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Tuberculosis testing finally moves into the 21st century

IT HAS taken 100 years, but at last we have developed a quick and reliable test for tuberculosis.

IT HAS taken 100 years, but at last we have developed a quick and reliable test for tuberculosis.

Researchers have struggled to find an alternative to the standard tuberculin skin test, developed a century ago by the German bacteriologist Robert Koch. It involves injecting a witch鈥檚 brew of 200 or so proteins extracted from Mycobacterium tuberculosis, the bacterium that causes TB, into the skin of the arm. Infected people develop a red lump after about a week.

However, deciding whether a mild reaction is severe enough to count as a positive result is subjective. What鈥檚 more, people who have had a BCG vaccination can incorrectly test positive. Finally, getting any result depends on people returning to a clinic a week later, and many don鈥檛 bother.

Unlike any previous test for any disease, the new test, called ELISPOT, relies on the disease-fighting white blood cells. A few T cells in people with TB are sensitised to M. tuberculosis and pump out copious amounts of an immune messenger called gamma interferon when they encounter it.

To detect these cells, Ajit Lalvani and his team at the John Radcliffe Hospital in Oxford separate out the white cells from a blood sample and expose them to two proteins he found to be unique to M. tuberculosis and absent from all known vaccines and kindred mycobacteria. The mixture is left overnight in a container lined with antibodies that capture the gamma interferon protein.

Then the cells are washed away and a dye is added to reveal any interferon trapped by the antibodies, which shows up as vivid blue spots. 鈥淓ach spot is a 鈥榝ootprint鈥 of where a sensitised T cell has been,鈥 says Lalvani.

The new test was compared with the traditional skin test during a 2001 TB outbreak at a school in Leicestershire by double-checking the results against lung X-rays and tests for the TB bug in sputum. Out of 535 pupils, 121 cases were correctly identified both by the skin test and the ELISPOT test. But the new test also spotted 26 cases missed by the old one and correctly showed that another 34 children who tested positive in the skin test were not in fact infected (The Lancet, vol 361, p1168).

While the test should greatly improve TB diagnosis, there is still no quick and easy cure for TB. Treatment regimes last six months and are not always successful.

Tuberculosis testing finally moves into the 21st century

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