Guide to the Application of Genotyping to Tuberculosis Prevention and Control
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
Kansas Department of Health and Environment