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JAC Advance Access published online on April 21, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh224
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received December 13, 2002
Revised December 11, 2003
Accepted March 3, 2004

Original article

Effects of specific treatment on parasitological and histopathological parameters in mice infected with different Trypanosoma cruzi clonal genotypes

M. J. O. Toledo 1*, M. T. Bahia 2, V. M. Veloso 2, C. M. Carneiro 3, G. L. L. Machado-Coelho 4, C. F. Alves 2, H. R. Martins 3, R. E. Cruz 3, W. L. Tafuri 5, M. Lana 3

1 Departamento de Análises Clínicas, Centro de Ciências da Saúde, Bloco I-90, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900, Maringá, PR; Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG;
2 Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Campus Universitário Morro do Cruzeiro, Universidade Federal de Ouro Preto (UFOP), 35400-000, Ouro Preto, MG;
3 Departamento de Análises Clínicas, Escola de Farmácia, Rua Costa Sena, 171, UFOP, 35400-000, Ouro Preto, MG, Brazil
4 Departamento de Farmácia, Escola de Farmácia, Rua Costa Sena, 171, UFOP, 35400-000, Ouro Preto, MG, Brazil
5 Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG; Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Campus Universitário Morro do Cruzeiro, Universidade Federal de Ouro Preto (UFOP), 35400-000, Ouro Preto, MG;

* To whom correspondence should be addressed. E-mail: mjotoledo{at}uem.br.


  Abstract

The goal of this study was to verify the effect of specific treatment on parasitological and histopathological parameters in mice experimentally infected with different Trypanosoma cruzi clonal genotypes. Twenty cloned stocks were selected, representative of the whole phylogenetic diversity of the protozoan and belonging to the clonal genotypes 19 and 20 (T. cruzi I) and 39 and 32 (T. cruzi II). The stocks were inoculated in 40 BALB/c mice divided into four groups: (i) treated with benznidazole, (ii) treated with itraconazole and (iii and iv) untreated control groups (NT) for each drug, respectively. Seven parameters related to parasitaemia curves and histopathological lesions were analysed. Four during the acute phase (AP) and three during both the AP and chronic phase (CP) of infection. Statistical comparison between benznidazole-treated and NT groups for the biological parameters showed significant differences for all genotypes. Benznidazole treatment led to lower patent period, maximum of parasitaemia, day of maximum parasitaemia and area under the parasitaemia curve for all genotypes analysed. Percentage of positive haemoculture during AP and CP was lower for genotypes 19 and 32. Tissue parasitism (TP) and inflammatory process (IP) during AP were lower for genotypes 19 and 32, respectively. In general, itraconazole treatment induced a smaller reduction in these same parameters between treated and NT animals in relation to benznidazole treatment. Our results indicate that phylogenetic divergence among T. cruzi clonal genotypes must be taken in account in chemotherapy and studies dealing with all aspects of the parasite and the disease.

Key Words: Keywords: experimental chemotherapy, benznidazole, itraconazole, genetic groups


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