Accurate diagnosis takes tests and time

July 16, 2007|Mary Beckman | Special to The Times

Georgia attorney Andrew Speaker shocked many people by traveling internationally with a form of tuberculosis that can't be cured easily. Tests on his TB from the Centers for Disease Control and Prevention in Atlanta and Denver's National Jewish Medical and Research Center indicated different levels of drug resistance, with the initial CDC testing indicating that Speaker had the most serious form of the disease, known as extensively drug-resistant (XDR) TB.

Here's a look at how two internationally respected organizations came up with conflicting results.

Tuberculosis is caused by a bacterium, Mycobacterium tuberculosis. Most of the 14,000 or so U.S. cases of tuberculosis diagnosed each year are found when a person comes in coughing blood. Patients are treated with two first-line drugs that cure 95% to 97% of them. If those drugs don't kill the bacteria, the TB is called drug-resistant. Experts estimate that only 70% of drug-resistant TB cases can be cured.

A simple skin test can determine if someone has been exposed to TB (but doesn't say if the person is still infected). Doctors inject fluid from Mycobacterium tuberculosis just under the skin. After about two days, a person who has been exposed will have a little hard bump where injected, indicating the immune system has reacted to the culture.

To tell if someone has an active infection, the person must cough up some sputum, which a technician then smears on a microscope slide and stains. If Mycobacterium tuberculosis is detected in the sputum, the sample is "smear-positive." This method picks up only about half of the TB cases. "If it's early in the disease, and you're not spewing out thousands and thousands of bacilli, you [a physician] might miss it," says Dr. Robert Gilman, a tropical diseases expert at Johns Hopkins Bloomberg School of Public Health in Baltimore. In a 1999 study, 17% of people with smear-negative sputum still infected others.

The gold standard test is to grow a TB culture out of a sputum sample or a sample of tissue from the lung. In the case of infection, technicians will be able to detect bacterial growth, sometimes with the help of an automated machine.

But TB bacteria grow extremely slowly: growing up a culture takes two to four weeks. While waiting, physicians treat patients as if they have TB. They start with the two best drugs for the job -- isoniazid and rifampin -- and periodically check sputum for bacteria. If no bacteria grow in the cultures, the person doesn't have TB.

If TB does grow, technicians test the culture to see how susceptible it is to different drugs. This takes another few weeks; only then do the physicians know whether the TB is easy to kill.

"Now you're two months out," says Barry Kreiswirth, director of the tuberculosis center at New Jersey Medical School in Newark. "The long and short of TB testing is that it is not as simple as a lot of people would like it to be."

Any TB that grows in the presence of isoniazid and rifampin is considered multidrug resistant, or MDR. To be termed "extremely drug resistant," or XDR, bacteria must resist second-tier drugs, fluoroquinolones, and at least one of three other drugs.

In the Speaker case, the CDC originally found his TB to be XDR in late May, almost two months after his initial diagnosis. In early July, National Jewish found his TB to be MDR.

Both groups grew the cultures similarly, but the CDC used a lung sample and National Jewish a sputum sample.

While the CDC used one type of test to determine the drug-resistance status, National Jewish used two, performed on multiple cultures. Because its tests were more rigorous, officials went with the National Jewish designation.

Experts say that conflicting results happen often in TB testing. "It's a frustration that we have to deal with," says Dr. Charles Daley of Denver's National Jewish Hospital.

Kreiswirth adds that tests looking for the mutations in DNA that confer drug resistance can be done in a day -- but those methods are very expensive. "It's terrible," he says, "we don't have more rapid, affordable detection methods."

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