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1.
Bern C, Kjos S, Yabsley MJ, Montgomery SP, 2011. Trypanosoma cruzi and Chagas’ disease in the United States. Clin Microbiol Rev 24: 655–681.
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2.
Bern C, Montgomery SP, 2009. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 49: e52–e54.
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Jurberg C, 2009. Chagas: one hundred years later. Bull World Health Organ 87: 491–492.
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Kirchhoff LV, 2011. Epidemiology of American trypanosomiasis (Chagas disease). Adv Parasitol 75: 1–18.
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Coura JR, Vinas PA, 2010. Chagas disease: a new worldwide challenge. Nature 465: S6–S7.
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Brown EL, Roellig DM, Gompper ME, Monello RJ, Wenning KM, Gabriel MW, Yabsley MJ, 2010. Seroprevalence of Trypanosoma cruzi among eleven potential reservoir species from six states across the southern United States. Vector Borne Zoonotic Dis 10: 757–763.
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Urbina JA, 2010. Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Trop 115: 55–68.
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Molina I et al.., 2014. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med 370: 1899–1908.
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Molina I, Salvador F, Sanchez-Montalva A, 2015. The use of posaconazole against Chagas disease. Curr Opin Infect Dis 28: 397–407.
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Urbina JA, 2015. Recent clinical trials for the etiological treatment of chronic Chagas disease: advances, challenges and perspectives. J Eukaryot Microbiol 62: 149–156.
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16.
Morillo CA et al..; STOP-CHAGAS Investigators, 2017. Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers: the STOP-CHAGAS Trial. J Am Coll Cardiol 69: 939–947.
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Abitbol H, Boris E, Piulats E, Podesta D, Maranon J, 1964. Therapeutic action of amphotericin B in acute Chagas’ disease. Bol Chil Parasitol 19: 132–134.
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Cencig S, Coltel N, Truyens C, Carlier Y, 2011. Parasitic loads in tissues of mice infected with Trypanosoma cruzi and treated with AmBisome. PLoS Negl Trop Dis 5: e1216.
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19.
Yardley V, Croft SL, 1999. In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections. Am J Trop Med Hyg 61: 193–197.
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Cordeiro FD, Martins-Filho OA, Da Costa Rocha MO, Adad SJ, Correa-Oliveira R, Romanha AJ, 2001. Anti-Trypanosoma cruzi immunoglobulin G1 can be a useful tool for diagnosis and prognosis of human Chagas’ disease. Clin Diagn Lab Immunol 8: 112–118.
| Past two years | Past Year | Past 30 Days | |
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Lack of Efficacy of Liposomal Amphotericin B Against Acute and Chronic Trypanosoma cruzi Infection in Mice
Karl V. Clemons
Karl V. Clemons
California Institute for Medical Research, San Jose, California;
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California;
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Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California;
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Raymond A. Sobel
Raymond A. Sobel
Department of Pathology, Stanford University, Stanford, California;
Department of Pathology, Veterans Administration Medical Center, Palo Alto, California;
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Department of Pathology, Veterans Administration Medical Center, Palo Alto, California;
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Marife Martinez
Marife Martinez
California Institute for Medical Research, San Jose, California;
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Rodrigo Correa-Oliveira
Rodrigo Correa-Oliveira
Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil
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David A. Stevens
David A. Stevens
California Institute for Medical Research, San Jose, California;
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California;
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Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California;
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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
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.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Bern C, Kjos S, Yabsley MJ, Montgomery SP, 2011. Trypanosoma cruzi and Chagas’ disease in the United States. Clin Microbiol Rev 24: 655–681.
-
2.
Bern C, Montgomery SP, 2009. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 49: e52–e54.
-
3.
Jurberg C, 2009. Chagas: one hundred years later. Bull World Health Organ 87: 491–492.
-
4.
Kirchhoff LV, 2011. Epidemiology of American trypanosomiasis (Chagas disease). Adv Parasitol 75: 1–18.
-
5.
Tanowitz HB, Kirchhoff LV, Simon D, Morris SA, Weiss LM, Wittner M, 1992. Chagas’ disease. Clin Microbiol Rev 5: 400–419.
-
6.
World Health Organization, 2015. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 90: 33–44.
-
7.
Coura JR, Vinas PA, 2010. Chagas disease: a new worldwide challenge. Nature 465: S6–S7.
-
8.
Brown EL, Roellig DM, Gompper ME, Monello RJ, Wenning KM, Gabriel MW, Yabsley MJ, 2010. Seroprevalence of Trypanosoma cruzi among eleven potential reservoir species from six states across the southern United States. Vector Borne Zoonotic Dis 10: 757–763.
-
9.
Urbina JA, 2010. Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Trop 115: 55–68.
-
10.
Buckner FS, Navabi N, 2010. Advances in Chagas disease drug development: 2009–2010. Curr Opin Infect Dis 23: 609–616.
-
11.
Coura JR, Borges-Pereira J, 2012. Chagas disease: what is known and what should be improved: a systemic review. Rev Soc Bras Med Trop 45: 286–296.
-
12.
Lescure FX, Le Loup G, Freilij H, Develoux M, Paris L, Brutus L, Pialoux G, 2010. Chagas disease: changes in knowledge and management. Lancet Infect Dis 10: 556–570.
-
13.
Molina I et al.., 2014. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med 370: 1899–1908.
-
14.
Molina I, Salvador F, Sanchez-Montalva A, 2015. The use of posaconazole against Chagas disease. Curr Opin Infect Dis 28: 397–407.
-
15.
Urbina JA, 2015. Recent clinical trials for the etiological treatment of chronic Chagas disease: advances, challenges and perspectives. J Eukaryot Microbiol 62: 149–156.
-
16.
Morillo CA et al..; STOP-CHAGAS Investigators, 2017. Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers: the STOP-CHAGAS Trial. J Am Coll Cardiol 69: 939–947.
-
17.
Abitbol H, Boris E, Piulats E, Podesta D, Maranon J, 1964. Therapeutic action of amphotericin B in acute Chagas’ disease. Bol Chil Parasitol 19: 132–134.
-
18.
Cencig S, Coltel N, Truyens C, Carlier Y, 2011. Parasitic loads in tissues of mice infected with Trypanosoma cruzi and treated with AmBisome. PLoS Negl Trop Dis 5: e1216.
-
19.
Yardley V, Croft SL, 1999. In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections. Am J Trop Med Hyg 61: 193–197.
-
20.
Cordeiro FD, Martins-Filho OA, Da Costa Rocha MO, Adad SJ, Correa-Oliveira R, Romanha AJ, 2001. Anti-Trypanosoma cruzi immunoglobulin G1 can be a useful tool for diagnosis and prognosis of human Chagas’ disease. Clin Diagn Lab Immunol 8: 112–118.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 690 | 547 | 20 |
| Full Text Views | 321 | 8 | 0 |
| PDF Downloads | 95 | 11 | 0 |