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Antimicrobial Agents and Chemotherapy, April 2005, p. 1521-1528, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1521-1528.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

Simone Garcia,1,2 Carolina O. Ramos,1 Juliana F. V. Senra,1 Fabio Vilas-Boas,3 Maurício M. Rodrigues,4 Antonio C. Campos-de-Carvalho,2 Ricardo Ribeiro-dos-Santos,1 and Milena B. P. Soares1*

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz,1 Hospital Santa Izabel, Salvador, Bahia,3 Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro,2 Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil4

Received 20 July 2004/ Returned for modification 26 September 2004/ Accepted 20 December 2004

Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2ß, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of ß1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.

* Corresponding author. Present address: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Brotas, Salvador, BA CEP 40295-001, Brazil. Phone: (55) (71) 356-8787, ext. 260. Fax: (55) (71) 356-8784, ext. 292. E-mail: milena{at}cpqgm.fiocruz.br.

Antimicrobial Agents and Chemotherapy, April 2005, p. 1521-1528, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1521-1528.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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