Enrique Arias

Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution

The efficacy of treatment with nifurtimox and/or benznidazole among adults with chronic Chagas disease with no previous electrocardiographic disturbances was evaluated over a mean follow-up of 21 years, by means of conventional serology, xenodiagnosis, clinical examination, electrocardiograms and chest X-ray. One hundred and eleven patients, between 17 and 46 years old, were studied: 54 underwent treatment (nifurtimox 27, benznidazole 27) and 57 remained untreated (control group). Xenodiagnosis was performed on 65% of them: 36/38 of the treated and 9/34 of the untreated patients had previous positive xenodiagnosis. Post-treatment, 133 xenodiagnoses were performed on 41 patients, all resulting negative. In the control group, 29 xenodiagnoses were performed on 14 patients; 2 resulted positive. Sera stored during the follow-up were simultaneously analyzed through conventional serology tests (IHA; DA-2ME; IIF). The serological evolution in the treated group was: a) 37% underwent negative seroconversion (nifurtimox 11, benznidazole 9); b) 27.8% decreased titers (nifurtimox 9, benznidazole 6), 9 showed inconclusive final serology (nifurtimox 7, benznidazole 2); c) 35.2% remained positive with constant titers (nifurtimox 7; benznidazole 12). The control group conserved the initial antibody levels during the follow-up. In the clinical evolution, 2/54 (3.7%) of the treated and 9/57 (15.8%) of the untreated patients showed electrocardiographic disturbances attributable to Chagas myocardiopathy, with a statistically relevant difference (p<0.05). Treatment caused deparasitation in at least 37% of the chronically infected adults and a protective effect on their clinical evolution.

Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic chagasic patients

The aim of this work was to compare the evolution of chronic chagasic untreated patients (UTPs) with that of benznidazole or nifurtimox-treated patients (TPs). A longitudinal study from a low endemic area (Santa Fe city, Argentina) was performed during an average period of 14 years. Serological and parasitological analyses with clinical exams, ECG and X-chest ray were carried out. At the onset, 19/198 infected patients showed chagasic cardiomyopathy (CrChM) while 179 were asymptomatic. In this latter group the frequency of CrChM during the follow-up was lower in TPs compared with UTPs (3.2% vs 7%). Within the CrChM group, 2/5 TPs showed aggravated myopathy whereas this happened in 9/14 UTPs. Comparing the clinical evolution of all patients, 5.9% of TPs and 13% of UTPs had unfavourable evolution, but the difference is not statistically relevant. Serological titers were assessed by IIF. Titers equal to or lower than 1/64 were obtained in 86% of the TPs, but only in 38% of UTPs. The differences were statistically significant (geometric mean: 49.36 vs. 98.2). Antiparasitic assessment of the drugs (xenodiagnosis) proved to be effective. The low sensitivity in chronic chagasic patients must be born in mind. Despite treated patients showed a better clinical evolution and lower antibody levels than untreated ones, it is necessary to carry on doing research in order to improve therapeutic guidelines, according to the risk/benefit equation and based on scientific and ethical principles.

Estudo longitudinal e quimioterapia específica em crianças, com doença de Chagas crônica, residentes em área de baixa endemicidade da República Argentina

Clinical and epidemiological results of 95 treated and untreated chronic chagasic children, with an up to 24 years follow-up period are presented. This population studied in the 1/14 age bracket, residing in Santa Fe city, Argentina, was diagnosed through Chagas-specific conventional serologic reactions. Clinical examination was supplemented with electrocardiogram, chest X-rays, and blood and urine tests for evaluating hepatic function. The drugs employed were nifurtimox or benznidazole. In post treatment period xenodiagnosis was made in 33 patients. Regarding Trypanosoma cruzi transmission, the studied individuals presented multi-risk antecedents: vectorial, congenital and/or blood transfusion. Among 24 untreated children 14 were controlled during 8/24 years: all this patients maintained the initial antibody concentration and clinical status. From 71 treated patients 49 were followed-up 4/24 years: 14 remained positive, 6 presented dubious results, and 29 showed final non-reactive results. 9 of this presented sometimes oscilating results. In 1/6 age bracket children, the serology turned negative after 3.5 years (median) once the treatment was finished, while patients treated in the 7/14 age bracket, the median of negativization was 8 years. 3.8% did not tolerate the drug. None of the groups changed their clinical condition. The untreated children did not change the serology. The percentage of treated children presenting negative serological results decrease according to the age when treatment was given: 75% became negative when treated at < or =4 years old and 43% when treated at > or =9 years old.

Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease

This work compared the time at which negative seroconversion was detected by conventional serology (CS) and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.

Humoral Immune Response against P2β from Trypanosoma cruzi in Persons with Chronic Chagas Disease: Its Relationship with Treatment Against Parasites and Myocardial Damage

We investigated the relationship between potentially pathogenic antibodies against a Trypanosoma cruzi ribosomal protein (P2β) and the evolution of Chagas disease and the effect of trypanocidal treatment on these variables. Seventy-eight patients with chronic Chagas disease who were followed-up for more than 20 years were divided into three groups: 30 asymptomatic persons undergoing specific treatment (group A), 37 asymptomatic persons not undergoing specific treatment (group B), and 11 patients with chronic chagasic cardiomyopathy (CCC) who were not treated. Five patients in group B showed evolution to myocardial abnormalities. Among persons with CCC, six showed no changes; the remaining persons showed progression of cardiac involvement. Levels of antibodies to P2β in persons in group A decreased from their initial values. This finding was not observed in persons in groups B and C. Comparisons at the end of the follow-up showed lower amounts of antibodies to P2β in groups A and C. These findings support the benefits of specific treatment during chronic infection.

Evaluación de ELISA F29 como marcador de eficacia del tratamiento etiológico en la enfermedad de Chagas

DIANA FABBRO*, ELSA VELAZQUEZ**, NORBERTO MENDOZA*, MIRTHA STREIGER*, ENRIQUEARIAS*, SUSANA DENNER*, MONICA DEL BARCO*, NORBERTO AMICONE*, CARLOS PRAVIA**NORA MALAGRINO**, y ANDRES MARIANO RUIZ*** Centro de Investigaciones Endemias Nacionales (CIEN), Facultad de Bioquimica y Ciencias Biologicas, UniversidadNacional del Litoral, Santa Fe.** Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben, Buenos Aires.