Comparing Testing Methods for Latent Tuberculosis Among Diverse High-Risk Populations

Researchers assessed and compared 3 tests for latent tuberculosis infection among high-risk individuals in the US.

Results of an observational cohort study conducted by the Centers for Disease Control and Prevention (CDC) found evidence to support the preferential use of interferon (IFN)-g assays among high-risk populations for diagnosing latent tuberculosis (TB) infection. These findings were published in The Lancet Infectious Diseases.

At 18 TB Epidemiologic Studies Consortium (TBESC)-affiliated centers, patients at increased risk for latent TB were recruited between July 2012 and May 2017. Patients (N=21,846) were assessed for demographic and clinical risk factors, had their blood drawn for 2 IFN-g release testing (QuantiFERON and T-SPOT.TB), and underwent tuberculin skin testing (TST). The primary endpoints included the proportion of positive test results by test type stratified by risk group and test concordance by risk group for patients with valid results for all 3 test types.

Among a patients included in the final analysis, 51.2% were men, the median age was 31 years (range, 7 weeks-101 years), 82.5% were born outside the US, 44.9% were refugees, and 61.5% and 23.9% of patients resided in or had visited a country with an increased risk for incident latent TB infection for 30 days or longer, respectively. In addition, 9.6% of patients had a potential exposure to TB infection, 8.6% had HIV infection, and 6.0% were unhoused.

Among non-US-born patients, the risk ratio (RR) for a positive TST was 1.6 (95% CI, 1.6-1.7) when compared with the QuantiFERON test and 2.0 (95% CI, 1.9-2.1) when compared with the T-SPOT.TB test. Among US-born patients, the RRs for the proportion of positive TST were 0.9 (95% CI, 0.8-1.0) when compared with the QuantiFERON test and 1.3 when compared with T-SPOT.TB (95% CI, 1.2-1.6). In addition, an RR of 1.5 was observed when comparing the 2 IFN-g tests (95% CI, 1.3-1.7).

The investigators noted that a positive result of the 2 IFN-g assays was associated with increased age (P <.0001), however, this was observed only among non-US-born patients (P <.0001). They also noted an inverse relationship between positive TSTs and patient age, and found that non-US-born children younger than 5 years of age had significantly increased positivity rates with the QuantiFERON (RR, 7.3; 95% CI, 5.1-10.5) and T-SPOT.TB tests (RR, 17.2; 95% CI, 9.9-29.8).

Among all included patients, 15.4% tested positive for latent TB infection on all 3 tests, 56.2% tested negative on all 3 tests, and the remainder had discordant test results. After stratification by birthplace, the rates of positive results on a single test among US-born and non-US-born patients were 4.4% and 21.0% for TST, 3.2% and 2.3% for the QuantiFERON test, 0.7% and 0.7% for the T-SPOT.TB test, 1.5% and 4.6% for the TST and QuantiFeron tests, 0.3% and 1.7% for the TST and T-SPOT.TB tests, and 1.6% and 1.6% for both IFN-g tests, respectively.

After stratification by age group, concordance between TST and IFN-g assays increased age as did being negative with TST and positive with IFN-g tests. The investigators noted that positive results with TST and negative results with IFN-g were inversely related with age, occurring more often among younger patients.

These findings may have been biased by the differing protocols across sites, in which some centers performed daily testing while other sites froze samples and ran batch assays weekly.

The investigators concluded that high-risk populations would benefit from IFN-g testing for latent TB infection, and that non-institutionalized US-born patients without additional risk factors should not be tested for latent TB infection.


Ho CS, Feng P-J I, Narita M, et al. Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study. Lancet Infect Dis. 2021;S1473-3099(21)00145-6. doi:10.1016/S1473-3099(21)00145-6