Influência da infecção crônica por Schistosoma mansoni na resposta à quimioterapia específica contra a infecção experimental aguda por Trypanosoma cruzi

Abstract

This research aimed to evaluate the effectiveness to the treatment with benznidazole (BZL) in acute infection by Trypanosoma cruzi, in mice with chronic infection by Schistosoma mansoni. For the experiment, 66 Balb/c mice divided into 6 experimental groups were used, the group 1 (G1): Healthy; group 2 (G2): infected by S. mansoni; group 3 (G3): infected by T. cruzi, group 4 (G4): infected by T. cruzi and treated with BZL, group 5 (G5): co-infected by S. mansoni/T.cruzi and group 6 (G6): co-infected by S. mansoni/T. cruzi end treated with BZL. Weight, mortality and parasitaemia of animals were registered and, at the end of the experiment, blood was collected for the dosage of BZL and cytokine analysis. The animals were sacrificed, organs were weighed and fixed for histological analysis, and a cardiac parasitism qPCR analyses were performed. The results showed that the co-infected animals had parasitaemia 5 times higher than those observed among infected mice by T. cruzi (G5: 6x106 vs. G3: 1.3x106 trypomastigotes/0,1mL of blood; p<0.05), but after the peak of parasitaemia, the co-infected animals effectively controlled the parasitism in the myocardium more effectively than G3 (G5: 39.48 vs. G3: 158.6 parasites/25ng DNA tissue; p<0.05). Despite the lower parasite load in the myocardium of co-infected animals on the 13th day of infection with T. cruzi, myocarditis was higher in these animals (G5: 284 vs. G3: 246 number of cells in the myocardium; p<0.05). The BZL, as expected, controlled parasitaemia by T. cruzi among animals of G3, but it is also effective in controlling the parasitaemia even among the co-infected animals belonging to G6 (G4: 325 e G6: 417 means of trypomastigotes/0,1mL of blood; p>0.05). The evaluation of body weight and mortality also showed that BZL promoted an improvement in these parameters among G6 mice when compared to co-infected animals from G5, in the same way

as occurred with the evaluation of cardiac parasitism and myocarditis (G5 vs. G6, p<0.05). The co- infection reduces the polarization of the anti-inflammatory and pro-inflammatory profiles of

cytokines induced by parasites in a situation of simple infection, and BZL promoted a decrease in anti-inflammatory cytokines in co-infected animals with a single effect on inflammation. Liver and spleen weights were exacerbated in co-infected animals when compared to other experimental groups (p<0.05). The BZL normalized spleen weight, helped prevent hepatocyte loss and minimized liver inflammation (G5 vs. G6, p<0.05), but increased hepatomegaly in G6 animals (G5: 0.089 vs. G6: 0.10g mean relative weight of the liver; p<0.05). Co-infection or BZL did not influence the number of hepatic granulomas, their area or cell density (G5 e G6 vs. G2, p>0.05), but among the co-infected there was an increase in the percentages of animals with pulmonary granulomas (G2: 40, G5: 60 and G6: 89% of animals with granulomas in the lung) and intestinal (G2: 50, G5: 90 and G6: 75% of animals with granulomas in the small intestine). All groups with schistosomiasis showed high inflammation in the small intestine, with no significant changes in the large. Finally, the quantification of BZL showed that the co-infection did not significantly influence drug levels in blood among the analysed times (G4 vs. G6, p>0.05). The results allow us to conclude that treatment with BZL is efficient in minimizing body weight loss, mortality and splenomegaly, in addition to suppressing T. cruzi parasitism and parasitaemia in mice chronically co-infected with S. mansoni.