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Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.
Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O'Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL
(2017) Clin Infect Dis 64: 111-115
MeSH Terms: Adult, Age Factors, Child, Humans, Latent Tuberculosis, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis, Pulmonary
Show Abstract · Added March 14, 2018
BACKGROUND - Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.
METHODS - A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS - Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional.
CONCLUSIONS - These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
0 Communities
1 Members
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8 MeSH Terms
Pediatric multidrug-resistant tuberculosis clinical trials: challenges and opportunities.
McAnaw SE, Hesseling AC, Seddon JA, Dooley KE, Garcia-Prats AJ, Kim S, Jenkins HE, Schaaf HS, Sterling TR, Horsburgh CR
(2017) Int J Infect Dis 56: 194-199
MeSH Terms: Adult, Antitubercular Agents, Child, Clinical Trials as Topic, Humans, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary
Show Abstract · Added March 14, 2018
On June 17, 2016, RESIST-TB, IMPAACT, Vital Strategies, and New Ventures jointly hosted the Pediatric Multidrug Resistant Tuberculosis Clinical Trials Landscape Meeting in Arlington, Virginia, USA. The meeting provided updates on current multidrug-resistant tuberculosis (MDR-TB) trials targeting pediatric populations and adult trials that have included pediatric patients. A series of presentations were given that discussed site capacity needs, community engagement, and additional interventions necessary for clinical trials to improve the treatment of pediatric MDR-TB. This article presents a summary of topics discussed, including the following: current trials ongoing and planned; the global burden of MDR-TB in children; current regimens for MDR-TB treatment in children; pharmacokinetics of second-line anti-tuberculosis medications in children; design, sample size, and statistical considerations for MDR-TB trials in children; selection of study population, design, and treatment arms for a trial of novel pediatric MDR-TB regimens; practical aspects of pediatric MDR-TB treatment trials; and strategies for integrating children into adult tuberculosis trials. These discussions elucidated barriers to pediatric MDR-TB clinical trials and provided insight into necessary next steps for progress in this field. Investigators and funding agencies need to respond to these recommendations so that important studies can be implemented, leading to improved treatment for children with MDR-TB.
Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
0 Communities
1 Members
0 Resources
7 MeSH Terms
Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.
Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O'Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL
(2017) Clin Infect Dis 64: e1-e33
MeSH Terms: Adult, Age Factors, Child, Humans, Latent Tuberculosis, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis, Pulmonary
Show Abstract · Added March 14, 2018
BACKGROUND - Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.
METHODS - A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS - Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional.
CONCLUSIONS - These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Four-month fluoroquinolone-containing regimens are inferior to standard 6-month tuberculosis treatment.
Sterling TR
(2015) Evid Based Med 20: 128-9
MeSH Terms: Antitubercular Agents, Female, Fluoroquinolones, Humans, Male, Mycobacterium tuberculosis, Tuberculosis, Pulmonary
Added February 17, 2016
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1 Members
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7 MeSH Terms
A comparison of interview methods to ascertain fluoroquinolone exposure before tuberculosis diagnosis.
Van Der Heijden YF, Maruri F, Holt E, Mitchel E, Warkentin J, Sterling TR
(2015) Epidemiol Infect 143: 960-5
MeSH Terms: Adult, Anti-Bacterial Agents, Databases, Factual, Delayed Diagnosis, Drug Resistance, Bacterial, Female, Fluoroquinolones, Humans, Interviews as Topic, Male, Medical History Taking, Medical Records, Middle Aged, Pharmacies, Surveys and Questionnaires, Tennessee, Tuberculosis, Tuberculosis, Pulmonary
Show Abstract · Added February 17, 2016
SUMMARY Fluoroquinolone use before tuberculosis (TB) diagnosis delays the time to diagnosis and treatment, and increases the risk of fluoroquinolone-resistant TB and death. Ascertainment of fluoroquinolone exposure could identify such high-risk patients. We compared four methods of ascertaining fluoroquinolone exposure in the 6 months prior to TB diagnosis in culture-confirmed TB patients in Tennessee from January 2007 to December 2009. The four methods included a simple questionnaire administered to all TB suspects by health department personnel (FQ-Form), an in-home interview conducted by research staff, outpatient and inpatient medical record review, and TennCare pharmacy database review. Of 177 TB patients included, 72 (41%) received fluoroquinolones during the 6 months before TB diagnosis. Fluoroquinolone exposure determined by review of inpatient and outpatient medical records was considered the gold standard for comparison. The FQ-Form had 61% [95% confidence interval (CI) 48-73] sensitivity and 93% (95% CI 85-98) specificity (agreement 79%, kappa = 0.56) while the in-home interview had 28% (95% CI 18-40) sensitivity and 99% (94-100%) specificity (agreement 68%, kappa = 0.29). A simple questionnaire administered by health department personnel identified fluoroquinolone exposure before TB diagnosis with moderate reliability.
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18 MeSH Terms
Simultaneous inhibition of T helper 2 and T regulatory cell differentiation by small molecules enhances Bacillus Calmette-Guerin vaccine efficacy against tuberculosis.
Bhattacharya D, Dwivedi VP, Kumar S, Reddy MC, Van Kaer L, Moodley P, Das G
(2014) J Biol Chem 289: 33404-11
MeSH Terms: Animals, Anti-Allergic Agents, Arylsulfonates, Benzamides, Cell Differentiation, Imidazoles, Mice, Mice, Inbred BALB C, Mycobacterium bovis, Mycobacterium tuberculosis, Sulfonium Compounds, T-Lymphocytes, Regulatory, Th2 Cells, Tuberculosis Vaccines, Tuberculosis, Pulmonary
Show Abstract · Added January 20, 2015
Tuberculosis affects nine million individuals and kills almost two million people every year. The only vaccine available, Bacillus Calmette-Guerin (BCG), has been used since its inception in 1921. Although BCG induces host-protective T helper 1 (Th1) cell immune responses, which play a central role in host protection, its efficacy is unsatisfactory, suggesting that additional methods to enhance protective immune responses are needed. Recently we have shown that simultaneous inhibition of Th2 cells and Tregs by using the pharmacological inhibitors suplatast tosylate and D4476, respectively, dramatically enhances Mycobacterium tuberculosis clearance and induces superior Th1 responses. Here we show that treatment with these two drugs during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in the development of T cell memory, favoring central memory T (Tcm) cell responses over effector memory T (Tem) cell responses. Collectively, our findings provide evidence that simultaneous inhibition of Th2 cells and Tregs during BCG vaccination promotes vaccine efficacy.
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
0 Communities
1 Members
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15 MeSH Terms
Tuberculosis and the risk of infection with other intracellular bacteria: a population-based study.
Huaman MA, Fiske CT, Jones TF, Warkentin J, Shepherd BE, Ingram LA, Maruri F, Sterling TR
(2015) Epidemiol Infect 143: 951-9
MeSH Terms: Adolescent, Adult, Aged, Antitubercular Agents, Child, Child, Preschool, Chlamydia Infections, Chlamydia trachomatis, Coinfection, Dysentery, Bacillary, Female, HIV Infections, Humans, Incidence, Listeria monocytogenes, Listeriosis, Male, Middle Aged, Mycobacterium tuberculosis, Risk Factors, Salmonella Infections, Shigella, Tennessee, Tuberculosis, Tuberculosis, Pulmonary, Yersinia Infections, Young Adult
Show Abstract · Added February 17, 2016
SUMMARY Persons who develop tuberculosis (TB) may have subtle immune defects that could predispose to other intracellular bacterial infections (ICBIs). We obtained data on TB and five ICBIs (Chlamydia trachomatis, Salmonella spp., Shigella spp., Yersinia spp., Listeria monocytogenes) reported to the Tennessee Department of Health, USA, 2000-2011. Incidence rate ratios (IRRs) comparing ICBIs in persons who developed TB and ICBIs in the Tennessee population, adjusted for age, sex, race and ethnicity were estimated. IRRs were not significantly elevated for all ICBIs combined [IRR 0.87, 95% confidence interval (CI) 0.71-1.06]. C. trachomatis rate was lowest in the year post-TB diagnosis (IRR 0.17, 95% CI 0.04-0.70). More Salmonella infections occurred in extrapulmonary TB compared to pulmonary TB patients (IRR 14.3, 95% CI 1.67-122); however, this appeared to be related to HIV co-infection. TB was not associated with an increased risk of other ICBIs. In fact, fewer C. trachomatis infections occurred after recent TB diagnosis. Reasons for this association, including reduced exposure, protection conferred by anti-TB drugs or macrophage activation by Mycobacterium tuberculosis infection warrant further investigation.
0 Communities
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27 MeSH Terms
Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.
White MJ, Tacconelli A, Chen JS, Wejse C, Hill PC, Gomes VF, Velez-Edwards DR, Østergaard LJ, Hu T, Moore JH, Novelli G, Scott WK, Williams SM, Sirugo G
(2014) Genes Immun 15: 370-7
MeSH Terms: Adult, African Continental Ancestry Group, Alleles, Epiregulin, Epistasis, Genetic, Gambia, Gene Frequency, Genetic Predisposition to Disease, Genotype, Guinea-Bissau, Humans, Linkage Disequilibrium, Logistic Models, Male, Odds Ratio, Polymorphism, Single Nucleotide, Tuberculosis, Pulmonary, Vacuolar Proton-Translocating ATPases
Show Abstract · Added February 22, 2016
We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322 controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1 (TCIRG1)) using single and multilocus analyses to determine whether previously described associations with pulmonary tuberculosis (PTB) in Vietnamese and Italians would replicate in African populations. We did not detect any significant single locus or haplotype associations in either sample. We also performed exploratory pairwise interaction analyses using Visualization of Statistical Epistasis Networks (ViSEN), a novel method to detect only interactions among multiple variables, to elucidate possible interaction effects between SNPs and demographic factors. Although we found no strong evidence of marginal effects, there were several significant pairwise interactions that were identified in either the Guinea-Bissau or the Gambian samples, two of which replicated across populations. Our results indicate that the effects of EREG and TCIRG1 variants on PTB susceptibility, to the extent that they exist, are dependent on gene-gene interactions in West African populations as detected with ViSEN. In addition, epistatic effects are likely to be influenced by inter- and intra-population differences in genetic or environmental context and/or the mycobacterial lineages causing disease.
0 Communities
1 Members
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18 MeSH Terms
High proportion of heteroresistance in gyrA and gyrB in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates.
Eilertson B, Maruri F, Blackman A, Herrera M, Samuels DC, Sterling TR
(2014) Antimicrob Agents Chemother 58: 3270-5
MeSH Terms: Anti-Bacterial Agents, DNA Gyrase, DNA, Bacterial, Drug Resistance, Multiple, Bacterial, Fluoroquinolones, Mutation, Mycobacterium tuberculosis, Phenotype, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary
Show Abstract · Added May 27, 2014
Heteroresistance is the coexistence of populations with differing nucleotides at a drug resistance locus within a sample of organisms. Although Sanger sequencing is the gold standard for sequencing, it may be less sensitive than deep sequencing for detecting fluoroquinolone heteroresistance in Mycobacterium tuberculosis. Twenty-seven fluoroquinolone monoresistant and 11 fluoroquinolone-susceptible M. tuberculosis isolates were analyzed by Sanger and Illumina deep sequencing. Individual sequencing reads were analyzed to detect heteroresistance in the gyrA and gyrB genes. Heteroresistance to fluoroquinolones was identified in 10/26 (38%) phenotypically fluoroquinolone-resistant samples and 0/11 (P = 0.02) fluoroquinolone-susceptible controls. One resistant sample was excluded because of contamination with the laboratory strain M. tuberculosis H37Rv. Sanger sequencing revealed resistance-conferring mutations in 15 isolates, while deep sequencing revealed mutations in 20 isolates. Isolates with fluoroquinolone resistance-conferring mutations by Sanger sequencing all had at least those same mutations identified by deep sequencing. By deep sequencing, 10 isolates had a single fixed (defined as >95% frequency) mutation, while 10 were heteroresistant, 5 of which had a single unfixed (defined as <95% frequency) mutation and 5 had multiple unfixed mutations. Illumina deep sequencing identified a higher proportion of fluoroquinolone-resistant M. tuberculosis isolates with heteroresistance than did Sanger sequencing. The heteroresistant isolates frequently demonstrated multiple mutations, but resistant isolates with fixed mutations each had only a single mutation.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
0 Communities
2 Members
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10 MeSH Terms
Higher rates of AIDS during the first year of antiretroviral therapy among migrants: the importance of tuberculosis.
Antiretroviral Therapy Cohort Collaboration (ART-CC), Shepherd BE, Jenkins CA, Parrish DD, Glass TR, Cescon A, Masabeu A, Chene G, de Wolf F, Crane HM, Jarrin I, Gill J, del Amo J, Abgrall S, Khaykin P, Lehmann C, Ingle SM, May MT, Sterne JA, Sterling TR
(2013) AIDS 27: 1321-9
MeSH Terms: Acquired Immunodeficiency Syndrome, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Cohort Studies, Developed Countries, Developing Countries, Female, Humans, Male, Middle Aged, Survival Rate, Time Factors, Transients and Migrants, Tuberculosis, Pulmonary
Show Abstract · Added May 29, 2014
OBJECTIVE - In lower-income countries rates of AIDS-defining events (ADEs) and death are high during the first year of combination antiretroviral therapy (ART). We investigated differences between foreign-born (migrant) and native-born (nonmigrant) patients initiating ART in Europe, the US and Canada, and examined rates of the most common ADEs and mortality during the first year of ART.
DESIGN - Observational cohort study.
METHODS - We studied HIV-positive adults participating in one of 12 cohorts in the Antiretroviral Therapy Cohort Collaboration (ART-CC).
RESULTS - Of 48 854 patients, 25.6% were migrants: 16.1% from sub-Saharan Africa, 5.6% Latin America, 2.3% North Africa/Middle East, and 1.6% Asia. Incidence of ADEs during the first year of ART was 60.8 per 1000 person-years: 69.9 for migrants and 57.7 for nonmigrants [crude hazard ratio (HR) 1.18; 95% confidence interval (CI) 1.08-1.29], adjusted HR (for sex, age, CD4, HIV-1 RNA, ART regimen, prior ADE, probable route of infection and year of initiation, and stratified by cohort) 1.21 (95% CI 1.09-1.34). Rates of tuberculosis were substantially higher in migrants than nonmigrants (14.3 vs. 6.3; adjusted HR 1.94; 95% CI 1.53-2.46). In contrast, mortality was higher among nonmigrants than migrants (crude HR 0.71; 95% CI 0.61-0.84), although excess mortality was partially explained by patient characteristics at start of ART (adjusted HR 0.91; 95% CI 0.76-1.09).
CONCLUSIONS - During the first year of ART, HIV-positive migrants had higher rates of ADEs than nonmigrants. Tuberculosis was the most common ADE among migrants, highlighting the importance of screening for tuberculosis prior to ART initiation in this population.
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1 Members
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15 MeSH Terms