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Guide to the Application of Genotyping to Tuberculosis Prevention and Control										Related Pages
										**Tuberculosis Genotyping Case Studies: How TB Programs Have Used Genotyping**
**Investigation of a Genotyping Cluster in a Low-Incidence State**
Universal genotyping using spoligotyping and MIRU analysis was implemented in Wisconsin in 2001 as part of a CDC-sponsored research project to study the impact of genotyping in states with low TB rates. The following case study illustrates how the Wisconsin TB control program used genotyping results, demographic data, results of contact investigations, and a follow-up cluster investigation with the patients to identify a previously unrecognized cluster of cases involved in the same chain of recent transmission.
Six patients were identified whose *M. tuberculosis* isolates all had an identical spoligotype and MIRU type. On the basis of these results, the genotyping laboratory assigned each isolate the same PCR cluster designation (Both the spoligotype and MIRU analysis are based on PCR, and together they are referred to as PCR-based genotyping tests—isolates that have matching spoligotypes and MIRU types are automatically assigned the same PCR cluster designation.)
The TB program staff reviewed data from previous interviews with the six patients and recognized that they were predominantly middle-aged, U.S.-born, non-Hispanic black males who lived in close proximity to each other; three patients admitted to excessive use of alcohol and drugs. Based on this information, the staff concluded that these six TB patients had possible epidemiologic links and, therefore, the genotyping cluster could represent ongoing transmission (see Chapter 4, *Combining Genotyping Results and Epidemiologic Data to Improve Our Understanding of Tuberculosis Transmission*, for definitions of epidemiologic links).
The TB program requested that the genotyping laboratory perform IS*6110*-based RFLP analysis on the six isolates to confirm the matching spoligotype and MIRU results. The RFLP analysis revealed a matching 9-band pattern, and, on the basis of this additional data, the genotyping laboratory assigned each isolate the same PCR/IS*6110* cluster designation.
The TB program now had stronger (but still not confirmatory) evidence that the six patients were involved in the same chain of recent transmission, so they conducted a cluster investigation to determine if the possible epidemiologic links between the patients that they had detected could be confirmed.
Five patients were interviewed again (one patient was deceased); however this time, greater detail was extracted about where they spent time and with whom (over the previous 5 years in some cases). The cluster investigation was worthwhile, as it revealed known epidemiologic links between the six patients. The cluster investigation also identified five high-risk sites (a single room occupancy hotel, two homeless shelters, a crack house, and a bar), where TB transmission could have occurred. Patient interviews revealed three additional cluster-related patients who had matching genotypes and similar epidemiologic links to the other clustered patients.
TB screening at one of the homeless shelters and at a crack house was conducted. The city of Milwaukee is in the process of investigating current screening practices at homeless shelters and is providing TB-related education to health-care providers in the community to help them recognize and treat suspected TB patients promptly.
							
					
						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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