Guide to the Application of Genotyping to Tuberculosis Prevention and Control

Tuberculosis Genotyping Case Studies: How TB Programs Have Used Genotyping

In this chapter, we will provide examples of how TB programs have used genotyping to assist them in conducting important TB control activities. Specifically, this chapter provides examples of how genotyping results have helped identify new, previously unrecognized transmission links between patients with TB, how they have been used effectively during outbreak investigations, and how these results can be used in the future to detect outbreaks at early stages. We will also describe how genotyping has been used to monitor epidemiologic trends, evaluate program performance, and identify instances of false-positive cultures that can result from mislabeling clinical specimens, cross-contamination of cultures, or other problems.

In the past, most programs have submitted only selected M. tuberculosis isolates for genotyping. Although selective genotyping provides new insights into TB transmission, the power of genotyping is increased considerably when isolates from all patients with culture-positive TB are genotyped, even before contact investigations or outbreak investigations raise the suspicion that there might be a link between patients. In reading the case studies that follow, pay attention to what advantages accrue to programs that institute selective genotyping and what advantages accrue only to programs that institute universal genotyping.

Most of the data that has been gathered about the utility of TB genotyping is based on the genotyping approach used by the TB programs that participated in the National Tuberculosis Genotyping and Surveillance Network (NTGSN) (Castro 2002). A special issue of the journal Emerging Infectious Diseases was devoted to presenting the findings of the NTGSN study and is available at http://wwwnc.cdc.gov/eid/articles/issue/8/11/table-of-contents.

The NTGSN study was based on IS6110-based RFLP analysis supplemented by spoligotyping for certain isolates. Data are still limited about how this past approach will compare with the current approach used by the CDC Tuberculosis Genotyping Program, which is based on spoligotyping and MIRU analysis of all isolates, with IS6110-based RFLP for only selected isolates (see Chapter 5, Developing a Tuberculosis Genotyping Program, for details about when RFLP is helpful). The first three of the following examples were reported by TB programs that are using the current approach; the others come from the National Tuberculosis Genotyping and Surveillance Network.