New TB Test is Faster, More Accurate

The current tuberculosis test has been used for more than a century

FRIDAY, April 4, 2003 (HealthDayNews) -- The century-old, skin-prick test for tuberculosis may soon become medical history.

Researchers in England report they've come up with a new test for tuberculosis (TB) that's faster and more accurate than the current method.

The new test measures the concentration of T-cells in the blood, an indicator the immune system is responding to a TB infection.

"This test is going to replace the skin-prick test," says Dr. Ajit Lalvani, lead author of the study and a senior research fellow at the University of Oxford's John Radcliffe Hospital. "The skin-prick test is 100 years old. It's incredible we are still using it in an era of genomic and molecular medicine."

The study results appear in the April 5 issue of The Lancet.

Tuberculosis is a tricky disease to track. When a person is first infected, they have no symptoms and they're not infectious. About 10 percent of those infected will eventually develop the full-blown disease, which is characterized by fever, coughing, weight loss and progressive pneumonia.

The symptoms may not appear for several weeks to many years, Lalvani says: "It's very, very variable."

During this period, the infected person is also highly contagious. So, the goal of public health officials is to catch people infected with tuberculosis before they become ill, both to prevent individual suffering and the spread of the disease, Lalvani says.

The only diagnostic method currently available is the skin-prick test, in which a mixture of some 200 proteins from the tuberculin bacteria are placed under the skin.

If you've been infected, the immune system will recognize the bacteria and cause an inflammation. That takes about two to three days.

"If the bump is big, you have TB infection. If there's no bump you probably haven't got latent TB infection. That's how crude it is," Lalvani says.

A second limitation of the skin-prick test is that it's prone to false-positive results, especially in people who've been inoculated with the BCG vaccine, which offers limited protection against tuberculosis. The BCG vaccine shares some of the same proteins as the tuberculosis bacteria, Lalvani explains.

BCG vaccine is no longer routinely used in the United States, but it is widely used in some European and developing countries.

The new test, called ELISPOT (for enzyme-linked immunospot), is the first diagnostic tool that uses T-cells, a component of the immune system, to spot infection, Lalvani says.

In the ELISPOT test, the results are available the morning after the blood sample is taken.

In the skin prick test, results are available in two or seven days, Lalvani says.

In their study, Lalvani and his colleagues compared the skin-prick test to ELISPOT to detect tuberculosis in students at a secondary school in Leicestershire, England. The school was the site of England's largest outbreak of tuberculosis since World War II. All of the infections resulted from one child with active tuberculosis.

Of 535 students at the school, 121 tested positive for tuberculosis by both tests. Another 26 tested positive for tuberculosis using the ELISPOT test.

"Those were the kids the skin-prick test missed," Lalvani says.

How do researchers know that those kids weren't false positives?

They don't know for certain, because there is no "gold-standard" test.

However, previous research shows there are two main factors that influence who will be infected with tuberculosis after coming into contact with a person sick from it: proximity to the sick person and the length of time spent in the same room.

In the case of the school outbreak, researchers had classroom schedules and attendance records, so they knew precisely where each child was throughout the day.

The children who had the most contact with the sick child were the most likely to test positive with the ELISPOT test.

In fact, every child who'd spent at least 130 hours in the same room as the sick child were infected with tuberculosis.

"What we found was that the ELISPOT correlated significantly better with exposure to TB than did the skin test," Lalvani says. "As you got more and more exposure to TB, they were more likely to be positive in the skin test and more likely to be positive in the ELISPOT. But, the strength of the link in the ELISPOT was stronger. That leads us to believe we are detecting more cases in infection correctly."

The researchers plan to continue testing ELISPOT and hope to receive regulatory approval to bring the test to market in England in about a year. In the United States, they anticipate the process taking two to three years.

TB rates have been falling in the United States, says Dr. Kamran Khan, a specialist in infectious disease and public health at St. Michael's Hospital in Toronto.

In 2001, there were about 16,000 cases, down from 20,000 in 1997, according to the U.S. Centers for Disease Control and Prevention.

Despite the falling numbers, there's great need for a new, updated test, Khan says. Many of the cases are occurring among foreign-born residents, who are more likely to have received the BCG vaccine.

"Overall, the study adds considerable support that this new test is much better than the tuberculin skin tests when it comes to correctly identifying latent TB infection," Khan says.

The only problem could be cost, he says: "It's a fairly high-tech test and likely to have high costs in relation to the TB skin test."

More information

Visit the American Lung Association or the National Institutes of Health for more on tuberculosis.

SOURCES: Ajit Lalvani, M.D., senior research fellow, Nuffield Department of Clinical Medicine, University of Oxford's John Radcliffe Hospital, Oxford, England; Kamran Khan, M.D., specialist, infectious disease and public health, St. Michael's Hospital, Toronto; April 5, 2003, The Lancet
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