Two Ways to Tackle Tuberculosis

WEDNESDAY June 3, 2009 -- In the minds of most Americans, tuberculosis is a disease of the past.

However, statistics show it's still a major global health problem.

That's why two studies in the June 4 issue of the New England Journal of Medicine are important -- one describes an international effort to detect tuberculosis (TB) among immigrants and refugees coming to the United States, the other reports on highly promising results of a new drug to treat the disease.

According to the World Health Organization, there are nearly 9 million new TB cases and perhaps 1.5 million deaths from the disease annually. Even in the United States, the U.S. Centers for Disease Control and Prevention tallied up 13,293 new cases of TB in 2007.

The research on the new screening program is important because "a substantial portion of newly diagnosed cases in the United States is among foreign-born individuals," explained study author John A. Painter, a team leader for immigrant, refugee and migrant help at the CDC. The TB rate in that group is 9.8 times higher than among U.S.-born individuals -- 20.6 cases per 100,000 people versus 2.1 per 100,000 people for the native-born. Nearly 58 percent of the new TB cases in the United States in 2007 were diagnosed in the foreign-born group.

"The effort to identify persons with tuberculosis in this group is crucial in controlling the disease in the United States," Painter said.

The disease is not always easy to detect in a screening program, he said. "Someone may be infected with TB without having an active disease," Painter said. "One standard technology is a sputum smear. You look under a microscope for the disease. Unfortunately, it is not very sensitive. A new technique is to culture a specimen for six to eight weeks, which allows detection of even a low-level infection. This is more recent and somewhat more involved. It is not universally done. We are focusing on countries where there is a high rate and a large number of cases."

Those countries include Vietnam, the Philippines and China, Painter said.

In many cases, infection does not mean active disease, since the TB bacteria can lie dormant for years, he explained. "Ten percent of those who are infected will develop active TB in their lifetimes," Painter said.

So, follow-up exams often are required when an immigrant or refugee enters the United States. "Overseas screening can identify a large number of people at high risk for tuberculosis," said Yecai Liu, a CDC medical statistician who contributed to the report. "To maximize the benefit of the overseas program depends on local control programs. We have an active outreach policy, with a home visit and telephone calls recommended."

Treatment follows detection, and the other journal report describes promising results of a new drug tested in a controlled trial of individuals with a virulent form of the disease, called multidrug-resistant tuberculosis.

This is not the most dangerous form of TB. That title is held by a strain called extensively drug-resistant TB. There was an international public health scare in 2007 when an Atlanta lawyer was believed to have flown overseas for a European honeymoon with the extensively drug-resistant version of the disease, a fear that turned out to be unfounded.

But the multidrug-resistant form is deadly enough so that a new drug to fight it would be welcome.

The drug, designated TMC207, was discovered at the Belgian research laboratory of Tibotec, a subsidiary of the American drug company Johnson & Johnson. It has a unique strategy for attacking the tuberculosis bacterium, said Dr. David F. McNeeley, global medical leader for clinical development at Tibotec.

"All existing medications have different ways of attacking," McNeeley said. "Some interrupt protein synthesis, some interfere with DNA replication, some interrupt cell wall construction."

The new drug cripples the activity of ATP synthase, an enzyme that plays a key role in biological energy metabolism. It does that only in the TB bacterium, not in other cells.

The journal report describes a trial in which 47 people with multidrug-resistant tuberculosis were given either the usual cocktail of TB drugs and TMC207, or the usual cocktail and a placebo. After eight weeks, the TB bacteria was not found in 48 percent of those getting TMC207, compared to 9 percent of those getting conventional treatment.

That trial is just the first step in testing the effectiveness of TMC207, McNeeley said. "We are now enrolling another 150 patients to get six months' treatment," he said. "When those results come in, we will be able to decide what else to do with the drug."

It's impossible to say now whether TMC207 will ever be front-line treatment for tuberculosis, McNeeley said. "We still are in the early stage of development," he noted.

More information

Learn about tuberculosis and its treatment from the U.S. Centers for Disease Control and Prevention.

Posted: June 2009


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