Researchers combat tuberculosis - help may come from protective protein

Mar 23 2006

Most Americans think of tuberculosis as a disease of the past, but with HIV and drug-resistant strains fueling epidemics in India and Africa, TB kills someone every six seconds across the world.

Now University of Florida and Indian scientists suspect they are on the path to solving a piece of the puzzle. The researchers are studying a protective protein they believe may boost bacteria-battling defenses, protecting against TB and giving infected patients an easier recovery.

Alcohol consumption likely reduces the amount of this protective protein, called heme oxygenase 1, weakening the body's defenses against TB, said Veena Antony, M.D., a UF professor of pulmonary medicine and division chief of pulmonary and critical care medicine for the College of Medicine. The researchers hope to pinpoint the role of alcoholism in the global epidemic by studying a population of HIV- and tuberculosis-infected patients in India. The researchers are collecting data for the National Institutes of Health-funded project and hope to have answers within two to three years, Antony said.

The epidemic may be more prevalent in resource-poor countries like India right now, but with immigrants unknowingly carrying bacteria that cause TB into the United States each year, this crisis could spread to American soil if left untended, Antony warns.

"We cannot build walls high enough to keep these organisms out," she said. "In the U.S., we cannot afford to grow complacent about TB. This is a disease that appears in many forms, many guises. We will never be able to eradicate it from the U.S. unless we eradicate it from the world."

The increasing number of multidrug-resistant strains of TB makes the disease even more troublesome, Antony says. The only currently approved treatment for TB requires patients to go to a clinic every day for up to nine months, and people often do not complete the full course of therapy, breeding new bacteria that are immune to the drugs. There is currently no way to treat large populations infected with drug-resistant strains of the disease, Antony said. The drug-resistant organism is one of several the federal government lists as a potential bioterrorism threat.

But the combination of HIV and TB currently poses the biggest problem globally. Patients with HIV are more apt to develop tuberculosis after they have contracted bacteria that cause TB, said Amy Davidow, Ph.D., an associate professor of preventive medicine and community health at the University of Medicine and Dentistry of New Jersey.

"The rule of thumb is if you have been infected (with TB) and are otherwise healthy, there is a 5 to 10 percent chance you will (ever) develop active disease," Davidow said. "The immune system keeps the infection in check so it never develops. HIV depresses the immune system, so certain infections (such as TB) can become active."

Tuberculosis can affect any organ in the body but causes more problems in the lungs, resulting in painful coughing and respiratory problems. Coupled with HIV, the two diseases form a deadly one-two punch that could be just as dangerous to the public as it is to the HIV- and TB-infected patient. Because TB develops more quickly in a person with HIV, the organism is more prevalent in the body and may spread more easily to other people, other research has shown.

"In resource-poor societies there is a meeting of HIV and tuberculosis, so that one disease is fueling the other disease," Antony said. "That is true in Africa. That is true in India where the HIV epidemic is just beginning to explode.

"Because of this concern, we believe we have to find novel ways of killing the organism. We have shown that heme oxygenase 1 is effective in boosting the cell's ability to protect itself."

In India, outbreaks of HIV and TB have erupted along highways where truck drivers often solicit prostitutes, Antony said. Doctors at the Post Graduate Institute of Medical Education and Research in India treat many of these patients, which is one of the reasons why UF researchers chose to collaborate with them for this research project, Antony said.

UF researchers also hope to initiate an international training program with PGIMER, allowing Indian researchers to come to Florida to learn sophisticated techniques and giving UF trainees firsthand experience in dealing with the epidemic there.

"One single patient with tuberculosis can infect hundreds of people," Antony said. "One-third of the world's population is infected with the organism that causes tuberculosis. We're going out into the field to meet the disease head-on and try to find answers."

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