Serological based monitoring of a cohort of patients with chronic Chagas disease treated with benznidazole in a highly endemic area of northern Argentina

This study aimed to evaluate well-documented diagnostic antigens, named B13, 1F8 and JL7 recombinant proteins, as potential markers of seroconversion in treated chagasic patients. Prospective study, involving 203 patients treated with benznidazole, was conducted from endemic areas of northern Argentina. Follow-up was possible in 107 out of them and blood samples were taken for serology and PCR assays before and 2, 3, 6, 12, 24 and 36 months after treatment initiation. Reactivity against Trypanosoma cruzi lysate and recombinant antigens was measured by ELISA. The rate of decrease of antibody titers showed nonlinear kinetics with an abrupt drop within the first three months after initiation of treatment for all studied antigens, followed by a plateau displaying a low decay until the end of follow-up. At this point, anti-B13, anti-1F8 and anti-JL7 titers were relatively close to the cut-off line, while anti-T. cruzi antibodies still remained positive. At baseline, 60.8% (45/74) of analysed patients tested positive for parasite DNA by PCR and during the follow-up period in 34 out of 45 positive samples (75.5%) could not be detected T. cruzi DNA. Our results suggest that these antigens might be useful as early markers for monitoring antiparasitic treatment in chronic Chagas disease.

Contribucion del proyecto genoma de Trypanosoma cruzi a la compresion de la patogenesis de la cardiomiopatia chagasica cronica / Contribution of the Trypanosoma cruzi Genome Project to the understanding of Chagas disease

El proyecto genoma de Trypanosoma cruzi (PGTc) es una iniciativa multinacional desarrollada dentro del marco de dos organizaciones internacionales OMS/TDR y CYTED. Debe considerarse com una herramienta de sumo valor para el estudio de diversos aspectos de la enfermedad de Chagas. Pone a disposición de investigadores básicos y clínicos una cantidad de información sobre los genes expresados por el parásito (ver base de datos de PGTc, http://gene.dbbm.fiocruz.br y una importante cantidad de bibliotecas genómicas y sondas de genes expresados (ESTs). Presentamos cuatro ejemplos sobre el uso de este material en el estudio de la patogénesis de esta infección crónica. 1) Demostramos la posibilidad de derivar antígenos a partir de ESTs, parea de relevancia para comprender la reactividad anti-receptores cardíacos presente en el suero de pacientes chagásicos. 2) Introducimos los conceptos de proteoma, vacunoma y patonoma, conjunción de técnicas necesarias para analizar la información que surge del PGTc. 3) Demostramos cómo las regiones ya secuenciadas del genoma dan claves sobre el carácter dinámico y flexible del mismo, y por último 4) mostramos cómo la información del PGTc puede ser utilizada para estudiar el AND del parásito asociado a la lesión cardíaca crónica.

Los anticuerpos antiproteínas ribosomales P estimulan al receptor ß adrenérgico en la enfermedad de Chagas pero no en el lupus eritematoso sistémico / Antibodies to ribosomal P protein of Trypanosoma cruzi in Chagas's disease possess functional autorreactivity with heart tissue and differ from anti P autoantibodies in lupus

En la búsqueda de marcadores serológicos de daño miocárdico activo en pacientes con infección crónica chagásica, se demuestra que el suero de aquéllos que presentan cardiomiopatía manifiesta reconoce las regiones C-terminales de las proteínas ribosomales P del Trypanosoma cruzi. En este estudio se demuestra que la infección no induce la respuesta autoinmune anti P que caracteriza a los pacientes con lupus, sino origina una respuesta anti P característica, expresada por los niveles elevados de anticuerpos contra las regiones polianiónicas presentes en dichas proteínas. Los anticuerpos anti P chagásicos son responsables del efecto estimulante de la IgG de los pacientes con cardiomiopatía chagásica crónica sobre los receptores ß1 adrenérgicos cardíacos, razón por la cual podrían participar en la patogenia de algunas manifestaciones de la cardiomiopatía chagásica crónica, en particular en las arritmias ventriculares. Los resultados de este trabajo indican que la actividad funcional (y patogenicidad) sobre el tejido miocárdico de los anticuerpos generados contra antígenos intracelulares del parásito resultan de su capacidad para reaccionar en forma cruzada con proteínas de la membrana celular cardíaca. Esta demostración obliga a replantear la utilización de quimioterápicos tripanomicidas eficientes y tolerados a largo plazo para anular la producción de esos anticuerpos

The Trypanosoma cruzi genome project: nuclear karyotype and gene mapping of clone CL Brener

By using improved pulsed field gel electrophoresis conditions, the molecular karyotype of the reference chromosomal bands ranging in size from 0.45 to 3.5 Magabase pairs (Mbp) were resolved in a single run. The weighted sum of the chromosomal bands was approximately 87 Mbp. Chromoblots were hybridized with 39 different homologous probes, 13 of which identified single chromosomes. Several markers linkage and four different linkage groups were identified, each comprising two markers. Densitometric analysis suggests that most of the chromosomal bands contain two or more chromosomes representing either homologous chromosomes and/or heterologous chromosomes with similar sizes.

Parasite genome projects and the Trypanosoma cruzi genome initiative

Since the start of the human genome project, a great number of genome projects on other "model" organism have been initiated, some of them already completed. Several initiatives have been started on parasite genomes, mainly through support from WHO/TDR, involving North-South and South-South collaborations, and great hopes are vested in that these initiatives will lead to new tools for disease control and prevention, as well as to the establishment of genomic research technology in developing countries. The Trypanosoma cruzi genome project, using the clone CL-Brener as starting point, has made considerable progress through the concerted action of more than 20 laboratories, most of them in the South. A brief overview of the current state of the project is given.