Fig 1.
(A) Survival of mice infected with Silvio X10/7 strain of T.cruzi in a model of acute Chagas Disease. Note all vehicle alone (solutol) treated mice died by 25 days, whereas both benznidazole and 9/10 posaconazole-treated mice survived one year. One posaconazole-treated mouse died early likely from gavage trauma. (B) Posaconazole-treated mice were statistically similar to uninfected mice in weight gain over one year. While benznidazole-treated mice also gained weight, they did so at a significantly slower pace.
Fig 2.
Parasite burden in heart (A) and G.I. tract (B) in acute model of infection as assessed by PCR (see Methods). Six of nine posaconazole-treated mice had negative PCR as did the uninfected controls. One of the PCR-positive mice treated with posaconazole had no detectable cardiac inflammation (Fig 3). Combined results from two independent studies color coded as #1 (red) and #2 (blue).* Statistically significant versus Uninfected samples, p≤ 0.05; ❖ Statistically significant versus benznidazole treated mice, p≤ 0.05.
Fig 3.
(A-E) Inflammatory infiltrates associated with parasite infection, in heart muscle. Heart muscle fibers are pink with eosin-stain while the inflammatory infiltrate associated with nests of parasites is recognized by the presence of dark-blue lymphocytes. (F) Quantification of inflammatory infiltrate by number of lymphocytes through image processing (see Methods).
Fig 4.
Survival (A) and weight (B) curves from mice infected with T. cruzi, Brazil strain. Note in Fig 4B that only the benznidazole-treated mice gained significant weight over the one-year period of observation.
Fig 5.
Parasite burden in heart (A) and G.I. tract (B) in chronic model of infection. Only the benznidazole-treated mice were PCR negative at one year in the chronic disease model of T.cruzi infection. * Statistically significant versus Uninfected samples, p≤ 0.05; ❖ Statistically significant versus Solutol treated mice (vehicle), p≤ 0.05.
Fig 6.
Histopathology analysis of heart tissue of mice infected with T. cruzi, Brazil strain and treated with compounds in the chronic phase of the disease.
(A-E) Examples of inflammatory infiltrates in vehicle-alone treated and posaconazole-treated mice. (F) Echocardiographic analysis of left ventricular size adjusted to mice weight (in mm/g) prior to necropsy of mice in the chronic disease model. Note significant wall hypertrophy in the vehicle-alone and posaconazole-treated mice.