ATHENS, Ga. -- New evidence by scientists from the University of Georgia indicates that victims of a common tropical disease may be receiving inadequate treatment because of a major misunderstanding of how the illness progresses.
Chagas' disease, caused by a protozoan parasite, infects up to 18 million people in Latin America, and 90 million individuals are at risk of infection. Most people die from heart failure during the chronic phase of the disease rather than complications of acute infection. Indeed, Chagas' disease is thought to be the single most common cause of congestive heart failure in the world.
In a new study, however, scientists have shown through heart transplants in mice that heart damage associated with Chagas' disease is not caused by autoimmune reactions as was commonly thought. Instead, heart damage -- and its resulting sudden death -- among victims of the disorder are almost certainly caused by the immune reaction to parasites in the heart itself.
"The results of these studies have considerable implications for the treatment or prevention of Chagas' disease," said Dr. Rick Tarleton, a cellular biologist. "This study provides definitive data show we should reduce the parasite load in patients to prevent disease progression."
The research was funded by the National Institutes of Health and the Burroughs Wellcome Fund and was published in April in the Proceedings of the National Academy of Sciences. Co-authors of the study were Dr. Myron Downs of the University of Georgia's College of Veterinary Medicine, and Lei Zhang, a student in the department of cellular biology.
Chagas' disease is caused by the parasite Trypanosoma cruzi. The disorder causes numerous varieties of sickness, but none is more deadly than heart failure. Scientists had thought for years that sudden cardiac death was caused by the body's autoimmune response to heart tissue, but Tarleton and his colleagues showed that is clearly not the case. Instead, they found that the actual presence of the parasites appear to promote heart disease -- something that had been discounted because of the sheer difficulty of finding T. cruzi in heart tissue.
Indeed, many researchers still consider autoimmunity to be the likely cause of Chagas' disease, but Tarleton said that hypothesis is "largely circumstantial."
In order to test his hypothesis, Tarleton took advantage of a routine technique to test immune rejection -- the transplantation of a living heart from a mouse into the ear skin of another genetically identical mouse. One might think such a heart would die immediately, but it doesn't. In fact, it develops its own vasculature and begins to beat within several days.
"The transplanted hearts must be from newborns or those just about to be born," said Tarleton. "Though the transplanted heart serves no useful function, it gives us a way to see how it reacts to the presence of the parasites in the host animal."
If, as other scientists have theorized, Chagas' disease is caused by an autoimmune reaction to heart tissue, then the hearts transplanted into mice with chronic T. cruzi infections should have been rejected by this same anti-self immune response. Instead, the new hearts continued to beat for months and months with no signs of disease. Even more interesting, they showed no sign of acquiring parasites, even months after transplantation, showing just how efficient the anti-parasite immune response is in controlling the spread of parasites to other areas of the body. Tarleton credited Zhang with developing a very sensitive technique for the discovery of parasites in the mouse hearts.
"It is strange that the theory for Chagas' disease as an autoimmune disorder is so shaky yet so widely accepted," said Tarleton. "The autoimmune theory dominates treatment and prevention protocols for the disease."
Treatment for the disease usually comes in the acute phase, when the body is first reacting to the presence of the parasites. After that phase has passed, victims of the disease usually are not treated at all, largely because physicians have considered the autoimmune response would be difficult, if not impossible to treat. Treatments that are used are harsh and can cause severe side effects, leading many people to refuse it entirely. Unfortunately, those with chronic Chagas' disease are susceptible to sudden death from heart failure associated with the disorder. Tarleton now calls this lack of treatment for chronic-disease sufferers a "serious miscalculation."
A Brazilian doctor has made medical history in the past few years by actually cutting part of the heart muscle away from victims of Chagas' disease suffering from congestive heart failure. The risky surgery is now being performed in the United States on rare occasions.
Despite the millions of people at risk, there is currently no vaccine-development program in progress to prevent infection with T. cruzi. The main reason appears to be the previous ideas of an autoimmune origin for the disease.
"A vaccine only heightens the immune response, so the fear has been that a vaccine would make those infected even sicker," said Tarleton. "My gut feeling is that the autoimmune component of the disease is inconsequential. We can't prove that autoimmunity doesn't exist, but even if autoimmunity is a component, we cannot treat this as an autoimmune disease. We must treat it as a parasitic infection. We must develop protocols to clear the parasites. If we do that, we can get rid of the disease."
From a practical point of view, Tarleton believes that the development of a vaccine could hold the promise of a major new tool in the fight against a disease that sickens millions each year.
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Journal
Proceedings of the National Academy of Sciences