Guide to the Application of Genotyping to Tuberculosis Prevention and Control
Tuberculosis Genotyping Case Studies: How TB Programs Have Used Genotyping
Investigation of a Genotyping Cluster in a Low-Incidence State
Universal genotyping using spoligotyping and MIRU analysis was implemented in Wisconsin in 2001 as part of a CDC-sponsored research project to study the impact of genotyping in states with low TB rates. The following case study illustrates how the Wisconsin TB control program used genotyping results, demographic data, results of contact investigations, and a follow-up cluster investigation with the patients to identify a previously unrecognized cluster of cases involved in the same chain of recent transmission.
Six patients were identified whose M. tuberculosis isolates all had an identical spoligotype and MIRU type. On the basis of these results, the genotyping laboratory assigned each isolate the same PCR cluster designation (Both the spoligotype and MIRU analysis are based on PCR, and together they are referred to as PCR-based genotyping tests—isolates that have matching spoligotypes and MIRU types are automatically assigned the same PCR cluster designation.)
The TB program staff reviewed data from previous interviews with the six patients and recognized that they were predominantly middle-aged, U.S.-born, non-Hispanic black males who lived in close proximity to each other; three patients admitted to excessive use of alcohol and drugs. Based on this information, the staff concluded that these six TB patients had possible epidemiologic links and, therefore, the genotyping cluster could represent ongoing transmission (see Chapter 4, Combining Genotyping Results and Epidemiologic Data to Improve Our Understanding of Tuberculosis Transmission, for definitions of epidemiologic links).
The TB program requested that the genotyping laboratory perform IS6110-based RFLP analysis on the six isolates to confirm the matching spoligotype and MIRU results. The RFLP analysis revealed a matching 9-band pattern, and, on the basis of this additional data, the genotyping laboratory assigned each isolate the same PCR/IS6110 cluster designation.
The TB program now had stronger (but still not confirmatory) evidence that the six patients were involved in the same chain of recent transmission, so they conducted a cluster investigation to determine if the possible epidemiologic links between the patients that they had detected could be confirmed.
Five patients were interviewed again (one patient was deceased); however this time, greater detail was extracted about where they spent time and with whom (over the previous 5 years in some cases). The cluster investigation was worthwhile, as it revealed known epidemiologic links between the six patients. The cluster investigation also identified five high-risk sites (a single room occupancy hotel, two homeless shelters, a crack house, and a bar), where TB transmission could have occurred. Patient interviews revealed three additional cluster-related patients who had matching genotypes and similar epidemiologic links to the other clustered patients.
TB screening at one of the homeless shelters and at a crack house was conducted. The city of Milwaukee is in the process of investigating current screening practices at homeless shelters and is providing TB-related education to health-care providers in the community to help them recognize and treat suspected TB patients promptly.