FIG 4.

Curative benznidazole therapy prevents the development of cardiac fibrosis in BALB/c mice infected with T. cruzi CL Brener when treatment is initiated in the acute stage but not when initiated in the chronic stage. Infected mice were either nontreated (NT; n = 19), or treated (T) with benznidazole for 20 days, as outlined in the legend to Fig. 2, commencing day 14 postinfection (n = 10), day 22 (n = 12), day 66 (n = 12), or day 110 (n = 12). Groups of noninfected mice, either nontreated (NT; n = 7), or treated (T) (starting on day 66, n = 4, or on day 110, n = 4) were run in parallel. Cardiac tissue was harvested and assessed for inflammation and fibrosis (see Materials and Methods). (A) Quantitative histopathological analysis of inflammation. The number of nuclei per 6 × 10⁴ μm² was quantified as a myocarditis index. Data are shown as mean ± standard deviation. (B) Representative myocardial sections stained with H&E demonstrating inflammation. (C) Quantification of collagen content (blue area in Masson's trichrome-stained sections) as a marker of cardiac fibrosis. (D) Masson's trichrome-stained photomicrographs demonstrating fibrosis in mice heart sections. In panels B and D, the magnification is 400×. Bar, 30 μm. (E) Pearson correlation analysis of myocarditis against cardiac fibrosis scores. Data are from samples obtained at 169 days postinfection from the groups shown in panels A and C.