Table 1. Recommendations on Interferon Gamma Release Assays (IGRAs) for specific indications or subgroups.

No.	Specific subgroup or clinical indication	Previous ACS recommendation [CCDR 2008]	Updated recommendation [2010]	Comments
1	Diagnosis of active TB in adults with suspected TB disease	IGRAs are not recommended for the diagnosis of active TB in adults. Clinicians who manage patients with suspected TB disease should align their practice with the Canadian Tuberculosis Standards and the International Standards for Tuberculosis Care, and use sputum smear microscopy and culture to investigate adult patients with suspected active TB.	Same	No change
2	Diagnosis of active TB in children (under age 18) with suspected TB disease	Evidence of TB infection in children is often used in making a diagnosis of active TB, in addition to symptoms, radiological abnormalities, history of exposure, and microbiological investigations such as microscopy and culture. While collection of clinical specimens for definitive micro biologic diagnosis remains paramount, IGRAs may be used as a supplementary diagnostic aid in combination with the TST and other investigations to help support a diagnosis of TB. However, IGRA should not be a substitute for, or obviate the need for, appropriate specimen collection.	Evidence of TB infection in children is often used in making a diagnosis of active TB, in addition to symptoms, radiological abnormalities, history of exposure, and microbiological investigations such as microscopy and culture. While collection of clinical specimens for definitive micro biologic diagnosis remains paramount, IGRAs may be used as a supplementary diagnostic aid in combination with the TST and other investigations to help support a diagnosis of TB. However, IGRA should not be a substitute for, or obviate the need for, appropriate specimen collection. In addition, IGRAs (and the TST) may fail to detect patients with active TB. A negative IGRA (or TST) does NOT rule out active TB at any age and especially not in young children.	This revised recommendation emphasizes that although IGRAs may be useful as a supplementary diagnostic aid in children with suspected TB disease, a negative test does not rule out active TB.
3	Adult and childhood contacts of a case of active infectious tuberculosis	1. IGRAs may be used as a confirmatory test for a positive TST in contacts (adult or child) who, on the basis of an assessment of the duration and degree of contact with an active infectious case, are felt to have a low pretest probability of recently acquired LTBI and who have no other high risk factors for progression to active disease if infected. 2. For close contacts or those contacts who have high or increased risk of progression to active disease if infected, a TST (or both TST and IGRA) should be used, and if either is positive the contact should be considered to have LTBI. 3. If both TST and IGRA testing will be used, it is recommended that blood be drawn for IGRA on or before the day when the TST is read whenever possible.	Same	No change
4	‘Low risk’ adults and children age 5-17 years with a positive TST result	IGRA may be performed in TST-positive, immunocompetent adults and children who are at relatively low risk of being infected with TB and of progressing to active disease if infected. Persons with a positive IGRA result may be considered for treatment of LTBI.	IGRA may be performed as a confirmatory test in a TST-positive, immunocompetent adult or child age 5-17 years who is considered to have a low pretest probability of LTBI and EITHER has no high risk factor, per the Canadian Tuberculosis Standards, Chapter 4, Table 2, for progression to active disease if infected, OR is not on treatment with glucocorticoids or tumor necrosis factor (TNF)-alpha inhibitors, does not have diabetes mellitus and is not age 0-4 years.	IGRA may be used as a confirmatory test when the only increased risk factor for progression to active disease is cigarette smoking, underweight or abnormal chest x-ray due to granuloma.
5	Immuno-compromised adults and children (under age 18)	1. In an immunocompromised person (adult or child), the TST should be the initial test used to detect LTBI. If the TST is positive, the person should be considered to have LTBI. 2. However, in light of the known problem with false-negative TST results in immuno-compromised populations, a clinician still concerned about the possibility of LTBI in an immuno-compromised person with a negative initial TST result may perform an IGRA test. If the IGRA result is positive, the person might be considered to have LTBI. If the IGRA result is indeterminate, the test should be repeated to rule out laboratory error. If the repeat test is also indeterminate, the clinician should suspect anergy and rely on the person’s history, clinical features, and any other laboratory results to make a decision as to the likelihood of LTBI. Although both IGRAs may be used as described above, there is evidence that the T-SPOT.TB assay may be more sensitive than the QFT assay in active TB, and this characteristic might be especially relevant in immuno-compromised populations. While the approach of accepting either test result (TST or IGRA) as positive will improve the sensitivity of detecting LTBI in immunocompromised populations, there are no data supporting the efficacy of preventive therapy in TST-negative but IGRA-positive individuals. Thus the clinician must weigh the potential benefit of detecting more persons with positive test results against the lack of evidence for the benefit of preventive therapy in such persons.	Same	Immuno-compromised refers to HIV infection Organ transplantation (related to immune suppressant therapy) Other immuno-suppressive drugs, e.g. corticosteroids (equivalent of ≥ 15 mg/day of prednisone for 1 month, risk of TB disease increases with higher dose and longer duration) • Extracted from Canadian Tuberculosis Standards, Chapter 6, Table 6
6	Routine immigrant screening	Routine or mass screening for LTBI of all immigrants (adults and children), with either TST or IGRA, is not recommended. However, targeted screening for LTBI after arrival in Canada is recommended among foreign-born individuals and Travellers (adults and children) with risk factors for reactivation of LTBI (these risk groups are listed below and aside from 14 and 15 are the same as those for non-immigrant Canadians). For these persons, recommendations 1, 2, 3 and 5 apply. Immigrants who should receive targeted screening: 1. HIV infection 2. transplantation (related to immunosuppressant therapy) 3. silicosis 4. chronic renal failure requiring hemodialysis 5. carcinoma of head and neck 6. recent TB infection (≤ 2 years) 7. abnormal chest radiographic result – fibronodular disease 8. treatment with glucocorticoids 9. treatment with tumor necrosis factor (TNF)-alpha inhibitors 10. diabetes mellitus (all types) 11. underweight (for TB purposes, this is a body mass index < 20 for most persons) 12. cigarette smoker 13. abnormal chest radiographic result–granuloma 14. children under the age of 15 years who have lived in a country with high TB incidence and have immigrated within the past 2 years 15. persons aged 15 years and older who have lived in a country with high TB incidence, have immigrated within the past 2 years and have either been living with or in known contact with a TB case in the past or are at high risk of development of active TB.	The word “Travellers” was removed.	See Recommendation No. 7 regarding Travellers. Recommendations for routine immigrant screening remain unchanged from 2008.
7	Travellers	Recommendation No. 6	See specific TST recommendations in “Risk Assessment and Prevention of Tuberculosis Among Travellers,” published by the Committee to Advise on Tropical Medicine and Travel (CATMAT) at http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/acs-dcc-5/index-eng.php. For IGRA testing, Recommendations 1, 2 and 5 apply. Confirmatory IGRA testing is not recommended as travellers with a positive TST post-travel are considered recent converters or at high risk of reactivation.	The publication of specific TST recommendations for travellers by CATMAT since the 2008 version of IGRA recommendations necessitates this clarification.
8	Serial testing of healthcare workers, prison inmates and staff, and in employee screening programs	There is insufficient published evidence to recommend serial IGRA testing in populations exposed to TB, such as health care workers or prison staff and inmates. Serial screening for LTBI should continue to be done using the TST, as recommended by the Canadian Tuberculosis Standards. IGRAs may be used as a confirmatory test for a positive baseline TST in an immuno-competent health care worker or prison staff/inmate who is felt to have a low pretest probability of LTBI and who has no other high or increased risk factor for progression to active disease if infected. Persons with a positive IGRA result may be considered for treatment of LTBI. If an IGRA is negative, this person could be tested again with IGRA, if an exposure occurs (i.e. post-exposure testing). In the absence of data on optimum timing for post-exposure IGRA testing, the time-window recommended by the Canadian Tuberculosis Standards for repeating TST after exposure (i.e. at least 8 weeks after the last exposure) may be used for IGRA as well.	There is insufficient published evidence to recommend serial IGRA testing in populations exposed to TB, such as health care workers or prison staff and inmates. Serial screening for LTBI should continue to be done using the TST, as recommended by the Canadian Tuberculosis Standards. IGRAs may be used as a confirmatory test for a positive baseline TST in an immuno-competent health care worker or prison staff/inmate who is considered to have a low pretest probability of LTBI and EITHER has no high risk factor, per the Canadian Tuberculosis Standards, Chapter 4, Table 2, for progression to active disease if infected, OR is not on treatment with glucocorticoids or tumor necrosis factor (TNF)-alpha inhibitors and does not have diabetes mellitus. Persons with a positive IGRA result may be considered for treatment of LTBI. If an IGRA is negative, this person could be tested again with IGRA, if an exposure occurs (i.e. post-exposure testing). In the absence of data on optimum timing for post-exposure IGRA testing, the time-window recommended by the Canadian Tuberculosis Standards for repeating TST after exposure (i.e. at least 8 weeks after the last exposure) may be used for IGRA as well.
9	Population (or community-based) surveys for prevalence of LTBI	While IGRAs may be useful research tools for prevalence estimation, there is insufficient published evidence to recommend the routine use of IGRAs in population or community-based surveys for estimating the prevalence of LTBI. Prevalence surveys should continue to be done using the TST.	Same	No change