WHO, 2015. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 90: 33–43.
Gascon J, Bern C, Pinazo M-J, 2010. Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop 115: 22–27.
Requena-Méndez A, Aldasoro E, de Lazzari E, Sicuri E, Brown M, Moore DA, Gascon J, Muñoz J, 2015. Prevalence of Chagas disease in Latin-American migrants living in Europe: a systematic review and meta-analysis. PLoS Negl Trop Dis 9: e0003540.
Conners EE, Vinetz JM, Weeks JR, Brouwer KC, 2016. A global systematic review of Chagas disease prevalence among migrants. Acta Trop 156: 68–78.
Pérez-Molina JA, Molina I, 2018. Chagas disease. Lancet 391: 82–94.
Bern C et al. 2007. Evaluation and treatment of Chagas disease in the United States. JAMA 298: 2171–2181.
Russomando G, de Tomassone MM, de Guillen I, Acosta N, Vera N, Almiron M, Candia N, Calcena MF, Figueredo A, 1998. Treatment of congenital Chagas’ disease diagnosed and followed up by the polymerase chain reaction. Am J Trop Med Hyg 59: 487–491.
Schijman AG, Altcheh J, Burgos JM, Biancardi M, Bisio M, Levin MJ, Freilij H, 2003. Aetiological treatment of congenital Chagas’ disease diagnosed and monitored by the polymerase chain reaction. J Antimicrob Chemother 52: 441–449.
Cançado JR, 1999. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz 94 (Suppl 1): 331–335.
Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti A, 2006. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med 144: 724–734.
Pérez-Molina JA, Pérez-Ayala A, Moreno S, Fernández-González MC, Zamora J, López-Velez R, 2009. Use of benznidazole to treat chronic Chagas’ disease: a systematic review with a meta-analysis. J Antimicrob Chemother 64: 1139–1147.
Morillo CA et al. BENEFIT Investigators, 2015. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med 373: 1295–1306.
Viotti R et al. Latin American Network for Chagas Disease, NHEPACHA, 2014. Towards a paradigm shift in the treatment of chronic Chagas disease. Antimicrob Agents Chemother 58: 635–639.
Torrico F, Gascon J, Ortiz L, Alonso-Vega C, Pinazo M-J, Schijman A, Almeida IC, Alves F, Strub-Wourgaft N, Ribeiro I; E1224 Study Group, 2018. Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial. Lancet Infect Dis 18: 419–430.
Villar JC, Perez JG, Cortes OL, Riarte A, Pepper M, Marin-Neto JA, Guyatt GH, 2014. Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection. Cochrane Database Syst Rev 5: CD003463.
Andrade JP et al. 2011. I Latin American guidelines for the diagnosis and treatment of Chagas’ heart disease: executive summary. Arq Bras Cardiol 96: 434–442.
Pérez de Ayala A, Pérez-Molina JA, Navarro M, López-Vélez R, 2009. Enfermedad de Chagas en Personas Procedentes de Latinoamérica Residentes en España. Madrid, Spain: Ministerio de Sanidad y Política Social, Centro de Publicaciones.
Aldasoro E, Posada E, Requena-Méndez A, Calvo-Cano A, Serret N, Casellas A, Sanz S, Soy D, Pinazo MJ, Gascon J, 2018. What to expect and when: benznidazole toxicity in chronic Chagas’ disease treatment. J Antimicrob Chemother 73: 1060–1067.
Hasslocher-Moreno AM, do Brasil PE, de Sousa AS, Xavier SS, Chambela MC, Sperandio da Silva GM, 2012. Safety of benznidazole use in the treatment of chronic Chagas’ disease. J Antimicrob Chemother 67: 1261–1266.
Pinazo M-J, Munoz J, Posada E, Lopez-Chejade P, Gallego M, Ayala E, del Cacho E, Soy D, Gascon J, 2010. Tolerance of benznidazole in treatment of Chagas’ disease in adults. Antimicrob Agents Chemother 54: 4896–4899.
Molina I, Salvador F, Sánchez-Montalvá A, Treviño B, Serre N, Sao Avilés A, Almirante B, 2015. Toxic profile of benznidazole in patients with chronic Chagas disease: risk factors and comparison of the product from two different manufacturers. Antimicrob Agents Chemother 59: 6125–6131.
Wirtz VJ, Manne-Goehler J, Reich MR, 2015. Access to care for Chagas disease in the United States: a health systems analysis. Am J Trop Med Hyg 93: 108–113.
Sartor P, Colaianni I, Cardinal MV, Bua J, Freilij H, Gürtler RE, 2017. Improving access to Chagas disease diagnosis and etiologic treatment in remote rural communities of the Argentine Chaco through strengthened primary health care and broad social participation. PLoS Negl Trop Dis 11: e0005336.
Manne JM, Snively CS, Ramsey JM, Salgado MO, Bärnighausen T, Reich MR, 2013. Barriers to treatment access for Chagas disease in Mexico. PLoS Negl Trop Dis 7: e2488.
Ribeiro I, Sevcsik A-M, Alves F, Diap G, Don R, Harhay MO, Chang S, Pecoul B, 2009. New, improved treatments for Chagas disease: from the R&D pipeline to the patients. PLoS Negl Trop Dis 3: e484.
Viotti R, Vigliano C, Lococo B, Alvarez MG, Petti M, Bertocchi G, Armenti A, 2009. Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities. Expert Rev Anti Infect Ther 7: 157–163.
Chatelain E, 2017. Chagas disease research and development: is there light at the end of the tunnel? Comput Struct Biotechnol J 15: 98–103.
Drugs for Neglected Diseases initiative (DNDi). Fexinidazole (Chagas)—DNDi. Available at: https://www.dndi.org/diseases-projects/portfolio/fexinidazole-chagas/. Accessed May 20, 2018.
Pinazo MJ, Espinosa G, Gallego M, Lopez-Chejade PL, Urbina JA, Gascon J, 2010. Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus. Am J Trop Med Hyg 82: 583–587.
Álvarez MG et al. 2016. New scheme of intermittent benznidazole administration in patients chronically infected with Trypanosoma cruzi: a pilot short-term follow-up study with adult patients. Antimicrob Agents Chemother 60: 833–837.
Sperandio da Silva GM, Mediano MFF, Alvarenga Americano do Brasil PE, da Costa Chambela M, da Silva JA, de Sousa AS, Xavier SS, Rodrigues da Costa A, Magalhães Saraiva R, Hasslocher-Moreno AM, 2014. A clinical adverse drug reaction prediction model for patients with chagas disease treated with benznidazole. Antimicrob Agents Chemother 58: 6371–6377.
Salvador F et al. 2015. Evaluation of cytokine profile and HLA association in benznidazole related cutaneous reactions in patients with Chagas disease. Clin Infect Dis 61: 1688–1694.
Olivera MJ, Cucunubá ZM, Valencia-Hernández CA, Herazo R, Agreda-Rudenko D, Flórez C, Duque S, Nicholls RS, 2017. Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease. PLoS One 12: e0185033.
Pinazo M-J, Guerrero L, Posada E, Rodríguez E, Soy D, Gascon J, 2013. Benznidazole-related adverse drug reactions and their relationship to serum drug concentrations in patients with chronic Chagas disease. Antimicrob Agents Chemother 57: 390–395.
Górgolas M, Robles I, Cabello A, Pérez-Tanoira R, Peremarch CP-J, Fernández-Roblas R, Williams F, Rincón JM, 2013. The use of steroids to prevent cutaneous reactions to benznidazole in patients with Chagas disease. Pathog Glob Health 107: 157–160.
Puerta-Alcalde P, Gomez-Junyent J, Requena-Mendez A, Pinazo MJ, Álvarez-Martínez MJ, Rodríguez N, Gascon J, Muñoz J, 2018. High prevalence of S. Stercoralis infection among patients with Chagas disease: a retrospective case-control study. PLoS Negl Trop Dis 12: e0006199.
ClinicalTrials.gov NCT03378661. BENDITA BEnznidazole New Doses Improved Treatment and Associations. Available at: https://clinicaltrials.gov/ct2/show/NCT03378661. Accessed May 16, 2018.
Navarrete MN, Gutiérrez-Gutiérrez B, de Arellano-Ramos R, del Castillo S-F, Domínguez-Castellano Á, 2016. Low incidence of adverse effects using a progressive regimen of benznidazole in Chagas disease. Clin Infect Dis 62: 1052.
WHO Expert Committee, 2002. Control of Chagas Disease, Vol. 2. World Health Organization Technical Report Series No. 905. Geneva, Switzerland: World Health Organization, 1–109.
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In this retrospective cohort study, we aimed to assess whether introducing benznidazole at escalating doses reduces the probability of adverse events or treatment discontinuation compared with a full-dose scheme. We collected data from patients who had chronic Trypanosoma cruzi infection and underwent treatment from July 2008 to January 2017 in a referral center in Madrid. Dose was adjusted to body weight (5 mg/kg/day), with treatment introduction with full dose or escalating dose according to local consensus and protocols. Among the 62 patients treated, benznidazole was introduced at full dose in 28 patients and on escalating dose in the remaining 34. We found no statistical differences in the number of adverse events, treatment discontinuations, days of treatment, or sociodemographic profiles. There is insufficient evidence to support escalating dose as a strategy for reducing the adverse effects of benznidazole. Further research is needed to evaluate this approach.
Authors’ addresses: Irene Losada Galván, International Health Department, ISGlobal, Hospital Clínic–Universitat de Barcelona, Barcelona, Spain, E-mail: irenelosada@gmail.com. Olaya Madrid Pascual, Juan María Herrero-Martínez, and Manuel Lizasoain Hernández, Internal Medicine Department, Hospital Universitario 12 de Octubre, Madrid, Spain, E-mails: olayamadrid@gmail.com, juanmariaherrero@yahoo.es, and manuel.lizasoain@salud.madrid.org. Ana Pérez-Ayala, Microbiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain, E-mail: anpayala@hotmail.com.
WHO, 2015. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 90: 33–43.
Gascon J, Bern C, Pinazo M-J, 2010. Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop 115: 22–27.
Requena-Méndez A, Aldasoro E, de Lazzari E, Sicuri E, Brown M, Moore DA, Gascon J, Muñoz J, 2015. Prevalence of Chagas disease in Latin-American migrants living in Europe: a systematic review and meta-analysis. PLoS Negl Trop Dis 9: e0003540.
Conners EE, Vinetz JM, Weeks JR, Brouwer KC, 2016. A global systematic review of Chagas disease prevalence among migrants. Acta Trop 156: 68–78.
Pérez-Molina JA, Molina I, 2018. Chagas disease. Lancet 391: 82–94.
Bern C et al. 2007. Evaluation and treatment of Chagas disease in the United States. JAMA 298: 2171–2181.
Russomando G, de Tomassone MM, de Guillen I, Acosta N, Vera N, Almiron M, Candia N, Calcena MF, Figueredo A, 1998. Treatment of congenital Chagas’ disease diagnosed and followed up by the polymerase chain reaction. Am J Trop Med Hyg 59: 487–491.
Schijman AG, Altcheh J, Burgos JM, Biancardi M, Bisio M, Levin MJ, Freilij H, 2003. Aetiological treatment of congenital Chagas’ disease diagnosed and monitored by the polymerase chain reaction. J Antimicrob Chemother 52: 441–449.
Cançado JR, 1999. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz 94 (Suppl 1): 331–335.
Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti A, 2006. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med 144: 724–734.
Pérez-Molina JA, Pérez-Ayala A, Moreno S, Fernández-González MC, Zamora J, López-Velez R, 2009. Use of benznidazole to treat chronic Chagas’ disease: a systematic review with a meta-analysis. J Antimicrob Chemother 64: 1139–1147.
Morillo CA et al. BENEFIT Investigators, 2015. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med 373: 1295–1306.
Viotti R et al. Latin American Network for Chagas Disease, NHEPACHA, 2014. Towards a paradigm shift in the treatment of chronic Chagas disease. Antimicrob Agents Chemother 58: 635–639.
Torrico F, Gascon J, Ortiz L, Alonso-Vega C, Pinazo M-J, Schijman A, Almeida IC, Alves F, Strub-Wourgaft N, Ribeiro I; E1224 Study Group, 2018. Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial. Lancet Infect Dis 18: 419–430.
Villar JC, Perez JG, Cortes OL, Riarte A, Pepper M, Marin-Neto JA, Guyatt GH, 2014. Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection. Cochrane Database Syst Rev 5: CD003463.
Andrade JP et al. 2011. I Latin American guidelines for the diagnosis and treatment of Chagas’ heart disease: executive summary. Arq Bras Cardiol 96: 434–442.
Pérez de Ayala A, Pérez-Molina JA, Navarro M, López-Vélez R, 2009. Enfermedad de Chagas en Personas Procedentes de Latinoamérica Residentes en España. Madrid, Spain: Ministerio de Sanidad y Política Social, Centro de Publicaciones.
Aldasoro E, Posada E, Requena-Méndez A, Calvo-Cano A, Serret N, Casellas A, Sanz S, Soy D, Pinazo MJ, Gascon J, 2018. What to expect and when: benznidazole toxicity in chronic Chagas’ disease treatment. J Antimicrob Chemother 73: 1060–1067.
Hasslocher-Moreno AM, do Brasil PE, de Sousa AS, Xavier SS, Chambela MC, Sperandio da Silva GM, 2012. Safety of benznidazole use in the treatment of chronic Chagas’ disease. J Antimicrob Chemother 67: 1261–1266.
Pinazo M-J, Munoz J, Posada E, Lopez-Chejade P, Gallego M, Ayala E, del Cacho E, Soy D, Gascon J, 2010. Tolerance of benznidazole in treatment of Chagas’ disease in adults. Antimicrob Agents Chemother 54: 4896–4899.
Molina I, Salvador F, Sánchez-Montalvá A, Treviño B, Serre N, Sao Avilés A, Almirante B, 2015. Toxic profile of benznidazole in patients with chronic Chagas disease: risk factors and comparison of the product from two different manufacturers. Antimicrob Agents Chemother 59: 6125–6131.
Wirtz VJ, Manne-Goehler J, Reich MR, 2015. Access to care for Chagas disease in the United States: a health systems analysis. Am J Trop Med Hyg 93: 108–113.
Sartor P, Colaianni I, Cardinal MV, Bua J, Freilij H, Gürtler RE, 2017. Improving access to Chagas disease diagnosis and etiologic treatment in remote rural communities of the Argentine Chaco through strengthened primary health care and broad social participation. PLoS Negl Trop Dis 11: e0005336.
Manne JM, Snively CS, Ramsey JM, Salgado MO, Bärnighausen T, Reich MR, 2013. Barriers to treatment access for Chagas disease in Mexico. PLoS Negl Trop Dis 7: e2488.
Ribeiro I, Sevcsik A-M, Alves F, Diap G, Don R, Harhay MO, Chang S, Pecoul B, 2009. New, improved treatments for Chagas disease: from the R&D pipeline to the patients. PLoS Negl Trop Dis 3: e484.
Viotti R, Vigliano C, Lococo B, Alvarez MG, Petti M, Bertocchi G, Armenti A, 2009. Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities. Expert Rev Anti Infect Ther 7: 157–163.
Chatelain E, 2017. Chagas disease research and development: is there light at the end of the tunnel? Comput Struct Biotechnol J 15: 98–103.
Drugs for Neglected Diseases initiative (DNDi). Fexinidazole (Chagas)—DNDi. Available at: https://www.dndi.org/diseases-projects/portfolio/fexinidazole-chagas/. Accessed May 20, 2018.
Pinazo MJ, Espinosa G, Gallego M, Lopez-Chejade PL, Urbina JA, Gascon J, 2010. Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus. Am J Trop Med Hyg 82: 583–587.
Álvarez MG et al. 2016. New scheme of intermittent benznidazole administration in patients chronically infected with Trypanosoma cruzi: a pilot short-term follow-up study with adult patients. Antimicrob Agents Chemother 60: 833–837.
Sperandio da Silva GM, Mediano MFF, Alvarenga Americano do Brasil PE, da Costa Chambela M, da Silva JA, de Sousa AS, Xavier SS, Rodrigues da Costa A, Magalhães Saraiva R, Hasslocher-Moreno AM, 2014. A clinical adverse drug reaction prediction model for patients with chagas disease treated with benznidazole. Antimicrob Agents Chemother 58: 6371–6377.
Salvador F et al. 2015. Evaluation of cytokine profile and HLA association in benznidazole related cutaneous reactions in patients with Chagas disease. Clin Infect Dis 61: 1688–1694.
Olivera MJ, Cucunubá ZM, Valencia-Hernández CA, Herazo R, Agreda-Rudenko D, Flórez C, Duque S, Nicholls RS, 2017. Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease. PLoS One 12: e0185033.
Pinazo M-J, Guerrero L, Posada E, Rodríguez E, Soy D, Gascon J, 2013. Benznidazole-related adverse drug reactions and their relationship to serum drug concentrations in patients with chronic Chagas disease. Antimicrob Agents Chemother 57: 390–395.
Górgolas M, Robles I, Cabello A, Pérez-Tanoira R, Peremarch CP-J, Fernández-Roblas R, Williams F, Rincón JM, 2013. The use of steroids to prevent cutaneous reactions to benznidazole in patients with Chagas disease. Pathog Glob Health 107: 157–160.
Puerta-Alcalde P, Gomez-Junyent J, Requena-Mendez A, Pinazo MJ, Álvarez-Martínez MJ, Rodríguez N, Gascon J, Muñoz J, 2018. High prevalence of S. Stercoralis infection among patients with Chagas disease: a retrospective case-control study. PLoS Negl Trop Dis 12: e0006199.
ClinicalTrials.gov NCT03378661. BENDITA BEnznidazole New Doses Improved Treatment and Associations. Available at: https://clinicaltrials.gov/ct2/show/NCT03378661. Accessed May 16, 2018.
Navarrete MN, Gutiérrez-Gutiérrez B, de Arellano-Ramos R, del Castillo S-F, Domínguez-Castellano Á, 2016. Low incidence of adverse effects using a progressive regimen of benznidazole in Chagas disease. Clin Infect Dis 62: 1052.
WHO Expert Committee, 2002. Control of Chagas Disease, Vol. 2. World Health Organization Technical Report Series No. 905. Geneva, Switzerland: World Health Organization, 1–109.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 28 | 28 | 21 |
Full Text Views | 599 | 176 | 1 |
PDF Downloads | 106 | 20 | 1 |