Hope grows for new TB test

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(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)

To confirm that you have TB, the doctor will ask you to cough up at least a teaspoonful of phlegm, or sputum. You’ll have to come back to the hospital twice more to provide samples, and technicians will painstakingly culture the slow-growing bacteria from the sputum.
 A few weeks after that third visit — by which point you may have exposed others — the doctor should be able to tell you whether you have TB.

This crude sputum diagnostic test is 100 years old. “The situation is fairly horrendous,” says Dr. Suman Laal, Ph.D., associate professor of pathology and mircrobiology.

There are a
few expensive alternatives: fluorescent microscopy, automated culture systems, and tests for the bacterial DNA. But 90 percent of the disease is concentrated in the poorest parts of the world, where these options are not feasible.

Clinically, TB symptoms can be difficult to distinguish from those of
 other bacterial or fungal infections, pneumonia, or certain tumors. Diagnosis with X-rays is subjective and all but useless 
in people who are HIV-positive, and
 a commonly used skin test gives false positives in anyone who has been immunized with the BCG vaccine or 
has been infected with the TB bug’s bacterial cousins.

The ideal test for TB would be fast, cheap, and would deliver a simple Yes or No answer — much like a dipstick pregnancy test. But developing a test like that has proved challenging.

The DNA of the bacterium that causes TB twists and coils into a structure that was difficult to unravel with old-fashioned sequencing techniques. In 1998, when researchers finally decoded its enormous genome, they found that some 500 of the bacteria’s 4,000 genes belonged to a previously unknown genetic family.

Applying what they’ve since learned about the bacterium’s proteins, several teams are trying to develop simple TB tests. Dr. Laal and other researchers across the U.S. and in India have been working to develop a urine- or serum-based test that would detect one or more of the bacterium’s proteins, even in someone infected with HIV. Her quest has taken Dr. Laal back to her native India at least once every year. The country has sizable epidemics of both TB and HIV.

The combination of proteins made 
by the bacteria change as the infection progresses, so researchers have tried to find ones that are expressed throughout the course of the disease. From a promising list of 12 proteins, they found two in particular that signal active TB infection well before symptoms become obvious and irrespective of HIV infection.

Researchers 
are now trying to identify a small piece of each protein that would be cheaper and easier to produce en masse. “I think we’re pretty close to having a set of peptides that can replace the smear test,” says Dr. Laal.

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