Summary of recommendations for identifying and managing latent tuberculosis infection (LTBI) in at-risk populations.
| Categories | Canadian Standards19,22 | US Recommendations20,23,26 | UK NICE Guidelines21 | BTS Guidelines24 | European TBNET Consensus Statement27 |
|---|---|---|---|---|---|
| At-risk populations discussed | Immune suppression due to advanced age; treatment with corticosteroids*; cancer therapy agents; HIV infection; TNF antagonists; silicosis; endstage renal disease; diabetes; carcinoma of head and neck; immunosuppressant medication (transplantation) | Organ transplants, other immunosuppressed patients, including patients receiving or candidates for TNF antagonists | New entrants§; street homeless; healthcare workers: new employees/occupational health; prisons and remand centers | Patients due to start TNF antagonists | Candidates for TNF antagonist therapy |
| Testing recommended TST (Mantoux method) | Yes | Yes | Yes | Yes, only in patients not immunosuppressed with a normal chest radiograph Not helpful for patients on immunosuppressive therapy with normal chest radiograph | Yes, no BCG history |
| Interpreting TST | Negative TST < 5 mm if taking TNF antagonists False-negative result can be caused by poor injection technique, immune suppression (including TNF antagonists), malnutrition, severe illness, major viral illness, very young age Positive TST ≥ 5 mm: if patient is immunosuppressed (TNF antagonists, chemotherapy) False-positive result can be caused by NTM or previous BCG vaccination Rule out active TB by medical examination including a chest radiograph, then recommend therapy | Negative TST < 5 mm for organ transplants and other immunosuppressed patients False-negative: HIV+ patients may have a compromised ability to react because of cutaneous anergy Positive TST ≥ 5 mm for organ transplants and other immunosuppressed patients because of disease (e.g., HIV infection) or drugs (e.g., corticosteroids*, TNF antagonists) False-positive results may be due to infection with various NTM or BCG vaccination‡ Rule out active TB by medical evaluation including a chest radiograph, then recommend therapy | — | Negative TST 0–5 mm if no immunosuppressive therapy, no BCG history 0–14mm if no immunosuppressive therapy, prior BCG history Positive TST > 6 mm if no immunosuppressive therapy, no BCG history > 15 mm if no immunosuppressive therapy, prior BCG history (may represent either latent infection or BCG effect, requires a risk assessment) | Positive TST ≥ 10 mm, generally no need for a confirmatory IGRA Rule out active TB by chest radiograph |
| IGRA | May be performed if concerned about LTBI in an immunocompromised person with a negative initial TST QuantiFERON-TB Gold T-SPOT.TB | TST and IGRA routine testing not generally recommended; although both tests might be useful when the initial test (TST or IGRA) is negative and when the risk for infection, the risk for progression, and the risk for a poor outcome are increased (e.g., persons with HIV infection or children aged < 5 yrs at increased risk for TB) | Yes, if TST is positive (or in people for whom TST could be less reliable) | — | Yes†† |
| Interpreting IGRA | Positive IGRA Consider LTBI (TST+ or TST−) Indeterminate IGRA 2 indeterminate results (TST−): suspect anergy, rely on history, clinical features, and other lab results 1 indeterminate results (TST+): consider LTBI Negative IGRA Consider LTBI (TST+) | Positive IGRA or positive TST Consider LTBI Negative IGRA Does not exclude LTBI | Positive IGRA Exclude active TB by chest radiograph and examination, then consider LTBI therapy Inconclusive IGRA Refer to a TB specialist | — | Positive IGRA or positive TST Consider LTBI |
| LTBI general treatment guidelines | INH: QD for 6 or 9 mo (SAP) INH: 2×/wk for 6 or 9 mo (DOT) RMP: QD for 4 mo (SAP ± DOT)† INH, RMP: 2×/wk for 6 mo (DOT) | INH: QD or 2×/wk for 9 mo (DOT) INH: QD or 2×/wk for 6 mo (DOT; not for HIV+) RMP: QD for 4 mo (SAP) RMP + pyrazinamide: QD for 2 mo or 2×/wk for 2–3 mo (DOT) | RMP + INH: 3 mo or INH: 6 mo HIV+: INH: 6 mo | INH: 6 mo or RMP + INH: 3 mo | INH: 9–12 mo or RMP + INH: 3 mo |
↵* ≥ 15 mg/day prednisone for 1 month or more.
↵† Isoniazid (INH) resistance or intolerance.
↵‡ In persons who are at an increased risk of progression to active TB disease, a newly detected positive TST should be treated regardless of BCG status.
↵§ People who have recently arrived in or returned to the UK from high-incidence countries.
↵†† Expert opinion suggests using QFT-GIT or T-SPOT.TB or, as an alternative, TST in individuals with no BCG history. IGRA tests should be preferred over TST in patients with BCG vaccination. BCG: Bacille Calmette-Guérin; BTS: British Thoracic Society; TBNET: Tuberculosis Network European Trials Group; HIV: human immunodeficiency virus; TNF: tumor necrosis factor; TST: tuberculin skin test; DOT: directly observed therapy; ind: indeterminate; INH: isoniazid; RMP: rifampin; NICE: National Institute for Health and Clinical Excellence; NTM: nontuberculous mycobacteria; IGRA: interferon-γ release assays; SAP: self-administered preventive therapy.