Translational research in the etiological treatment of Chagas disease.
DOI:
https://doi.org/10.35954/SM2014.33.1.5Keywords:
Benznidazol; Chagas disease; Translational research; Posaconazol; Ravuconazol; Chagas diseaseAbstract
Chagas disease is one of the most important endemic diseases in tropical regions worldwide. Although the etiological agent, the protozoan Trypanosoma cruzi, was described more than 100 years ago, there is currently no effective pharmacological treatment against the microorganism in its parasitic state in the patient's tissues. The active principles described for etiological treatment have proven to be efficient, beyond their relevant adverse effects, in the acute stage of the disease, where T. cruzi can be localized in the blood of patients. However, the efficacy of these same agents in the chronic stage of the disease, where the parasite is nested in tissues, has not been proven so far. In this sense, in the last 15 years a series of translational investigations have been developed to confirm the efficacy of some of these drugs in the chronic stage of the disease. This review will present the studies carried out with benznidazole, TRAENA and BENEFIT studies, and with the antifungal agents posaconazole, CHAGAZASOL and STOP-CHAGAS studies, and the ravuconazole prodrug, E1224.
Received for review: June 2014.
Accepted for publication: August 2014.
Contact e-mail: megonzal@fq.edu.uy
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(1) The 17 neglected tropical diseases. Disponible en: http://www.who.int/neglected_diseases/diseases/en/ [Consulta 27/09/2014].
(2) Drugs for Neglected Diseases. Chagas. Disponible en: http://www.dndi.org/diseases-projects/diseases/chagas.html [Consulta 27/09/2014].
(3) Barret MP, Burchmore RJS, Stich A, Lazzari JO, Frasch AC, Cazzulo JJ, Krishna S. The trypanosomiases. Lancet 2003; 362(9394):1469-1480.
(4) Rassi A Jr, Rassi A, Marin-Neto JA, Chagas disease. Lancet 2010; 375(9723):1388-1402.
(5) Bringaud F, Rivière L, Coustou V. Energy metabolism of trypanosomatids: adaptation to available carbon sources. Mol Biochem Parasitol 2006;149(1):1-9.
(6) Elias MC, da Cunha JPC, de Faria FP, Mortara RA, Freymuller E, Schenkman S. Morphological events during the Trypanosoma cruzi cell cycle. Protist 2007;158(2):147-5.
(7) Sosa-Estani1 S, Dri L, Touris C, Abalde S, Dell'Arciprete A, Braunstein J. Transmisión vectorial y congénita del Trypanosoma cruzi en Las Lomitas-Formosa. Medicina (Bs As). 2009; 69(4):424-30.
(8) Alarcón de Noya B, Colmenares C, Ruiz-Guevara R, Díaz-Bello Z, Noya O. La transmisión oral de la enfermedad de Chagas. Revista Facultad de Medicina 2010; 33: 78-86.
(9) Tálice R, Miranda N, Costa R. Primer caso en el país de forma aguda mortal de enfermedad de Chagas (41º caso uruguayo) observado en el departamento de Rivera (Minas de Corrales). Anales de la Facultad de Medicina (Montevideo) 1939; 24: 69-78.
(10) Salvatella R. Una visión de la enfermedad de Chagas desde su propia historia. En: La enfermedad de Chagas a la puerta de los 100 años del conocimiento de una endemia americana ancestral. Buenos Aires: Organización Panamericana de la Salud, Fundación Mundo Sano 2007; 19-22.
(11) Guerri-Guttemberg RA, Guana DR, Ambrosio G, Milei J. Chagasic cardiomyopathy: Europe is not spared! Eur Heart J 2008; 29(21):2587-91.
(12) Schmunis GA. Epidemiology of Chagas Disease in non endemic countries. Memorias del Instituto Oswaldo Cruz 2007; 102: 75-85.
(13) De Ayala AP, Pérez-Molina JA, Norman F, López Vélez R. Chagasic cardiomyopaty in immigrants from Latin America to Spain. Emerg Infect Dis 2009;15(4):607-8.
(14) Soiza Larrosa A. La enfermedad de Chagas en el Uruguay: el primer hallazgo por Rodolfo Tálice. Salud Mil 2013; 32(1): 56-64.
(15) Dias JCP. O controle da doença de Chagas no Brasil, En: Silveira AC, editor. El control de la enfermedad de Chagas en los países del Cono Sur de América. Historia de una iniciativa internacional 1991/2001, Organizacion Panamericana de la Salud 2002; 146-250.
(16) Jannin J, Salvatella R. Estimación cuantitativa de la enfermedad de Chagas en las Américas. Montevideo, Organizacion Panamericana de la Salud 2006.
(17) Alfonso A, Núñez R, Porta L, Gagliano G, Pirotto R, Garrone S. Prevalencia de seropositividad para Trypanosoma cruzi en donantes de sangre del H.C.FF.AA, período 2005-2012. Uruguay. Salud Mil 2013; 32(1):28-31.
(18) Salvatella R. El control de la enfermedad de Chagas en Uruguay, En: Silveira AC (Ed.), El control de la enfermedad de Chagas en los paises del Cono Sur de America. Historia de una iniciativa internacional 1991/2001, Organizacion Panamericana de la Salud. Universidade Federal do Triangulo Mineiro 2002; 301-316.
(19) Parodi C, Padilla AM, Basombrío MA. Protective immunity against Trypanosoma cruzi. Mem Inst Oswaldo Cruz 2009; 104(Suppl 1):288-94.
(20) Lannes-Vieira J, de Araújo-Jorge TC, Soeiro MdNC, Gadelha P, Corrêa-Oliveira R. The centennial of the discovery of Chagas disease: Facing the current challenges. PLoS Negl Trop Dis 2010; 4(6):e645.
(21) Camargo EP. Perspectives of vaccination in Chagas disease revisited. Mem Inst Oswaldo Cruz 2009;104 (Suppl 1):275-80.
(22) Cazorla SI, Frank FM, Becker PD, Arnaiz M, Mirkin GA, Corral RS, Guzmán CA, Malchiodi EL. Redirection of the immune response to the functional catalytic domain of the cystein proteinase cruzipain improves protective immunity against Trypanosoma cruzi infection. J Infect Dis 2010; 202(1):136-44.
(23) Giddings OK, Eickhoff CS, Sullivan NL, Hoft DF. Intranasal vaccinations with the trans-sialidase antigen plus CpG adjuvant induce mucosal immunity protective against conjunctival Trypanosoma cruzi challenges. Infect Immun 2010; 78(3):1333-8.
(24) Wizel B, Nunes M, Tarleton RL. Identification of Trypanosoma cruzi trans-sialidase family members as targets of protective CD8+ TC1 responses. J Immunol 1997; 159(12):6120-30.
(25) Wizel B, Garg N, Tarleton RL. Vaccination with trypomastigote surface antigen 1-encoding plasmid DNA confers protection against lethal Trypanosoma cruzi infection. Infect Immun 1998; 66(11):5073-81.
(26) Costa F, Franchin G, Chioccola VLP, Ribeirão M, Schenkman S, Rodrigues MM. Immunization with a plasmid DNA containing the gene of trans-sialidase reduces Trypanosoma cruzi infection in mice. Vaccine 1998; 16(8):768-774.
(27) Boscardin SB, Ramirez MI, Santori F, Yoshida N, Franco da Silveira J. DNA vaccination with a gene that encodes the glycoprotein of 82 kDa (gp82) of metacyclic trypomastigotes of Trypanosoma cruzi. Memorias del Instituto Oswaldo Cruz 1999; 94: 182.
(28) Machado A, Cardoso J, Claser C, Rodrigues M, Gazzinelli R, Bruna-Romero O. Long-term protective immunity induced against Trypanosoma cruzi infection after vaccination with recombinant adenoviruses encoding amastigote surface protein-2 and trans-sialidase. Hum Gene Ther 2006; 17(9):898-908.
(29) Sanchez-Burgos G, Mezquita-Vega RG, Escobedo-Ortegon J, Ramirez-Sierra MJ, Arjona-Torres A, Ouaissi A, Rodrigues MM, Dumonteil E. Comparative evaluation of therapeutic DNA vaccines against Trypanosoma cruzi in mice. FEMS Immunol Med Microbiol 2007; 50(3):333-41.
(30) Cerecetto H, González M. Chemotherapy of Chagas' disease: status and new developments. Curr Top Med Chem 2002; 2(11):1187-213.
(31) Cerecetto H, González M. Synthetic medicinal chemistry in Chagas’ disease: Compounds at the final stage of “hit-to-lead” phase. Pharmaceuticals 2010; 3:810-838.
(32) Urbina JA. Ergosterol biosynthesis and drug development for Chagas disease. Memorias del Instituto Oswaldo Cruz 2009; 104: 311-318.
(33) Bermejo J, Heras M, Segovia J, Alfonso F. Traslational cardiovascular medicine. Now or never. Revista Española de Cardiología (Engl Ed) 2009; 62: 66-68.
(34) Wehling M. Translational medicine: science or wishful thinking? J Transl Med 2008; 6:31.
(35) Zerhoni EA. Translational and clinical science–time for a new vision. New Eng J Med 2005; 353:1621-1623.
(36) Riarte A, Velázquez E, Prado N, Schijman AG, Ramírez JC, De Rissio AM, Hernández Y, Esteva M, Luna C, Sinagra A, Ruiz AM. “TRAENA” TRAtamiento EN pacientes Adultos. Una evaluación preliminar de un ensayo clínico aleatorizado con Benznidazol en la enfermedad de Chagas crónica. En: VIII Taller sobre la enfermedad de Chagas importada. Avances en el tratamiento antiparasitario. Esmon Publicidad S.A. 2012; 30-35.
(37) Kuschnir E, Sgammini H, Castro R, Evequoz C, Ledesma R, Brunetto J. Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy. Arq Bras Cardiol 1985; 45(4):249-56.
(38) Marin-Neto JA, Rassi A, Morillo CA, Avezum A, Connolly SJ, Sosa-Estani S, Rosas F, Yusuf S. Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas' cardiomyopathy: The BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT). Am Heart J 2008; 156(1):37-43.
(39) Moreira OC, Ramírez JD, Velázquez E, Melo MF, Lima-Ferreira C, Guhl F, Sosa-Estani S, Marin-Neto JA, Morillo CA, Britto C. Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: a substudy from the BENEFIT trial. Acta Tropica 2013; 125:23-31.
(40) Molina I, Gómez i Prat J, Salvador F, Treviño B, Sulleiro E, Serre N, Pou D, Roure S, Cabezos J, Valerio L, Blanco-Grau A, Sánchez-Montalvá A, Vidal X, Pahissa A. Randomized trial of posaconazole and benznidazole for chronic Chagas' disease. New Eng J Med 2014; 370(20):1899-1908.
(41) Pinazo MJ, Espinosa G, Gállego M, López-Chejade PL, Urbina JA, Gascón J. Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus. Am J Trop Med Hyg 2010; 82(4):583-7.
(42) A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267) (STOP CHAGAS). Disponible en: http://clinicaltrials.gov/show/NCT01377480[Consulta 27/09/2014].
(43) Urbina J. Comunicación personal.
(44) First placebo-controlled study in adults with Chagas disease highlights urgent need to scale up treatment for millions of patients at risk. Disponible en: http://www.dndi.org/ [Consulta 27/09/2014].
(45) Proof-of-Concept Study of E1224 to Treat Adult Patients With Chagas Disease. Disponible en: http://clinicaltrials.gov/ct2/show/study/NCT01489228 [Consulta 27/09/2014].
(46) Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Baudin E, Buard V, Kazadi-Kyanza S, Ilunga M, Mutangala W, Pohlig G, Schmid C, Karunakara U, Torreele E, Kande V. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet 2009; 374(9683):56-64.M
(47) Murcia L, Carrilero B, Saura D, Iborra MA, Segovia M. Diagnóstico y tratamiento de la enfermedad de Chagas. Enfermedades Infecciosas y Microbiología Clínica 2013; 1(Supl.1): 26-34.
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