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Guide to the Application of Genotyping to Tuberculosis Prevention
and Control
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Developing a Tuberculosis Genotyping Program
False-Positive Cultures
An important use of genotyping is to detect or confirm suspected
false-positive cultures that are due to cross contamination, mislabeled
specimens, and other errors. Procedures for dealing with false-positive
cultures differ somewhat, depending on whether the error was suspected
before the genotyping results were known or the error was identified
as a result of the genotyping laboratory report.
“Genotyping of TB isolates is
particularly useful in the evaluation of patients who have
only a single culture-positive specimen, a population
for whom up to 40% of the isolates are false-positive. Timely
evaluation of these isolates prevents unwarranted isolation,
treatment and contact investigations. Genotyping is also useful
over the intermediate time period of months to several years
in clarifying the role of recent transmission in
high-risk populations and methods of intervention. Genotyping
in Denver identified a large outbreak that was introduced
by a patient who defaulted from TB treatment in Louisiana.
This data lead to an ongoing TB screening program that
has detected such cases earlier and lead us to aggressively
pursue the location of defaulters who leave our area.”
Randall Reves, MD
Director
Denver Metropolitan TB Program
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Suspected False-Positive Cultures
A laboratory may suspect that an M. tuberculosis-positive
culture represents an error when two or more specimens processed
on the same day become positive or when only one culture out of
many from the same patient becomes positive. A clinician may suspect
a false-positive culture when TB is diagnosed for a patient on the
basis of a single culture but the patient has an incompatible clinical
picture.
When a false-positive culture is suspected, the laboratory or clinician
may want to verify this suspicion before they report the patient
as having a new case. The TB Genotyping Isolate Submission Form
includes a field to identify an isolate as a possible false-positive
culture (the column title is “suspected_false_positive”). When the
suspicion of a false-positive culture is flagged on the form, the
genotyping laboratory will send the genotyping results to the submitting
laboratory and to the TB program. The TB program should discuss
this procedure with laboratories in its jurisdiction and agree on
a process for submission of the isolates, either directly or through
the state laboratory, and perhaps use an expedited protocol. All
isolates submitted to the genotyping laboratory will receive rapid
turnaround, so there is no need to request expedited typing. When
the spoligotype and MIRU type for a suspected false-positive culture
match the genotype of the putative source isolate, this provides
strong evidence that the culture is false-positive. In this case,
there is no need for confirmation by IS6110-based RFLP
analysis.
Unsuspected False-Positive Cultures
False-positive cultures can also be detected by analysis of genotyping
results. A TB program’s genotyping plan should include a procedure
for evaluating all matching isolates for the possibility that one
or more represent an unsuspected false-positive culture. Unsuspected
false-positive culture results that are identified on the basis
of matching PCR genotyping results should be confirmed with RFLP
analysis. The genotyping laboratories will not have sufficient patient
or laboratory information to help decide whether particular matching
isolates represent false-positive cultures, except in the instance
of contamination with common laboratory control strains.
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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