An evaluation of benznidazole as a Chagas disease therapeutic

References

• Perez-Molina J, Molina I. Chagas disease. Lancet. 2018;391:82–94.
   PubMed Web of Science ®Google Scholar
• WHO, World health organization: Chagas disease (American trypanosomiasis). Accessed May 01, 2019. https://www.who.int/chagas/home_more/en/
   Google Scholar
• Antinori S, Galimberti L, Bianco R, et al. Chagas disease in Europe: A review for the internist in the globalized world. Eur J Intern Med. 2017;43:6–15.
   PubMed Web of Science ®Google Scholar
• Echeverria LE, Morillo CA. American Trypanosomiasis (Chagas disease). Infect Dis Clin North Am. 33(1)119–134 2019.
   PubMed Web of Science ®Google Scholar
• Nogueira SS, Felizardo AA, Caldas IS, et al. Challenges of immunosuppressive and antitrypanosomal drug therapy after heart transplantation in patients with chronic Chagas disease: A systematic review of clinical recommendations. Transplant Rev. 2018;32:157–167.
   Web of Science ®Google Scholar
• Luquetti AO, Rassi A. Diagnóstico laboratorial da infecção pelo Trypanosoma cruzi. In: Breener Z, Andrade AZ, Baral-Neto M, editors. Trypanosma cruzi e doença de Chagas. 2nd ed. Guanabara Koogan: Rio de Janeiro; 2000. p. 344–378.
   Google Scholar
• Prata A. Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis. 2001;1(2):92–100.
   PubMedGoogle Scholar
• Urbina JA. Recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives. J Eukaryot Microbiol. 2015;62(1):149–156.
   PubMed Web of Science ®Google Scholar
• de Lana M, Martins-Filho OA. Revisiting the posttherapeutic cure criterion in chagas disease: Time for new methods, more questions, doubts, and polemics or time to change old concepts? Biomed Res Int. 2015;2015:652985.
   PubMed Web of Science ®Google Scholar
• Bonney KM, Luthringer DJ, Kim SA, et al. Pathology and pathogenesis of Chagas heart disease. Annu Rev Pathol. 2019;14:421–447.
   PubMed Web of Science ®Google Scholar
• Matsuda NM, Miller SM, Evora PR. The chronic gastrointestinal manifestations of Chagas disease. Clinics. 2009;64(12):1219–1224.
   PubMed Web of Science ®Google Scholar
• Teixeira AR, Nitz N, Guimaro MC, et al. Chagas disease. Postgrad Med J. 2006;82(974):788–798.
   PubMed Web of Science ®Google Scholar
• Rassi Jr A Jr, Marin-Neto JA, Rassi A. Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the benznidazole evaluation for interrupting trypanosomiasis (BENEFIT) trial. Mem Inst Oswaldo Cruz. 2017;112:224–235.
   PubMed Web of Science ®Google Scholar
• AAS M, Coelho CM, Veloso MP, et al. Relevance of trypanothione reductase inhibitors on Trypanosoma cruzi infection: A systematic review, meta-analysis, and in silico integrated approach. Oxid Med Cell Longev. 2018;2018:8676578.
   PubMedGoogle Scholar
• Freitas HFG, Chizzola PR, ÂT P, et al. Risk stratification in a Brazilian hospital-based cohort of 1220 outpatients with heart failure: role of Chagas’ heart disease. Int J Cardiol. 2005;102(2):239–247.
   PubMed Web of Science ®Google Scholar
• Muñoz MJ, Murcia L, Segovia M. The urgent need to develop new drugs and tools for the treatment of Chagas disease. Expert Rev Anti Infect Ther. 2011;9(1):5–7.
   PubMed Web of Science ®Google Scholar
• Ãnez N, Carrasco H, Parada H, et al. Myocardial parasite persistence in chronic Chagasic patients. Am J Trop Med Hyg. 1999;60:726–732.
   PubMed Web of Science ®Google Scholar
• Pérez-Molina JA, Pérez-Ayala A, Moreno S, et al. Use of benznidazole to treat chronic Chagas’ disease: a systematic review with a meta-analysis. J Antimicrob Chemother. 2009;64(6):1139–1147.
   PubMed Web of Science ®Google Scholar
• Andrade JP, Marin-Neto JA, Paola AA, et al. I Latin American Guidelines for the diagnosis and treatment of Chagas’ heart disease. Arq Bras Cardiol. 2011;97(2 Suppl 3):1–48.
   PubMedGoogle Scholar
• Morillo CA, Marin-Neto JA, Avezum A, et al. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med. 2015;373(14):1295–1306.
   PubMed Web of Science ®Google Scholar
• Urbina JA, Docampo R. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol. 2003;19(11):495–501.
   PubMed Web of Science ®Google Scholar
• Torrico F, Gascon J, Ortiz L, et al. Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomized, placebo-controlled trial. Lancet Infect Dis. 2018;3099(17):30538.
   Google Scholar
• Altcheh J, Moscatelli G, Mastrantonio G, et al. Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults. PLoS Negl Trop Dis. 2014;8(5):e2907.
   PubMed Web of Science ®Google Scholar
• Molina I, Salvador F, Sánchez-Montalvá A, et al. Pharmacokinetics of benznidazole in healthy volunteers and implications in future clinical trials. Antimicrob Agents Chemother. 2017;61(4):e01912–16.
   PubMed Web of Science ®Google Scholar
• Wiens MO, Kanters S, Mills E, et al. Systematic review and meta-analysis of the pharmacokinetics of benznidazole in the treatment of Chagas disease. Antimicrob Agents Chemother. 2016;60(12):7035–7042.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA), Center for Drug Evaluation and Research. Guidance for industry: bioavailability and bioequivalence studies for orally administered drug products—general considerations. Rockville, MD: Center for Drug Evaluation and Research, Food and Drug Administration, U.S. Department of Health and Human Services; 2003.
   Google Scholar
• Fernández ML, Marson ME, Ramirez JC, et al. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole. Mem Inst Oswaldo Cruz. 2016;111(3):218–221.
   PubMed Web of Science ®Google Scholar
• Patterson S, Wyllie S. Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects. Trends Parasitol. 2014;30(6):289–298.
   PubMed Web of Science ®Google Scholar
• Wilkinson SR, Kelly JM. Trypanocidal drugs: mechanisms, resistance and new targets. Expert Rev Mol Med. 2009;11:e31.
   PubMed Web of Science ®Google Scholar
• Trochine A, Creek DJ, Faral-Tello P, et al. Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics. PLoS Negl Trop Dis. 2014;8(5):e2844.
   PubMed Web of Science ®Google Scholar
• Hall BS, Wilkinson SR. Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrob Agents Chemother. 2012;56(1):115–123.
   PubMed Web of Science ®Google Scholar
• Werner AB, Zulantay IA. Estado actual en el tratamento de la enfermedad de Chagas. Rev Med Chile. 2011;139:247–257.
   PubMedGoogle Scholar
• Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6:1–6.
   Web of Science ®Google Scholar
• Burgos JM, Altcheh J, Petrucelli N, et al. Molecular diagnosis and treatment monitoring of congenital transmission of Trypanosoma cruzi to twins of a triplet delivery. Diagn Microbiol Infect Dis. 2009;65(2009):58–61.
   PubMedGoogle Scholar
• Shikanai-Yasuda MA, Lopes MH, Tolezano JE, et al. Acute Chagas’ disease: transmission routes, clinical aspects and response to specific therapy in diagnosed cases in an urban center. Rev Inst Med Trop Sao Paulo. 1990;32(1):16–27.
   PubMed Web of Science ®Google Scholar
• Bahia-Oliveira LM, Gomes JA, Cancado JR, et al. Immunological and clinical evaluation of Chagasic patients subjected to chemotherapy during the acute phase of Trypanosoma cruzi infection 14–30 years ago. J Infect Dis. 2000;182(2):634–638.
   PubMed Web of Science ®Google Scholar
• Pinto AYN, Valente VC, Coura JR, et al. Clinical follow-up of responses to treatment with benznidazol in Amazon: A cohort study of acute Chagas disease. PLoS ONE. 2013;8(5):e64450.
   PubMed Web of Science ®Google Scholar
• Añez N, Crisante G, Rojas A, et al. A follow-up study of Chagasic patients with special reference to Trypanosoma cruzi persistence and criteria of Chagas disease cure. Int J Clin Med Res. 2015;2(3):20–29.
   Google Scholar
• Vera de Bilbao NI, Elías EII, Martínez JIII, et al. Serologic and parasitologic evolution post-treatment of patients with recent chronic Chagas disease. Mem Inst Invest Cienc Salud. 2006;4(1):5–10.
   Google Scholar
• Escriba JM, Ponce E, Romero AD, et al. Treatment and seroconversion in a cohort of children suffering from recent chronic Chagas infection in Yoro, Honduras. Mem Inst Oswaldo Cruz. 2009;104(7):986–991.
   PubMed Web of Science ®Google Scholar
• Sosa-Estani S, Cura E, Velazquez E, et al. Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission. Rev Soc Bras Med Trop. 2009;42(5):484–487.
   PubMed Web of Science ®Google Scholar
• Rumi MMM, Brandan P, Gil JF, et al. Benznidazole treatment in chronic children infected with Trypanosoma cruzi: serological and molecular follow-up of patients and identification of discrete typing units. Acta Trop. 2013;128(1):130–136.
   PubMed Web of Science ®Google Scholar
• Sánchez AG, Alvarellos E, Kohout I, et al. Detection of Trypanosoma cruzi and treatment monitoring by PCR from dried blood spot samples in children. Rev Fac C Med. 2016;73(3):176–180.
   Google Scholar
• Brum-Soares L, Juan-Carlos C, Burgos I, et al. High seroconversion rates in Trypanosoma cruzi chronic infection treated with benznidazole in people under 16 years in Guatemala. Rev Soc Bras Med Trop. 2016;49(6):721–727.
   PubMed Web of Science ®Google Scholar
• Ferreira HO. Treatment of the undetermined form of Chagas disease with nifurtimox and benzonidazole. Rev Soc Bras Med Trop. 1990;23(4):209–211.
   PubMedGoogle Scholar
• Viotti R, Vigliano C, Armenti H, et al. Treatment of chronic Chagas’ disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J. 1994;127(1):151–162.
   PubMed Web of Science ®Google Scholar
• Fragata Filho AA, Silva MAD, Boainain E. Ethiological treatment of acute and chronic Chagas’ heart disease. Sao Paulo Med J. 1995;113(2):867–872.
   PubMedGoogle Scholar
• Levi GC, Lobo IMF, Kallás EG, et al. Etiological drug treatment of human infection by Trypanosoma cruzi. Rev Inst Med Trop S Paulo. 1996;38(1):35–38.
   PubMedGoogle Scholar
• Coura JR, Abreu LL, Willcox HPF, et al. Estudo comparativo controlado com emprego de benznidazole, nifurtimox e placebo, na forma crônica da doença de Chagas, em uma área de campo com transmissão interrompida. I. Avaliação preliminar. R Soc Bras Med Trop. 1997;30(2):139–144.
   PubMedGoogle Scholar
• Britto C, Cardoso A, Silveira C, et al. Polymerase chain reaction (PCR) as a laboratory tool for the evaluation of the parasitological cure in Chagas disease after specific treatment. Medicina (B Aires). 1999;59(Supl.II):176–178.
   PubMedGoogle Scholar
• De Castro AM, Luquetti AO, Rassi A, et al. Detection of parasitemia profiles by blood culture after treatment of human chronic Trypanosoma cruzi infection. Parasitol Res. 2006;99:379–383.
   PubMed Web of Science ®Google Scholar
• Fabbro DL, Streiger ML, Arias E, et al. Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe City (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution. R Soc Bras Med Trop. 2007;40(1):1–10.
   PubMed Web of Science ®Google Scholar
• Negrette OS, FJS V, Lacunza CD, et al. Serological evaluation of specific-antibody levels in patients treated for chronic Chagas’ disease. Clin Vaccine Immunol. 2008;15(2):297–302.
   PubMed Web of Science ®Google Scholar
• Fernandes CD, Tiecher FM, Balbinot MM, et al. Efficacy of benznidazol treatment for asymptomatic chagasic patients from state of Rio Grande do Sul evaluated during a three years follow-up. Mem Inst Oswaldo Cruz. 2009;104(1):27–32.
   PubMed Web of Science ®Google Scholar
• Lana M, Lopes LA, Martins HR, et al. Clinical and laboratory status of patients with chronic Chagas disease living in a vector-controlled area in Minas Gerais, Brazil, before and nine years after aetiological treatment. Mem Inst Oswaldo Cruz. 2009;104(8):1139–1147.
   PubMed Web of Science ®Google Scholar
• Viotti R, Vigliano C, Alvarez MG, et al. Impact of aetiological treatment on conventional and multiplex serology in chronic Chagas disease. PLoS Negl Trop Dis. 2011;5(9):e1314.
   PubMed Web of Science ®Google Scholar
• Aguiar C, Batista AM, Pavan TBS, et al. Serological profiles and evaluation of parasitaemia by PCR and blood culture in individuals chronically infected by Trypanosoma cruzi treated with benzonidazole. Trop Med Int Health. 2012;17(3):368–373.
   PubMed Web of Science ®Google Scholar
• Bertocchi GL, Vigliano AC, Lococo BG, et al. Clinical characteristics and outcome of 107 adult patients with chronic Chagas disease and parasitological cure criteria. Trans R Soc Trop Med Hyg. 2013;107:372–376.
   PubMed Web of Science ®Google Scholar
• Machado-de-Assis GF, Diniz GL, Montoya RA, et al. A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention. Mem Inst Oswaldo Cruz. 2013;108(7):873–880.
   PubMed Web of Science ®Google Scholar
• Gomes ML, Cassarotti DJ, Toledo MJO, et al. Systematic monitoring of patients with Chagas disease reveals benefits of etiological treatment. Braz J Surg Clin Res. 2015;12(2):05–08.
   Google Scholar
• Niborski LL, Grippo V, Lafón SO, et al. Serological based monitoring of a cohort of patients with chronic Chagas disease treated with benznidazole in a highly endemic area of northern Argentina. Mem Inst Oswaldo Cruz. 2016;111(6):365–371.
   PubMed Web of Science ®Google Scholar
• Murcia L, Carrilero B, Ferrer F, et al. Success of benznidazole chemotherapy in chronic Trypanosoma cruzi-infected patients with a sustained negative PCR result. Eur J Clin Microbiol Infect Dis. 2016;35:1819–1827.
   PubMed Web of Science ®Google Scholar
• Antunes AP, Ribeiro ALP, Sabino EC, et al. Benznidazole therapy for Chagas disease in asymptomatic Trypanosoma cruzi-seropositive former blood donors: evaluation of the efficacy of different treatment regimens. Rev Soc Bras Med Trop. 2016;49(6):713–720.
   PubMed Web of Science ®Google Scholar
• Álvarez MG, Hernández Y, Bertocchi G, et al. 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. 2016;60(2):833–837.
   PubMed Web of Science ®Google Scholar
• Sartor P, Colaianni I, Cardinal MV, et al. 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. 2017;11(2):e0005336.
   PubMed Web of Science ®Google Scholar
• Cardoso CS, Ribeiro ALP, Oliveira CDL, et al. Beneficial effects of benznidazole in Chagas disease: NIH SaMi-Trop cohort study. PLoS Negl Trop Dis. 2018;12(11):e0006814.
   PubMed Web of Science ®Google Scholar
• Cançado JR. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz. 1999;94(Suppl. I):331–335.
   PubMed Web of Science ®Google Scholar
• Machado-de-Assis GF, Silva AR, Do Bem VA, et al. Posttherapeutic cure criteria in Chagas’ disease: conventional serology followed by supplementary serological, parasitological, and molecular tests. Clin Vaccine Immunol. 2012;19(8):1283–1291.
   PubMed Web of Science ®Google Scholar
• Pinazo MJ, Thomas MC, Bustamante J, et al. Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives. Mem Inst Oswaldo Cruz. 2015;110(3):422–432.
   PubMed Web of Science ®Google Scholar
• Guedes PM, Silva GK, Gutierrez FR, et al. Current status of Chagas disease chemotherapy. Expert Rev Anti Infect Ther. 2011;9(5):609–620.
   PubMed Web of Science ®Google Scholar
• Zingales B, Andrade SG, Briones MR, et al. Second Satellite Meeting. A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem Inst Oswaldo Cruz. 2009;104(7):1051–1054.
   PubMed Web of Science ®Google Scholar
• Zingales B1, Miles MA, Campbell DA, et al. The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect Genet Evol. 2012;12(2):240–253.
   PubMed Web of Science ®Google Scholar
• Andrade SG, Rassi A, Magalhaes JB, et al. Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strains. Trans R Soc Trop Med Hyg. 1992;86(6):624–626.
   PubMed Web of Science ®Google Scholar
• Filardi LS, Brener Z. Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease. Trans R Soc Trop Med Hyg. 1987;81(5):755–759.
   PubMed Web of Science ®Google Scholar
• Viotti R, Vigliano C, Lococo B, et al. Clinical predictors of chronic chagasic myocarditis progression. Rev Esp Cardiol. 2005;58(9):1037–1044.
   PubMed Web of Science ®Google Scholar
• Brener Z, Andrade ZA, Barral-Neto M. Trypanosoma cruzi e doença de Chagas. In: Brener Z, Andrade ZA and Barral-Neto M, editors. 2nd ed. Guanabara Koogan; 2000. p. 431.
   Google Scholar
• Britto C, Silveira C, Cardoso MA, et al. Parasite persistence in treated Chagasic patients revealed by xenodiagnosis and polymerase chain reaction. Mem Inst Oswaldo Cruz. 2001;96:823–826.
   PubMed Web of Science ®Google Scholar
• Castro AM, Luquetti AO, Rassi A, et al. Blood culture and polymerase chain reaction for the diagnosis of the chronic phase of human infection with Trypanosoma cruzi. Parasitol Res. 2002;88(10):894–900.
   PubMed Web of Science ®Google Scholar
• Zulantay I, Honores P, Solari A, et al. Use of polymerase chain reaction (PCR) and hybridization assays to detect Trypanosoma cruzi in chronic chagasic patients treated with itraconazole or allopurinol. Diagn Microbiol Infect Dis. 2004;48(4):253–257.
   PubMed Web of Science ®Google Scholar
• Chiari E, Dias JC, Lana M, et al. Hemocultures for the parasitological diagnosis of human chronic Chagas’ disease. Rev Soc Bras Med Trop. 1989;22(1):19–23.
   PubMedGoogle Scholar
• Cerisola JÁ, Rohwedder R, Segura EL, et al. El xenodiagnóstico. In: Buenos Aires. Imp Inst Nac Invest Cardiovasc. 1974. p. 157p.
   Google Scholar
• Blanco SB, Segura EL, Cura EN, et al. Congenital transmission of Trypanosoma cruzi: an operational outline for detecting and treating infected infants in northwestern Argentina. Trop Med Int Health. 2000;5(4):293–301.
   PubMed Web of Science ®Google Scholar
• Jean-Philippe C, Clavijo ANS, Santalla JA, et al. Antibody drop in newborns congenitally infected by Trypanosoma cruzi treated with benznidazole. Trop Med Int Health. 2010;15(1):87–93.
   PubMed Web of Science ®Google Scholar
• Schijman AG, Altcheh J, Burgos JM, et al. Aetiological treatment of congenital Chagas’ disease diagnosed and monitored by the polymerase chain reaction. J Antimicrob Chemother. 2003;52(3):441–449.
   PubMed Web of Science ®Google Scholar
• Russomando G, De Tomassone MM, De Guillen I, et al. Treatment of congenital Chagas’ disease diagnosed and followed up by the polymerase chain reaction. Am J Trop Med Hyg. 1998;59(3):487–491.
   PubMed Web of Science ®Google Scholar
• De Andrade AL, Zicker F, De Oliveira RM, et al. Randomized trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet. 1996;348(9039):1407–1413.
   PubMed Web of Science ®Google Scholar
• Sosa Estani S, Segura EL, Ruiz AM, et al. Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas’ disease. Am J Trop Med Hyg. 1998;59(4):526–529.
   PubMed Web of Science ®Google Scholar
• Streiger ML, Del Barco ML, Fabbro DL, et al. Longitudinal study and specific chemotherapy in children with chronic Chagas’ disease, residing in a low endemicity area of Argentina. Rev Soc Bras Med Trop. 2004;37(5):365–375.
   PubMedGoogle Scholar
• Galvao LMC, Nunes RMB, Cançado JR, et al. Lytic antibody titer as a means of assessing cure after treatment of Chagas disease: a 10 years follow-up study. Trans R Soc Trop Med Hyg. 1993;87:220–223.
   PubMed Web of Science ®Google Scholar
• Fabbro De Suasnábar D, Arias E, Streiger ML, et al. Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic chagasic patients. Rev Inst Med Trop Sao Paulo. 2000;42(2):99–109.
   PubMedGoogle Scholar
• Cançado JR. Long term evaluation of etiological treatment of Chagas disease with benznidazole. Rev Inst Med Trop Sao Paulo. 2002;44(1):29–37.
   PubMedGoogle Scholar
• Lauria-Pires L, Braga MS, Vexenat AC, et al. Progressive chronic chagas heart disease ten years after treatment with anti-Trypanosoma cruzi nitroderivatives. Am J Trop Med Hyg. 2000;63(3–4):111–118.
   PubMed Web of Science ®Google Scholar
• Silveira CA, Castillo E, Castro C. Evaluation of an specific treatment for Trypanosoma cruzi in children, in the evolution of the indeterminate phase. Rev Soc Bras Med Trop. 2000;33(2):191–196.
   PubMedGoogle Scholar
• Solari AS, Ortiz A, Soto C, et al. Treatment of Trypanosoma cruzi-infected children with nifurtimox: a 3 year follow-up by PCR. J Antimicrob Chemother. 2001;48(4):515–519.
   PubMed Web of Science ®Google Scholar
• Morillo CA, Waskin H, Sosa-Estani S, et al. Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers: The STOP-CHAGAS Trial. J Am Col Cardiol. 2017;69(8):939–947.
   PubMed Web of Science ®Google Scholar
• Gomes ML, Galvao LM, Macedo AM, et al. Chagas’ disease diagnosis: comparative analysis of parasitologic, molecular, and serologic methods. Am J Trop Med Hyg. 1999;60(2):205–210.
   PubMed Web of Science ®Google Scholar
• Parada H, Carrasco HA, Añez N, et al. Cardiac involvement is a constant finding in acute Chagas’ disease: a clinical, parasitological and histopathological study. Int J Cardiol. 1997;60(1):49–54.
   PubMed Web of Science ®Google Scholar
• Inglessis I, Carrasco HA, Añez N, et al. Clinical, parasitological and histopathologic follow-up studies of acute Chagas patients treated with benznidazole. Arch Inst Cardiol Mex. 1998;68(5):405–410.
   PubMedGoogle Scholar
• Andrade AL, Martelli CM, Oliveira RM, et al. Short report: benznidazole efficacy among Trypanosoma cruzi-infected adolescents after a six-year follow-up. Am J Trop Med Hyg. 2004;71(5):594–597.
   PubMed Web of Science ®Google Scholar
• Fragata Filho AA, Silva MAD, Boainain E. Tratamento etiológico da doença de Chagas nas fases aguda e crônica. Rev Soc Cardiol Estado De São Paulo. 1994;4:192–197.
   Google Scholar
• Viotti R, Alarcón de Noya B, Araujo-Jorge T, et al. Latin American network for chagas disease, NHEPACHA. Towards a paradigm shift in the treatment of chronic Chagas disease. Antimicrob Agents Chemother. 2014;58(2):635–639.
   PubMed Web of Science ®Google Scholar