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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**
**A Misdiagnosis that Was Identified with Genotyping**
A 36-year-old woman came to the emergency room with a 2-day history of fevers, cough, and right-sided pleuritic chest pain. She had no known history of tuberculosis exposure. Her past medical history was notable for injection drug use (heroin) up to the time of her admission. Her physical examination showed a fever of 39C and signs of consolidation at the right lung base. A chest radiograph showed right lower lobe infiltrates with an associated small pleural effusion. The patient was admitted to respiratory isolation and treated with intravenous ceftriaxone. She responded quickly and became afebrile after 2 days of therapy. A standard sputum culture grew normal oral flora; blood culture results were negative. Three sputum specimens were acid-fast bacilli (AFB) smear-negative, but she had a 15-mm response to tuberculin skin testing (TST). A human immunodeficiency virus (HIV) test was negative. She was discharged to complete 7 days of therapy with amoxicillin for community-acquired pneumonia.
She was called back to the TB Clinic 1 month after discharge when one of the three sputum specimens grew drug-susceptible *M. tuberculosis*, and she was given a diagnosis of tuberculosis. By that time she reported feeling back to normal, and a repeat chest radiograph was normal. Two additional sputum specimens were collected and were AFB smear- and eventually culture-negative. She was treated with isoniazid (INH), rifampin, pyrazinamide, and ethambutol for 2 months and then with isoniazid and rifampin for 4 additional months. The TB control program also performed a relatively large contact investigation. Two years later, during a study in which all *M. tuberculosis* isolates underwent genotyping, her isolate was found to match that of a specimen from a laboratory proficiency test specimen that underwent initial processing on the same day.
This case has several characteristic features of a false-positive culture result. First, and most importantly, the clinical case was atypical for tuberculosis with an acute onset and rapid resolution with antibiotic therapy having no activity against mycobacteria. Although the patient had latent tuberculosis (the positive tuberculin skin test), the fact that the infiltrate completely resolved within 1 month, essentially without anti-tuberculosis therapy, is not consistent with tuberculosis. Second, only one of several specimens grew *M. tuberculosis* (a single-positive culture result). Routine review of single-positive culture results is one method to detect potential false-positive cultures. Treating this patient for TB required the TB program to use valuable resources and exposed the patient to the toxicity of unnecessary multidrug therapy.
							
					
						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
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