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

Abstract

SUMMARYThe 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.

Genotyping of Trypanosoma cruzi Sublineage in Human Samples from a North-East Argentina Area by Hybridization with DNA Probes and Specific Polymerase Chain Reaction (PCR)

“…In that context, a correlation between clinical manifestation and the genotypes could be hypothesized as the cardiac sign that Chagas disease is predominant in Santa Fe province and in all of the country of Argentina. [47][48][49][50] This hypothesis would be supported by the correlation of cardiac signs with TcII strains described by other authors, 51,52 even though more evidences of this assumption should be obtained.…”

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

“…The few studies that attempted to demonstrate the effectiveness of etiologic treatment were only performed during the last decade of the 20th century, probably based on molecular biology evidence that, at that time, proved that the parasite remained in targeted tissues meaning that they could no longer attribute the etiopathogeny exclusively to immunological mechanisms (Villa et al 2007). Observational studies found that benznidazole treatment for patients with chronic Chagas disease delayed or prevented clinical progression of heart damage, but was not believed to be able to eliminate the parasite during the chronic phase of infection (Viotti et al 1994, Fabbro De Suasnábar et al 2000, Cançado 2002). Conversely, immunosuppressive treatments aggravated inflammatory responses in both experimental models and humans (Andrade et al 1987, Silva & Rossi 1990, Bocchi & Fiorelli 2001.…”

Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects

“…In fact, Bz has been used not only in the acute phase, but also in the indeterminate and even in the chronic phase with some positive results, according to several researchers (Viotti et al 1994, Pinto Dias et al 2000, Fabbro et al 2000, García et al 2005, Reyes & Vallejo 2005, Sosa-Estani & Segura 2006. In light of the above described considerations, the potential use of Nfx in the chronic or even in the indeterminate phase of Chagas disease should be considered with caution, since oxidative damage was reported to occur during development of the cardiomyopathy itself (Wen et al 2006).…”

“…These findings might be particularly relevant, given that cardiac manifestations of the disease have critical implications for treated patients. No equivalent studies are available in the literature concerning potential effects of Bz on the heart, despite the fact that Bz has been used as the drug of choice in many Latin American countries, not only to treat the acute or indeterminate phases of the disease, but also in patients who have entered the chronic phase (Viotti et al 1994, Fabbro et al 2000, Gallerano & Sosa 2000, Coura & de Castro 2002, García et al 2005, Sosa-Estani & Segura 2006.…”