IGRAs Are TB Test Alternative After Age 5 Years

VAIL, COLO. – Interferon-gamma release assays offer significant advantages over conventional tuberculin skin testing under certain circumstances, but not in children younger than 5 years old.

The IFN-gamma release assays (IGRAs) have not been well studied in children younger than age 5 years, plus the available data suggest that the test results are less reliable in this age group. Given the high rate of progression from latent to active disease as well as the high rates of severe disease in this younger population, the Centers for Disease Control and Prevention recommends using the tuberculin skin test (TST) for these young children, Dr. Donna Curtis said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Beyond age 5 years, however, the sensitivity and specificity of IGRAs and the TST are similar, and the tests can be used interchangeably, added Dr. Curtis of the University of Colorado at Denver.

IGRAs are blood tests that measure IFN-gamma production by WBCs in response to stimulation by TB antigens. The two Food and Drug Administration–approved IGRAs on the market are Cellistis’s QuantiFERON–TB Gold In-Tube test and Oxford Immunotec’s T-SPOT.TB test. The test results are reported from the laboratory as positive, negative, or indeterminate.

Among the IGRAs’ advantages are that only a single patient visit is required and results are available 24 hours after laboratory processing. Also, there are no false-positives due to previous BCG (bacille Calmette-Guérin) vaccination, a big problem with TSTs in foreign-born patients. And unlike the TST, there is no boosting phenomenon with repeated IGRA tests.

On the other hand, an IGRA requires fresh blood and plenty of it – 4 tubes’ worth – and it must be transported promptly to the laboratory for processing. The cost, albeit variable, is often more than that of a TST.

An IGRA is clearly the preferred test in patients older than age 5 years who have received a BCG vaccine, and in those with a reduced likelihood of returning for a second visit to have their TST read (such as substance abusers, people with transportation difficulties, and patients in homeless shelters).

As with TSTs, IGRAs should be used only to test patients with a TB exposure or risk factors. Otherwise, the odds of a false-positive test are greatly increased. After all, fewer than 1% of the noninstitutionalized U.S. population with no risk factors has a latent TB infection.

The CDC recommends both the IGRA and TST in patients whose first test is negative but who have a high risk of infection or progression to active disease. The health agency also recommends both tests as useful when the first test is positive and additional evidence is needed to convince the patient or family to undergo treatment.

Dr. Curtis noted that a recent Croatian study involving 142 BCG-vaccinated children younger than age 5 with a known TB exposure – all of whom had both a TST and IGRA – found a high rate of discordant results. The investigators concluded that both tests should routinely be used in this age group, and that a child should be considered infected if either or both results are positive (Pediatr. Infect. Dis. J. 2011 May 12 [Epub ahead of print]).

However, Dr. John W. Ogle commented that the dual-test strategy for younger children is fraught with problems.

"There are no normative data for IGRAs in kids under age 5 years. The IGRAs are standardized on adult patients. The amount of interferon that you make in response to an antigen is age dependent; kids less than age 5 make much less compared to adults. So if you do an IGRA in a young kid, you’re much more likely to have a false-negative result. Families will beg you to do an IGRA because they’ve learned this on the Internet and they don’t want their child to have to be exposed to the medical treatment," explained Dr. Ogle, professor and vice chair of pediatrics at the University of Colorado at Denver and director of pediatric services at Denver Health Medical Center.

A year ago, the CDC issued updated guidelines for the use of IGRAs (MMWR 2010; 59[RR-5];1-25).Dr. Curtis said physicians with any questions about IGRAs will find this publication quite helpful, even though it includes studies published only through 2008.

She declared having no financial conflicts.

VAIL, COLO. – Interferon-gamma release assays offer significant advantages over conventional tuberculin skin testing under certain circumstances, but not in children younger than 5 years old.

The IFN-gamma release assays (IGRAs) have not been well studied in children younger than age 5 years, plus the available data suggest that the test results are less reliable in this age group. Given the high rate of progression from latent to active disease as well as the high rates of severe disease in this younger population, the Centers for Disease Control and Prevention recommends using the tuberculin skin test (TST) for these young children, Dr. Donna Curtis said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Beyond age 5 years, however, the sensitivity and specificity of IGRAs and the TST are similar, and the tests can be used interchangeably, added Dr. Curtis of the University of Colorado at Denver.

IGRAs are blood tests that measure IFN-gamma production by WBCs in response to stimulation by TB antigens. The two Food and Drug Administration–approved IGRAs on the market are Cellistis’s QuantiFERON–TB Gold In-Tube test and Oxford Immunotec’s T-SPOT.TB test. The test results are reported from the laboratory as positive, negative, or indeterminate.

Among the IGRAs’ advantages are that only a single patient visit is required and results are available 24 hours after laboratory processing. Also, there are no false-positives due to previous BCG (bacille Calmette-Guérin) vaccination, a big problem with TSTs in foreign-born patients. And unlike the TST, there is no boosting phenomenon with repeated IGRA tests.

On the other hand, an IGRA requires fresh blood and plenty of it – 4 tubes’ worth – and it must be transported promptly to the laboratory for processing. The cost, albeit variable, is often more than that of a TST.

An IGRA is clearly the preferred test in patients older than age 5 years who have received a BCG vaccine, and in those with a reduced likelihood of returning for a second visit to have their TST read (such as substance abusers, people with transportation difficulties, and patients in homeless shelters).

As with TSTs, IGRAs should be used only to test patients with a TB exposure or risk factors. Otherwise, the odds of a false-positive test are greatly increased. After all, fewer than 1% of the noninstitutionalized U.S. population with no risk factors has a latent TB infection.

The CDC recommends both the IGRA and TST in patients whose first test is negative but who have a high risk of infection or progression to active disease. The health agency also recommends both tests as useful when the first test is positive and additional evidence is needed to convince the patient or family to undergo treatment.

Dr. Curtis noted that a recent Croatian study involving 142 BCG-vaccinated children younger than age 5 with a known TB exposure – all of whom had both a TST and IGRA – found a high rate of discordant results. The investigators concluded that both tests should routinely be used in this age group, and that a child should be considered infected if either or both results are positive (Pediatr. Infect. Dis. J. 2011 May 12 [Epub ahead of print]).

However, Dr. John W. Ogle commented that the dual-test strategy for younger children is fraught with problems.

"There are no normative data for IGRAs in kids under age 5 years. The IGRAs are standardized on adult patients. The amount of interferon that you make in response to an antigen is age dependent; kids less than age 5 make much less compared to adults. So if you do an IGRA in a young kid, you’re much more likely to have a false-negative result. Families will beg you to do an IGRA because they’ve learned this on the Internet and they don’t want their child to have to be exposed to the medical treatment," explained Dr. Ogle, professor and vice chair of pediatrics at the University of Colorado at Denver and director of pediatric services at Denver Health Medical Center.

A year ago, the CDC issued updated guidelines for the use of IGRAs (MMWR 2010; 59[RR-5];1-25).Dr. Curtis said physicians with any questions about IGRAs will find this publication quite helpful, even though it includes studies published only through 2008.

She declared having no financial conflicts.

VAIL, COLO. – Interferon-gamma release assays offer significant advantages over conventional tuberculin skin testing under certain circumstances, but not in children younger than 5 years old.

The IFN-gamma release assays (IGRAs) have not been well studied in children younger than age 5 years, plus the available data suggest that the test results are less reliable in this age group. Given the high rate of progression from latent to active disease as well as the high rates of severe disease in this younger population, the Centers for Disease Control and Prevention recommends using the tuberculin skin test (TST) for these young children, Dr. Donna Curtis said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Beyond age 5 years, however, the sensitivity and specificity of IGRAs and the TST are similar, and the tests can be used interchangeably, added Dr. Curtis of the University of Colorado at Denver.

IGRAs are blood tests that measure IFN-gamma production by WBCs in response to stimulation by TB antigens. The two Food and Drug Administration–approved IGRAs on the market are Cellistis’s QuantiFERON–TB Gold In-Tube test and Oxford Immunotec’s T-SPOT.TB test. The test results are reported from the laboratory as positive, negative, or indeterminate.

Among the IGRAs’ advantages are that only a single patient visit is required and results are available 24 hours after laboratory processing. Also, there are no false-positives due to previous BCG (bacille Calmette-Guérin) vaccination, a big problem with TSTs in foreign-born patients. And unlike the TST, there is no boosting phenomenon with repeated IGRA tests.

On the other hand, an IGRA requires fresh blood and plenty of it – 4 tubes’ worth – and it must be transported promptly to the laboratory for processing. The cost, albeit variable, is often more than that of a TST.

An IGRA is clearly the preferred test in patients older than age 5 years who have received a BCG vaccine, and in those with a reduced likelihood of returning for a second visit to have their TST read (such as substance abusers, people with transportation difficulties, and patients in homeless shelters).

As with TSTs, IGRAs should be used only to test patients with a TB exposure or risk factors. Otherwise, the odds of a false-positive test are greatly increased. After all, fewer than 1% of the noninstitutionalized U.S. population with no risk factors has a latent TB infection.

The CDC recommends both the IGRA and TST in patients whose first test is negative but who have a high risk of infection or progression to active disease. The health agency also recommends both tests as useful when the first test is positive and additional evidence is needed to convince the patient or family to undergo treatment.

Dr. Curtis noted that a recent Croatian study involving 142 BCG-vaccinated children younger than age 5 with a known TB exposure – all of whom had both a TST and IGRA – found a high rate of discordant results. The investigators concluded that both tests should routinely be used in this age group, and that a child should be considered infected if either or both results are positive (Pediatr. Infect. Dis. J. 2011 May 12 [Epub ahead of print]).

However, Dr. John W. Ogle commented that the dual-test strategy for younger children is fraught with problems.

"There are no normative data for IGRAs in kids under age 5 years. The IGRAs are standardized on adult patients. The amount of interferon that you make in response to an antigen is age dependent; kids less than age 5 make much less compared to adults. So if you do an IGRA in a young kid, you’re much more likely to have a false-negative result. Families will beg you to do an IGRA because they’ve learned this on the Internet and they don’t want their child to have to be exposed to the medical treatment," explained Dr. Ogle, professor and vice chair of pediatrics at the University of Colorado at Denver and director of pediatric services at Denver Health Medical Center.

A year ago, the CDC issued updated guidelines for the use of IGRAs (MMWR 2010; 59[RR-5];1-25).Dr. Curtis said physicians with any questions about IGRAs will find this publication quite helpful, even though it includes studies published only through 2008.

She declared having no financial conflicts.