Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection --- United States, 2010

Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection --- United States, 2010
Recommendations and Reports
June 25, 2010 / 59(RR05);1-25


Prepared by

Gerald H. Mazurek, MD, John Jereb, MD, Andrew Vernon, MD, Phillip LoBue, MD, Stefan Goldberg, MD, Kenneth Castro, MD

Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC



The material in this report originated in the National Center for HIV, STD, and TB Prevention, Kevin Fenton, MD, PhD, Director; and the Division of Tuberculosis Elimination, Kenneth G. Castro, MD, Director.

Corresponding preparer: Gerald H. Mazurek, MD, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC, 1600 Clifton Rd., N.E., MS E-10, Atlanta, GA 30333. Telephone: 404-639-8174 begin_of_the_skype_highlighting 404-639-8174 end_of_the_skype_highlighting; Fax: 404-639-8961; E-mail: gym6@cdc.gov.



Summary
In 2005, CDC published guidelines for using the QuantiFERON-TB Gold test (QFT-G) (Cellestis Limited, Carnegie, Victoria, Australia) (CDC. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR;54[No. RR-15]:49--55). Subsequently, two new interferon gamma (IFN- γ) release assays (IGRAs) were approved by the Food and Drug Administration (FDA) as aids in diagnosing M. tuberculosis infection, both latent infection and infection manifesting as active tuberculosis. These tests are the QuantiFERON-TB Gold In-Tube test (QFT-GIT) (Cellestis Limited, Carnegie, Victoria, Australia) and the T-SPOT.TB test (T-Spot) (Oxford Immunotec Limited, Abingdon, United Kingdom). The antigens, methods, and interpretation criteria for these assays differ from those for IGRAs approved previously by FDA.

For assistance in developing recommendations related to IGRA use, CDC convened a group of experts to review the scientific evidence and provide opinions regarding use of IGRAs. Data submitted to FDA, published reports, and expert opinion related to IGRAs were used in preparing these guidelines. Results of studies examining sensitivity, specificity, and agreement for IGRAs and TST vary with respect to which test is better. Although data on the accuracy of IGRAs and their ability to predict subsequent active tuberculosis are limited, to date, no major deficiencies have been reported in studies involving various populations.

This report provides guidance to U.S. public health officials, health-care providers, and laboratory workers for use of FDA-approved IGRAs in the diagnosis of M. tuberculosis infection in adults and children. In brief, TSTs and IGRAs (QFT-G, QFT-GIT, and T-Spot) may be used as aids in diagnosing M. tuberculosis infection. They may be used for surveillance purposes and to identify persons likely to benefit from treatment. Multiple additional recommendations are provided that address quality control, test selection, and medical management after testing.

Although substantial progress has been made in documenting the utility of IGRAs, additional research is needed that focuses on the value and limitations of IGRAs in situations of importance to medical care or tuberculosis control. Specific areas needing additional research are listed.

Introduction
Before 2001, the tuberculin skin test (TST) was the only practical and commercially available immunologic test for Mycobacterium tuberculosis infection approved in the United States (1). Recognition that interferon gamma (IFN-γ) plays a critical role in regulating cell-mediated immune responses to M. tuberculosis infection led to development of interferon gamma release assays (IGRAs) for the detection of M. tuberculosis infection (2--4). IGRAs detect sensitization to M. tuberculosis by measuring IFN-γ release in response to antigens representing M. tuberculosis. In 2001, the QuantiFERON-TB test (QFT) (Cellestis Limited, Carnegie, Victoria, Australia) became the first IGRA approved by the Food and Drug Administration (FDA) as an aid for diagnosing M. tuberculosis infection (5,6). In 2005, the QuantiFERON-TB Gold test (QFT-G) (Cellestis Limited, Carnegie, Victoria, Australia) became the second IGRA approved by FDA as an aid for diagnosing M. tuberculosis infection (7,8). CDC published guidelines for using QFT in 2003 and for using QFT-G in 2005 (6,8).

Updated IGRA guidelines are needed because since 2005, two new IGRAs have been approved by FDA, and several hundred peer-reviewed articles describing clinical studies of IGRAs have been published. This report provides updated guidance to U.S. public health officials, health-care providers, and laboratory workers for use of FDA-approved IGRAs in the diagnosis of M. tuberculosis infection in adults and children.

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Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection --- United States, 2010