Heart Problems In Victims Of Tropical Disease May Not Be Caused By Autoimmune Reaction; New Treatment Indicated

September 04, 1997

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.


University of Georgia

Related Heart Failure Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Machining the heart: New predictor for helping to beat chronic heart failure
Researchers from Kanazawa University have used machine learning to predict which classes of chronic heart failure patients are most likely to experience heart failure death, and which are most likely to develop an arrhythmic death or sudden cardiac death.

Heart attacks, heart failure, stroke: COVID-19's dangerous cardiovascular complications
A new guide from emergency medicine doctors details the potentially deadly cardiovascular complications COVID-19 can cause.

Autoimmunity-associated heart dilation tied to heart-failure risk in type 1 diabetes
In people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle (the heart's main pumping chamber), increased muscle mass, and reduced pumping function (ejection fraction), features that are associated with higher risk of failure in the general population

Transcendental Meditation prevents abnormal enlargement of the heart, reduces chronic heart failure
A randomized controlled study recently published in the Hypertension issue of Ethnicity & Disease found the Transcendental Meditation (TM) technique helps prevent abnormal enlargement of the heart compared to health education (HE) controls.

Beta blocker use identified as hospitalization risk factor in 'stiff heart' heart failure
A new study links the use of beta-blockers to heart failure hospitalizations among those with the common 'stiff heart' heart failure subtype.

Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.

Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.

How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.

Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.

Read More: Heart Failure News and Heart Failure Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.