The purpose of this review is to describe research findings regarding chronic Chagas disease in Argentina that have changed the standards of care for patients with Trypanosoma cruzi infection. Indirect techniques (serological tests) are still the main tools for the primary diagnosis of infection in the chronic phase, but polymerase chain reaction has been shown to be promising. The prognosis of patients with heart failure or advanced stages of chagasic cardiomyopathy is poor, but a timely diagnosis during the initial stages of the disease would allow for prescription of appropriate therapies to offer a better quality of life. Treatment of T. cruzi infection is beneficial as secondary prevention to successfully cure the infection or to delay, reduce or prevent the progression to disease and as primary disease prevention by breaking the chain of transmission. Current recommendations have placed the bulk of the diagnostic and treatment responsibility on the Primary Health Care System. Overall, the current research priorities with respect to Chagas disease should be targeted towards (i) the production of new drugs that would provide a shorter treatment course with fewer side effects; (ii) the development of new tools to confirm cure after a full course of treatment during the chronic phase and (iii) biomarkers to identify patients with a high risk of developing diseases.

To determine the effect of benznidazol therapy on memory T cells specific for Trypanosoma cruzi, 47 patients between 30 and 50 years old and three positive serological tests for T. cruzi without cardiopathy were selected. Benznidazol was administered in a dose of 5 mg/kg/d during 30 days. Serological, immunological and clinical assessment was performed at basal (time 0) and at 2, 6 and 12 months following treatment, and once a year thereafter. IFN-ã ELISPOT assay was used to evaluate T cell responses against a T. cruzi lysate obtained from amastigotes. The frequency of IFN-ã - producing memory T lymphocytes specific for T. cruzi was significantly lower in the treatment group (n=33) compared to the control group (n=14) 12 months after the therapy. IFN- ã response became negative in 11 patients in the treatment group (44%). Among these 11 patients, conventional serology also became negative in 4 patients (36%) after 2 years of treatment. No clinical manifestations occurred during follow-up. These findings show that benznidazol is capable of modulating T cell responses specific for T. cruzi. Measuring the frequency of memory T lymphocytes producing IFN-ã might become a more sensitive test to determine earlier the impact and/or efficacy of the specific treatment against this parasite.

Para determinar el efecto del tratamiento con benznidazol sobre las células T de memoria específica para Trypanosoma cruzi, se seleccionaron 47 pacientes con tres reacciones serológicas positivas para T. cruzi, sin cardiopatía y edades comprendidas entre los 30 y los 50 años. El tratamiento se realizó con benznidazol en dosis de 5 mg/kg/d por 30 días. Se efectuó una evaluación serológica, inmunológica y clínica pretratamiento (tiempo 0) y a los 2, 6 y 12 meses postratamiento. Posteriormente, los controles se hicieron anualmente. La respuesta de linfocitos T frente a un lisado de amastigotas de T. cruzi se evaluó por la técnica de ELISPOT para IFN-ã. La frecuencia de linfocitos T de memoria productores de IFN-ã específicos para T. cruzi disminuyó significativamente en el grupo tratado (n = 33) versus el no tratado (n = 14) 12 meses después del seguimiento. Once de 25 (44%) pacientes que recibieron benznidazol negativizaron la respuesta para IFN-ã. Cuatro de los 11 (36%) pacientes con ELISPOT (+) que negativizaron la respuesta por ELISPOT para IFN-ã también negativizaron la serología convencional a los 2 años postratamiento. Durante el seguimiento no se observaron alteraciones clínicas. Estos hallazgos muestran que el benznidazol es capaz de modular la respuesta celular T de memoria específica para T. cruzi. La medición de la frecuencia de linfocitos T de memoria productores de IFN-ã podría constituir un ensayo más sensible y precoz para determinar el impacto/eficacia del tratamiento específico contra este parásito.

A multicenter, randomized, triple blind and controlled trial was designed to determine whether the combination with thioctic acid (TA), an antioxidant agent, can reduce the intolerance rate to Benznidazol (BZ) in patients infected with Trypanosoma cruzi. Four regimens were assigned randomly for 3 age intervals, administrating placebo or TA orally at daily doses of 50 to 100 mg in association with BZ at a dose of 5 mg/k/day for 30 days. In some, medication was given during a run-in period. Safety controls were carried out on days 10, 20, 37 and 52 days after therapy initiation. A total of 249 patients between 15 and 44 years old were enrolled. At the end of the trial, 70.3% of the patients had completed the treatment, while 17.7% required its suspension due to BZ related adverse reactions. The proportion of individuals affected with at least one side effect ranged from 54.8% to 58%; however, none were serious. Reported side effects included: cutaneous maculopapular rush (28%), pruritus (13.6%), headache (8%), epigastralgia (6.2%), fever (6.2%), fatigue (4.3%), nausea (4%), myalgias (4.3%), others (21.5%). The incidence of these reactions did not differ significantly among the 4 therapeutic regimens, nor even among the age intervals considered. It can be concluded that the association with TA did not prevent the occurrence of adverse reactions related to BZ administration. However, a single month cycle of this parasiticide permitted a high compliance rate to therapy among infected outpatients.

Se realizó un ensayo clínico controlado, multicéntrico, a triple ciego, para evaluar si el tratamiento oral combinado del ácido tióctico (AT), reduce la incidencia de los efectos secundarios asociados al tratamiento con benznidazol (BZ) en pacientes infectados con Trypanosoma cruzi. Cuatro esquemas fueron asignados al azar pareados por edad, administrando placebo o AT por vía oral a razón de 50-100 mg día a dosis e intervalos variables (con y sin período pre-inducción) en combinación con BZ a dosis de 5 mg/kg/día por 30 días. Se realizaron evaluaciones en los días 10, 20, 37 y 52 de iniciado el tratamiento. Fueron enrolados 249 pacientes con edades entre 15 y 44 años. El 70.3% de los pacientes completó el tratamiento y el 17.7% restante debió suspender la medicación por causas relacionadas al BZ. La proporción de personas afectadas por al menos un efecto adverso, fue semejante entre los 4 grupos: entre 54.8 y 58%, aunque en ninguno de ellos resultó de carácter grave. Las manifestaciones clínicas adversas fueron: exantema morbiliforme (28%); prurito (13.6%); cefalea (8%); epigastralgia (6.2%); fiebre (6.2%); astenia (4.3%); náuseas (4.0%); mialgias (4.3%); vómitos (3.2%); otros (21.5%). La incidencia de experiencias adversas no difirió significativamente entre los 4 esquemas terapéuticos, ni entre los diferentes intervalos de edad de los pacientes. La asociación con ácido tióctico no demostró prevenir las manifestaciones de intolerancia a este agente. No obstante, la administración de BZ en un ciclo mensual único a pacientes infectados logró una elevada tasa de adherencia al tratamiento ambulatorio.