Guide to the Application of Genotyping to Tuberculosis Prevention and Control

Developing a Tuberculosis Genotyping Program

Establishing Procedures for Submitting Additional Isolates from the Same Patient

Under normal circumstances, the genotyping laboratories will genotype only one isolate from each patient with TB. Like drug-susceptibility test results, there is usually no benefit in testing additional isolates. There are exceptions to this rule, however, and some of them are discussed in the following sections.

Evaluate Likelihood of Exogenous Reinfection versus Relapse

Patients who recently completed therapy but subsequently become ill may have been infected with a different strain of M. tuberculosis (i.e., exogenous reinfection), or they may have had a relapse of their initial infection that was caused by the same M. tuberculosis strain. Genotyping the subsequent isolates will help distinguish between these two possibilities.

Assess Discrepant Drug Susceptibility Test Results

A second patient isolate should be submitted for genotyping when drug susceptibility results differ substantially among isolates from the same patient. Although discrepant results can indicate that the patient’s isolate has developed secondary drug resistance, the results may be caused by a false-positive culture. Genotyping the subsequent isolate will help distinguish between these two possibilities.

Evaluate Questionable Genotyping Results

A second isolate from the same patient may be considered for submission when the genotyping results from the first isolate are not compatible with epidemiologic information. For example, if two TB patients were identified as having spent a prolonged period of time together in the same place but their isolate genotype patterns do not match, a second isolate should be submitted for genotyping to evaluate the possibility that an error occurred. Such errors can occur during the following steps: submission of the isolate, processing of the isolate at the genotyping laboratories, or transmission of the results to the TB program. If the genotyping results for the second isolate are identical to those of the first isolate, the most likely explanation is that the initial epidemiologic information was incorrect or not relevant to the actual chain of transmission.