A new study published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine shows that from the three TB diagnosis tests commercially available in the U.S., the majority of positives prove to be false positives in populations with a low prevalence of tuberculosis (TB).

James Mancuso, MD, Dr PH, of the Walter Reed Army Institute of Research Preventive Medicine Residency Program explained: “We compared commercially available tests for latent tuberculosis infection (LTBI) in a diverse population with a low LTBI prevalence. Our results suggest that in low-prevalence populations, most positive results obtained with these tests are false positives.”

Researchers conducted a cross-sectional study involving 2,017 military recruits at Fort Jackson in South Carolina. The participants were asked to complete a risk factor questionnaire and were checked for TB with the 3 commercially available tests, consisting of the tuberculin skin test (TST), the interferon gamma release assays (IGRAs) QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and the TSPOT® TB test (T-Spot). Researchers also conducted the Battey Skin Test (BST) on all participants to assess the impact of non-tuberculosis mycobacteria (NTM) reactivity on test discordance.

The results demonstrated that there was no substantial difference between the TST, QFT-GIT, and T-Spot tests. From 88 positive test results, 68 participants (77%) showed positive to one test, 10 participants (11.4%) showed positive in two tests, and only 10 people (11.4%) were positive to all three tests.

The researchers linked Bacille Calmette Guerin vaccination, the tuberculosis prevalence in the country of birth, and Battey skin test reaction size to being TST positive with IGRA negative test discordance. This supports evidence that false positive TST results can be caused by NTM sensitization. Greater quantitative test results and higher TB risk levels were linked to a higher agreement between tests.

Dr. Mancuso explained: “Our data support a high proportion of false positives with any of these three tests in a low- prevalence population as 77 percent of our subjects had positive results with only one test. Lower quantitative results were associated with a smaller risk for TB exposure and single positive tests, and lower risk for TB exposure was associated with decreasing test agreement.”

The limitations of the study, such as the lack of a gold standard for establishing whether an M. tuberculosis infection is present, as well as administrative restrictions that led to a higher proportion of inadequate blood draws and TST reading times that were marginally shorter than optimal.

Dr. Mancuso concluded: “Low positive predictive value (PPV) is a well-known issue with the TST, and risk stratification is recommended to guide interpretation of the test. Our study suggests that risk stratification may also increase the PPV and reduce the number of false positives with the IGRAs. In accordance with the CDC’s recommendation, people at minimal risk of TB infection should not be targeted for LTBI testing, regardless of which test is used.”

Written by: Grace Rattue