This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Toledo, M. J. d. O. Articles by de Lana, M. Search for Related Content PubMed PubMed Citation Articles by Toledo, M. J. d. O. Articles by de Lana, M.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2003, p. 223-230, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.223-230.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Chemotherapy with Benznidazole and Itraconazole for Mice Infected with Different Trypanosoma cruzi Clonal Genotypes

Departamento Análises Clínicas, Centro de Ciências da Saúde, Universidade Estadual de Maringá, Maringá, Paraná,¹ Departamento Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais,² Centro de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais,⁵ Departamento Ciências Biológicas, Instituto de Ciências Exatas e Biológicas,³ Departamento Análises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil,⁴ Génétique des Maladies Infectieuses, Unité Mixte de Recherche No. 9926, Centre National de la Recherche Scientifique/Institut de Recherche pour le Développement, 34032, Montpellier, Cedex 1, France⁶

Received 29 July 2002/ Returned for modification 16 September 2002/ Accepted 17 October 2002

The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.

This article has been cited by other articles:

• Martins, H. R., Figueiredo, L. M., Valamiel-Silva, J. C. O., Carneiro, C. M., Machado-Coelho, G. L. L., Vitelli-Avelar, D. M., Bahia, M. T., Martins-Filho, O. A., Macedo, A. M., Lana, M. (2008). Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes. J Antimicrob Chemother 61: 1319-1327 [Abstract] [Full Text]  
• Martins, H. R., Silva, R. M., Valadares, H. M. S., Toledo, M. J. O., Veloso, V. M., Vitelli-Avelar, D. M., Carneiro, C. M., Machado-Coelho, G. L. L., Bahia, M. T., Martins-Filho, O. A., Macedo, A. M., Lana, M. (2007). Impact of Dual Infections on Chemotherapeutic Efficacy in BALB/c Mice Infected with Major Genotypes of Trypanosoma cruzi. Antimicrob. Agents Chemother. 51: 3282-3289 [Abstract] [Full Text]  
• Coronado, X., Zulantay, I., Rozas, M., Apt, W., Sanchez, G., Rodriguez, J., Ortiz, S., Solari, A. (2006). Dissimilar distribution of Trypanosoma cruzi clones in humans after chemotherapy with allopurinol and itraconazole. J Antimicrob Chemother 58: 216-219 [Abstract] [Full Text]  
• Guedes, P. M. d. M., Urbina, J. A., de Lana, M., Afonso, L. C. C., Veloso, V. M., Tafuri, W. L., Machado-Coelho, G. L. L., Chiari, E., Bahia, M. T. (2004). Activity of the New Triazole Derivative Albaconazole against Trypanosoma (Schizotrypanum) cruzi in Dog Hosts. Antimicrob. Agents Chemother. 48: 4286-4292 [Abstract] [Full Text]  
• Toledo, M. J. O., Bahia, M. T., Veloso, V. M., Carneiro, C. M., Machado-Coelho, G. L. L., Alves, C. F., Martins, H. R., Cruz, R. E., Tafuri, W. L., Lana, M. (2004). Effects of specific treatment on parasitological and histopathological parameters in mice infected with different Trypanosoma cruzi clonal genotypes. J Antimicrob Chemother 53: 1045-1053 [Abstract] [Full Text]