Both the TST and IGRA exhibit low predictive value for the development of TB disease.10 Although predictive value for TB disease is low, studies consistently show risk of TB disease is highest in the first 2 years following infection, then subsequently declines thereafter.54
How well a positive TST and/or IGRA correlates with risk of developing TB disease is a key consideration when offering TPT, and thus may influence a decision to test. Knowing the annual risk of developing TB (i.e., the incidence rate) after a positive test is therefore especially useful in clinical settings. As both TST and IGRA sensitivity is imperfect, even people testing negative with either or both may still go on to develop TB disease. Knowing how much greater risk an individual has for developing TB disease with a positive vs negative test (ie, the incidence rate ratio [IRR]) is also useful in clinical settings to support decisions on which test to use, as well as to support TPT decisions once a test result is known.
Four systematic reviews published in 2020 evaluated the incidence rate of TB disease among different populations testing positive with a TST or IGRA who did not receive TPT.2,55–57 These reviews also evaluated the IRR of TB disease among different populations testing positive vs. negative with a TST or IGRA. The findings of these reviews are summarized in Table 2 and categorized based on very high, high, moderate, or low risk of TB disease among persons testing positive. For populations thought to be at increased risk of TB disease where estimates of risk after a positive TST or IGRA were unavailable, risks were extrapolated from studies comparing risk of TB disease among persons with vs without a risk factor. The following sub-sections further describe the evidence base supporting Table 2.
Table 2. Risk of TB disease and the incidence rate ratio of TB disease among different populations stratified by risk.
|Risk factor||Annual risk of TB disease for the first 2-3 years after testing positive (%) a||Reference|
|VERY HIGH RISK|
|People living with HIV||1.7 to 2.7||2 , 56|
|Child or adolescent (<18 y) tuberculosis contact||2.9 to 14.6||56 , 57|
|Adult (≥18 y) tuberculosis contact||0.8 to 3.7||2 , 56|
|Stage 4 or 5 chronic kidney disease with or without dialysis||0.3 to 1.2||2|
|Transplant recipients (solid organ or hematopoietic)||0.1 to 0.7||2|
|Fibronodular disease||0.2 to 0.6||Extrapolated from:
|Receiving immunosuppressing drugs (eg, tumor necrosis factor α inhibitors or steroids)b||0.5||2|
|Cancer (lung, sarcoma, leukemia, lymphoma or gastrointestinal)||0.1 to 0.4||Extrapolated from:
|Granuloma on chest x-ray||0.1||Extrapolated from:
77 , 78
|Diabetes||0.1 to 0.2||Extrapolated from:
|Heavy alcohol use (at least 3 drinks/day)||0.1 to 0.2||Extrapolated from:
|Heavy tobacco cigarette smoker (at least 1 pack/day)||0.1||Extrapolated from:
|General (adult) population with no known risk factor||0.03||2|
|Persons with a positive two-step TST booster and no known risk factor||0.02||Extrapolated from:
84 , 85
Abbreviations: TB, tuberculosis; HIV, human immunodeficiency virus; TST, tuberculin skin test.
aRisks are expected to halve after this period and continue to decrease subsequently.
bRisk does not appear significantly elevated with low-dose steroids (i.e., prednisone), but elevated with moderate or high dose (low dose, ≤9 mg/day; medium dose, 10–19 mg/day; and high dose, ≥20 mg/day).86
3.4.1. General (adult) population
Contemporary estimates of TB disease risk in the general (adult) population suggest risks are low. Among three studies58–60 (from British Columbia, Saskatchewan and Florida) estimating the absolute risk of TB disease among 33,811 healthy, low-risk tuberculin reactors (TST ≥10 mm) followed for an average of 7.4 years, only 55 (0.2%) developed TB disease. This is equivalent to an annual risk of TB disease of approximately 0.03% per year.
3.4.2. TB contacts
Persons with recent tuberculosis exposure (tuberculosis contacts) are a priority group for TB infection screening and treatment, because of their high risk of progression to TB disease. Risk for progression to TB disease is highest among child and adolescent contacts (<18 years; highest among those <5 years).2,56,57 TB infection diagnostic tests also have good ability to discriminate risk among adult contacts with IRRs ranging from 4.1 to 19.0.2
3.4.3. People living with HIV
People living with HIV are another priority group for TB infection screening and treatment. Among people living with HIV, the use of antiretroviral therapy has been shown to reduce risk of progression to TB disease.61 Provision of TPT further reduces this risk.62 In a systematic review, both the TST and IGRA exhibited identical ability to discriminate between people living with HIV at high vs. low risk of progression, with an IRR of 11.0.2 Among people living with HIV not receiving antiretroviral therapy and with a negative TST or IGRA, re-testing after antiretroviral therapy has been established may be warranted in certain clinical contexts, as high rates of conversion 6-12 months after initiation due to immune reconstitution have been observed; this effect may be modulated by CD4 levels.63–68
3.4.4. People with non-HIV immunocompromising conditions
Risk of progression to TB disease among populations with non-HIV immunocompromising conditions is elevated, although the data are more limited and heterogeneous.2,56 In nearly all populations, the IRR of both TST and IGRA are diminished due to reduced immune function. 2
Risk of TB disease among persons with chronic kidney disease increases with worsening kidney function caused by uremia-induced immune impairment. One study estimated a 5% increase in TB disease risk for every 10 mL/min/1.73 m2 decrease in the estimated glomerular filtration rate.69 TB disease risk among persons with a positive TST or IGRA is highest among those requiring dialysis, estimated to be 0.3 to 1.2% per year in a meta-analysis.2 Among persons who had received a transplant, annual risk of TB disease among those with a positive TST or IGRA is 0.1 to 0.7%.2,56 Similarly, persons receiving immunosuppressant drugs for inflammatory diseases (such as tumor necrosis factor α inhibitors or steroids), have an annual risk of TB disease of 0.5% with a positive TST or IGRA.2 Certain cancers have been implicated in risk of TB disease. A large retrospective study of migrants to British Columbia suggests risk of TB disease is highest among those with lung cancer, sarcoma, leukemia, lymphoma and gastrointestinal cancers, on the order of 3 to 11 times that of persons without these cancers after adjusting for several potential confounders.70 This extrapolates to an annual risk of TB disease of approximately 0.1 to 0.4% among persons with these cancers. Systematic reviews have also found that cancers elevate the risk of TB.71 Among people with diabetes, risk is likely increased by other health conditions (eg, chronic kidney disease) and is higher among those with poorly controlled diabetes, although data are mixed.2,72–74
3.4.5. Other populations
Primary data for the absolute risk of progression to TB disease among populations with certain habits or chest x-ray abnormalities and a positive TST or IGRA are scarce. However, many studies have evaluated the relative risk of TB disease based on these risk factors,75–82 allowing approximations of absolute risk based on a known general population risk.2
Good practice statement
Among people living with human immunodeficiency virus not receiving antiretroviral therapy and with a negative tuberculin skin test or interferon-gamma release assay, re-testing after antiretroviral therapy has been established may be warranted if the individual’s risk for TB infection is elevated (such as known previous contact).
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