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More aggressive treatment of latent tuberculosis infections in non-U.S.-born residents in New York City could reduce the very high rate of the active disease in this population, according to an analysis of the disease during the last decade by researchers at Columbia University's College of Physicians & Surgeons and Mailman School of Public Health, the Public Health Research Institute, and the New York City Department of Health Tuberculosis Control Program.

The findings, which will be published in the May 9 New England Journal of Medicine, suggest current public health strategies that target only active infections will not reduce TB in non-U.S.-born residents in New York. The results also point to the need for better international tuberculosis control.

"The data show that if we want tuberculosis to go down further, we need a different strategy that includes more treatment of latent infection in those arriving in New York from countries in which TB is common," says senior author Dr. Neil Schluger, associate professor of medicine at P&S and environmental health sciences at the Mailman School of Public Health, and clinical chief of the Division of Pulmonary, Allergy, and Critical Care Medicine at Columbia Presbyterian Medical Center.

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

Tuberculosis is caused by the Mycobacterium tuberculosis bacterium, a slow-growing microbe 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. In 10 percent of people, though, the latent bacteria eventually begin to grow again. At this point, the tuberculosis is considered active, contagious, and a potential killer unless treated with a suite 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.

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 acquired before entering the United States.

To arrive at their conclusion, the researchers analyzed the DNA of the tuberculosis bacteria from 546 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 targeting latent TB cases in the United States is not sufficient to solve the problem, Dr. Schluger says. "You cannot eliminate the TB problem in the United States without looking at the disease outside our borders," Dr. Schluger says. "We should be heavily involved in reducing TB around the world."

The study was supported in part by the National Institutes of Health.

Other Columbia University Health Sciences researchers who participated in the research were Elvin Geng, a medical student at Columbia's College of Physicians & Surgeons and a graduate student in the Mailman School of Public Health; Dr. Joseph Burzynski, instructor in clinical medicine; Dr. Phyllis Della-Latta, associate clinical professor of pathology (in medicine); and Cynthia Driver, graduate student at Mailman.