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Guide to the Application of Genotyping to Tuberculosis Prevention and Control										Related Pages
										**Introduction to Tuberculosis Genotyping**
**Overview of Tuberculosis Genotyping**
CDC has initiated a laboratory program to provide genotyping services to TB control programs. TB genotyping has the potential to change significantly how TB control is conducted in this country. By helping to identify TB patients who are involved in recent transmission, TB genotyping will have the following impact:
Outbreaks will be detected earlier and controlled more rapidly.
Incorrect TB diagnoses based on false-positive culture results will be identified more easily.
Unsuspected relationships between cases and new and unusual transmission settings will be discovered.
Transmission that occurs between patients who reside in different jurisdictions will be detected more readily.
TB programs will be able to evaluate completeness of routine contact investigations and progress toward TB elimination by monitoring surrogate measures of recent TB transmission.**How does TB genotyping help TB prevention and control practices?**
TB genotyping results, when combined with epidemiologic data, help to distinguish TB patients who are involved in the same chain of recent transmission. In the same way, TB genotyping helps to identify TB patients whose disease is the result of reactivation of a TB infection that was acquired in the past. Since TB prevention and control efforts directed at preventing TB transmission are fundamentally different from efforts to prevent reactivation, genotyping offers a powerful tool to help direct the application of these different efforts. Furthermore, TB genotyping allows us for the first time to monitor our progress toward eliminating TB transmission.
TB genotyping identifies genetic links between *Mycobacterium tuberculosis* isolates from different TB patients. If two TB patients have isolates with **nonmatching genotypes**, this indicates (with very rare exceptions, discussed in Chapter 4, *Combining Genotyping and Epidemiologic Data to Improve Our Understanding of Tuberculosis Transmission*) that the two patients are not involved in the **same chain of recent transmission** (recent transmission is defined as TB transmission that has occurred within the previous 2 years). The situation is more complex when two patients have isolates with **matching genotypes**, since, in some of these situations, the two patients will be involved in the same chain of recent transmission, but in other situations these patients will not be involved in the same chain of recent transmission. The key to determining if TB patients with matching genotypes are involved in the same chain of recent transmission is to investigate whether the patients share **epidemiologic links** that can explain where and how they might have transmitted TB among themselves.
If two patients with TB are known to have been in the same place when one of them was infectious, the two patients are said to share **known epidemiologic links**. If two patients have isolates with matching genotypes and they also share known epidemiologic links, this provides strong evidence that they are involved in the same chain of recent transmission. Patients who have isolates with matching genotypes are said to belong to the same **genotyping cluster**. Patients in the same genotyping cluster who share known epidemiologic links are said to belong to an **epidemiologically confirmed genotyping cluster**.
If two patients have isolates with matching genotypes but have not been found to have even possible epidemiologic links (i.e., they live in different locations, work in different locations and at different types of jobs, share no risk factors, and did not spend time at any common location), it is possible that, despite belonging to the same genotyping cluster, the two patients are not involved in the same chain of recent transmission.
If two patients have matching genotypes and share **possible epidemiologic links**, additional information is needed to decide if the two patients are involved in the same chain of recent transmission. For example, the two patients might live in the same neighborhood or they might share a common risk factor (e.g., use of illegal drugs or alcohol). In these cases, TB programs should consider conducting what we will call in later chapters of this guide a **cluster investigation.** This type of investigation allows programs to reexamine the information already gathered about the patients who belong to the same genotyping cluster and reinterview them to search for additional information that might confirm the hypothesis that the patients are involved in the same chain of recent transmission.
Chapter 4, *Combining Genotyping and Epidemiologic Data to Improve Our Understanding of Tuberculosis transmission* describes these definitions in more detail and provides a conceptual framework for combining genotyping and epidemiologic information to better understand TB transmission dynamics.“Through the use of universal genotyping, Kansas has been able to identify clusters of cases that would have been hard to identify through standard contact and epidemiologic investigations. We have found the use of genotyping particularly useful in working in the homeless communities where contact investigations traditionally are very vague and difficult to pursue due to the general anonymous nature of the population. Universal Genotyping drew our attention back to active cases who had no apparent epidemiological link, but as a result of more intensified investigations, further cases were not only linked, but additional case finding activities led to new cases being diagnosed early in the disease process. Maybe even more significant was the fact the genotyping results provided indisputable evidence of case to case transmission. As a result, the shelters who have housed the homeless have become far more willing and interested in partnering with public health efforts to control and eliminate TB in their population. Universal Genotyping has demonstrated significant value well beyond the obvious expectations of the program by opening many new doors of opportunity that were previously not accessible.”
Gianfranco Pezzino, MD, MPH
State Epidemiologist
Kansas Department of Health and Environment
							
					
						Page last reviewed:  September 1, 2012					Content source: 	Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention homeGuide to the Application of Genotyping to Tuberculosis Prevention and Control
Acknowledgments
Introduction to Tuberculosis Genotypingplus icon
Introduction to this Guide
Overview of Tuberculosis Genotyping
Overview of the CDC Tuberculosis Genotyping Program
TB Program Eligibility and Application Procedures
Tuberculosis Genotyping Case Studiesplus icon
Investigation of a Genotyping Cluster in a Low-Incidence State
Apparent Genotyping Cluster among Recent Immigrants from the Philippines
False-Positive Culture Investigation
Algorithm to Detect False-Positive Cultures
A Misdiagnosis that was Identified with Genotyping
Genotyping Used to Improve Contact and Cluster Investigations
Identification of Nontraditional Transmission Settings
Investigation of a Multistate Tuberculosis Outbreak
Homeless Shelter Outbreak Investigation
Using Genotyping to Evaluate the Impact of a Screening Program
CDC Tuberculosis Genotyping Laboratory Proceduresplus icon
Science behind Tuberculosis Genotyping
Description of Genotyping Methods
Submission of Isolates
Genotyping Results, Designation of Clusters, and Reporting
Suspected False-Positive Cultures
IS*6110*-based RFLP Analysis
Combining Genotyping and Epidemiologic Data to Improve Our Understanding of TB Transmissionplus icon
Definitions
Reading the Genotyping Laboratory Report
Comparing Genotyping and Epidemiologic Results from Two TB Patients
Comparing Genotyping and Epidemiologic Results from Three or More TB Patients
Clustering as a Surrogate Measure of Recent Transmission
Developing a Tuberculosis Genotyping Programplus icon
Developing a Written Plan
Initial Decisions
Establishing Procedures for:plus icon
Submitting Isolates
Receiving and Acting on Genotyping Results
Requesting RFLP Analysis
Submitting Additional Isolates from the Same Patient
Comparing Genotyping Results between Jurisdictions
False-Positive Cultures
Database Management and Quality Control
Special Issues
Applying Genotyping Results to Tuberculosis Control Practicesplus icon
Evaluating Matching Genotypes
Evaluating Nonmatching Genotypes
Suspected False-Positive Culture Investigations
Expanded Contact Investigations
Outbreak Investigations
Cluster Investigations
Monitoring Trends
Appendicesplus icon
Appendix A: Glossary and Abbreviations
Appendix B: References and Useful Resourcesplus icon
References Cited in the Guide
NTGSN Special Issue References
Information on Packaging and Shipping Infectious Substances
Core Steps of an Outbreak Investigation
Consultants Available to Offer Guidance To receive email updates about this page, enter your email address: Email Address			What's this?				Submit


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