Anti-M2 muscarinic receptor autoantibodies in Trypanosoma cruzi-infected pediatric patients treated with benznidazole

La presencia de autoanticuerpos con actividad adrenérgica y colinérgica, capaces de modificar la actividad de los receptores a neurotransmisores, ha sido asociada a la patogénesis de la Miocardiopatia chagásica. Hemos investigado la existencia de autoanticuerpos contra receptores muscarínicos M2 en la fracción IgG de 14 pacientes pediátricos con Enfermedad de Chagas y en 18 controles no infectados. Encontramos una mayor frecuencia y un incremento de 6,2 mais ou menos 1,8 veces en el nivel de autoanticuerpos contra receptores cardíacos en los niños infectados con T. cruzi respecto de los controles no infectados. Luego del tratamiento parasiticida específico, los pacientes fueron evaluados prospectivamente, comprobándose una tendencia lineal descendente significativa en la reactividad de estos autoanticuerpos. Al producirse la seroconversión negativa para T. cruzi como consecuencia directa del tratamiento, los pacientes presentaron títulos de autoanticuerpos contra receptores cardíacos similares a los detectados en los niños no infectados. Concluimos que en pacientes pediátricos la respuesta de autoanticuerpos contra receptores muscarínicos M2 se manifesta tempranamente en el curso de la infección con T. cruzi y decrece después de la quimioterapia especifica. Por lo tanto, la administración de BZ a estos pacienes no sólo sería efectiva para eliminar el parásito sino también para reducir respuestas autoinmunes potencialmente patogénicas.

In vitro activity of Etanidazole against the protozoan parasite Trypanosoma cruzi

We investigated the in vitro action of an hydrosoluble 2-nitroimidazole, Etanidazole (EZL), against Trypanosoma cruzi, the etiologic agent of Chagas disease. EZL displayed lethal activity against isolated trypomastigotes as well as amastigotes of T. cruzi (RA strain) growing in Vero cells or J774 macrophages, without affecting host cell viability. Although not completely equivalent to Benznidazole (BZL), the reference drug for Chagas chemotherapy, EZL takes advantage in exertingits anti-T. cruzi activity for longer periods without serious toxic side effects, as those recorded in BZL-treated patients. Our present results encourage further experiments to study in depth the trypanocidal properties of this drug already licensed for use in human cancers.

Evaluación del método de ELISA para detección de antígenos y complejos inmunes circulantes de Trypanosoma cruzi a través de un estudio de campo en una zona endémica de Argentina / Evaluation of an ELISA technique for detection of antigens and circulating immune complexes of Trypanosoma cruzi by a field study in an endemic zone of Argentina

The ELISA technique for detection of T. cruzi circulating antigens (cAg) and immune complexes (CIC) in the sera of chronic chagasic patients was field-tested in a well-known endemic area of Argentina (San Luis province). Of 215 individuals screened, 51 were positive for ELISA-CIC and 45 for ELISA-cAg. Seventy four subjects were considered por T. cruzi-infected, as they showed serologic reactivity at least by two different techniques. In this group, 49 (66.21) were ELISA-CIC positive, whereas in 43 (58.11) of them cAg was found by ELISA. Unspecific reactions were observed in only 2 cases with reactive serology for Chagas disease. Within the group considered as noninfected, a false-positive outcome was obtained at low dilution by one of the serologic tests in 16 (11.35) of 141 individuals. These sera yielded consistently negative results by ELISA-CIC and cAg, showing the utility of antigen detection in situations of conflictive serology. While antibody determination merely provides an indirect proof of infection, our ELISA tests for demonstration of T. cruzi-specific antigenic fractions in the host's circulation allow a parasitologic diagnosis in chronic patients, with higher sensitivity than that exhibited by traditional methods for detection of the whole parasite.