Guide to the Application of Genotyping to Tuberculosis Prevention and Control

Tuberculosis Genotyping Case Studies: How TB Programs Have Used Genotyping

Apparent Genotyping Cluster Among Recent Immigrants from the Philippines: IS6110-based RFLP Needed to Discriminate Between Isolates Belonging to the Manila Strain

Previous results from the National Tuberculosis Genotyping and Surveillance Network and other studies showed that spoligotyping alone was not particularly helpful in distinguishing between isolates that belonged to a group generally referred to as the Beijing family of M. tuberculosis isolates. Data from CDC suggest that MIRU analysis, especially when combined with RFLP analysis, will be more discriminatory than spoligotyping alone. At the same time, we are beginning to see new genotyping families that contain isolates that are often not distinguished by spoligotyping plus MIRU analysis. The following case study describes patients with isolates from one such family, which has been named the Manila strain family because of its predominance in patients from Manila.

During 2000--2003, isolates from seven patients were identified as belonging to the same PCR cluster (i.e., each isolate had the same spoligotype and MIRU type). On the basis of the spoligotype and MIRU type, the CDC recognized that these isolates belonged to the Manila family. Analysis of data from the initial case-patient interviews revealed that they were all recent immigrants from the Philippines, but they lived in different regions of Wisconsin. The contact investigations of the cases did not reveal epidemiologic links between any of the patients.

Because no epidemiologic links were identified for these PCR-clustered cases, the TB program requested that the seven isolates be analyzed by RFLP, which revealed seven distinct patterns. Therefore, despite identical spoligotypes and MIRU types, these seven isolates were shown to be genetically distinct by RFLP analysis. The TB program did not undertake a cluster investigation, since the seven isolates were shown not to belong to the same genotyping cluster.