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Antimicrobial Agents and Chemotherapy, September 2007, p. 3282-3289, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.01590-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Impact of Dual Infections on Chemotherapeutic Efficacy in BALB/c Mice Infected with Major Genotypes of Trypanosoma cruzi

Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto,¹ Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto,² Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais,³ Departamento de Análises Clínicas, Universidade Estadual de Maringá, Pr,⁴ Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto,⁵ Centro de Pesquisas René Rachou, FIOCRUZ,⁶ Departamento de Análises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto, MG, Brazil⁷

Received 20 December 2006/ Returned for modification 17 March 2007/ Accepted 21 June 2007

The aim of this work was to investigate the impact of dual infections with stocks of Trypanosoma cruzi major genotypes on benznidazole (BZ) treatment efficacy. For this purpose, T. cruzi stocks representative of the genetic T. cruzi lineages, displaying different susceptibilities to BZ, belonging to the major T. cruzi genotypes broadly dispersed in North and South America and important in Chagas’ disease epidemiology were used. Therapeutic efficacy was observed in 27.8% of the animals treated. Following BZ susceptibility classification, significant differences were observed in dual infections on the major genotype level, demonstrating that combinations of genotypes 19+39 and genotypes 19+32 led to a shift in the expected BZ susceptibility profile toward the resistance pattern. Analysis on the T. cruzi stock level demonstrated that 9 out of 24 dual infections shifted the expected BZ susceptibility profile compared with the respective single infections, including shifts toward lower and higher BZ susceptibilities. Microsatellite identification was able to identify a mixture of T. cruzi stocks in 7.7% of the T. cruzi isolates from infected and untreated mice (6.9%) and infected and treated but not cured mice (9.0%), revealing in some mixtures of BZ-susceptible and -resistant stocks that the T. cruzi stock identified after BZ treatment was previously susceptible in single infections. Considering the clonal structure and evolution of T. cruzi, an unexpected result was the identification of parasite subpopulations with distinct microsatellite alleles in relation to the original stocks observed in 12.2% of the isolates. Taken together, the data suggest that mixed infections, already verified in nature, may have an important impact on the efficacy of chemotherapy.

Published ahead of print on 16 July 2007.

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]