Chagas Disease

• Chagas disease is a leading cause of infectious heart disease.
• There are approximately 8-11 million cases in Latin America and the U.S.
• Chagas disease is becoming a serious threat to the U.S. blood supply.

IDRI's Efforts

IDRI's research on Trypanosoma cruzi, the parasite that causes Chagas disease, has emphasized three measures: (1) diagnostic tests to screen the blood supply for T. cruzi, (2) vaccines to prevent T. cruzi infection, and (3) therapeutics to treat Chagas disease. To facilitate these three goals, IDRI researchers are investigating both the immune response that provides protection against the parasite and the pathologic immune response that causes Chagas disease.

In collaboration with Corixa Corporation, IDRI scientists have developed an effective blood test for Chagas disease. The test is now being implemented in South America, but further development is needed to use the test in the U.S. This test will be the most effective way to prevent spread of Chagas disease through the blood supply.

Another way to reduce the number of infected individuals is vaccination. IDRI scientists have developed a prototype vaccine that may be effective against both leishmaniasis and Chagas disease, due to the similarity of these organisms. Such a vaccine would dramatically reduce the number of new cases of Chagas disease each year, ultimately saving millions of lives. When used in combination with a blood-screening test, Chagas disease could be eliminated in the next generation.

About Chagas Disease

Chagas disease is prevalent in Latin America. It is caused by chronic infection of the parasite T. cruzi, which is most commonly transmitted to individuals through insects, blood transfusions, or pregnancy. The parasite disseminates throughout the body, invading many different cell and tissue types. The infection may trigger a chronic inflammatory disease in 30% of individuals. If left untreated, the disease usually impairs the heart and digestive system. Chagas disease is a leading cause of heart disease in Latin America. In adults, the decline in health develops slowly, occurring 20-30 years after the initial infection. In children, however, the disease can be devastating; congenital infection with T. cruzi can cause miscarriage and newborn death.

Because T. cruzi infection can persist in asymptomatic adults for many years, the parasite has contaminated the blood supply in many areas of Latin America. Currently, 100,000 immigrants to the United States from Central and South America are infected with T. cruzi, and contamination of the U.S. blood supply is now becoming a serious problem. There is no test in use to screen the U.S. blood supply for T. cruzi and no effective therapies or vaccines available to treat or prevent Chagas disease.

What More is Needed to Stop Chagas Disease?

IDRI scientists investigating the immune responses triggered by T. cruzi that are protective and pathological are focusing on two aspects of the immune response: the conventional effector MHC class II (MHCII)-restricted T cell response and the regulatory natural killer T (NKT) cell response.

The research on the conventional MHCII T cells investigates the response to the surface protein superfamily of the parasite. These T cells are stimulated by small peptides (epitopes), and amino acid variation of the epitopes is known to have profound inhibitory affects on T cell responses. The parasite's surface protein superfamily encodes many proteins with variant epitope amino acid sequences. Therefore, during T. cruzi infection the T cell response to the surface protein superfamily is being investigated to understand the effect of epitope variation on the protective and pathologic immune responses. IDRI scientists have discovered that MHCII-restricted T cells that recognize a single epitope of the parasite's surface protein superfamily can be manipulated through immunization or adoptive transfer to provide protection. How these T cells affect chronic inflammation is unknown, and furthermore, how naïve T cells that recognize this epitope respond during T. cruzi infection is unknown. Research to understand these aspects of this potentially protective vaccine against T. cruzi is currently underway.

The regulatory NKT cells are a subset of T cells that utilize an invariant T cell receptor (TCR), and, unlike conventional T cells, are stimulated by glycolipids. NKT cells can regulate immune responses by rapidly producing cytokines that initiate protective responses, or by producing cytokines that inhibit unnecessary responses. In many mouse models of infection or chronic inflammation, and in two human chronic inflammatory diseases, scleroderma and type 1 diabetes, NKT cell function appears to be compromised. IDRI scientists have discovered that during T. cruzi infection NKT cells contribute to the protective immune response, and that manipulation of NKT cell responses with glycolipids treatments before T. cruzi infection can augment the protective immune response. How NKT cells affect the chronic inflammatory response, and if glycolipid responses can be used to treat the chronic inflammatory response remain unknown. Research to understand these aspects of this potentially protective treatment against T. cruzi is currently underway.