Blood tests may be better than standard skin test for diagnosing latent tuberculosis

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Two blood tests for diagnosing latent tuberculosis (TB) infection can each produce fewer false-positive results than the standard tuberculin skin test in patients presumed to be HIV-negative, according to a study in this week's issue of The Lancet.

However, the two tests may not produce interchangeable results, the authors warn, and may produce different results in clinical practice, suggesting the need for further studies in populations where TB is endemic.

The standard diagnostic test for latent TB - the century-old tuberculin skin test - is unreliable, often producing false negative results in high-risk groups such as HIV-positive people and false positives in others, such as those who have received BCG vaccine. Two commercially available blood tests, T-SPOT.TB and QuantiFERON-TB Gold, might be more reliable.

Glossary

latent TB

A form of TB that is not active. Persons with latent TB are infected with M. tuberculosis but do not have any symptoms and they cannot spread TB infection to others. Only specific tests will tell if anyone has latent TB. Treatment for latent TB is recommended in people living with HIV. 

false negative

When a person has a medical condition but is diagnosed as not having it.

false positive

When a person does not have a medical condition but is diagnosed as having it.

indeterminate test result

‘Indeterminate’ means that the test didn't provide a clear negative or positive result. Someone with an indeterminate HIV test result could be in the early stages of HIV infection, a time during which an HIV test might show a result somewhere between negative and positive. Or the person may not have HIV, with the indeterminate result caused by a different viral infection, or just non-specific antibodies in the blood.

specificity

When using a diagnostic test, the probability that a person without a medical condition will receive the correct test result (i.e. negative).

Both tests use ELISA-type technology (similar to the system used for HIV antibody tesing) to detect immune reactivity to TB, but do not look for antibodies to TB. Instead they detect interferon gamma produced by T-cells in specific response to Mycobacterium tuberculosis.

Researchers from the University of Modena in Italy compared the two new blood tests for latent TB with the tuberculin skin test in order to see how they performed in routine clinical practice in Italy.

The study recruited 393 patients with suspected TB and compared the perfomance of the three tests. The researchers found that:

  • Overall, similar levels of agreement were seen between between the three tests, but there were different patterns of `false positive` and `false negative` results.
  • Both blood tests resulted in fewer positive results in BCG-vaccinated individuals.
  • Indeterminate results were significantly more common when using the Quantiferon TB Gold test (11%) than with T-Spot TB (3%, p<0.0001) and were associated with receipt of immunosuppressive treatment such as cancer chemotherapy or steroid treatment. Indeterminate results were also more common in children under the age of five years when using the Quantiferon test.
  • The T-Spot TB test was the only test to identify all individuals with extrapulmonary TB correctly.

Dr Richeldi stated: "QuantiFERON-TB Gold and T-SPOT.TB show good diagnostic agreement with the skin test, but have higher specificity. As such either in combination with or as a substitute for the skin test, they could increase the diagnostic sensitivity of testing for latent TB infection."

However, he went on to comment: “The blood tests were affected by factors potentially associated with reduced functioning of the cellular immune system.”

References

Ferrara G et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. The Lancet 367: 1328- 1334, 2006.