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Published on: January 27, 2019
Effects of specific treatment on parasitological and histopathological parameters in mice infected with different
M J O Toledo1, M T Bahia, V M Veloso
1Departamento de Análises Clínicas, Centro de Ciências da Saúde, Bloco I-90, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900, Maringá, PR. mjotoledo@uem.br
Abstract:
The goal of this study was to verify the effect of specific treatment on parasitological and histopathological parameters in mice experimentally infected with different Trypanosoma cruzi clonal genotypes. Twenty cloned stocks were selected, representative of the whole phylogenetic diversity of the protozoan and belonging to the clonal genotypes 19 and 20 (T. cruzi I) and 39 and 32 (T. cruzi II). The stocks were inoculated in 40 BALB/c mice divided into four groups: (i) treated with benznidazole, (ii) treated with itraconazole and (iii and iv) untreated control groups (NT) for each drug, respectively. Seven parameters related to parasitaemia curves and histopathological lesions were analysed. Four during the acute phase (AP) and three during both the AP and chronic phase (CP) of infection. Statistical comparison between benznidazole-treated and NT groups for the biological parameters showed significant differences for all genotypes. Benznidazole treatment led to lower patent period, maximum of parasitaemia, day of maximum parasitaemia and area under the parasitaemia curve for all genotypes analysed. Percentage of positive haemoculture during AP and CP was lower for genotypes 19 and 32. Tissue parasitism (TP) and inflammatory process (IP) during AP were lower for genotypes 19 and 32, respectively. In general, itraconazole treatment induced a smaller reduction in these same parameters between treated and NT animals in relation to benznidazole treatment. Our results indicate that phylogenetic divergence among T. cruzi clonal genotypes must be taken in account in chemotherapy and studies dealing with all aspects of the parasite and the disease.
Insights
Benznidazole effectively reduced Trypanosoma cruzi infection markers in mice across different genotypes. Phylogenetic differences among T. cruzi strains influence treatment outcomes, highlighting the need for personalized chemotherapy.
Area of Science:
- Parasitology
- Infectious Diseases
- Drug Discovery
Background:
- Trypanosoma cruzi causes Chagas disease, a neglected tropical illness.
- The parasite exhibits significant phylogenetic diversity, impacting disease progression and treatment efficacy.
- Understanding genotype-specific responses to antiparasitic drugs is crucial for effective Chagas disease management.
Purpose of the Study:
- To evaluate the impact of benznidazole and itraconazole on parasitological and histopathological parameters in mice infected with diverse Trypanosoma cruzi clonal genotypes.
- To determine if T. cruzi phylogenetic divergence influences treatment outcomes.
Main Methods:
- Experimental infection of BALB/c mice with 20 T. cruzi cloned stocks representing genotypes T. cruzi I and T. cruzi II.
- Treatment groups included benznidazole, itraconazole, and untreated controls.
- Analysis of seven parameters: parasitaemia curves (acute and chronic phases) and histopathological lesions (acute phase).
Main Results:
- Benznidazole significantly reduced patent period, peak parasitaemia, and parasite load across all tested T. cruzi genotypes.
- Lower parasitaemia and tissue parasitism were observed with benznidazole for specific genotypes (19 and 32).
- Itraconazole demonstrated a less pronounced effect compared to benznidazole.
Conclusions:
- Phylogenetic diversity among T. cruzi clonal genotypes is a critical factor in chemotherapy effectiveness.
- Benznidazole is a promising treatment option, but its efficacy can vary depending on the parasite genotype.
- Future research and treatment strategies for Chagas disease should consider T. cruzi phylogenetic divergence.
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