New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: a Pilot Short-Term Follow-Up Study with Adult Patients

• Autores: Alvarez, María Gabriela; Hernández, Yolanda; Bertocchi, Graciela; Fernández, Marisa; Lococo, Bruno; Ramírez, Juan Carlos; Cura, Carolina Inés; Lopez-Albízu, Constanza; Schijman, Alejandro; Abril, Marcelo; Sosa-Estani, Sergio; Viotti, Rodolfo
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Antimicrobial Agents and Chemotherapy 2016;60(2):833-837
• Materia: Enfermedad de Chagas; Trypanosoma cruzi; Adulto
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Alvarez, María Gabriela. Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.
Fil: Hernández, Yolanda. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Bertocchi, Graciela. Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.
Fil: Fernández, Marisa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Lococo, Bruno. Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.
Fil: Ramírez, Juan Carlos. Instituto de Ingeniería Genética y Biología Molecular (INGEBI), Buenos Aires; Argentina.
Fil: Cura, Carolina Inés. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Lopez Albizu, Constanza. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Schijman, Alejandro. Instituto de Ingeniería Genética y Biología Molecular (INGEBI), Buenos Aires; Argentina. .
Fil: Abril, Marcelo. Fundación Mundo Sano, Buenos Aires; Argentina.
Fil: Sosa-Estani, Sergio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Viotti, Rodolfo. Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.
There is a clinical need to test new schemes of benznidazole administration that are expected to be at least as effective as the current therapeutic scheme but safer. This study assessed a new scheme of benznidazole administration in chronic Chagas disease patients. A pilot study with intermittent doses of benznidazole at 5 mg/kg/day in two daily doses every 5 days for a total of 60 days was designed. The main criterion of response was the comparison of quantitative PCR (qPCR) findings prior to and 1 week after the end of treatment. The safety profile was assessed by the rate of suspensions and severity of adverse effects. Twenty patients were analyzed for safety, while qPCR was tested for 17 of them. The average age was 43 ± 7.9 years; 55% were female. Sixty-five percent of treated subjects showed detectable qPCR results prior to treatment of 1.45 (0.63 to 2.81) and 2.1 (1.18 to 2.78) parasitic equivalents per milliliter of blood (par.eq/ml) for kinetoplastic DNA (kDNA) qPCR and nuclear repetitive sequence satellite DNA (SatDNA) qPCR, respectively. One patient showed detectable PCR at the end of treatment (1/17), corresponding to 6% treatment failure, compared with 11/17 (65%) patients pretreatment (P = 0.01). Adverse effects were present in 10/20 (50%) patients, but in only one case was treatment suspended. Eight patients showed mild adverse effects, whereas moderate reactions with increased liver enzymes were observed in two patients. The main accomplishment of this pilot study is the promising low rate of treatment suspension. Intermittent administration of benznidazole emerges a new potential therapeutic scheme, the efficacy of which should be confirmed by long-term assessment posttreatment.