3.4. In vivo BNZ resistance profile
First, parasitaemia profiles were monitored during the acute-phase
(Figure 5A ). Significant differences were observed between
untreated and BNZ-treated mice, showing a remarkable parasitaemia
reduction even at subcurative BNZ doses. Second, the experimental cure
was determined using a double checking widely used in in vivotrypanocidal assays: immunosuppression and PCR (Figure 5A-B )
(Santos et al. , 2010; Francisco et al. , 2016;
Martín-Escolano et al. , 2020c). Mice whose parasitaemia and PCR
remain negative after immunosuppression (enhancing the reactivation of
any residual infection) are considered cured.
Finally, organomegaly of spleens and hearts was measured (Figure
6 ). They are manifested in both the acute- and chronic-phases of CD,
allow us to characterise the pathogenesis of the T. cruziArequipa strain, and also allow us an indirect evaluation of the BNZ
efficacy since they are directly associated with the parasitic load
(Martín-Escolano et al. , 2018, 2019, 2020d). Splenomegaly and
cardiomegaly occurred in experimentally infected mice in both phases of
CD, during which the spleens of infected mice were approximately twice
the mass of those from uninfected mice. The hearts also suffered a
significant enlargement. Importantly, treatment with BNZ reduced
infection-induced splenomegaly and cardiomegaly, even at subcurative
doses and in the absence of a parasitological cure, since it is linked
to a reduction of the parasite load (Francisco et al. , 2015).