Treatment and Vaccine Prospects

Treatment in the Acute Stage

Nifurtimox is the main drug used to treat Chagas' in the acute and early chronic stages of the disease. It inhibits intracellular development of T. cruzi in tissue culture and acts against the blood and intracellular stages of T. cruzi. It is administered orally for an extended period of time and young patients tend to tolerate it better than older ones.

Nifurtimox

http://arachosia.univ-lille2.fr/labos/parasito/Internat/medicam/tryp_me.html

Benznidazole is the drug that has traditionally been used to treat Chagas' since 1971 in Argentina, Brazil, and Chile. In contrast with nifurtimox, which has had variable results in clinical trials, benznidazole has had consistent antiparasitic effects. The mechanism of action is thought to be through inhibition of nucleic acid synthesis in the parasite. Allopurinol is another drug that seems to be effective in treating Chagas'. Enzymes of the parasite transform the drug into toxic adenosine analogues. It is important to note that all of the drugs mentioned above are effective only in the acute and possibly in the early chronic stages of the disease. Once Chagas' has proceeded to its full blown chronic stage, there is as of yet no cure, although research is in progress. Only supportive care for congestive heart failrue and for other symptoms of the chronic disease is available.

Benznidazole

http://arachosia.univ-lille2.fr/labos/parasito/Internat/medicam/tryp_me.html

There is currently only one planned clinical trial for patients with Chagas' disease, and it does not involve any experimental treatment. The National Institute of Allergy and Infectious Diseases (NIAID) simply plans "to evaluate, treat, and follow patients with parasitic infections," one of which is Chagas' disease. (Clinical Trial: Evaluation, Treatment, and Monitoring of Patients with a Known or Suspected Parasitic Infection)

Another recent study has shown that green tea catechins have trypanocidal activity. In the study, purified compounds from green tea lysed more than 50% of the parasites in the blood of infected mice and also were effective at killing the intracellular form of the trypanosome. These results suggest that these compounds can be used to sterilize blood and, eventually, as therapeutic agents for Chagas' disease. (Antimicrob Agents Chemother. 2004 Jan; 48(1): 69-74)

Another interesting study investigated cross reactivity between phytomonas serpans, a tomato parasite, and T. cruzi. The results indicate that ingestion by humans or animals of living plant trypanomastids present in naturally infected edible fruits could potentially prime the immune response to T. cruzi antigens and interfere with the development of T. cruzi infection. (FEMS Immunol Med Microbiol. 2003 Dec 5; 39(3): 257-64)

Treatment in the Chronic Stage

Thus far, the chronic stage of Chagas' disease has been virtually untreatable, other than providing supportive care to alleviate the symptoms. A progressive destruction of the myocardium occurs in 30% of individuals infected with T. cruzi, causing chronic cardiomyopathy. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. Results from one study show that bone marrow transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy. (Am J Pathology. 2004 Feb; 164(2): 441-7)

Vaccine Prospects

Because of the burden of Chagas' disease, either a therapeutic or protective vaccine would be highly effective in control and treatment efforts. Many studies have been done in search of a vaccine, some of which are highlighted below.

A study published in May 2003 took a slightly different approach to the potential for a recombinant DNA vaccine than other studies had used. Previous studies had used plasmids containing genes encoding for antigens expressed by the trypomastigote form of T. cruzi. In this study, however, the plasmids contained genes encoding for the antigen surface protein 2 (ASP-2) expressed by amastigotes, the intracellular, replicating form of the parasite. The mice that were immunized with this recombinant plasmid showed reduced parasitemia and survived a lethal dose of T. cruzi. (Infect Immun. 2003 May; 71(5): 2744-57)

Another study investigated the immunization of mice with recombinant paraflagellar rod protein against T. cruzi. This induced protective immunity due to a highly polarized type 1 cytokine production profile. (Vaccine. 2003 Jun 20; 21(21-22): 3058-69)

A third study analyzed the ability of a vaccine composed of the major cysteine protease of T. cruzi plus synthetic oligodeoxynucleotides containing CpG-motifs to induce immunoprotection against a lethal challenge with trypomastigotes. It was shown that mice immunized with this combination had the lowest blood parasitemia and 100% survival to acute infection. This study plus others provide the basis for the design of a multicomponent of anti-T. cruzi vaccine which may be used not only to protect humans at risk for infection, but also may alleviate or prevent the pathogenic responses characteristic of chronic Chagas' disease by reducing or perhaps eliminating tissue parasites from infected patients. (Vaccine. 2003 Dec 8; 22(1): 77-86)