Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes

Abstract

Our results confirm that NSC-FC-ALTA and blood PCR are the most suitable methods to early detect therapeutic failure in acute murine T. cruzi infection. Additionally, our data show that BC positivity is highly dependent upon the T. cruzi genotype combination. Moreover, our findings demonstrated that PCR tests performed on tissues from animals considered cured after benznidazole treatment still detected T. cruzi DNA, most probably indicating residual infection.

Ergosterol biosynthesis and drug development for Chagas disease

“…These results have now been confirmed using PCR-based methods in both humans and experimental animals (Anez et al 1999, Britto et al 2001, Garcia et al 2005, Martins et al 2008, Fernandes et al 2009). The reasons for the marked difference in the antiparasitic efficacy of nitro-heterocyclic compounds in the acute and chronic stages of the disease are unclear (Cançado 2002), but they may be related to unfavourable pharmacokinetic properties, such as relatively short half-lives and limited tissue penetration (Raaflaub & Ziegler 1979, Raaflaub 1980, Workman et al 1984, which will limit their action in the chronic stage when the parasites are mostly confined in deep tissues and undergo slow replication (Urbina 1999a, Urbina & Docampo 2003.…”

“…The reasons for the marked difference in the antiparasitic efficacy of nitro-heterocyclic compounds in the acute and chronic stages of the disease are unclear (Cançado 2002), but they may be related to unfavourable pharmacokinetic properties, such as relatively short half-lives and limited tissue penetration (Raaflaub & Ziegler 1979, Raaflaub 1980, Workman et al 1984, which will limit their action in the chronic stage when the parasites are mostly confined in deep tissues and undergo slow replication (Urbina 1999a, Urbina & Docampo 2003. In any case, verifying a true parasitological cure in chronic infection, where the levels of circulating parasites can be extremely low or undetectable even with the most sensitive PCR methods available (Martins et al 2008), remains an extremely challenging problem that requires developing other criteria, such as immunological assays that measure T-cell responses to drug treatment (Bustamante et al 2008).…”

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)

“…[5][6][7][8] Furthermore, different T. cruzi genotypes have been correlated with different virulence and antibiotic resistance. [9][10][11][12][13] These findings indicate that the genotype identification may be relevant to provide a prognosis of disease progression and/or differential treatment decisions based on the infective strain.…”

Current and Future Chemotherapy for Chagas Disease

“…A recent a promising discovery in the field has been the identification of unusual fragments of human apolipoprotein A1 (APOA1) that are specifically present in chagasic patients and seem to disappear after treatment with nifurtimox 71 . In mouse models, different methodologies to access parasitological cures were used after treatment with benznidazole and found out that even mice considered cured by hematological criteria still showed positive PCR tissues, either indicating a residual infection or residential parasite nucleic acid 72 .…”