligand stayed inside the active pocket of protein during the explored time scale. This identified benzamide inhibitor against the α-subunit of TRPS from M. tuberculosis could be considered as candidate for drug discovery against TB and will be further evaluated for enzyme-based inhibition in future studies.

Tuberculosis Outbreak in a Primary School, Milan, Italy

PubMed Central

Faccini, Marino; Codecasa, Luigi Ruffo; Ciconali, Giorgio; Cammarata, Serafina; Borriello, Catia Rosanna; De Gioia, Costanza; Za, Alessandro; Marino, Andrea Filippo; Ferrarese, Maurizio; Gesu, Giovanni; Mazzola, Ester; Castaldi, Silvana

2013-01-01

Investigation of an outbreak of tuberculosis (TB) in a primary school in Milan, Italy, found 15 schoolchildren had active TB disease and 173 had latent TB infection. TB was also identified in 2 homeless men near the school. Diagnostic delay, particularly in the index case-patient, contributed to the transmission of infection. PMID:23621942

[Tuberculosis and drug-resistance tuberculosis in prisoners. Colombia, 2010-2012].

PubMed

Gómez, Ingrid T; Llerena, Claudia R; Zabaleta, Angie P

2015-01-01

To characterize tuberculosis drug-resistance using anti-tuberculosis drug-sensitivity tests in Colombian prisoners. Descriptive-retrospective analyses were performed on cases of tuberculosis in prisoners. Samples were evaluated by the National Reference Laboratory. Conditions like gender, TB/VIH co-infection and drug-resistance were evaluated. Anti-tuberculosis drug-sensitivity tests were carried out on 72 prisoners. Results showed a distribution of 90.7 % of cases in males and 9.3 % of cases in females. 12 % of cases were TB/VIH co-infections, 94 % of the cases had not received any anti-tuberculosis treatment before, six isolates were drug-resistant corresponding to 8.8 % of total cases, and two cases were multi drug-resistant representing 1.3 % of the cases. Of the drug-resistant cases, 83.3 % were TB/VIH co-infected. Previously treated cases corresponded to 5.6 % of the total cases analyzed. One case with TB/VIH co-infection and rifampicin resistance was observed, representing 1.3 % of the total cases. The government must create a clear policy for prisoners in Colombia, because a high rate of disease in prisoners was observed. In addition, the results showed an association between drug-resistance and TB/VIH co-infection. Overcrowding and low quality of life in penitentiaries could become an important public health problem.

Tuberculosis knowledge, attitudes, and practices among northern Ethiopian prisoners: Implications for TB control efforts.

PubMed

Adane, Kelemework; Spigt, Mark; Johanna, Laturnus; Noortje, Dorscheidt; Abera, Semaw Ferede; Dinant, Geert-Jan

2017-01-01

Although awareness is an important component in tuberculosis (TB) control, we do not know how much Ethiopian prisoners know about TB. This study assessed the level of knowledge, attitudes, and practices (KAP) of prisoners about TB in eight northern Ethiopian prisons. Data were collected cross-sectionally from 615 prisoners using a standardized questionnaire between March and May 2016. The outcome variables were defined considering the basic elements about TB. Out of 615 prisoners, only 37.7% mentioned bacteria as a cause of TB while 21.7% related TB to exposure to cold wind. Eighty-eight per cent correctly mentioned the aerial route of TB transmission and 27.3% had perceived stigma towards TB. The majority (63.7%) was not aware of the possibility of getting multi-drug-resistant strains when they would not adhere to treatment. Overall, only 24% knew the basic elements about TB, 41% had favorable attitudes, and 55% had a good practice. Prisoners who were urban residents were generally more knowledgeable than rural residents (adjusted OR = 2.16; 95% CI = 1.15-4.06). Illiterates were found to be less knowledgeable (adjusted OR = 0.17; 95% CI = 0.06-0.46), less likely to have a favorable attitude (adjusted OR = 0.31; 95% CI = 0.15-0.64), and less good practice (adjusted OR = 0.35; 95% CI = 0.18-0.69). Significant differences were also observed between the different study prisons. Knowledge of prisoners regarding the cause of TB and consequences of non-adherence to TB treatment was low. Knowledge on the transmission, symptoms, and prevention was fairly high. Health education interventions, focused on the cause and the translation of the knowledge to appropriate practices, are needed in all the study prisons. Special attention should be given to less educated prisoners, and to prisons with a high number of prisoners and those in remote areas.

The multidrug-resistant tuberculosis challenge to public health efforts to control tuberculosis.

PubMed Central

Villarino, M E; Geiter, L J; Simone, P M

1992-01-01

After years of steady decline, there has been an unprecedented resurgence of tuberculosis (TB) in the United States and outbreaks of multidrug-resistant tuberculosis (MDR-TB). The authors assess the nature, epidemiology, and implications of MDR-TB; provide suggestions for preventing drug resistance among patients with drug-susceptible TB; and offer recommendations for managing patients with MDR-TB. They outline the National Action Plan to Combat MDR-TB. Close collaboration among medical practitioners and staff members of TB control programs is needed to ensure the most effective management of patients with TB and their contacts. This collaboration is one of the most important steps for successful control of MDR-TB. PMID:1454973

Knowledge and attitude of key community members towards tuberculosis: mixed method study from BRAC TB control areas in Bangladesh.

PubMed

Paul, Sukanta; Akter, Rahima; Aftab, Afzal; Khan, Antora M; Barua, Mrittika; Islam, Shayla; Islam, Akramul; Husain, Ashaque; Sarker, Malabika

2015-01-31

Bangladesh National Tuberculosis (TB) Control Programme adopted a number of strategies to facilitate TB diagnosis and treatment. 'Advocacy, Communication and Social Mobilization' (ACSM) was one of the key strategies implemented by BRAC (Bangladesh Rural Advancement Committee, a non-governmental development organization) TB control program. The purpose of this study is to assess the knowledge and attitudes of the key community members (KCMs) participated in ACSM in BRAC TB control areas. This study combined quantitative and qualitative methods using a mixed method approach. KCMs in three districts with low TB case detection rates were targeted to assess the ACSM program. The quantitative survey using a multi-stage random-sampling strategy was conducted among 432 participants. The qualitative study included in-depth interviews (IDIs) of a sub sample of 48 respondents. For quantitative analysis, descriptive statistics were reported using frequencies, percentages, and Chi square tests, while thematic analysis was used for qualitative part. Most (99%) of the participants had heard about TB, and almost all knew that TB is a contagious yet curable disease. More than half (53%) of the KCMs had good knowledge regarding TB, but BRAC workers were found to be more knowledgeable compared to other KCMs. However, considerable knowledge gaps were observed among BRAC community health workers. Qualitative results revealed that the majority of the KCMs were aware about the signs, symptoms and transmission pathways of TB and believed that smoking and addiction were the prime causes of transmission of TB. The knowledge about child TB was poor even among BRAC health workers. Stigma associated with TB was not uncommon. Almost all respondents expressed that young girls diagnosed with TB. This study finding has revealed varying levels of knowledge and mixed attitudes about TB among the KCMs. It also provides insight on the poor knowledge regarding child TB and indicate that despite the

Associations between national tuberculosis program budgets and tuberculosis outcomes: an ecological study.

PubMed

Chapple, Will; Katz, Alan Roy; Li, Dongmei

2012-01-01

The objective of this study is to explore the associations between national tuberculosis program (NTP) budget allocation and tuberculosis related outcomes in the World Health Organization's 22 high burden countries from 2007-2009. This ecological study used mixed effects and generalized estimating equation models to identify independent associations between NTP budget allocations and various tuberculosis related outcomes. Models were adjusted for a number of independent variables previously noted to be associated with tuberculosis incidence. Increasing the percent of the NTP budget for advocacy, communication and social mobilization was associated with an increase in the case detection rate. Increasing TB-HIV funding was associated with an increase in HIV testing among TB patients. Increasing the percent of the population covered by the Directly Observed Therapy (DOT) program was associated with an increase in drug susceptibility testing. Laboratory funding was positively associated with tuberculosis notification. Increasing the budgets for first line drugs, management and multi-drug resistant tuberculosis (MDR-TB) was associated with a decrease in smear positive deaths. Effective TB control is a complex and multifaceted challenge. This study revealed a number of budget allocation related factors associated with improved TB outcome parameters. If confirmed with future longitudinal studies, these findings could help guide NTP managers with allocation decisions.

Associations between national tuberculosis program budgets and tuberculosis outcomes: an ecological study

PubMed Central

Chapple, Will; Katz, Alan Roy; Li, Dongmei

2012-01-01

Introduction The objective of this study is to explore the associations between national tuberculosis program (NTP) budget allocation and tuberculosis related outcomes in the World Health Organization's 22 high burden countries from 2007–2009. Methods This ecological study used mixed effects and generalized estimating equation models to identify independent associations between NTP budget allocations and various tuberculosis related outcomes. Models were adjusted for a number of independent variables previously noted to be associated with tuberculosis incidence. Results Increasing the percent of the NTP budget for advocacy, communication and social mobilization was associated with an increase in the case detection rate. Increasing TB-HIV funding was associated with an increase in HIV testing among TB patients. Increasing the percent of the population covered by the Directly Observed Therapy (DOT) program was associated with an increase in drug susceptibility testing. Laboratory funding was positively associated with tuberculosis notification. Increasing the budgets for first line drugs, management and multi-drug resistant tuberculosis (MDR-TB) was associated with a decrease in smear positive deaths. Conclusion Effective TB control is a complex and multifaceted challenge. This study revealed a number of budget allocation related factors associated with improved TB outcome parameters. If confirmed with future longitudinal studies, these findings could help guide NTP managers with allocation decisions. PMID:23024825

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)

[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

Tuberculosis in Poland in 2014

PubMed

Korzeniewska-Koseła, Maria

To evaluate the main features of TB epidemiology in 2014 in Poland and to compare with the data on the same phenomena in EU/EEA countries. Analysis of case- based data on TB patients from National TB Register, data on anti-TB drugsusceptibility testing results in cases notified in 2014, data from National Institute of Public Health- NationalInstitute of Hygiene on cases of tuberculosis as AIDS-defining disease, data from Central Statistical Office ondeaths from tuberculosis based on death certificates, data from ECDC report „ European Centre for DiseasePrevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2016. Stockholm: European Centre for Disease Prevention and Control, 2016”. 6 698 TB cases were reported in Poland in 2014. The incidence rate was 17.4 cases per 100 000, withlarge variability between voivodeships from 9.3 to 26.5 per 100 000. The mean annual decrease of TB incidence in 2010- 2014 was 2.1%. 6 066 cases had no history of previous treatment i.e. 15.8 per 100 000. 632 cases i.e. 1.6 per 100 000 – 9.4% of all registered subjects were relapses. The number of all notified pulmonary tuberculosis cases in 2014 was 6311 i.e. 16.4 per 100 000. Pulmonary cases represented 94.2% of all TB cases. In the presented year 387 extrapulmonary TB cases were reported. Children with TB (70 cases) accounted for 1.0% of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.2 per 100 000 among children to 30.4 per 100 000 among patients 65 years old and older. The incidence among men i.e. 24.6 per 100 000 was 2.3 times higher than among women i.e. 10.7 per 100 000. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 45 to 49 years – 40.4 vs. 9.3. The TB incidence in rural population was lower than in urban, respectively 17.0 per 100 000 and 17.7 per 100 000. The number of all registered culture positive TB cases, including relapses, was 4

Drug resistant Mycobacterium tuberculosis in Mexico.

PubMed

Zazueta-Beltran, Jorge; León-Sicairos, Claudia; Canizalez-Roman, Adrián

2009-04-30

Tuberculosis (TB) remains a serious public health problem, worsened by an increased frequency of multidrug-resistant (MDR) Mycobacterium tuberculosis strains. The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) launched the Global Project on Anti-Tuberculosis Drug Resistance Surveillance to measure the prevalence of drug resistance. Data from the global reports on resistance to anti-tuberculosis (anti-TB) drugs have shown that drug resistance still presents worldwide and that MDR-TB is present in almost all the world. Though the Global Project (WHO) has been operating since 1994, very few countries and states have reported new information. Data from repeated surveys employing comparable methodologies over several years are essential to determine with any certainty in which direction the prevalence of drug resistance is moving. Drug-resistant tuberculosis and MDR-TB have been identified in Mexico, even with the existence of a National Tuberculosis Program based on Directly Observed Treatment, Short-course (DOTS). This review discusses available surveillance data on drug susceptibility data for TB in different states of Mexico.

Public-private mix for control of tuberculosis and TB-HIV in Nairobi, Kenya: outcomes, opportunities and obstacles.

PubMed

Chakaya, J; Uplekar, M; Mansoer, J; Kutwa, A; Karanja, G; Ombeka, V; Muthama, D; Kimuu, P; Odhiambo, J; Njiru, H; Kibuga, D; Sitienei, J

2008-11-01

Nairobi, the capital of Kenya. To promote standardised tuberculosis (TB) care by private health providers and links with the public sector. A description of the results of interventions aimed at engaging private health providers in TB care and control in Nairobi. Participating providers are supported to provide TB care that conforms to national guidelines. The standard surveillance tools are used for programme monitoring and evaluation. By the end of 2006, 26 of 46 (57%) private hospitals and nursing homes were engaged. TB cases reported by private providers increased from 469 in 2002 to 1740 in 2006. The treatment success rate for smear-positive pulmonary TB treated by private providers ranged from 76% to 85% between 2002 and 2005. Of the 1740 TB patients notified by the private sector in 2006, 732 (42%) were tested for human immunodeficiency virus (HIV), of whom 372 (51%) were positive. Of the 372 HIV-positive TB patients, 227 (61%) were provided with cotrimoxazole preventive treatment (CPT) and 136 (37%) with antiretroviral treatment (ART). Private providers can be engaged to provide TB-HIV care conforming to national norms. The challenges include providing diagnostics, CPT and ART and the capacity to train and supervise these providers.

Tuberculosis Data and Statistics

MedlinePlus

... TB programs can use to design and prioritize effective public health interventions. Tuberculosis — United States, 2017 (Provisional Data) Take on Tuberculosis Infographic and Social Media Graphics Customizable Take on TB Infographic with Instructions ...

Tuberculosis: Is the landscape changing?

PubMed

Khatua, Sutapa; Geltemeyer, Abby M; Gourishankar, Anand

2017-01-01

Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of tuberculosis (TB). During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing mycobacterium tuberculosis. TB is the second most common cause of death from infectious diseases after HIV/AIDS. Drug-resistant TB poses serious challenge to effective management of TB worldwide. Multidrug-resistant TB accounted for about half a million new cases and over 200,000 deaths in 2013. Whole-genome sequencing (first done in 1998) technologies have provided new insight into the mechanism of drug resistance. For the first time in 50 y, new anti TB drugs have been developed. The World Health Organization (WHO) has recently revised their treatment guidelines based on 32 studies. In United States, latent TB affects between 10 and 15 million people, 10% of whom may develop active TB disease. QuantiFERON TB Gold and T-SPOT.TB test are used for diagnosis. Further research will look into the importance of newly discovered gene mutations in causing drug resistance.

Detection of circulating Mycobacterium tuberculosis-specific DNA by droplet digital PCR for vaccine evaluation in challenged monkeys and TB diagnosis.

PubMed

Song, Neng; Tan, Yang; Zhang, Lingyun; Luo, Wei; Guan, Qing; Yan, Ming-Zhe; Zuo, Ruiqi; Liu, Weixiang; Luo, Feng-Ling; Zhang, Xiao-Lian

2018-04-24

Mycobacterium tuberculosis (M. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant TB and co-infection of human immunodeficiency virus (HIV). The development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early TB diagnosis, and TB treatment. Droplet digital polymerase chain reaction (ddPCR) is a newly developed sensitive PCR method for the absolute quantification of nucleic acid concentrations. Here, we used ddPCR to quantify the circulating virulent M. tb-specific CFP10 (10-kDa culture filtrate protein, Rv3874) and Rv1768 DNA copy numbers in the blood samples from Bacille Calmette-Guerin (BCG)-vaccinated and/or virulent M. tb H37Rv-challenged rhesus monkeys. We found that ddPCR was more sensitive compared to real-time fluorescence quantitative PCR (qPCR), as the detection limits of CFP10 were 1.2 copies/μl for ddPCR, but 15.8 copies/μl for qPCR. We demonstrated that ddPCR could detect CFP10 and Rv1768 DNA after 3 weeks of infection and at least two weeks earlier than qPCR in M.tb H37Rv-challenged rhesus monkey models. DdPCR could also successfully quantify CFP10 and Rv1768 DNA copy numbers in clinical TB patients' blood samples (active pulmonary TB, extrapulmonary TB (EPTB), and infant TB). To our knowledge, this study is the first to demonstrate that ddPCR is an effective and sensitive method of measuring the circulating CFP10 and Rv1768 DNA for vaccine development, bacterial load evaluation in vivo, and early TB (including EPTB and infant TB) diagnosis as well.

Breaking Transmission with Vaccines: The Case of Tuberculosis.

PubMed

Gonzalo-Asensio, Jesus; Aguilo, Nacho; Marinova, Dessislava; Martin, Carlos

2017-07-01

Members of the Mycobacterium tuberculosis complex (MTBC) have evolved causing tuberculosis (TB) in different mammalian hosts. MTBC ecotypes have adapted to diverse animal species, with M. bovis being the most common cause of TB in livestock. Cattle-to-human transmission of M. bovis through ingestion of raw milk was common before introduction of the pasteurization process. TB in humans is mainly caused by M. tuberculosis . This bacterium is considered a genetically clonal pathogen that has coevolved with humans due to its ability to manipulate and subvert the immune response. TB is a major public health problem due to airborne person-to-person transmission of M. tuberculosis . The essential yet unanswered question on the natural history of TB is when M. tuberculosis decides to establish latent infection in the host (resambling the lysogenic cycle of lambda phage) or to cause pulmonary disease (comparable to the lytic cycle of lambda phage). In this latter case, M. tuberculosis kills the host with the aim of achieving transmission to new hosts. Combating the TB epidemic requires stopping transmission. M. bovis BCG, the present vaccine against TB, is derived from M. bovis and only protects against disseminated forms of TB. Thus, a priority in TB research is development of new effective vaccines to prevent pulmonary disease. Attenuated vaccines based on M. tuberculosis as MTBVAC are potential candidates that could contribute to break the TB transmission cycle.

User experience analysis of e-TB Manager, a nationwide electronic tuberculosis recording and reporting system in Ukraine

PubMed Central

Sawyer, Kelly; Nizova, Nataliya

2017-01-01

Ukraine has successfully implemented e-TB Manager nationwide as its mandatory national tuberculosis registry after first introducing it in 2009. Our objective was to perform an end-of-programme evaluation after formal handover of the registry administration to Ukraine's Centre for Disease Control in 2015. We conducted a nationwide, cross-sectional, anonymous, 18-point user experience survey, and stratified the registry's transaction statistics to demonstrate usability. Contrary to initial implementation experience, older users (aged >50 years), often with limited or no computer proficiency prior to using the registry, had significantly better user experience scores for at least six of the 12 measures compared to younger users (aged 18–29 years). Using the registry for >3 years was associated with significantly higher scores for having capacity, adequacy of training received and satisfaction with the registry. Of the 5.9 million transactions over a 4-year period, nine out of 24 oblasts (regions) and Kiev city accounted for 62.5% of all transactions, and corresponded to 59% of Ukraine's tuberculosis burden. There were 437 unique active users in 486 rayons (districts) of Ukraine, demonstrating extensive reach. Our key findings complement the World Health Organization and European Respiratory Society's agenda for action on digital health to help implement the End TB Strategy. PMID:28512634

Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe: A tuberculosis network European Trialsgroup (TBNET) study.

PubMed

Bothamley, Graham H; Lange, Christoph

2017-11-01

Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing. 68/105 responses gave valid information and were from countries within the WHO European Region. Inpatient beds matched demand, but single rooms with negative pressure were only available in low incidence countries; ultraviolet decontamination was used in 5 sites, all with >10 patients with M/XDR-TB per year. Molecular tests for mutations associated with rifampicin resistance were widely available (88%), even in lower income and especially in high incidence countries. Molecular tests for other first line and second line drugs were less accessible (76 and 52% respectively). A third of physicians considered that drug susceptibility results were delayed by > 2 months. Infection control for inpatients with M/XDR-TB remains a problem in high incidence countries. Rifampicin resistance is readily detected, but tests to plan regimens tailored to the drug susceptibilities of the strain of Mycobacterium tuberculosis are significantly delayed, allowing for further drug resistance to develop. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protein-calorie malnutrition, macronutrient supplements, and tuberculosis.

PubMed

Koethe, J R; von Reyn, C F

2016-07-01

Protein-calorie malnutrition (PCM) is a risk factor for tuberculosis (TB) disease and may affect treatment outcomes. There is currently no recommended macronutrient intervention for improving the outcome of anti-tuberculosis treatment. We reviewed current literature on PCM and low body mass index (BMI) as risk factors for tuberculous infection and TB disease, and their effects on anti-tuberculosis treatment. We summarize clinical trials of macronutrient supplementation in the treatment of TB. PCM is a well-established risk factor for TB disease; however, data on malnutrition and the risk of tuberculous infection are limited. Malnutrition is associated with an increased risk of mortality and relapse of active TB. Clinical trials of macronutrient supplementation during treatment confirm a 2-3 kg improvement in weight gain at 2 months, and may result in improvement in physical function, sputum conversion and treatment completion, but they have not been powered to assess effects on mortality or relapse. Assessment of dietary intake, food security, and baseline BMI should be standard practice in anti-tuberculosis treatment, along with dietary counselling. As macronutrient supplementation may have modest benefits and is not associated with adverse events, patients with BMI values <18.5 kg/m(2) should be provided with balanced macronutrient supplementation whenever possible.

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai.

PubMed

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-05-10

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies.

Severe hypovitaminosis D in active tuberculosis patients and its predictors.

PubMed

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

2018-06-01

Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM on TB and the possible mechanism are still uncertain. We carried out this study to identify the nutritional status of vitamin D (VD) in TB patients in a northern city in China (latitude 36° N) and investigate the possible predictors of severe vitamin D deficiency (SVDD). A cross-sectional study including 461 active TB patients (192 with and 269 without DM) were randomly selected from Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25 hydroxyvitamin D [25(OH)D], and investigated the association between sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial TB signs and symptoms (TB score) and VD status. Multivariate logistic regression analysis was used to define the possible predictors of SVDD. The median serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383 (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8 ng/mL]. The variables associated with serum 25(OH)D concentrations were DM, outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB score had nearly 5 fold higher risk of having SVDD compared with those in mild subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity level also increased the odds of SVDD, while DM and high fish consumption showed protect effects. Severe hypovitaminosis D is prevalent in active TB patients, and the main predictors of SVDD were severe TB score, low outdoor activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated with increased risk of TB in DM. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

PubMed

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

2004-08-15

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

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.

Estimating the impact of a television campaign on tuberculosis knowledge and intention to test for TB in South Korea.

PubMed

Lee, B; Oh, H J; Chon, B S

2018-01-01

To examine the effectiveness of a television campaign for preventing tuberculosis (TB) executed in South Korea in 2015. We used a genetic matching method to accurately test the effect of the campaign on changing people's knowledge and behaviour in a nationwide sample of 1000 adults; information was collected using face-to-face interviews. After matching individuals in treatment and controlled conditions using 11 covariates, we found that the campaign significantly improved people's knowledge about TB, and enhanced people's intention to undertake a TB test when they recognised the signs of TB. These data highlight the potential usefulness of genetic matching for enhancing statistical rigour when evaluating the effectiveness of a health campaign using a cross-sectional observational study.

Unmasking leading to a health care worker Mycobacterium tuberculosis transmission.

PubMed

Holden, Kerry L; Bradley, Craig W; Curran, Evonne T; Pollard, Christopher; Smith, Grace; Holden, Elisabeth; Glynn, Patricia; Garvey, Mark

2018-05-09

Mycobacterium tuberculosis is a major health burden worldwide. The disease can present as an individual case, community outbreak or more rarely a nosocomial outbreak. Even in countries with a low prevalence such as the UK, tuberculosis (TB) presents a risk to healthcare workers (HCWs). To report an outbreak which manifested 12 months after a patient with pulmonary tuberculosis was admitted to Queen Elizabeth Hospital Birmingham (QEHB). We present the epidemiological and outbreak investigations; the role of whole genome sequencing (WGS) in identifying the outbreak and control measures to prevent further outbreaks. Subsequent to a case of open tuberculosis in a patient transmission was confirmed in one healthcare worker (HCW) who had active TB; HCW cases of latent TB infection (LTBI) were also identified amongst 7 HCW contacts of the index case. Of note, all the LBTI cases had other risk factors for TB. Routine use of Whole Genome Sequencing (WGS) identified the outbreak link between the index case to the HCW with active TB disease, and also informed our investigations. Exposure most likely occurred during an aerosol generating procedure (AGP) which was done in accordance with national guidance at that time without using respiratory protection. Enhanced control measures were implemented following the outbreak. Copyright © 2018. Published by Elsevier Ltd.

Descriptive review of tuberculosis surveillance systems across the circumpolar regions.

PubMed

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

2016-01-01

Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. To establish baseline knowledge of tuberculosis surveillance systems used by ICS-TB member jurisdictions. Three questionnaires were developed to reflect the different surveillance levels (local, regional and national); all 3 were forwarded to the official representative of each of the 15 ICS-TB member jurisdictions in 2013. Respondents self-identified the level of surveillance conducted in their region and completed the applicable questionnaire. Information collected included surveillance system objectives, case definitions, data collection methodology, storage and dissemination. Thirteen ICS-TB jurisdictions [Canada (Labrador, Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Sweden, Russian Federation (Arkhangelsk, Khanty-Mansiysk Autonomous Okrug, Yakutia (Sakha Republic), United States (Alaska)] voluntarily completed the survey - representing 2 local, 7 regional and 4 national levels. Tuberculosis reporting is mandatory in all jurisdictions, and case definitions are comparable across regions. The common objectives across systems are to detect outbreaks, and inform the evaluation/planning of public health programmes and policies. All jurisdictions collect data on confirmed active tuberculosis cases and treatment outcomes; 11 collect contact tracing results. Faxing of standardized case reporting forms is the most common reporting method. Similar core data elements are collected; 8 regions report genotyping results. Data are stored using customized programmes (n=7) and commercial software (n=6). Nine jurisdictions provide monthly, bi-annual or annual reports to principally government and/or scientific/medical audiences. This review successfully establishes baseline knowledge on similarities and differences among circumpolar

Descriptive review of tuberculosis surveillance systems across the circumpolar regions

PubMed Central

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

2016-01-01

Background Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. Objective To establish baseline knowledge of tuberculosis surveillance systems used by ICS-TB member jurisdictions. Design Three questionnaires were developed to reflect the different surveillance levels (local, regional and national); all 3 were forwarded to the official representative of each of the 15 ICS-TB member jurisdictions in 2013. Respondents self-identified the level of surveillance conducted in their region and completed the applicable questionnaire. Information collected included surveillance system objectives, case definitions, data collection methodology, storage and dissemination. Results Thirteen ICS-TB jurisdictions [Canada (Labrador, Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Sweden, Russian Federation (Arkhangelsk, Khanty-Mansiysk Autonomous Okrug, Yakutia (Sakha Republic), United States (Alaska)] voluntarily completed the survey – representing 2 local, 7 regional and 4 national levels. Tuberculosis reporting is mandatory in all jurisdictions, and case definitions are comparable across regions. The common objectives across systems are to detect outbreaks, and inform the evaluation/planning of public health programmes and policies. All jurisdictions collect data on confirmed active tuberculosis cases and treatment outcomes; 11 collect contact tracing results. Faxing of standardized case reporting forms is the most common reporting method. Similar core data elements are collected; 8 regions report genotyping results. Data are stored using customized programmes (n=7) and commercial software (n=6). Nine jurisdictions provide monthly, bi-annual or annual reports to principally government and/or scientific/medical audiences. Conclusion This review successfully establishes baseline knowledge

Descriptive review of tuberculosis surveillance systems across the circumpolar regions.

PubMed

Bourgeois, Annie-Claude; Zulz, Tammy; Soborg, Bolette; Koch, Anders; On Behalf Of The International Circumpolar Surveillance-Tuberculosis Working Group

2016-01-01

Background Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. Objective To establish baseline knowledge of tuberculosis surveillance systems used by ICS-TB member jurisdictions. Design Three questionnaires were developed to reflect the different surveillance levels (local, regional and national); all 3 were forwarded to the official representative of each of the 15 ICS-TB member jurisdictions in 2013. Respondents self-identified the level of surveillance conducted in their region and completed the applicable questionnaire. Information collected included surveillance system objectives, case definitions, data collection methodology, storage and dissemination. Results Thirteen ICS-TB jurisdictions [Canada (Labrador, Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Sweden, Russian Federation (Arkhangelsk, Khanty-Mansiysk Autonomous Okrug, Yakutia (Sakha Republic), United States (Alaska)] voluntarily completed the survey - representing 2 local, 7 regional and 4 national levels. Tuberculosis reporting is mandatory in all jurisdictions, and case definitions are comparable across regions. The common objectives across systems are to detect outbreaks, and inform the evaluation/planning of public health programmes and policies. All jurisdictions collect data on confirmed active tuberculosis cases and treatment outcomes; 11 collect contact tracing results. Faxing of standardized case reporting forms is the most common reporting method. Similar core data elements are collected; 8 regions report genotyping results. Data are stored using customized programmes (n=7) and commercial software (n=6). Nine jurisdictions provide monthly, bi-annual or annual reports to principally government and/or scientific/medical audiences. Conclusion This review successfully establishes baseline knowledge on

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

PubMed Central

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

2011-01-01

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

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.

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

PubMed Central

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

2013-01-01

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

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

PubMed

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

2013-01-01

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

Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques

PubMed Central

Lin, Philana Ling; Dartois, Veronique; Johnston, Paul J.; Janssen, Christopher; Via, Laura; Goodwin, Michael B.; Klein, Edwin; Barry, Clifton E.; Flynn, JoAnne L.

2012-01-01

Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB. PMID:22826237

Rapid Serodiagnosis of Active Pulmonary Mycobacterium tuberculosis by Analysis of Results from Multiple Antigen-Specific Tests

PubMed Central

Okuda, Yoshinari; Maekura, Ryoji; Hirotani, Atsusi; Kitada, Seigo; Yoshimura, Kenji; Hiraga, Touru; Yamamoto, Yuoko; Itou, Masami; Ogura, Takeshi; Ogihara, Toshio

2004-01-01

We have prospectively analyzed three antigens for serodiagnosis of tuberculosis (TB). These antigens were tuberculous glycolipid antigen, lypoarabinomannan polysaccharide antigen, and antigen 60 (A60), which was derived from purified protein derivatives. Of the 131 patients with active pulmonary TB, 57 were both smear and culture negative and 14 had chronic active pulmonary TB that remained smear positive for >12 months of chemotherapy. One hundred twenty healthy adults were controls. The percentages of patients positive in all three tests were 58.8% for smear-positive active pulmonary TB and 71.4% for chronic active pulmonary TB. When the results of the three serodiagnostic tests were evaluated in combination, the sensitivity increased to 91.5% in patients with active pulmonary TB and to 86.0% in smear- and culture-negative patients. The false-positive rate of the three-test combination was 12.5% in the healthy control groups. In conclusion, it was not possible to detect all of the antibodies against antigenic substances in the cell walls of the tuberculous bacilli in the sera of all TB patients by using available serodiagnostic tests. However, the combined use of tests with three separate antigens maximizes the effectiveness of serodiagnosis. PMID:15004065

Tuberculosis in Hispanics/Latinos

MedlinePlus

... Compartir ( PDF – 672k) Spanish Tuberculosis in Hispanics/Latinos Tuberculosis (TB) is a disease that is spread from person to person through the air. TB bacteria usually attack the lungs, but it can attack any part of the ...

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…

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-08-01

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

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai

PubMed Central

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-01-01

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies. PMID:29863175

Direct Application of the INNO-LiPA Rif.TB Line-Probe Assay for Rapid Identification of Mycobacterium tuberculosis Complex Strains and Detection of Rifampin Resistance in 360 Smear-Positive Respiratory Specimens from an Area of High Incidence of Multidrug-Resistant Tuberculosis

PubMed Central

Viveiros, Miguel; Leandro, Clara; Rodrigues, Liliana; Almeida, Josefina; Bettencourt, Rosário; Couto, Isabel; Carrilho, Lurdes; Diogo, José; Fonseca, Ana; Lito, Luís; Lopes, João; Pacheco, Teresa; Pessanha, Mariana; Quirim, Judite; Sancho, Luísa; Salfinger, Max; Amaral, Leonard

2005-01-01

The INNO-LiPA Rif.TB assay for the identification of Mycobacterium tuberculosis complex strains and the detection of rifampin (RIF) resistance has been evaluated with 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis (MDR-TB). The sensitivity when compared to conventional identification/culture methods was 82.2%, and the specificity was 66.7%; the sensitivity and specificity were 100.0% and 96.9%, respectively, for the detection of RIF resistance. This assay has the potential to provide rapid information that is essential for the effective management of MDR-TB. PMID:16145166

Management of multidrug-resistant tuberculosis in human immunodeficiency virus patients

NASA Astrophysics Data System (ADS)

Jamil, K. F.

2018-03-01

Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis(MTB). 10.4 million new TB cases will appear in 2015 worldwide. There were an estimated 1.4 million TB deaths in 2015, and an additional 0.4 million deaths resulting from TB disease among people living with human immunodeficiency virus (HIV). Multidrug- resistant and extensively drug-resistant tuberculosis (MDR and XDR-TB) are major public health concerns worldwide. 480.000 new cases of MDR-TB will appear in 2015 and an additional 100,000 people with rifampicin-resistant TB (RR-TB) who were also newly eligible for MDR-TB treatment. Their association with HIV infection has contributed to the slowing down of TB incidence decline over the last two decades, therefore representing one important barrier to reach TB elimination. Patients infected with MDR-TB require more expensive treatment regimens than drug-susceptible TB, with poor treatment.Patients with multidrug- resistant tuberculosis do not receive rifampin; drug interactions risk is markedly reduced. However, overlapping toxicities may limit options for co-treatment of HIV and multidrug- resistant tuberculosis.

Tuberculosis and infection control.

PubMed

Karim, Kelvin

Against a background of rising tuberculosis (TB) rates, increasing incidence of TB and human immunodeficiency virus (HIV) co-infection, coupled with the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), the need for effective TB infection control has never been more vital (World Health Organization (WHO), 2009). TB infection control has been defined as 'a combination of measures aimed at minimizing the risk of TB transmission within populations' (WHO, 2009: p.ix). Health professionals are frequently confused about appropriate infection control measures when caring for patients affected by infectious respiratory tuberculosis (Mohandas and Cunniffe, 2009). This article aims to address the key infection control measures required to optimize patient care and reduce the risk of TB transmission within hospital and community settings.

Analysis of multi drug resistant tuberculosis (MDR-TB) financial protection policy: MDR-TB health insurance schemes, in Chhattisgarh state, India.

PubMed

Kundu, Debashish; Sharma, Nandini; Chadha, Sarabjit; Laokri, Samia; Awungafac, George; Jiang, Lai; Asaria, Miqdad

2018-01-27

There are significant financial barriers to access treatment for multi drug resistant tuberculosis (MDR-TB) in India. To address these challenges, Chhattisgarh state in India has established a MDR-TB financial protection policy by creating MDR-TB benefit packages as part of the universal health insurance scheme that the state has rolled out in their effort towards attaining Universal Health Coverage for all its residents. In these schemes the state purchases health insurance against set packages of services from third party health insurance agencies on behalf of all its residents. Provider payment reform by strategic purchasing through output based payments (lump sum fee is reimbursed as per the MDR-TB benefit package rates) to the providers - both public and private health facilities empanelled under the insurance scheme was the key intervention. To understand the implementation gap between policy and practice of the benefit packages with respect to equity in utilization of package claims by the poor patients in public and private sector. Data from primary health insurance claims from January 2013 to December 2015, were analysed using an extension of 'Kingdon's multiple streams for policy implementation framework' to explain the implementation gap between policy and practice of the MDR-TB benefit packages. The total number of claims for MDR-TB benefit packages increased over the study period mainly from poor patients treated in public facilities, particularly for the pre-treatment evaluation and hospital stay packages. Variations and inequities in utilizing the packages were observed between poor and non-poor beneficiaries in public and private sector. Private providers participation in the new MDR-TB financial protection mechanism through the universal health insurance scheme was observed to be much lower than might be expected given their share of healthcare provision overall in India. Our findings suggest that there may be an implementation gap due to weak

Virologic and immunologic outcome of HAART in Human Immunodeficiency Virus (HIV)-1 infected patients with and without tuberculosis (TB) and latent TB infection (LTBI) in Addis Ababa, Ethiopia.

PubMed

Kassa, Desta; Gebremichael, Gebremedhin; Alemayehu, Yodit; Wolday, Dawit; Messele, Tsehaynesh; van Baarle, Debbie

2013-01-01

HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB. A total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation. The majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml). Our data show that

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

PubMed

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

2012-01-01

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

Mycobacterium tuberculosis: ecology and evolution of a human bacterium.

PubMed

Bañuls, Anne-Laure; Sanou, Adama; Anh, Nguyen Thi Van; Godreuil, Sylvain

2015-11-01

Some species of the Mycobacterium tuberculosis complex (MTBC), particularly Mycobacterium tuberculosis, which causes human tuberculosis (TB), are the first cause of death linked to a single pathogen worldwide. In the last decades, evolutionary studies have much improved our knowledge on MTBC history and have highlighted its long co-evolution with humans. Its ability to remain latent in humans, the extraordinary proportion of asymptomatic carriers (one-third of the entire human population), the deadly epidemics and the observed increasing level of resistance to antibiotics are proof of its evolutionary success. Many MTBC molecular signatures show not only that these bacteria are a model of adaptation to humans but also that they have influenced human evolution. Owing to the unbalance between the number of asymptomatic carriers and the number of patients with active TB, some authors suggest that infection by MTBC could have a protective role against active TB disease and also against other pathologies. However, it would be inappropriate to consider these infectious pathogens as commensals or symbionts, given the level of morbidity and mortality caused by TB.

Tuberculosis Relief Belt Supporting Project (Tuberculosis Patient Management Project for Poverty Group).

PubMed

Kim, Jae Kyoung; Jeong, Ina; Lee, Ji Yeon; Kim, Jung Hyun; Han, Ah Yeon; Kim, So Yeon; Joh, Joon Sung

2018-03-07

The "Tuberculosis Relief Belt Supporting Project (Tuberculosis Patient Management Project for Poverty Groups)" is a national program for socioeconomically vulnerable tuberculosis (TB) patients. We sought to evaluate the clinical and socioeconomic characteristics of poverty-stricken TB patients, and determined the need for relief. We examined in-patients with TB, who were supported by this project at the National Medical Center from 2014 to 2015. We retrospectively investigated the patients' socioeconomic status, clinical characteristics, and project expenditures. Fifty-eight patients were enrolled. Among 55 patients with known income status, 24 (43.6%) had no income. Most patients (80%) lived alone. A total of 48 patients (82.8%) had more than one underlying disease. More than half of the enrolled patients (30 patients, 51.7%) had smear-positive TB. Cavitary disease was found in 38 patients (65.5%). Among the 38 patients with known resistance status, 19 (50%) had drug-resistant TB. In terms of disease severity, 96.6% of the cases had moderate-to-severe disease. A total of 14 patients (26.4%) died during treatment. Nursing expenses were supported for 12 patients (20.7%), with patient transportation costs reimbursed for 35 patients (60%). In terms of treatment expenses for 31 people (53.4%), 93.5% of them were supported by uninsured benefits. Underlying disease, infectivity, drug resistance, severity, and death occurred frequently in socioeconomically vulnerable patients with TB. Many uninsured treatment costs were not supported by the current government TB programs, and the "Tuberculosis Relief Belt Supporting Project" compensated for these limitations. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

Integrating HIV testing and care into tuberculosis services in Benin: programmatic aspects.

PubMed

Ferroussier, O; Dlodlo, R A; Capo-Chichi, D; Boillot, F; Gninafon, M; Trébucq, A; Fujiwara, P I

2013-11-01

Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin. The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities. The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression.

PubMed

Coppola, Mariateresa; Arroyo, Leonar; van Meijgaarden, Krista E; Franken, Kees Lmc; Geluk, Annemieke; Barrera, Luis F; Ottenhoff, Tom H M

2017-09-01

Tuberculosis (TB) occurs in only 3-10% of Mycobacterium tuberculosis (Mtb) infected individuals, suggesting that natural immunity can contain Mtb infection, although this remains poorly understood. Next to T-cells, a potentially protective role for B-cells and antibodies has emerged recently. However, the Mtb antigens involved remain ill-defined. Here, we investigated in a TB-endemic setting IgG levels against 15 Mtb antigens, representing various phases of Mtb infection and known to be potent human T-cell antigens. IgG levels against ESAT6/CFP10, Rv0440, Rv0867c, Rv1737c, Rv2029c, Rv2215, Rv2389c, Rv3616c and Mtb purified protein derivative (PPD) were higher in TB patients than in endemic and non-endemic controls. The only exception was Rv1733c that was preferentially recognized by antibodies from endemic controls compared to TB patients and non-endemic controls, suggesting a potential correlation with control of TB infection and progression. In patients, IgG levels against Ag85B and Rv2029c correlated with Mtb loads, while immunoglobulins against Rv0440 differed between genders. Our results support the potential role of certain Mtb antigen-(Rv1733c) specific antibodies in the control of TB infection and progression, while other Mtb antigen-specific antibodies correlate with TB disease activity and bacillary loads. The findings for Rv1733c agree with previous T-cell results and have implications for including antibody-mediated immunity in designing new strategies to control TB. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessments of serum copper and zinc concentration, and the Cu/Zn ratio determination in patients with multidrug resistant pulmonary tuberculosis (MDR-TB) in Côte d'Ivoire.

PubMed

Bahi, Gnogbo Alexis; Boyvin, Lydie; Méité, Souleymane; M'Boh, Gervais Melaine; Yeo, Kadjowely; N'Guessan, Kouassi Raymond; Bidié, Alain Dit Philippe; Djaman, Allico Joseph

2017-04-11

In Côte d'Ivoire, multidrug-resistant tuberculosis (MDR-TB) is a serious public health problem with a prevalence estimated at 2.5% in 2006. Zinc and copper are essential Trace element needed to strengthen the immune system and also useful in the fight against tuberculosis. The Cu / Zn ratio is a good indicator of oxidative stress. The principal aim of this study was to evaluate the serum concentration of some trace element and determine the Cu / Zn ratio in patients with multidrug resistant pulmonary tuberculosis (MDR-TB) before and after second line treatment of TB. Blood samples were obtained from 100 MDR-TB patients after confirmation of their status through the microscopic and molecular diagnosis of resistance to Isoniazid and Rifampicin by GeneXpert. The concentration level of zinc and copper were determined using flame air / acetylene atomic absorption spectrometer (AAS) Type Varian Spectr AA-20 Victoria, Australlia. A significant decrease in zinc levels (P < 0.05) and an increased Cu / Zn ratio (P < 0.05) was observed in MDR-TB patients compared to controls TB free. During treatment a significant reduction in Cu / Zn ratio (P < 0.05) was observed compared to the initial result. The decrease in serum zinc level and the high Cu / Zn ratio could explain the immune system dysfunction and the high level of oxidative stress in patients with MDR-TB. Therefore the evaluation of the zinc and copper status could represent essential parameters in monitoring of TB second line treatment for better treatment management.

Activity of phosphino palladium(II) and platinum(II) complexes against HIV-1 and Mycobacterium tuberculosis.

PubMed

Gama, Ntombenhle H; Elkhadir, Afag Y F; Gordhan, Bhavna G; Kana, Bavesh D; Darkwa, James; Meyer, Debra

2016-08-01

Treatment of human immunodeficiency virus (HIV) is currently complicated by increased prevalence of co-infection with Mycobacterium tuberculosis. The development of drug candidates that offer the simultaneous management of HIV and tuberculosis (TB) would be of great benefit in the holistic treatment of HIV/AIDS, especially in sub-Saharan Africa which has the highest global prevalence of HIV-TB coinfection. Bis(diphenylphosphino)-2-pyridylpalladium(II) chloride (1), bis(diphenylphosphino)-2-pyridylplatinum(II) chloride (2), bis(diphenylphosphino)-2-ethylpyridylpalladium(II) chloride (3) and bis(diphenylphosphino)-2-ethylpyridylplatinum(II) (4) were investigated for the inhibition of HIV-1 through interactions with the viral protease. The complexes were subsequently assessed for biological potency against Mycobacterium tuberculosis H37Rv by determining the minimal inhibitory concentration (MIC) using broth microdilution. Complex (3) showed the most significant and competitive inhibition of HIV-1 protease (p = 0.014 at 100 µM). Further studies on its in vitro effects on whole virus showed reduced viral infectivity by over 80 % at 63 µM (p < 0.05). In addition, the complex inhibited the growth of Mycobacterium tuberculosis at an MIC of 5 µM and was non-toxic to host cells at all active concentrations (assessed by tetrazolium dye and real time cell electronic sensing). In vitro evidence is provided here for the possibility of utilizing a single metal-based compound for the treatment of HIV/AIDS and TB.

Within-Subject Interlaboratory Variability of QuantiFERON-TB Gold In-Tube Tests

DTIC Science & Technology

2012-09-06

QuantiFERONH-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection...viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test...release assays (IGRAs) are designed to detect both latent Mycobacterium tuberculosis infection (LTBI) and infections manifesting as active

Development of Diazaquinomycin Class Antibiotics for the Treatment of Drug-Resistant TB Infections

DTIC Science & Technology

2016-10-01

exhibited weak antibacterial activity by targeting thymidylate synthase, though no reports of their anti-TB activity existed and our studies have suggested...Murphy, B. T. Diaza-anthracene antibiotics from a freshwater-derived actinomycete with selective antibacterial activity toward M. tuberculosis. ACS Inf...freshwater-derived actinomycete with selective antibacterial activity toward M. tuberculosis. ACS Infectious Diseases, 2015. 1: p. 168-174. (17) Mullowney

Development and psychometric testing of the Knowledge, Attitudes and Practices (KAP) questionnaire among student Tuberculosis (TB) Patients (STBP-KAPQ) in China.

PubMed

Fan, Yahui; Zhang, Shaoru; Li, Yan; Li, Yuelu; Zhang, Tianhua; Liu, Weiping; Jiang, Hualin

2018-05-08

TB outbreaking in schools is extremely complex, and presents a major challenge for public health. Understanding the knowledge, attitudes and practices among student TB patients in such settings is fundamental when it comes to decreasing future TB cases. The objective of this study was to develop a Knowledge, Attitudes and Practices Questionnaire among Student Tuberculosis Patients (STBP-KAPQ), and evaluate its psychometric properties. This study was conducted in three stages: item construction, pilot testing in 10 student TB patients and psychometric testing, including reliability and validity. The item pool for the questionnaire was compiled from literature review and early individual interviews. The questionnaire items were evaluated by the Delphi method based on 12 experts. Reliability and validity were assessed using student TB patients (n = 416) and healthy students (n = 208). Reliability was examined with internal consistency reliability and test-retest reliability. Content validity was calculated by content validity index (CVI); Construct validity was examined using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA); The Public Tuberculosis Knowledge, Attitudes and Practices Questionnaire (PTB-KAPQ) was applied to evaluate criterion validity; As concerning discriminant validity, T-test was performed. The final STBP-KAPQ consisted of three dimensions and 25 items. Cronbach's α coefficient and intraclass correlation coefficient (ICC) was 0.817 and 0.765, respectively. Content validity index (CVI) was 0.962. Seven common factors were extracted by principal factor analysis and varimax rotation, with a cumulative contribution of 66.253%. The resulting CFA model of the STBP-KAPQ exhibited an appropriate model fit (χ2/df = 1.74, RMSEA = 0.082, CFI = 0.923, NNFI = 0.962). STBP-KAPQ and PTB-KAPQ had a strong correlation in the knowledge part, and the correlation coefficient was 0.606 (p < 0.05). Discriminant

Performance assessment of the Capilia TB assay and the BD ProbeTec ET system for rapid culture confirmation of Mycobacterium tuberculosis.

PubMed

Wang, Jann-Yuan; Lee, Li-Na; Lai, Hsin-Chih; Hsu, Hsiao-Leng; Jan, I-Shiow; Yu, Chong-Jen; Hsueh, Po-Ren; Yang, Pan-Chyr

2007-12-01

Because of the increasing numbers of nontuberculous mycobacterial isolates from clinical specimens, rapid and accurate methods for culture confirmation of Mycobacterium tuberculosis are urgently needed. The study evaluated the performance of the Capilia TB immunochromatographic assay (TAUNS, Numazu, Japan) for culture confirmation of M. tuberculosis using 242 culture-positive liquid media in 2 mycobacterial laboratories from November 2005 to February 2006. Among the 242 samples, 183 were also tested with the BD ProbeTec ET (CTB) assay (Becton Dickinson, Sparks, MD). The results of both assays were compared to the culture results and to each other. The overall sensitivity and specificity of the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 97.3% and 97.1%, respectively. The positive and negative predictive values for the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 98.2% and 95.8%, respectively. Among the 183 samples tested with both assays, 8 had discrepant results, including Capilia-TB-false-positive in 2, CTB-false-positive in another 2, CTB-false-negative in 2, Capilia TB-false-negative in 1, and both assays with false-negative results in the remaining one. This study demonstrated that the Capilia TB assay has a similar diagnostic value with the CTB assay. In addition, with the immunochromatographic method, it is less time-consuming and does not require other laboratory equipment.

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

PubMed

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

2018-02-26

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

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

PubMed Central

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

2018-01-01

BACKGROUND: Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. METHODS: We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. RESULTS: Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18–64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. INTERPRETATION: These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized. PMID:29483329

Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients: A Matched-Cohort Study.

PubMed

Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi

2017-11-01

Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p < 0.001]. Their major TB-AEs were fever (19%), rash (11%), and neutropenia (11%). TB-AEs were more severe in cases [Grade 3 or higher: cases (71%, 34/48) vs. controls (49%, 19/39), p < 0.001]. The time from treatment initiation to TB-AE was shorter in cases [median 18 (interquartile range 12-28) vs. 27 (15-57) days, p = 0.027], and 73% of TB-AEs in cases occurred within 4 weeks of starting anti-tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.

The strategic framework of tuberculosis control and prevention in the elderly: a scoping review towards End TB targets.

PubMed

Li, Jun; Chung, Pui-Hong; Leung, Cyrus L K; Nishikiori, Nobuyuki; Chan, Emily Y Y; Yeoh, Eng-Kiong

2017-06-01

With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included.Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets.TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and

Screening for tuberculosis upon admission to shelters and free-meal services.

PubMed

Solsona, J; Caylà, J A; Nadal, J; Bedia, M; Mata, C; Brau, J; Maldonado, J; Milà, C; Alcaide, J; Altet, N; Galdós-Tangüis, H

2001-01-01

The homeless are at very high risk of suffering tuberculosis (TB). The aims of this study were to determine the prevalence and risk factors for tuberculosis infection and disease among the homeless in Barcelona and to evaluate the roles of case finding and contact investigation. Observational prevalence study carried out between 1997 and 1998. 447 homeless patients (394 men and 53 women) were evaluated before admission to shelters and free-meal services. At the same time, 48 co-residents with smear-positive TB patients in 2 long-term shelters were evaluated too. A chest X-ray and Tuberculin Skin Test were performed on all subjects. Sputum smears were processed by the Ziehl-Neelsen and Löwenstein-Jensen procedures in patients with radiographic findings consistent with pulmonary TB. Of the 447 homeless examined, 335 (75%) were infected with Mycobacterium tuberculosis. Active pulmonary TB was diagnosed in five persons (1.11%), and 62 (13.8%) had radiographic evidence of inactive pulmonary TB. Tuberculosis infection was associated with age and smoking, but not with sex or alcohol abuse. No significant differences in infection rates were found between the main group and 48 homeless co-residents of smear-positive subjects. Only 16.9% of the homeless with active TB in Barcelona in the same period were diagnosed through active case-finding, the remainder being mainly detected in hospitals (69.8%) and other several centres (13.3%). Homeless individuals have a very high risk of TB infection and disease and contact investigation requires specific methods for them. Programmes of screening and supervised treatment should be ensured in this group.

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

PubMed Central

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L. C. M.; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M. Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H. M.; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates. PMID:25339944

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis.

PubMed

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L C M; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H M; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

Invariant NKT cells from HIV-1 or Mycobacterium tuberculosis-infected patients express an activated phenotype.

PubMed

Montoya, Carlos J; Cataño, Juan C; Ramirez, Zoraida; Rugeles, Maria T; Wilson, S Brian; Landay, Alan L

2008-04-01

The frequency, subsets and activation status of peripheral blood invariant NKT (iNKT) cells were evaluated in pulmonary tuberculosis (TB) patients and in chronically HIV-1-infected subjects. The absolute numbers of iNKT cells were significantly decreased in TB patients and in HIV-1+ individuals who were antiretroviral therapy naive or had detectable viremia despite receiving HAART. iNKT cell subset analysis demonstrated a decreased percentage of CD4(+) iNKT cells in HIV-1+ subjects, and a decreased percentage of double negative iNKT cells in TB patients. Peripheral blood iNKT cells from HIV-1+ and TB patients had significantly increased expression of CD69, CD38, HLA-DR, CD16, CD56, and CD62L. The expression of CD25 was significantly increased only on iNKT cells from TB patients. These findings indicate that peripheral blood iNKT cells in these two chronic infections show an up-regulated expression of activation markers, suggesting their role in the immune response to infection.

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

Gamma delta T cell responses associated with the development of tuberculosis in health care workers.

PubMed

Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

2005-03-01

This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB.

Drug resistance characteristics of Mycobacterium tuberculosis isolates to four first-line antituberculous drugs from tuberculosis patients with AIDS in Beijing, China.

PubMed

Gao, Gui-ju; Lian, Lulu; Sun, Yue; Wei, Jianhao; Xiao, Jiang; Wang, Xiaoying; Zhang, Ling; Zhao, Xiuqin; Yang, Di; Zhao, Hong-xin; Zhao, Hui; Wang, Hui-zhu; Wan, Kang-lin; Li, Xing-wang

2015-02-01

The objective of this study was to investigate the drug resistance characteristics of Mycobacterium tuberculosis isolates to four first-line antituberculous drugs (ATDs) from tuberculosis (TB) patients with AIDS in Beijing, China. All M. tuberculosis strains were isolated from specimens from TB patients with AIDS hospitalised between April 2010 and October 2012. Isolates were cultured by mycobacterial culture methods and were identified by multilocus PCR. Drug sensitivity testing was performed by the proportion method with the following first-line ATDs: isoniazid; rifampicin; streptomycin; and ethambutol. Results were compared with the drug resistance status of M. tuberculosis strains isolated from TB patients without HIV infection in Beijing. Among 41 M. tuberculosis isolates from TB patients with AIDS, the rates of total drug resistance (58.5%), initial drug resistance (46.7%) and acquired drug resistance (90.9%) were significantly higher than in TB patients without HIV infection (34.1%, 24.5% and 48.5%, respectively; P<0.05). In TB patients with AIDS, the rates of acquired drug resistance (90.9%) and acquired multidrug-resistant TB (MDR-TB) (54.5%) were significantly higher than the rates of initial drug resistance (46.7%) and initial MDR-TB (10.0%) (P<0.05). In patients with TB without HIV infection, the rate of acquired drug resistance (48.5%) was significantly higher than the rate of initial drug resistance (24.5%) (P<0.05). M. tuberculosis drug resistance in TB patients with AIDS is significantly more serious than in TB patients without HIV infection. These results showed that more attention should be paid to M. tuberculosis drug resistance in AIDS patients. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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

PubMed

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

2018-05-01

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

Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs.

PubMed

Luetkemeyer, Anne F; Kendall, Michelle A; Nyirenda, Mulinda; Wu, Xingye; Ive, Prudence; Benson, Constance A; Andersen, Janet W; Swindells, Susan; Sanne, Ian M; Havlir, Diane V; Kumwenda, Johnstone

2014-04-01

Earlier initiation of antiretroviral therapy (ART) in HIV-tuberculosis (TB) is associated with increased immune reconstitution inflammatory syndrome (IRIS). The severity, frequency, and complications of TB IRIS were evaluated in A5221, a randomized trial of earlier ART (within 2 weeks after TB treatment initiation) vs. later ART (8-12 weeks after TB treatment) in HIV-infected patients starting TB treatment. In 806 participants, TB IRIS was defined using published clinical criteria. Cases were classified as severe (hospitalization/death), moderate (corticosteroid use/invasive procedure), or mild (no hospitalization/procedures/steroids). Fisher exact, Wilcoxon, and log-rank tests were used for comparisons. TB IRIS occurred in 61 (7.6%) patients: 10.4% in earlier vs. 4.7% in later ART, 11.5% with CD4 <50 vs. 5.4% with CD4 ≥50 cells per cubic millimeter. The CD4/ART arm interaction was significant, P = 0.014, with 44.3% of TB IRIS occurring with CD4 <50 and earlier ART. TB IRIS occurred sooner with earlier vs. later ART initiation, at a median of 29 vs. 82 days after TB treatment initiation (P < 0.001). IRIS manifestations included lymphadenopathy (59.0%), constitutional symptoms (54.1%), and radiographic changes (41.0%); central nervous system TB IRIS was uncommon (6.6%). TB IRIS was mild in 27.9%, moderate in 41.0%, and severe in 31.1%. No TB IRIS-associated deaths occurred. IRIS management required ≥1 invasive procedures in 34.4%, hospitalization in 31.1%, and corticosteroids in 54.1%. TB IRIS was more frequent with earlier ART initiation and CD4 <50 cells per cubic millimeter. As ART is implemented earlier in HIV-TB coinfection, programs will require the diagnostic capabilities, clinical resources, and training necessary to manage TB IRIS.

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.

Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV Patients with Culture Confirmed Pulmonary Tuberculosis in India and the Potential Role of IL-6 in Prediction

PubMed Central

Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya

2013-01-01

Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062

Detection of Mycobacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS.

PubMed

Kruh-Garcia, Nicole A; Wolfe, Lisa M; Chaisson, Lelia H; Worodria, William O; Nahid, Payam; Schorey, Jeff S; Davis, J Lucian; Dobos, Karen M

2014-01-01

The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states.

Detection of Mycobacterium tuberculosis Peptides in the Exosomes of Patients with Active and Latent M. tuberculosis Infection Using MRM-MS

PubMed Central

Kruh-Garcia, Nicole A.; Wolfe, Lisa M.; Chaisson, Lelia H.; Worodria, William O.; Nahid, Payam; Schorey, Jeff S.; Davis, J. Lucian; Dobos, Karen M.

2014-01-01

The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states. PMID:25080351

Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study.

PubMed

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

2013-04-26

Despite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs. A cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART. The majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use. A comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV

Drug discovery in tuberculosis. New drug targets and antimycobacterial agents.

PubMed

Campaniço, André; Moreira, Rui; Lopes, Francisca

2018-04-25

Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy. However, despite success in identifying active compounds through phenotypic screens, the conversion of hits into novel chemical series and ultimately into clinical candidates is hampered by the poor efficacy in eliminating M. tuberculosis within different host compartments, including macrophages, as well as a lack of knowledge about the specific target(s) inhibited and/or upregulated. The current status of anti-TB lead generation has much improved over the last decade, as exemplified by the recent approval of bedaquiline and delamanid to treat MDR-TB and XDR-TB. This review provides a critical analysis on the strategies used to progress hit compounds into viable lead candidates, and how emerging targets may play a role in TB drug discovery in the near future. Four new relevant targets are addressed: the enoyl-acyl carrier protein reductase, InhA; the transmembrane transport protein large, MmpL3; the decaprenylphospho-beta-d-ribofuranose 2-oxidase, DprE1; and the ubiquinol-cytochrome C reductase, QcrB. Validated hit compounds for each target are presented and explored, and the medicinal chemistry strategies to expand SAR around novel chemotypes analyzed. In addition, very recent emerging targets are also discussed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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.

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

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

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

PubMed

McLaren, Zoë M; Schnippel, Kathryn; Sharp, Alana

2016-01-01

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. 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. 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-income households (β1 = -0

Influence of diabetes mellitus on immunity to human tuberculosis.

PubMed

Kumar Nathella, Pavan; Babu, Subash

2017-09-01

Type 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease. © 2017 John Wiley & Sons Ltd.

Mycothiol acetyltransferase (Rv0819) of Mycobacterium tuberculosis is a potential biomarker for direct diagnosis of tuberculosis using patient serum specimens.

PubMed

Zeitoun, H; Bahey-El-Din, M; Kassem, M A; Aboushleib, H M

2017-12-01

Mycobacterium tuberculosis infection constitutes a global threat that results in significant morbidity and mortality worldwide. Efficient and early diagnosis of tuberculosis (TB) is of paramount importance for successful treatment. The aim of the current study is to investigate the mycobacterial mycothiol acetyltransferase Rv0819 as a potential novel biomarker for the diagnosis of active TB infection. The gene encoding Rv0819 was cloned and successfully expressed in Escherichia coli. The recombinant Rv0819 was purified using metal affinity chromatography and was used to raise murine polyclonal antibodies against Rv0819. The raised antibodies were employed for direct detection of Rv0819 in patient serum samples using dot blot assay and competitive enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 68 confirmed new TB patients and 35 healthy volunteers as negative controls. The dot blot assay showed sensitivity of 64·7% and specificity of 100%, whereas the competitive ELISA assay showed lower sensitivity (54·4%) and specificity (88·57%). The overall sensitivity of the combined results of the two tests was found to be 89·7%. Overall, the mycobacterial Rv0819 is a potential TB serum biomarker that can be exploited, in combination with other TB biomarkers, for efficient and reliable diagnosis of active TB infection. The early and accurate diagnosis of tuberculosis infection is of paramount importance for initiating treatment and avoiding clinical complications. Most current diagnostic tests have poor sensitivity and/or specificity and in many cases they are too expensive for routine diagnostic testing in resource-limited settings. In the current study, we examined a novel mycobacterial serum biomarker, namely mycothiol acetyltransferase Rv0819. The antigen was detectable in serum specimens of a significant number of tuberculosis patients. This article proves the importance of Rv0819 and paves the way towards its future use as a useful

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. Copyright © 2014. Published by Elsevier Ltd.

Vitamin D and activated vitamin D in tuberculosis in equatorial Malaysia: a prospective clinical study.

PubMed

Ralph, Anna P; Rashid Ali, Muhammad Redzwan S; William, Timothy; Piera, Kim; Parameswaran, Uma; Bird, Elspeth; Wilkes, Christopher S; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M

2017-04-27

Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D] concentration) is often reported in tuberculosis. Adjunctive vitamin D has been tested for its potential to improve treatment outcomes, but has proven largely ineffective. To better understand vitamin D in tuberculosis, we investigated determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D (1,25D), their inter-relationship in tuberculosis, longitudinal changes and association with outcome. In a prospective observational study of adults with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial 25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome. Healthy control subjects were enrolled for comparison. 1,25D was elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p < 0.001), directly proportional to radiological severity (p < 0.001), and fell rapidly within one week of treatment commencement. Tuberculosis patients with higher baseline 1,25D achieved significantly higher percentage weight gain over time, including when controlling for baseline weight, however persistently elevated 1,25D was associated with worse residual x-ray changes and lower end-of-treatment BMI. 1,25D was inversely associated with PTH (p < 0.001), consistent with the extra-renal origin of the 1,25D. 25D did not differ between tuberculosis patients (mean 63.9 nmol/L, 95% CI: 60.6 - 67.3) and controls (61.3, 57.2- 65.3, p = 0.24), and was unassociated with outcomes. Among tuberculosis patients in multivariable analyses, sex, age and VDBP were associated with 25D, and age and albumin with 1,25D. 1,25-dihydroxyvitamin was not significantly asscociated with 25D. Vitamin D deficiency <25 nmol/L was uncommon, occurring in only five TB patients; 1,25D was elevated in three of them. In an

In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis

PubMed Central

Gautam, Uma S.; Foreman, Taylor W.; Bucsan, Allison N.; Veatch, Ashley V.; Alvarez, Xavier; Adekambi, Toidi; Golden, Nadia A.; Gentry, Kaylee M.; Doyle-Meyers, Lara A.; Didier, Peter J.; Blanchard, James L.; Kousoulas, K. Gus; Lackner, Andrew A.; Kalman, Daniel; Rengarajan, Jyothi; Khader, Shabaana A.; Kaushal, Deepak

2018-01-01

Mycobacterium tuberculosis continues to cause devastating levels of mortality due to tuberculosis (TB). The failure to control TB stems from an incomplete understanding of the highly specialized strategies that M. tuberculosis utilizes to modulate host immunity and thereby persist in host lungs. Here, we show that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing, reduced checkpoint signaling, and the relocation of effector T cells to the center of the granulomata. The enhanced killing of M. tuberculosis in macrophages in vivo by CD4+ T cells was also replicated in vitro, in cocultures of macaque macrophages and CD4+ T cells. Collectively, these results suggest that there exists a potential for using IDO inhibition as an effective and clinically relevant host-directed therapy for TB. PMID:29255022

Structural and functional characterization of Mycobacterium tuberculosis triosephosphate isomerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connor, Sean E.; Capodagli, Glenn C.; Deaton, Michelle K.

Tuberculosis (TB) is a major infectious disease that accounts for over 1.7 million deaths every year. Mycobacterium tuberculosis, the causative agent of tuberculosis, enters the human host by the inhalation of infectious aerosols. Additionally, one third of the world's population is likely to be infected with latent TB. The incidence of TB is on the rise owing in part to the emergence of multidrug-resistant strains. As a result, there is a growing need to focus on novel M. tuberculosis enzyme targets. M. tuberculosis triosephosphate isomerase (MtTPI) is an essential enzyme for gluconeogenetic pathways, making it a potential target for futuremore » therapeutics. In order to determine its structure, the X-ray crystal structure of MtTPI has been determined, as well as that of MtTPI bound with a reaction-intermediate analog. As a result, two forms of the active site were revealed. In conjunction with the kinetic parameters obtained for the MtTPI-facilitated conversion of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde-3-phosphate (D-GAP), this provides a greater structural and biochemical understanding of this enzyme. Additionally, isothermal titration calorimetry was used to determine the binding constant for a reaction-intermediate analog bound to the active site of MtTPI.« less

Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

PubMed Central

López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

2010-01-01

Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

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...

Bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

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

Colostrum proinflammatory cytokines as biomarkers of bovine immune response to bovine tuberculosis (bTB).

PubMed

Sánchez-Soto, Eduardo; Ponce-Ramos, Rosa; Hernández-Gutiérrez, Rodolfo; Gutiérrez-Ortega, Abel; Álvarez, Angel H; Martínez-Velázquez, Moisés; Absalón, Angel E; Ortiz-Lazareno, Pablo; Limón-Flores, Alberto; Estrada-Chávez, Ciro; Herrera-Rodríguez, Sara E

2017-02-01

Bovine colostrum contains compounds, which provide passive immune protection from mother to newborn calves. Little is known about cytokine levels and their role in bovine colostrum. Moreover, the capacity of bovine colostrum cells to mount specific immune responses after natural exposure to bovine tuberculosis (bTB) antigens in dairy herds has not been studied, thus far. The purpose of this study was to identify biomarkers for bTB infection measurable in bovine colostrum. The present study reveals that isolated-immune colostrum cells can mount a specific immune response against bTB antigens, by measuring the novo IFN-γ release in cell culture. We found that IFN-γ levels in the responders (Bov + ) to bTB antigen were higher than in non-responders (Bov - ). On the other hand, proinflammatory cytokines contained in colostrum's whey were tested in Tuberculin Skin Test (TST) reactor (TST + ) and non-reactor (TST - ) animals to assess their potential role as biomarker. We observed that IFN-γ levels were lower or undetectable, as opposed to IL4 levels were measurable, the TNF-α level was higher in TST - than TST + , while IL-6 levels showed the opposite reaction and with no statistical significance. Moreover, IL-1α mRNA expression levels were higher in colostrum mononuclear cells (CMC) in Bov + cattle. Collectively, these data suggest that the differential expression of pro and anti-inflammatory cytokines could have relevant value to diagnose bTB in cattle. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

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

Influence of age and nutritional status on the performance of the tuberculin skin test and QuantiFERON-TB gold in-tube in young children evaluated for tuberculosis in Southern India.

PubMed

Jenum, Synne; Selvam, Sumithra; Mahelai, Diana; Jesuraj, Nelson; Cárdenas, Vicky; Kenneth, John; Hesseling, Anneke C; Doherty, Timothy Mark; Vaz, Mario; Grewal, Harleen M S

2014-10-01

Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFNγ-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis' IFNγ-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children <2 years were more likely to test QFT indeterminate. A height-for-age Z score within the lowest quartile increased the odds ratio (OR) for a positive or indeterminate QFT result [OR 2.46 (1.19-5.06), OR 3.08 (1.10-8.58)], whereas the OR for a positive TST was reduced with a weight-for-height Z score within the lowest quartile [OR 0.17 (0.06-0.47)]. The sensitivities of the TST and QFT for clinical TB in children <3 years of age were equally poor in this population. Stunted children were more susceptible to Mycobacterium tuberculosis infection and more prone to indeterminate QFT results. TST was less reliable in children with wasting.

Mini epidemic of isoniazide resistant TB in rural TN: a need for supervised preventive therapy.

PubMed

Mehta, Jay; Keith, Rob; Al Hasan, Muhannad; Ryland, Byrd; Roy, Thomas

2009-08-01

With the resurgence of tuberculosis (TB) in the late 1980s, multi-drug-resistant TB (MDR-TB) also became a serious challenge to the TB control programs across the United States (US). While the incidence of TB resumed a downward trend in the mid 1900s, drug-resistant TB continues to be a national and international problem. We reviewed the public health data of drug-resistant TB cases (1996-2002) in Greene County, TN, with a detailed analysis of their contact investigation. Our study included demographic data of age, sex, race, human immunodeficiency virus (HIV) status and other known risk factors for drug-resistant TB. Contact investigation of two patients with isoniazide-resistant active pulmonary TB led to the discovery of two additional cases of active pulmonary tuberculosis, one of them being a 14-month-old child. All four of the patients were U.S. born, had negative HIV tests, and lacked other risk factors for drug-resistant TB. In all four cases, the Mycobacterium tuberculosis isolates were resistant to isoniazide, three were streptomycin resistant, and was ethambutol resistant. A total of 65 close contacts were identified, 11 of whom had a positive purified protein derivative (PPD) skin test indicating latent TB infection. Based on the American Thoracic Society's recommendations, the contacts with a positive PPD were prescribed rifampin for chemo-prevention rather than INH. However, one active case was detected from this infected contact who had failed to comply with chemo-preventive therapy. The second active case was a child who developed active pulmonary TB before chemoprevention could be initiated. Drug culture profile and DNA analysis (RFLP) confirmed the same source for TB transmission. The 11/65 (16.5 percent) infection rate among the contact was comparable to the state average (p < 0.05), but the case rate of 4/65 (6.15 percent) was high. In two out of four active cases, who were family members of the known cases, active infection could have been

Illness perception of tuberculosis (TB) and health seeking practice among urban slum residents of Bangladesh: a qualitative study.

PubMed

Bam, Kiran; Bhatt, Lokesh Prasad; Thapa, Rajshree; Dossajee, Hussein Karimjee; Angdembe, Mirak Raj

2014-08-27

Combating tuberculosis (TB) in urban slums is more complex than in rural areas due to reasons such as over-crowding, unhygienic living conditions and poverty. This study aimed to assess illness perception of TB and identify barriers and facilitators for health seeking practice among the residents of Badda slum, Dhaka, Bangladesh. The Badda slum was purposively selected. Convenience sampling was carried out to select participants aged 18 years and above. Twenty two in-depth interviews, two key informants' interviews and participatory rapid appraisal (PRA) were conducted. Data were analyzed manually by using defined a priori codes and color coding of the quotes in data matrix table. TB was commonly recognized as Jokkha (pulmonary TB), Sas rog (disease associated to breathing) followed by TB. More females than males had knowledge about TB related illness. Very few perceived of being at risk of TB despite the high risk behavior and environment. Prime barriers for health seeking practice of TB were cost along with other barriers like prevailing stigma on TB, lack of information on service sites and unavailability of accompanying person. Training and orientation to community organizations and people, awareness on TB and free treatment through advertisements/media, community level diagnostic and home based care were identified as the facilitators for the health seeking practice of TB. Perceptions of TB and knowledge associated with the disease shape the health seeking practice, therefore promotion of media awareness campaign, targeting the people of urban slums for reducing misconceptions and promotion of home based service is needed to encourage health seeking practice in the future.

Plants in our combating strategies against Mycobacterium tuberculosis: progress made and obstacles met.

PubMed

Gupta, Vivek Kumar; Kumar, M Madhan; Bisht, Deepa; Kaushik, Anupam

2017-12-01

Traditionally used plants for treating chest-related problems/tuberculosis (TB) have not been evaluated in detail and hence a thorough study is needed in this regard. This knowledge may find application in developing new anti-TB drugs. This article elaborates on studying the activity of medicinal plants against different forms of Mycobacterium tuberculosis (Mtb) using different model strains, in vitro and ex vivo assays for studying the tuberculocidal activity and discusses the results from different studies on the activity against different forms of Mtb and human immunodeficiency virus-tuberculosis (HIV-TB) co-infection. Scientific databases such as PubMed, Elsevier, Scopus, Google scholar, were used to retrieve the information from 86 research articles (published from 1994 to 2016) related to the topic of this review. Twenty-three plant species have been reported to possess active molecules against multi-drug resistant (MDR) isolates of Mtb. Seven plants were found to be active against intracellular Mtb and six against dormant bacilli. Seven plants were synergistically effective when combined with anti-TB drugs. Six studies suggest that the beneficial effects of plant extracts are due to their wide array of immuno-modulatory effects manifested by the higher expression of cytokines. Some studies have also shown the dual activity (anti-HIV and anti-TB) of plants. We emphasize on identifying plants based on traditional uses and testing their extracts/phytomolecules against MDR strains, intracellular Mtb as well as against dormant Mtb. This will help in future to shorten the current therapeutic regimens for TB and also for treating HIV-TB co-infection.

Accelerating TB notification from the private health sector in Delhi, India.

PubMed

Kundu, Debashish; Chopra, Kamal; Khanna, Ashwani; Babbar, Neeti; Padmini, T J

2016-01-01

In India, almost half of all patients with tuberculosis (TB) seek care in the private sector as the first point of care. The national programme is unable to support such TB patients and facilitate effective treatment, as there is no information on TB and Multi or Extensively Drug Resistant TB (M/XDR-TB) diagnosis and treatment in private sector. To improve this situation, Government of India declared TB a notifiable disease for establishing TB surveillance system, to extend supportive mechanism for TB treatment adherence and standardised practices in the private sector. But TB notification from the private sector is a challenge and still a lot needs to be done to accelerate TB notification. Delhi State TB Control Programme had taken initiatives for improving notification of TB cases from the private sector in 2014. Key steps taken were to constitute a state level TB notification committee to oversee the progress of TB notification efforts in the state and direct 'one to one' sensitisation of private practitioners (PPs) (in single PP's clinic, corporate hospitals and laboratories) by the state notification teams with the help of available tools for sensitising the PP on TB notification - TB Notification Government Order, Guidance Tool for TB Notification and Standards of TB Care in India. As a result of focussed state level interventions, without much external support, there was an accelerated notification of TB cases from the private sector. TB notification cases from the private sector rose from 341 (in 2013) to 4049 (by the end of March 2015). Active state level initiatives have led to increase in TB case notification. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

The Twin Epidemics of Tuberculosis and HIV.

PubMed

Varghese, George M; Janardhanan, Jeshina; Ralph, Ravikar; Abraham, Ooriapadickal C

2013-02-01

The deadly combination of tuberculosis (TB) and human immunodeficiency virus (HIV) currently ravaging the world, taking a toll of about 0.35 million people every year, is one of the major public health crises of the decade. Throughout the course of HIV infection, the risk of acquisition, reactivation, and reinfection of TB keeps increasing substantially as the immune deficiency progresses. TB coinfected patients inadvertently facilitate HIV infection by release of the proinflammatory cytokines and overexpression of coreceptors CXCR4 and CCR5; thereby, the progression of each is facilitated. The difficulties in diagnosing active tuberculosis in HIV-infected individuals poses a great challenge that is further complicated by the challenges in identification of latent TB infection, creating a setback to preventive therapy. Furthermore, prescribing antituberculous therapy and antiretroviral therapy together poses several management challenges, including drug interactions, added toxicities, and TB immune reconstitution inflammatory syndrome. The current approach to diagnosis, prevention, and treatment strategies in TB and HIV coinfected individuals, along with epidemiology and overview of pathogenetic interplay of both microbes, is reviewed here.

Better care provided to patients with tuberculosis at county designated TB hospitals (CTD) compared to non-CTDs in rural China.

PubMed

Yuan, Li; Zhang, Hui; Zhou, Changming; Jiang, Weili; Zhao, Qi; Biao, Xu

2017-01-13

The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants. A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces. All registered re-treated TB patients were investigated using a structured questionnaire covering information on demographics, socio-economic characteristics, and previous anti-TB treatment experiences. Totally, 75.3% of 544 patients visited CTD directly for initial treatment. Patients who were female (OR:1.71, 95% CI: 1.01-2.87), over 40 years of age (OR:2.80, 95% CI: 1.24-6.33), from Jiangsu (OR:3.07, 95% CI: 1.57-6.01) and Sichuan (OR:4.47, 95% CI: 2.29-8.73) and those diagnosed before 2005 (OR:6.87, 95% CI: 4.24-11.13) had a significant higher risk receiving their initial treatment at a non-CTD. Patients were more likely to have standardized diagnosis and treatment regimens in CTD (89.8%) than in non-CTDs (65.9%). Patients treated in non-CTDs versus in CTD had a lower possibility to complete their treatment course during first TB episode (χ 2  = 3.926, P = 0.048), but there was no significant difference in the cure rate between different facilities (CTD 60.8%, Non-CTDs 59.1%). Patients in non-CTDs incurred higher costs (1,360 CNY) than those treated in CTD (920CNY). CTD play a key role in the National Tuberculosis Control Program. Patients should be guided to seek health care in county designated hospital, where they are more likely to receive appropriate examinations, treatment regimens and rigorous supervision, and to bear a lighter economic burden.

Incidence of tuberculosis among school-going adolescents in South India.

PubMed

Uppada, Dharma Rao; Selvam, Sumithra; Jesuraj, Nelson; Lau, Esther L; Doherty, T Mark; Grewal, Harleen M S; Vaz, Mario; Lindtjørn, Bernt

2016-07-26

Tuberculosis (TB) incidence data in vaccine target populations, particularly adolescents, are important for designing and powering vaccine clinical trials. Little is known about the incidence of tuberculosis among adolescents in India. The objective of current study is to estimate the incidence of pulmonary tuberculosis (PTB) disease among adolescents attending school in South India using two different surveillance methods (active and passive) and to compare the incidence between the two groups. The study was a prospective cohort study with a 2-year follow-up period. The study was conducted in Palamaner, Chittoor District of Andhra Pradesh, South India from February 2007 to July 2010. A random sampling procedure was used to select a subset of schools to enable approximately 8000 subjects to be available for randomization in the study. A stratified randomization procedure was used to assign the selected schools to either active or passive surveillance. Participants who met the criteria for being exposed to TB were referred to the diagnostic ward for pulmonary tuberculosis confirmation. A total number of 3441 males and 3202 females between the ages 11 and less than 18 years were enrolled into the study. Of the 3102 participants in the active surveillance group, four subjects were diagnosed with definite tuberculosis, four subjects with probable tuberculosis, and 71 subjects had non-tuberculous Mycobacteria (NTM) isolated from their sputum. Of the 3541 participants in the passive surveillance group, four subjects were diagnosed with definite tuberculosis, two subjects with probable tuberculosis, and 48 subjects had non-tuberculosis Mycobacteria isolated from their sputum. The incidence of definite + probable TB was 147.60 / 100,000 person years in the active surveillance group and 87 / 100,000 person years in the passive surveillance group. The incidence of pulmonary tuberculosis among adolescents in our study is lower than similar studies conducted in South

Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers

PubMed Central

Esterhuyse, Maria M.; Weiner, January; Caron, Etienne; Loxton, Andre G.; Iannaccone, Marco; Wagman, Chandre; Saikali, Philippe; Stanley, Kim; Wolski, Witold E.; Mollenkopf, Hans-Joachim; Schick, Matthias; Aebersold, Ruedi; Linhart, Heinz; Walzl, Gerhard

2015-01-01

ABSTRACT An estimated one-third of the world’s population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high-throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type. PMID:26374119

Trends in the epidemiology of childhood tuberculosis in Greece.

PubMed

Syridou, G; Mavrikou, M; Amanatidou, V; Spyridis, N; Prasad, P; Papaventsis, D; Kanavaki, S; Zaoutis, Th; Tsolia, M N

2012-06-01

A hospital referral center for childhood tuberculosis (TB). To evaluate the epidemiological and clinical features of childhood TB in the Greater Athens area in the last decade. We retrospectively reviewed the medical records of patients aged <14 years treated for active TB between January 2000 and December 2009 at our pediatric TB clinic and compared the results with the patient turnover during the previous decade (1990-1999). Data concerning demographic and clinical characteristics were analyzed. A total of 321 children (median age 5.57 years, 157 males) with active TB were identified. About one third originated from areas where TB was previously recognized to be highly endemic. Twenty-three children (7%) had extra-pulmonary TB, and 61% of them originated from TB-endemic areas. Bacteriological confirmation was obtained in 40% of patients from whom specimens were obtained: 1 of 26 (3.8%) strains was multidrug-resistant. Most cases with drug-resistant Mycobacterium tuberculosis were noted among immigrant children. The average annual TB incidence was estimated at 5.37 per 100 000 for children aged <14 years in the Greater Athens area. Time trend analysis for the 20-year period revealed a significant reduction in the total number of TB cases (P = 0.002) and in TB among children from low-incidence countries (P < 0.0001). In our settings, active TB is decreasing among children of Greek origin; disease epidemiology and drug resistance is influenced by the increasing influx of immigrants from areas where the disease is highly prevalent.

Rifampin vs. rifapentine: what is the preferred rifamycin for tuberculosis?

PubMed

Alfarisi, Omamah; Alghamdi, Wael A; Al-Shaer, Mohammad H; Dooley, Kelly E; Peloquin, Charles A

2017-10-01

One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them. Expert commentary: Rifampin has shorter half-life, higher MIC against M.tb, lower protein binding, and better distribution into cavitary contents than rifapentine. Drug interactions for the two drugs maybe similar in magnitude. For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care. Safety profile of rifampin is better-described; adverse events differ somewhat for the two drugs. The registered once-weekly rifapentine regimen is inadequate, but higher doses of either drugs may shorten the treatment duration required for effective management of TB. Results of clinical trials evaluating high-dose rifamycin regimens are eagerly awaited.

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

PubMed Central

Shaik, Monisha; Danquah, Cynthia Amaning

2017-01-01

ABSTRACT To say that tuberculosis (TB) has regained a strong foothold in the global human health and wellbeing scenario would be an understatement. Ranking alongside HIV/AIDS as the top reason for mortality due to a single infectious disease, the impact of TB extends far into socio-economic context worldwide. As global efforts led by experts and political bodies converge to mitigate the predicted outcome of growing antimicrobial resistance, the academic community of students, practitioners and researchers have mobilised to develop integrated, inter-disciplinary programmes to bring the plans of the former to fruition. Enabling this crucial requirement for unimpeded dissemination of scientific discovery was the TB Summit 2016, held in London, United Kingdom. This report critically discusses the recent breakthroughs made in diagnostics and treatment while bringing to light the major hurdles in the control of the disease as discussed in the course of the 3-day international event. Conferences and symposia such as these are the breeding grounds for successful local and global collaborations and therefore must be supported to expand the understanding and outreach of basic science research. PMID:27813702

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.

Spatial analysis of pulmonary tuberculosis in Antananarivo Madagascar: tuberculosis-related knowledge, attitude and practice.

PubMed

Rakotosamimanana, Sitraka; Mandrosovololona, Vatsiharizandry; Rakotonirina, Julio; Ramamonjisoa, Joselyne; Ranjalahy, Justin Rasolofomanana; Randremanana, Rindra Vatosoa; Rakotomanana, Fanjasoa

2014-01-01

Tuberculosis infection may remain latent, but the disease is nevertheless a serious public health issue. Various epidemiological studies on pulmonary tuberculosis have considered the spatial component and taken it into account, revealing the tendency of this disease to cluster in particular locations. The aim was to assess the contribution of Knowledge Attitude and Practice (KAP) to the distribution of tuberculosis and to provide information for the improvement of the National Tuberculosis Program. We investigated the role of KAP to distribution patterns of pulmonary tuberculosis in Antananarivo. First, we performed spatial scanning of tuberculosis aggregation among permanent cases resident in Antananarivo Urban Township using the Kulldorff method, and then we carried out a quantitative study on KAP, involving TB patients. The KAP study in the population was based on qualitative methods with focus groups. The disease still clusters in the same districts identified in the previous study. The principal cluster covered 22 neighborhoods. Most of them are part of the first district. A secondary cluster was found, involving 18 neighborhoods in the sixth district and two neighborhoods in the fifth. The relative risk was respectively 1.7 (p<10-6) in the principal cluster and 1.6 (p<10-3) in the secondary cluster. Our study showed that more was known about TB symptoms than about the duration of the disease or free treatment. Knowledge about TB was limited to that acquired at school or from relatives with TB. The attitude and practices of patients and the population in general indicated that there is still a stigma attached to tuberculosis. This type of survey can be conducted in remote zones where the tuberculosis-related KAP of the TB patients and the general population is less known or not documented; the findings could be used to adapt control measures to the local particularities.

Molecular Diagnosis of Tuberculosis.

PubMed

Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

2018-01-01

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

[Tuberculosis pulmonum--"threaten us of epidemic"?].

PubMed

Chyczewska, Elzbieta

2008-01-01

Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide with 95% of cases and 98% of deaths occuring in developing countries (9 milion new cases, 1 million deaths annually) vs.WHO. Tuberculosis is on the increase in developed countries, because of AIDS, the use of immunosuppresive drugs which depress the host defence mechanism, decreased socioeconomic conditions, as well as increased immigration of persons from areas of high endemicity. The major reason for this increase was because of rapid rise in cases from sub-Saharan Africa (due to AIDS) nad Russia. Incidense of tuberculosis in Poland 2007--the number of notified cases was 8014. Pulmonary cases represented 92.7% of total all TB cases and 628 cases of extrapulmonary TB. Chidren TB cases represented 0.9% (74 cases) of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.1 in children do 41.2 among 65 and older. The incidence of men (31.5) was two times higher than in women--14.5 per 100 000 respectivly. There were 716 deaths due to pulmonary TB and 23 from extrapulmonary TB. Multidrug resistance (MDR) of Mycobacterium tuberculosis is a major therapeutic problem, in the world, with a high mortality and occurs mainly in HIV-infected patients. The WHO estimates that around 50 million people are infected with MDR-TB! WHO suggest that a greater investment in the establishment treatment strategy of DOTS (Directly Observed Treatment Short-course) into all posible regions.

Prevalence of latent tuberculosis infection among foreign students in Lübeck, Germany tested with QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus.

PubMed

Gallegos Morales, Elia Noemi; Knierer, Johannes; Schablon, Anja; Nienhaus, Albert; Kersten, Jan Felix

2017-01-01

The tuberculosis (TB) incidence rate in foreign-born individuals has been increasing in Germany in recent years. Foreign students may be an important source of latent tuberculosis infection (LTBI) in low-incidence countries. In Germany, there are no guidelines for LTBI screening of foreign students. The aim of the study was to estimate LTBI prevalence and evaluate associated risk factors among foreign students in Germany. The second purpose of our study was to compare the results of the new generation of QuantiFERON-TB Gold Plus (QFT-Plus) to those of its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT). This cross - sectional study was conducted between February 2016 and March 2016. Foreign students and young professionals attending the university and higher education institutes in Lübeck, Germany were tested with QFT-Plus and QFT-GIT. Participants filled out a questionnaire for the purpose of LTBI risk assessment and analysis. Variables associated with a positive test result were analyzed using logistic regression. One hundred thirty four students participated in the study. The overall prevalence as regards positive results from both tests, QFT-Plus and QFT-GIT, was 9.7%, and the prevalence of positive QFT-Plus results was 8.2%. The main independent variables associated with a positive QFT-Plus result were a) being born in a high-incidence country (OR = 6.7, 95% CI: 1.3-34.3) and b) previous contact with a person with active TB (OR = 4.5, 95% CI: 1.1-18.3). Higher age (OR = 2.8, 95% CI: 0.7-11.3) and male gender (OR = 1.6, 95% CI: 0.4-6.7) showed a tendency toward positive QFT-Plus results but this was not statistically significant. Agreement between QFT-Plus and QFT-GIT results was κ = 0.85, p  < 0.001. The LTBI prevalence among foreign students was about 10%. We recommend implementing a policy whereby all foreign students are screened by means of a questionnaire about LTBI risk factors, so that only students with present risk factors are tested

Potential Immunological Biomarkers for Detection of Mycobacterium tuberculosis Infection in a Setting Where M. tuberculosis Is Endemic, Ethiopia.

PubMed

Teklu, Takele; Kwon, Keehwan; Wondale, Biniam; HaileMariam, Milkessa; Zewude, Aboma; Medhin, Girmay; Legesse, Mengistu; Pieper, Rembert; Ameni, Gobena

2018-04-01

Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate Mycobacterium tuberculosis infection outcomes in a setting where it is endemic, Ethiopia. Whole blood from 90 participants was stimulated using the ESAT-6/CFP-10 antigen cocktail. The interferon gamma (IFN-γ)-based QuantiFERON diagnostic test was used to distinguish between LTBI and uninfected control cases. Forty cytokines/chemokines were detected from antigen-stimulated plasma supernatants (SPSs) and unstimulated plasma samples (UPSs) using human cytokine/chemokine antibody microarrays. Statistical tests allowed us to identify potential biomarkers that distinguish the TB, LTBI, and healthy control groups. As expected, the levels of IFN-γ in SPSs returned a high area under the receiver operating characteristic curve (AUC) value comparing healthy controls and LTBI cases (Z = 0.911; P < 0.001). The SPS data also indicated that interleukin 17 (IL-17) abundance discriminates LTBI from healthy controls (Z = 0.763; P = 0.001). RANTES and MIP-1β were significantly elevated in SPSs of TB-infected compared to healthy controls ( P < 0.05), while IL-12p40 and soluble tumor necrosis factor receptor II (sTNF-RII) were significantly increased in active TB cases compared to the combined LTBI and control groups ( P < 0.05). Interestingly, quantitative changes for RANTES were observed using both SPSs and UPSs, with P values of 0.013 and 0.012, respectively, in active TB versus LTBI cases and 0.001 and 0.002, respectively, in active TB versus healthy controls. These results encourage biomarker verification studies for IL-17 and RANTES. Combinations of these cytokines may complement IFN-γ measurements to diagnose LTBI and distinguish active TB from LTBI cases. Copyright © 2018 American Society for Microbiology.

How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India.

PubMed

Azman, Andrew S; Golub, Jonathan E; Dowdy, David W

2014-10-30

Current approaches are unlikely to achieve the aggressive global tuberculosis (TB) control targets set for 2035 and beyond. Active case finding (ACF) may be an important tool for augmenting existing strategies, but the cost-effectiveness of ACF remains uncertain. Program evaluators can often measure the cost of ACF per TB case detected, but how this accessible measure translates into traditional metrics of cost-effectiveness, such as the cost per disability-adjusted life year (DALY), remains unclear. We constructed dynamic models of TB in India, China, and South Africa to explore the medium-term impact and cost-effectiveness of generic ACF activities, conceptualized separately as discrete (2-year) campaigns and as continuous activities integrated into ongoing TB control programs. Our primary outcome was the cost per DALY, measured in relationship to the cost per TB case actively detected and started on treatment. Discrete campaigns costing up to $1,200 (95% uncertainty range [UR] 850-2,043) per case actively detected and started on treatment in India, $3,800 (95% UR 2,706-6,392) in China, and $9,400 (95% UR 6,957-13,221) in South Africa were all highly cost-effective (cost per DALY averted less than per capita gross domestic product). Prolonged integration was even more effective and cost-effective. Short-term assessments of ACF dramatically underestimated potential longer term gains; for example, an assessment of an ACF program at 2 years might find a non-significant 11% reduction in prevalence, but a 10-year evaluation of that same intervention would show a 33% reduction. ACF can be a powerful and highly cost-effective tool in the fight against TB. Given that short-term assessments may dramatically underestimate medium-term effectiveness, current willingness to pay may be too low. ACF should receive strong consideration as a basic tool for TB control in most high-burden settings, even when it may cost over $1,000 to detect and initiate treatment for each extra