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Antimicrobial Agents and Chemotherapy, April 2007, p. 1359-1364, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01170-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Anti-Trypanosoma cruzi Activity of Posaconazole in a Murine Model of Acute Chagas' Disease Is Less Dependent on Gamma Interferon than That of Benznidazole{triangledown}

Marcela L. Ferraz,1 Ricardo T. Gazzinelli,2,3 Rosana O. Alves,1 Julio A. Urbina,4 and Alvaro J. Romanha1*

Laboratório de Parasitologia Celular e Molecular,1 Laboratório de Imunopatologia, Centro de Pesquisa René Rachou, FIOCRUZ, 30190-002 Belo Horizonte, MG, Brazil,2 Departamento de Bioquímica e Imunologia, ICB-UFMG, 30270-010 Belo Horizonte, MG, Brazil,3 Laboratório de Química Biológica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Apartado 21827, Caracas 1020A, Brazil4

Received 20 September 2006/ Returned for modification 24 October 2006/ Accepted 30 December 2006

We have investigated the influences of gamma interferon (IFN-{gamma}) and interleukin-12 (IL-12) on the efficacy of posaconazole (POS) treatment of acute experimental infections with Trypanosoma cruzi; the standard drug, benznidazole (BZ), was used as a positive control. Wild-type (WT) mice infected with T. cruzi and treated with POS or BZ had no parasitemia, 100% survival, and cure rates of 86 to 89%. IFN-{gamma}-knockout (KO) mice infected with T. cruzi and treated with BZ controlled the infection during treatment but relapsed after the drug pressure ceased and had 0% survival, while those receiving POS better controlled the infection after the end of treatment and had 70% survival (P < 0.0001 compared to the results for both untreated and BZ-treated animals). IL-12-KO mice infected and treated with POS or BZ had intermediate results, displaying enhanced parasitemia, decreased survival (77 to 83%), and reduced cure rates (35 to 39%) compared with those of the WT animals. Our results demonstrate that either IFN-{gamma} or IL-12 deficiency reduces the efficacy of POS or BZ in this experimental model but also indicate that the anti-T. cruzi activity of POS is much less dependent on the activity of IFN-{gamma} than that of BZ is.

* Corresponding author. Mailing address: Laboratório de Parasitologia Celular e Molecular, Centro de Pesquisa René Rachou, FIOCRUZ, Av. Augusto de Lima, 1715, 30190-002 Belo Horizonte, MG, Brazil. Phone: 55-31-3349 7781. Fax: 55-31-3295 3115. E-mail: address: romanha{at}cpqrr.fiocruz.br

{triangledown} Published ahead of print on 12 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1359-1364, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01170-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rassi, A Jr, Dias, J C P, Marin-Neto, J A, Rassi, A (2009). Challenges and opportunities for primary, secondary, and tertiary prevention of Chagas' disease. Heart 95: 524-534 [Abstract] [Full Text]  
  • Ferraz, M. L., Gazzinelli, R. T., Alves, R. O., Urbina, J. A., Romanha, A. J. (2009). Absence of CD4+ T Lymphocytes, CD8+ T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection. Antimicrob. Agents Chemother. 53: 174-179 [Abstract] [Full Text]  


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