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Guide to the Application of Genotyping to Tuberculosis Prevention
and Control
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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
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Last Reviewed: 05/18/2008 Content Source: Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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