Kinetics of Biomarkers for Therapeutic Assessment in Swiss Mice Infected with a Virulent Trypanosoma cruzi Strain

TL;DR

This study tracks how Swiss mice respond to a virulent strain of T. cruzi over time, providing a detailed model for testing new Chagas disease treatments.

Contribution

The study introduces a kinetic integration of infection parameters in a defined mouse model for standardized preclinical testing.

Findings

Optimal infective dose and parasitemia dynamics were determined in Swiss mice.

Tissue damage and immune responses were tracked across multiple organs during acute infection.

A necropsy evaluation confirmed fatal outcomes and organ involvement at the end of the acute phase.

Abstract

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6–8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite’s discrete typing unit (DTU). This variability complicates the evaluation and comparison of new therapeutic compounds against existing drugs, namely benznidazole and nifurtimox. This study provides a comprehensive, kinetic, multifaceted characterization of the acute infection using the highly virulent T. cruzi Y strain (TcII) in outbred Swiss mice. Here, crucial infection parameters are presented, including the optimal infective dose, the parasitemia dynamics, tissue damage markers, hematological profiles, cytokine production (Th1/Th2/Th17/Th22), and molecular parasite identification in target organs (heart, colon, esophagus, spleen, and liver) across the span of the infection. The novelty of this study lies in the kinetic integration of these parameters within a defined model; rather than presenting isolated data points, we demonstrate how the biochemical, physiological, and clinical signs and immunological responses, with the resulting organ involvement, evolve and interact over time. To complete the report, a necropsy evaluation was performed at the end of the acute, fatal infection, and it is presented here. This study fulfills a long-standing recommendation from diverse drug discovery groups for the creation of a definitive reference model to standardize preclinical testing for anti-Chagasic agents.

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