Tuberculosis
- Topics
- Basic TB Facts
- Treatment
- Testing & Diagnosis
- TB & HIV Coinfection
- Infection Control & Prevention
- Drug-Resistant TB
- TB in Specific Populations
- African-American Community
- Correctional Facilities
- Table of Contents
- Introduction
- Strengthen TB Information Systems and Program Assessment
- Strengthen TB Environmental Controls and Isolation Practices
- Provide More Comprehensive and Timely Screening and Diagnostic Evaluations
- Develop and Strengthen Contact Investigation Protocols
- Increase HIV Counseling and Testing
- Increase Staff Training
- Strengthen Collaboration Between Health Departments and Jails
- International Travelers
- Pregnancy
- Disaster Responders
- Children
- Vaccines & Immunizations
- Laboratory Information
- Drug Susceptibility Testing
- The Uses of Nucleic Acid Amplification Tests for the Diagnosis of TB
- Rapid Molecular Testing to Detect Drug-Resistant TB in the US
- Executive Summary
- Introduction
- Background on Tests for Molecular Detection of DR
- General Considerations and Principles for a Molecular DR Testing Service�
- Possible Scenarios and Scope of Testing for a Molecular DR Testing Service
- Research Needs
- General Recommendations of the Expert Panel
- Communication Plan for the Report
- Recommendations
- References
- Panel Members and CDC Participants
- Appendix 1
- Appendix 2
- Appendix 3
- Interim Laboratory Biosafety Guidance for XDR Mycobacterium tuberculosis strains
- Molecular Detection of Drug Resistance (MDDR)
- Research
- TB Epidemiologic Studies Consortium
- Background
- Infrastructure
- Research Projects
- Publications
- Meetings
- Directory
- TBESC Committee Members
- Translating Research into Practice (TRIP)
- Contact TBESC
- Prospective Evaluation of Immunogenetic and Immunologic Markers for Susceptibility to Tuberculosis Infection and Progression from M. Tuberculosisinfection to active TB
- Zero Tolerance for Pediatric TB
- Models for Incorporating HIV Counseling, Testing, and Referral into Tuberculosis Contact Investigations
- Prevalence of Latent TB Infection Among High Risk Populations in the United States
- Regional Capacity-Building in Low-Incidence Areas
- Use of Network Analysis Methods to Characterize M. tuberculosis Transmission Patterns Among Women and Other High-Risk Populations
- An Analysis of Molecular Epidemiology of Multi-Drug Resistant M. tuberculosisin the United States
- Missed Opportunities for TB Prevention in Foreign-Born Population in the United States and Canada
- New Model for Assessing TB Surveillance and Action Performance and Cost
- Addressing TB Among African Americans in the Southeast: Identifying and Overcoming Barriers to Treatment Adherence for Latent TB Infection and TB Disease
- Assessing the TB Knowledge, Attitudes, Beliefs, and Practices Among Private Providers Serving Foreign-born Populations at Risk for TB
- Factors Associated with Acceptance of, Adherence to and Toxicity From Treatment for Latent TB Infection and Pilot Study of Treatment for Latent TB Infection Effectiveness
- Culturally Appropriate TB Educational Materials for Leaders and Staff of Hispanic Service Organizations
- Enhancing TB Programs� Capacity for Self-Evaluation: Testing New Tools and Developing an Evaluation Toolkit
- African Refugee Women�s Health Improvement Project
- Evaluation of the TK Medium: A New Rapid Solid Culture System for Tuberculosis
- Evaluation of New Interferon-y Release Assays in the Diagnosis of Latent TB Infection in Health Care Workers
- Request for Proposal
- TB Trials Consortium
- Behavioral & Social Science Research
- TB Epidemiologic Studies Consortium
- Data & Statistics
- Education & Training
- Resources for TB Programs
- Publications & Products
- Fact Sheets
- General
- Fact sheets - Spanish
- TB - General Information
- The Difference Between Latent TB Infection and Active TB Disease
- Diferencia entre la infección de tuberculosis latente y enfermedad de tuberculosis activa
- A Global Perspective on TB
- Tuberculosis Information for Employers in Non-Healthcare Settings
- Bovine Tuberculosis in Humans
- Tuberculosis Information for International Travelers
- TB Can Be Treated
- Exposure to TB
- TB and HIV/AIDS
- You Can Prevent TB
- Testing for TB
- Tuberculosis: informaci�n general
- Diferencia entre la infecci�n de tuberculosis latente y enfermedad de tuberculosis activa
- Informaci�n sobre la tuberculosis para los viajeros internacionales
- Exposición a la tuberculosis
- Usted puede prevenir la tuberculosis
- La tuberculosis puede ser tratada
- Tuberculosis y VIH/SIDA
- Usted puede prevenir la tuberculosis
- Pruebas para detectar la tuberculosis
- Data & Statistics
- A Global Perspective on TB
- Trends in Tuberculosis – United States
- The Revised Report of Verified Case of Tuberculosis
- The National Tuberculosis Indicators Project (NTIP)
- National Tuberculosis Indicators Project (NTIP): Frequently Asked Questions
- TB Genotyping
- TB Genotyping Information Management System (TB GIMS)
- Drug-Resistant TB
- Multidrug-Resistant Tuberculosis (MDR TB)
- Extensively Drug-Resistant Tuberculosis (XDR TB)
- CDC’s Role in Preventing Extensively Drug-Resistant Tuberculosis (XDR TB)
- Tuberculosis multirresistente (MDR)
- Tuberculosis extremadamente resistente (XDR)
- El papel de los CDC en la prevenci�n de la tuberculosis extremadamente resistente (XDR)
- Infection Control & Prevention
- TB in Specific Populations
- Tuberculosis Information for Employers in Non-Healthcare Settings
- Tuberculosis in Minorities
- Tuberculosis Information for International Travelers
- TB and HIV/AIDS
- Recommendations for Human Immunodeficiency Virus (HIV) Screening in Tuberculosis (TB) Clinics
- Treatment of Drug-Susceptible Tuberculosis Disease in HIV-Infected Persons
- Tuberculosis in Blacks
- Tuberculosis and Pregnancy
- Tuberculosis y embarazo
- Treatment
- TB Can Be Treated
- Treatment of Latent TB Infection
- Treatment of Latent Tuberculosis Infection: Maximizing Adherence
- Treatment Options for Latent Tuberculosis Infection
- Treatment of Drug-Resistant Tuberculosis
- Treatment of Drug-Susceptible Tuberculosis Disease in Persons Not Infected with HIV
- Treatment of Drug-Susceptible Tuberculosis Disease in HIV-Infected Persons
- Tratamiento de la infecci�n de tuberculosis latente
- Testing & Diagnosis
- TB Can Be Treated
- Testing for TB
- Recommendations for Human Immunodeficiency Virus (HIV) Screening in Tuberculosis (TB) Clinics
- Interferon-Gamma Release Assays (IGRAs)
- Tuberculin Skin Testing
- Diagnosis of Tuberculosis Disease
- Targeted Tuberculin Testing and Interpreting Tuberculin Skin Test Results
- Prueba cutánea de la tuberculina
- Diagnóstico de la tuberculosis activa
- Vaccines & Immunizations
- General
- Guidelines
- Guides & Toolkits
- Core Curriculum
- Self-Study Modules
- Report of Verified Case of Tuberculosis (RVCT)
- Forging Partnerships to Eliminate TB
- Understanding the TB Cohort Review Process
- Latent Tuberculosis Infection: A Guide for Primary Health Care Providers
- Effective TB Interviewing for Contact Investigation
- Mantoux Tuberculin Skin Testing Products
- Ethnographic Guides
- Newsletters
- Pamphlets, Brochures, Booklets
- Posters
- Mantoux Tuberculin Skin Test Wall Chart
- World TB Day
- Afiches
- 2011 Poster (English)
- 2011 Poster (Spanish)
- 2010 Poster (English)
- 2010 Poster (Spanish)
- 2008 Poster (English)
- 2008 Poster (Spanish)
- 2006 Poster (English)
- 2004 Poster (English)
- 2004 Poster (Spanish)
- 2003 Poster (English)
- 2003 Poster (Spanish)
- 2003 Now is the Time Poster (English)
- 2003 Now is the Time Poster (Spanish)
- Think TB
- Stop TB
- Reports & Articles
- Morbidity and Mortality Weekly Reports (MMWRs)
- Contact Investigations
- Control and Elimination
- Data & Statistics
- Drug-Resistant Tuberculosis
- Infection Control & Prevention
- Laboratory
- TB in Specific Populations
- Foreign-Born
- High-Risk Settings
- Homeless
- International
- Occupational Groups
- Travel
- TB & HIV
- Testing & Diagnosis
- Treatment
- LTBI Updates
- Vaccines & Immunizations
- World TB Day
- DTBE Authored Journal Articles
- Tuberculosis Laboratory Aggregate Reports
- Morbidity and Mortality Weekly Reports (MMWRs)
- Slide Sets
- Core Curriculum
- Self-Study Modules
- Prevention and Control of Tuberculosis in Correctional and Detention Facilities
- Guidelines for Preventing the Transmission of M. TB in Health care Settings
- Investigation of Contacts of Persons with Infectious TB
- Text-Only version
- Introduction
- Decisions to Initiate a Contact Investigation
- Investigating the Index Patient and Sites of Transmission
- Assigning Priorities to Contacts
- Diagnostic and Public Health Evaluation of Contacts
- Medical Treatment for Contacts with LTBI
- When to Expand a Contact Investigation
- Communicating Through the News Media
- Data Management and Evaluation of Contact Investigations
- Confidentiality and Consent in Contact Investigations
- Staff Training for Contact Investigations
- Contact Investigations in Special Circumstances
- Source-Case Investigations
- Cultural Competency and Social Network Analysis
- Resources
- Epidemiology of Pediatric Tuberculosis in the United States
- Text-Only version
- Introduction
- Pediatric TB Cases by Age and Race
- Pediatric TB Cases by Origin of Birth
- Pediatric Cases, Percentages and Rates by States
- Pediatric TB Cases by Case Verification Criterion and Site of Disease
- Pediatric TB Cases in Specific Groups
- Pediatric TB Cases Case Completion
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- Slide 21
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- Slide 25
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- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Treatment of TB
- Targeted Tuberculosis Testing and Treatment of Latent Tuberculosis Infection
- CD Roms
- Electronic Tools & Resources
- Web-Based Courses & Webinars
- Fact Sheets
- Global TB
- Events
- Links
- About Us
- Mission Statement and Activities
- Organization Chart
- Advisory Groups
- Federal TB Task Force
- Table of Contents
- Executive Summary
- Introduction
- Chronology in the Development of This Report
- Strategies for Maintaining Control of TB
- Strategies for Accelerating the Decline of TB
- Activities for Developing New Tools
- Global U.S. Actions
- Assessing the Impact of Actions Taken
- Federal TB Task Force Members and Others Involved in the Development of This Report
- Glossary
- References
- Federal TB Task Force Roster
- Table of Contents
- Executive Summary
- Introduction
- How to Eliminate TB? – The IOM Report
- Why Eliminate TB? – Rationale for Elimination
- Who Will Lead? – CDC's Response
- Goal I: Maintain control of TB
- Goal II: Accelerate the decline
- Goal III: Create new tools
- Goal IV: Reduce the global burden of TB
- Goal V: Summon and sustain support
- Goal VI: Track progress
- References
- Federal TB Task Force
- Funding
Report of Expert Consultations on Rapid Molecular Testing to Detect Drug-Resistant Tuberculosis in the United States
Background on molecular drug-resistance (DR) tests
Recent advances in the understanding of the molecular basis or genetics of drug resistance have enabled development of rapid, DNA-based, molecular tests to detect mutations associated with drug resistance. If a mutation thought to be associated with resistance is detected in such a rapid test, the bacteria are considered to be drug resistant. If no mutation is detected, the bacteria are assumed to be drug susceptible. The key advantage of the molecular tests is that they can provide results within 24 to 48 hours, because they take advantage of the speed of nucleic acid amplification. These tests have been referred to in various publications as genetic or molecular drug-susceptibility tests, genetic or molecular detection of drug resistance tests, molecular tests to detect drug (or antimicrobial or antibiotic)-resistance mutations, or tests to detect molecular or genetic markers of drug resistance. In this report, the tests will be referred to simply as molecular drug-resistance (DR) tests.
Mutations associated with resistance to many of the anti-TB drugs have been described (8,9). For example, ~95% of rifampin-resistant M. tuberculosis strains carry mutations within the rifampin resistance-determining region (RRDR), an 81-bp region of the rpoB gene. Because of the strong association between the presence of mutations in the RRDR and rifampin resistance, several molecular genetic tests to detect RRDR mutations have been developed and evaluated for their ability to detect resistance in clinical isolates. Genetic or molecular tests for detecting mutations are, in general, variations of nucleic acid amplification (NAA) tests. Typically, the polymerase chain reaction (PCR) is used to amplify a target sequence followed by a second assay to determine if the sequence contains a mutation associated with resistance, such as DNA sequencing or hybridization assays.
- For hybridization assays such as the INNO-LiPA® Rif.TB (Innogenetics) and GenoType® MTBDR(plus) (Hain LifeScience GmbH) line-probe assays, the region of a gene associated with resistance is PCR amplified, and the labeled PCR products hybridized to oligonucleotide probes immobilized on a nitrocellulose strip. Mutations are detected by lack of binding to wild-type probes or by binding to probes specific for commonly occurring mutations. Compared to culture-based DS tests, the MTBDR(plus) line probe assay displays a pooled sensitivity of 0.98 and a pooled specificity of 0.99 for detecting rifampin resistance in isolates or directly from clinical specimens (10–12).
- Molecular beacons are hybridization probes which emit fluorescence only when hybridized to their target and which can discriminate between targets differing only by a single nucleotide. In the California Microbial Diseases Laboratory, molecular beacon assays were designed to detect mutations in the rpoB gene directly from clinical specimens and from cultures. The results of rpoB molecular beacons tests showed 96% to 97% agreement with culture-based results in a series of ~1,000 clinical specimens and cultures (E. Desmond, personal communication).
- Validation studies conducted at the Wadsworth Center of an approach that combines PCR-amplification of the entire 81 bp RRDR with pyrosequencing revealed that the test displayed a sensitivity of <1 colony forming unit, 100% specificity, and 99% agreement in the 188 cultures and specimens tested (13–15; K. Musser, personal communication).
Molecular DR tests for other anti-TB drugs are much less developed than the tests for rifampin resistance. A meta-analysis of the performance of the Hain MTBDR(plus) assay for detecting isoniazid resistance revealed a pooled sensitivity of 0.85 (95%CI 0.77– 0.90) and a pooled specificity of 0.99 (95%CI 0.98–1.00) (11,12). Validation studies conducted in the California Microbial Diseases Laboratory using archived cultures revealed that the molecular beacon test displayed 82.7% sensitivity, 100% specificity, 100% positive predictive value, and 98.1% negative predictive value for detecting isoniazid resistance (16, E. Desmond, personal communication).
The critical contribution of molecular DR tests for TB treatment and control is earlier detection of resistance: they can reliably detect mutations associated with drug resistance in 1 to 2 days. Not only does this reduce the time to detect rifampin resistance, but for MDR TB patients this also reduces the time from TB diagnosis to the start of MDR TB treatment and from the first positive culture to culture conversion by six weeks and improves patient outcomes (2,3). The reduction of the estimated infectious period after diagnosis by six weeks should have a large impact on public health measures to stop the spread of MDR TB.
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