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Lack of Efficacy of Liposomal Amphotericin B Against Acute and Chronic Trypanosoma cruzi Infection in Mice

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  • 1 California Institute for Medical Research, San Jose, California;
  • | 2 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California;
  • | 3 Department of Pathology, Stanford University, Stanford, California;
  • | 4 Department of Pathology, Veterans Administration Medical Center, Palo Alto, California;
  • | 5 Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil

Acute and chronic infection with Trypanosoma cruzi affects millions of people. The current therapeutic options are highly toxic and often not effective. Liposomal amphotericin B (LAMB) has been demonstrated previously to have some activity in murine models. In our studies, higher dosages given multiple times were tested for activity against acute or chronic disease, exploring whether intermittent and brief regimens could be effective, as might then prove useful in human, particularly outpatient, therapy. For acute infection, LAMB 25 mg/kg intravenously (i.v.) given one to three times prolonged survival and caused a rapid disappearance of Y strain trypomastigotes from the blood. However, even four or six doses of LAMB 30 mg/kg i.v., did not result in the cure of Y strain infection, with all mice relapsing after being immunosuppressed with cyclophosphamide. Similarly, chronic infection due to the CL strain was found to be unaltered by 1–3 treatments with LAMB 25 mg/kg. All surviving mice had histopathological evidence of infection in one or more tissues and equivalent antibody titers regardless of treatment regimen. Overall, LAMB at doses up to 30 mg/kg i.v. prolonged survival, but these doses were not curative in the regimens studied.

Author Notes

Address correspondence to Karl V. Clemons, California Institute for Medical Research, 2260 Clove Dr., San Jose, CA 95128. E-mail: clemons@cimr.org

Financial support: These studies were funded in part by a grant from Gilead Sciences, who had no input to the interpretation of data, the writing, or the decision to publish.

Authors’ addresses: Karl V. Clemons, Marife Martinez, and David A. Stevens, California Institute for Medical Research, San Jose, CA, E-mails: clemons@cimr.org, martinez@cimr.org, and stevens@stanford.edu. Raymond A. Sobel, Department of Pathology, Veterans Administration Medical Center, Palo Alto, CA, E-mail: raysobel@stanford.edu. Rodrigo Correa-Oliveira, Laboratorio de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil, E-mail: correa@cpqrr.fiocruz.br.