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Genome of Rheumatic Fever Bacterium Revealed

Raises hopes for better diagnostics, therapies and vaccines

TUESDAY, March 26, 2002 (HealthDayNews) -- The genome sequence of the bacterium that causes acute rheumatic fever is giving researchers their first look at the secrets of this bug -- secrets that could ultimately lead to a vaccine against the potentially deadly condition.

Experts say the complete mapping of the M18 serotype of Group A Streptococcus (GAS), published in today's issue of the Proceedings of the National Academy of Sciences, offers researchers their first chance to fully understand why rheumatic fever develops in certain cases of GAS infections and not others.

Senior investigator Dr. James Musser, the chief of Human Bacterial Pathogenesis at the National Institute of Allergy and Infectious Diseases in Hamilton, Mont., says that although acute rheumatic fever (ARF) is the major cause of preventable childhood heart disease globally, how the disease occurs is not well understood. At the same time, he says, a vaccine and therapies are badly needed. His team has been working in this field for the last decade.

While millions of people contract strep throat, only about two out of 100 cases go on to become ARF. This is considered a rare complication of streptococcal infection in the United States, although isolated outbreaks still occur. It is most common in children between the ages of 5 and 15.

Roughly 18 days after an untreated strep infection, children with ARF commonly experience migratory arthritis affecting several joints, while some develop nodules under the skin or an expanding red rash. An acute attack may last for three months, and the most serious complication is inflammation of the heart, a potentially deadly condition. Existing therapy involves antibiotic treatment.

Patrick Schlievert, a professor of microbiology at the University of Minnesota in Minneapolis, says that there has been a resurgence in ARF in New York, Utah, and the Cleveland, Ohio, area since about 1987. "Normally, we think of rural, impoverished areas, but this is happening in middle-class populations," Schlievert says.

The vast majority of these outbreaks involved the M18 strain of GAS, he says. M18 refers to a protein found on the surface of the bacterium. The variants with low M numbers, such as M1, M3 and M18, are linked to rheumatic fever, whereas higher numbers, such as M49, M53 and M55, are linked to diseases such as acute glomerulonephritis, a kidney condition.

Musser and his colleagues found several bacterial viruses called phages within the bacterium's genome. "Virtually all of those bacterial viruses carry with them … genes that encode toxins," says Musser.

Musser says he was struck by how much these virus genes contributed to the bacterium's ability to cause illness. "We've known that these bacterial viruses exist, though we had no idea of the magnitude of the contribution was so considerable in Group A Strep," he says.

The strain includes genes carrying the instructions for a variety of secreted toxins, included those linked to scarlet fever.

Using technology known as gene chip analysis, the researchers compared 36 copies of M18 GAS strains from multiple ARF outbreaks. "Two very large outbreaks of rheumatic fever that occurred in the Salt Lake City area were both caused by the same strain of M18 Group A Strep," says Musser. "It's telling us that these epidemics are due to recycling of the same strain -- in some cases, 12 years apart."

Schlievert says the findings could have immediate research implications.

"This is the first time that I think we have a very good handle on this bona fide rheumatic fever strain," he says. "We can now begin to piece together how rheumatic fever comes about, using [this] as the base of knowledge."

Musser also anticipates more research now that the genome has been sequenced. "It has immediately stimulated new strategies for vaccine development against this organism," he says, adding that his own team is currently at work on such a project.

"The second area that is equally as important is the development of new treatment approaches for treating people with rheumatic fever," he says. "The third area is the development of new, more rapid diagnostic measures that can be used to determine if someone has rheumatic fever."

Most of these developments are three to eight years away from completion, he adds.

What to Do: You can learn more about Group A Streptococcus from the Centers for Disease Control and Prevention, Rockefeller University or the Association of State and Territorial Directors of Health Promotion and Public Health Education.

SOURCES: James M. Musser, M.D., Ph.D., chief, Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Mont.; Patrick M. Schlievert, Ph.D., professor, Department of Microbiology, University of Minnesota, Minneapolis; March 26, 2002, Proceedings of the National Academy of Sciences
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