What's New in Blood Testing for TB Infection?

From Centers for Disease Control and Prevention (CDC): Expert Commentary
CDC Expert Commentary
What's New in Blood Testing for TB Infection?
Rear Admiral Kenneth Castro, MD

Authors and Disclosures

Posted: 03/14/2011


VIDEO:
What's New in Blood Testing for TB Infection?


Hello. My name is Dr. Kenneth Castro. I'm Director of the Division of Tuberculosis Elimination at CDC. Our division collaborates with domestic and international partners with the goal of eliminating tuberculosis in the United States as well as controlling tuberculosis worldwide. Today, I am speaking to you as part of the CDC Expert Commentary Series on Medscape [Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection --- United States, 2010].

I will provide information about the new CDC guidelines on tuberculosis blood tests and outline the advantages and limitations of using such tests. Then, I will highlight recommendations on how to use these diagnostic tools.

The Mantoux tuberculin skin test, also known as the TST, has been for many years the standard method of determining whether a person is infected with Mycobacterium tuberculosis. More recently, blood tests called interferon gamma release assays (IGRAs) have also been approved for the detection of M tuberculosis.

IGRAs are whole-blood tests that can aid in the diagnosis of M tuberculosis infection, including both latent infection and tuberculosis disease. Three commercially available IGRAs are approved by the US Food and Drug Administration (FDA) and include:

•QuantiFERON®-TB Gold; Cellestis – Manufacturer of QuantiFERON® Diagnostics and Research Products

•QuantiFERON®-TB Gold In-Tube; Cellestis – Manufacturer of QuantiFERON® Diagnostics and Research Products : QuantiFERON - TB Gold In-Tube

and

•T-SPOT®.TB
TB Testing | Blood Test for TB | Tuberculosis Screening

IGRAs have several advantages over the TST. They require only a single patient visit to conduct the test, results can be available within 24 hours, IGRA tests do not boost responses measured by subsequent tests, and previous BCG vaccination does not cause a false-positive IGRA test result.

There are, however, some limitations to using IGRAs. Blood samples must be processed within 8-30 hours after collection, while white blood cells are still viable, and any errors in handling blood specimens or in performing the assay can decrease the accuracy of IGRAs. Also, there are limited data on the ability of IGRAs to predict the risk for progressing to tuberculosis disease in the future.

There are also limited data on the use of IGRAs for some populations. These include children younger than 5 years of age, persons recently exposed to M tuberculosis; immunocompromised persons; and persons undergoing serial or repeat testing. Use caution when interpreting IGRA results in these populations. Also, IGRA test kits are more expensive than supplies used for the TST.

IGRA tests work by measuring a person's immune reactivity to M tuberculosis. A positive result suggests that tuberculosis infection is likely, a negative result suggests that infection is not likely, and an indeterminate or borderline result indicates an uncertain likelihood of tuberculosis infection.

Some highlights of the CDC recommendations on using IGRA tests are as follows:

•IGRAs can be used in place of, but not in addition to, the TST in all situations in which CDC recommends the TST as an aid in diagnosing tuberculosis infection. However, there are preferences and special considerations.
•For example, IGRAs are preferred for testing persons who have received BCG (either as a vaccine or for cancer therapy); and also for persons from groups that historically have poor rates of return for the TST reading 2 to 3 days later.
•However, the TST test is preferred over IGRAs for testing children younger than 5 years of age. And as with TSTs, IGRAs generally should not be used for testing persons who have a low risk for infection and a low risk for disease due to tuberculosis.
•IGRA tests can be used for contact investigations, testing during pregnancy, and screening of healthcare workers and others undergoing serial evaluation for tuberculosis infection. Routine testing with both the TST and IGRA is not recommended. For more information on when to use the IGRA test, see the Web resources listed at the end of this page.
•Selecting the most suitable test or combination of tests for detection of tuberculosis infection should be based on the reasons and the context for testing, test availability, and overall cost of testing. Each institution and tuberculosis control program should endeavor to evaluate the availability and benefits of IGRAs in prioritizing their use.
In summary, I would like to emphasize the following points:

First, 3 commercially available IGRA tests have been approved by the FDA for use in the United States.

Second, IGRAs have several advantages and limitations.

And finally, CDC recommends that IGRAs be used in place of, but not in addition to, the TST in all situations, as an aid in diagnosing tuberculosis infection. For more information about the tuberculosis blood test, please visit www.cdc.gov/tb or call 1-800-CDC-INFO.

Thank you.

Web Resources

TB Testing and Diagnosis (Physician Information)
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

Interferon-Gamma Release Assays (IGRAs) - Blood Tests for TB Infection
CDC | TB | Fact Sheets | Interferon-Gamma Release Assays (IGRAs)

TB Testing and Diagnosis (Patient Information)
CDC | TB | Testing & Diagnosis | General Information about TB Blood Tests

State TB Control Offices
CDC | TB | State TB Control Offices

RADM Kenneth G. Castro, MD is Commanding Flag Officer, CDC/ATSDR Commissioned Corps Director, CDC's Division of Tuberculosis Elimination. Since January 1993, RADM Kenneth G. Castro, MD has served as Director, Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), CDC. In this role, Dr. Castro leads the team of technical experts devoted to tuberculosis (TB) elimination efforts in the United States. His division sponsors TB prevention, control, and research activities throughout the nation and other parts of the world. Since 1995, he has served as co-chair of the US Federal Tuberculosis Task Force. Recognizing the importance and magnitude of global TB, Dr. Castro has advanced the involvement by the US in global TB control efforts, serving as an expert advisor to the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Diseases. He is a founding member of the global Stop TB Partnership and member of its Coordinating and Executive Boards. He has been called upon on several occasions to provide congressional testimony to describe the serious public health problems posed by TB, HIV-associated TB, and multidrug-resistant TB, both domestically and globally. Since the 2006 description of extensively drug resistant TB, he has provided national and global leadership in the development of a coordinated response to this urgent health problem. In recent years he has also served other key leadership roles during temporary assignments, as Acting Chief Health Officer for CDC's Emergency Operations response to the 2009 pandemic Influenza A (H1N1) in May 2009, and as Acting Incident Commander of CDC's Emergency Operations response to the 2010 Haiti Earthquake in late January 2010 -- while the Incident Commander traveled to Haiti.

In an unusual distinction afforded to a division director, Castro, a Commissioned Corps Officer in the US Public Health Service, was promoted to the flag rank of Assistant Surgeon General (RADM, O-7) in May 2000. In September 2008, RADM Castro was designated Commanding Flag Officer, CDC/ATSDR Commissioned Corps. In this capacity he acts as the Flag representative with oversight for more than 900 Commissioned Officers at CDC/ATSDR.

Prior to serving as Director of CDC's Division of TB Elimination, Castro worked as the Assistant Director for TB and HIV, Office of HIV/AIDS at CDC from May to December 1992. He was appointed to the office of the Associate Director of HIV/AIDS to coordinate CDC-wide HIV-associated TB activities in May 1992, after serving for almost 2 years as the Assistant Chief of the Epidemiology Branch in the Division of HIV/AIDS in the National Center for Infectious Diseases. From July 1989 until August 1990, he served as Special Assistant to the Director for Science in the Division of HIV/AIDS. Castro began his career with CDC in 1983 as an Epidemic Intelligence Service (EIS) officer with the AIDS Program, where he became a staff medical epidemiologist after completing the EIS training in 1985.

A physician-scientist trained in epidemiology, Dr. Castro has a specialty in internal medicine and subspecialty in infectious diseases. He received his bachelor's degree in 1974 from the University of Puerto Rico and completed post-graduate biology studies at Northeastern University in Boston in 1976 and his medical doctorate from the State University of New York at Stony Brook School of Medicine in 1980. He completed his internal medicine postgraduate training in 1983 at the residency program in social medicine at the Montefiore Medical Center, Albert Einstein College of Medicine in New York. From 1988 until 1989, he completed a fellowship in infectious diseases at the Emory University School of Medicine, where his work focused on describing the increase in the number of people with TB and its association with the HIV/AIDS epidemic. In 2008-2009, he completed the National Preparedness Leadership Institute Program at the Harvard School of Public Health and Harvard Kennedy School of Government. Dr. Castro also holds an academic appointment as adjunct clinical faculty member of the Division of Infectious Diseases, Department of Medicine, Emory School of Medicine, and has hospital privileges at the infectious diseases clinic at Grady Health System in Atlanta.

An award-winning author of more than 120 scholarly publications, Dr. Castro serves as a peer reviewer for numerous scientific journals and is an associate editor for the journals International Journal of Tuberculosis and Lung Disease and Emerging infectious Diseases. He also maintains memberships in the leading scientific societies in his field. A native Puerto Rican, Castro speaks fluent Spanish and has frequently served as advisor to the Puerto Rico Department of Health, the Pan American Health Organization, World Health Organization, and several Ministries of Health in countries where TB and HIV constitute major public health problems. In 2008 Dr. Castro was recognized by the Hispanic Officers Advisory Committee, US Public Health Service Commissioned Corps with the prestigious Juan Carlos Finlay award.