New, More Effective Treatment For Toxic Shock Syndrome

Toxic Shock Syndrome is a rare, life-threatening bacterial infection that can cause multi-organ failure and death. A major cause of the disease is a superantigen called staphylococcal enterotoxin B (SEB), which is produced by Staphylococcus aureus bacteria. SEB binds to T-lymphocytes in the body causing the release of cytokines, resulting in the dramatic blood pressure drop seen in TSS.

Currently, TSS can be treated with antibiotics to kill the bacteria and antibodies to neutralize SEB. But, as published in the May 21, 2007 issue of Nature Medicine, scientists have engineered a new high-affinity molecule known as V-beta which blocks SEB's ability to bind to T-cells. By targeting the early stages of disease onset, V-beta neutralizes SEB at a rate 2000 times more effective than typical antibody treatment.

"The development and efficacy of V-beta in animal models is a very significant advancement in infectious disease treatment," said Patrick Schlievert, Ph.D., co-author of the paper and professor of microbiology at the University of Minnesota Medical School. "It represents an easily produced, potential treatment for diseases caused by SEB and other superantigens associated with TSS."

Schlievert and colleague Marnie Peterson, Pharm.D., Ph.D., co-author and assistant professor at the University of Minnesota College of Pharmacy Department of Experimental and Clinical Pharmacology, studied the effects of V-beta on SEB in rabbit models. The treatment of rabbits with SEB was successful when given V-beta following onset of disease, after SEB had caused a high fever and symptoms of TSS, and after rabbits had been exposed to SEB on a continuous basis.

"Not only is SEB a major cause of Toxic Shock Syndrome, it also is considered a potential biological weapon," explained Schlievert. "With that in mind, the small amount of V-beta needed for SEB neutralization makes this a truly significant discovery and useful therapy."

Approximately 3 out of every 100,000 people will get TSS annually. In addition, nearly 35,000 people die every year from post influenza infection, which is often caused by TSS or pneumonia. Symptoms of TSS include high fever, low blood pressure, vomiting and diarrhea, and a rash that looks similar to sunburn. While the infection often occurs in menstruating women and is associated with the use of superabsorbent tampons and contraceptive items, it can also affect men, children and postmenopausal women, particularly following respiratory viral infections. Other risk factors include skin wounds and surgery.

This study was supported by the National Institutes of Health.