BCR-ABL drugs attenuate ECM pathology and protect mice when provided before ECM symptoms develop. (A) Schematic overview of the ECM assay. Representative hematoxylin and eosin images of the brain and lung of uninfected (Un) and PbANKA-infected (Inf) mice euthanized on day 7 after infection with RMCBS score <8 (20×; scale bar = 50 μm). The arrowhead indicates brain hemorrhage. (B) Unsupervised hierarchical cluster map of brain and lung edema measured by Evans blue dye on day 7 after infection (gray scale) in comparison with the RMCBS clinical score (blue scale). (C) Schematic overview of the early-infection drug regimen (days 4 to 7). (D) Survival curves (mice were euthanized at an RMCBS score of ≤5; n = 18 Inf; 17 nilotinib [Nil]; 18 bosutinib [Bos]; 18 imatinib [Ima]). ∗P < .05; ∗∗∗∗P < .0001 determined using a log-rank test (Mantel Cox test) in comparison with the Inf group. (E) Parasitemia curves (n = 18 Inf; 17 Nil; 18 Bos; 18 Ima). (F) Brain edema measured by Evans blue assay on day 7 after infection (n = 6 Un; 12 Inf; 11 Nil; 11 Bos; 4 Ima). ∗∗∗∗P < .0001 determined using 1-way ANOVA, followed by Dunnett multiple comparison test (compared with the Inf group). (G) Lung edema measured by Evans blue assay on day 7 after infection (n = 6 Un; 12 Inf; 11 Nil; 11 Bos; 4 Ima). ∗P < .05; ∗∗P < .01 determined using a 1-way ANOVA, followed by Dunnett multiple comparison test (compared with the Inf group).