Guide to the Application of Genotyping to Tuberculosis Prevention and Control
Developing a Tuberculosis Genotyping Program
Establishing Procedures for Submitting Isolates
A challenging aspect of initiating a TB genotyping program is establishing procedures for submitting isolates to the genotyping laboratory. Each TB program will face unique issues; however, general aspects of the problems programs will have to address are discussed in the following sections.
Establishing a Relationship with Submitting Laboratories
The TB program will need to work with the state public health laboratory and other submitting laboratories to develop a plan for shipping isolates. TB programs will want to notify submitting laboratories about the genotyping program and ask about their willingness to submit isolates, either directly to the genotyping laboratories or to the state laboratory. A wide range of responses can be anticipated. TB programs should be prepared for requests for detailed instructions, shipping materials, reimbursement for shipping costs, and other conditions for participation, including the requirement for a specific request from the TB program for each isolate.
Negotiating Payment for Shipping Charges
Because neither the genotyping laboratories nor CDC will pay the shipping charges for isolates sent from the clinical laboratories or the state public health laboratory to the genotyping laboratory, payment procedures will need to be worked out by the TB Program. See Procedures to Reduce Shipping Costs.
Communicating Submission Procedures to Laboratories
The usefulness of genotyping results to the TB program is related directly to the timeliness of the information, and the genotyping laboratory procedures are designed to provide rapid turnaround. The most likely factor affecting how quickly the TB program will receive genotyping results will be the period of time that elapses between the identification of a culture as M. tuberculosis complex and the shipment of that isolate to the genotyping laboratory. Therefore, it is important for the TB program to establish procedures that minimize this delay. These procedures and information on acceptable and unacceptable material to be submitted should be shared with the submitting laboratories.
Procedures to Reduce Shipping Costs
Because complying with current biosafety standards can be expensive, procedures are needed for batching isolates in a single shipment to reduce costs. It costs approximately $50 to mail one container by an expedited carrier to a genotyping laboratory. One container can accommodate more than 40 2-ml freeze vials, but only eight L-J slants. If the state public health laboratory is the only laboratory that will submit isolates and isolates are shipped in freeze vials, the shipping costs will be very reasonable. On the other hand, if numerous laboratories submit and ship isolates as L-J slants, the costs will mount quickly. In establishing submission procedures, the TB program should balance the importance of timely submission of isolates with the cost savings associated with batching isolates.
Frequency of Shipments
The frequency of shipments will vary depending on the number of isolates obtained per week balanced with the needs of the TB program for rapid turnaround. For example, state laboratories that process 10 or more isolates per week should ship weekly. Laboratories with two or three isolates per week may want to ship every 2 weeks. TB programs in low-incidence areas may need to ship each isolate as soon as it is identified.
Avoiding Duplicate Submissions
TB programs should establish procedures to minimize the submission of duplicate specimens from the same patient. The following section titled, Establishing Procedures for Submitting Additional Isolates from the Same Patient, explains the rare exceptions to this rule. In the interest of maintaining rapid turnaround times, the genotyping laboratories will permit occasional inadvertent submission of duplicate isolates.
Isolate Tracking System
TB programs will have to establish a tracking database system to verify the submission of patient isolates and the receipt and genotyping of the isolates by the genotyping laboratory. A tracking system will also allow the TB program to send a reminder to the submitting laboratory if an isolate is not submitted in a timely fashion.
Additional Submission Procedures Required for Selective Genotyping
If only selected isolates are to be submitted, the TB program will have to take the following additional steps:
- Establish a procedure to identify all patients with newly diagnosed culture-positive TB.
- When a new diagnosis of culture-positive TB is made, review the information obtained during the contact investigation to determine whether the patient’s isolate is a high priority for genotyping.
- If the patient’s isolate is to be genotyped, contact the laboratory that has the isolate and request that it be sent to the genotyping laboratory.
- The submitting laboratory may need to subculture the specimen before sending it to the genotyping laboratory.
Programs that decide to adopt selective genotyping should consider what types of isolates would have the highest priority for submittal. The following four criteria, from the most important to the least important, can guide the selection of isolates.
- Cultures that represent suspected false-positive cultures
- Patients suspected to be part of an outbreak
- High-risk groups (e.g., homeless or other persons who live in congregate settings, HIV-infected or other immunocompromised persons, or children)
- Patients with recurrent TB