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For many Americans, the last time we heard about tuberculosis was in elementary or high school, when some of us had a skin test to measure our exposure to the bacterium. But in the rest of the world, the tuberculosis bacterium still infects the lungs of one-third of the population and kills millions each year.

To help prevent tuberculosis in the United States, legal immigrants must submit proof, in the form of a chest X-ray, that their lungs do not harbor active disease. Yet the rate of active tuberculosis in the year 2000 among foreign-born residents of the United States remains high at 25.8 per 100,000 compared with 3.5 per 100,000 among U.S.-born residents.

Now, in a study of 10 years of data from New York City tuberculosis cases, Dr. Neil Schluger, associate professor of medicine at P&S and public health at the Mailman School of Public Health, and colleagues have found strong evidence that many cases of TB in foreign-born residents flare from latent infections many years after they have arrived in this country. The results of the study, published in the May 9 New England Journal of Medicine, imply that treating latent infections could reduce the number of active TB cases among the non-U.S.-born in New York and elsewhere in the country.

"Although the findings deal with results from New York City, we should be treating latent infections in recently arrived immigrants throughout the country," Dr. Schluger says. "But the only way to get at the root of TB would be to better fight the bacterium internationally."

Tuberculosis is caused by the slow-growing microbe Mycobacterium tuberculosis that infects the lungs. People acquire the bacteria by inhalation and most of the time, the infection remains latent, never causes any symptoms, and is not contagious. Persons with latent tuberculosis infection look and feel healthy, and have normal chest X-rays. The only evidence of the latent infection is a positive tuberculin skin test. Ten percent of people with a latent infection of the bacterium will go on to develop active tuberculosis, characterized usually by fever, cough, weight loss, and destruction of lung tissue seen on a chest X-ray. At this point, the tuberculosis is considered active, contagious, and a potential killer unless treated with a six-month course of antibiotics.

Tuberculosis is the leading cause of death due to infectious disease among adults in the world, but efforts in the United States have been successful at reducing its incidence, except among the foreign born. In the 1980s and early 1990s, for example, New York City experienced a resurgence of TB but city public health officials focused on treating active infections and were able to bring down rates in U.S.-born residents in the city to all-time lows. The overall rate of active infections in New York City fell from 52 cases per 100,000 people in 1992 to 18.2 cases per 100,000 in 2000. The rate among the foreign-born, however, was significantly higher in 2000 at 28.7 cases per 100,000, while the U.S-born rate was 9.7 per 100,000. The foreign-born now account for more than 60 percent of New York City's TB cases.

In the study, the researchers wanted to understand what was responsible for the higher rate of tuberculosis among immigrants in New York City. They found that the high rate of active infections in the immigrants was not due to their acquiring new tuberculosis infections in the United States but, rather, due to an activation of a latent infection probably acquired before entering the United States.

To arrive at their conclusion, the researchers analyzed the DNA of the tuberculosis bacteria from 576 patients seen by Columbia physicians between 1991 and 1999. By studying the different DNA "fingerprints," or unique DNA banding patterns, of the different bacterial strains from the patients, the researchers could distinguish between bacteria that came from the United States and from abroad.

When the DNA fingerprint of a bacterial culture matched the fingerprint of one or more other cultures, the researchers surmised that the bacterial strain was one that was spreading among people in the New York area. When the DNA fingerprint was unique, the strain that was likely causing the disease was doing so through reactivation of a latent infection. The researchers found that the foreign-born were 2.5 times more likely to have a unique strain and, therefore, a reactivation of a latent infection acquired long ago.

The study results imply that treating latent infections would reduce the number of active infections among the non-U.S.-born and Dr. Schluger is now studying ways to improve the treatment of latent infections. The traditional protocol to treat latent infections lasts nine months and requires the patient to take 270 doses of the antibiotic isoniazid, a regimen that patients have difficulty complying with. In a study sponsored by the Tuberculosis Trial Consortium, a Centers for Disease Control and Prevention-funded organization Dr. Schluger chairs, patients will get a 12-dose regimen with two antibiotics, isoniazid and rifapentine, for a three-month period. "From a public health standpoint you can really make an impact with a shorter regimen because patients will continue the treatments," Dr. Schluger says.

But identifying the non-U.S.-born with latent infections, using TB skin tests, poses political problems. "A lot of bad things have been done to immigrants in the name of public health," Dr. Schluger says. A better option to reduce TB, Dr. Schluger says, may be investing more money to reduce TB in Latin America, Africa, and Asia. "You can't eliminate TB in the United States without looking outside its borders."


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