Caldas Ivo Santana, Menezes Ana Paula de Jesus, Diniz Lívia de Figueiredo, Nascimento Álvaro Fernando da Silva do, Novaes Rômulo Dias, Caldas Sérgio, Bahia Maria Terezinha
Institute of Biomedical Sciences, Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, MG, Brazil.
Laboratory of Parasitic Diseases, School of Medicine, Department of Biological Sciences and NUPEB, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
Acta Trop. 2019 Jan;189:30-38. doi: 10.1016/j.actatropica.2018.09.015. Epub 2018 Oct 2.
It is still unclear whether the progression of acute to chronic Chagas cardiomyopathy is predominantly associated with the limited efficacy of aetiological chemotherapy, or with the pharmacological resistance profiles and pathogenicity of specific Trypanosoma cruzi strains. Thus, we tested the hypothesis that parasitic load could be a limited target of aetiological chemotherapy to prevent chronic cardiomyopathy in dogs infected by different T. cruzi strains. Animals were infected with benznidazole-susceptible (Berenice-78) and -resistant (VL-10 and AAS) strains of T. cruzi. A quantitative real-time PCR strategy was developed to comparatively quantify the parasite load of the three different strains using a single standard curve. For dogs infected with the VL-10 strain, benznidazole treatment reduced cardiac parasitism during the acute phase of infection. However, similar parasite load and collagen deposition were detected in the myocardium of treated and untreated animals in the chronic phase of the infection. In animals infected with the AAS strain, benznidazole reduced parasite load, myocarditis and type III collagen deposition in the acute phase. However, increased type III collagen deposition was verified in the chronic phase. Dogs infected with the Berenice-78 strain showed a parasitological cure and no evidence of myocardial fibrosis. Parasitic load and cardiac fibrosis presented no correlation in acute or chronic phases of T. cruzi infection. Our findings in a canine model of Chagas disease suggest that parasite burden is a limited predictor for disease progression after treatment and show that benznidazole, although not inducing parasitological cure, is able to prevent total fibrosis in the early stages of infection, as well as complete prevention of cardiac damage when it eliminates parasites at the onset of infection.
急性查加斯心肌病向慢性的进展主要是与病因性化疗的疗效有限相关,还是与特定克氏锥虫菌株的药理抗性特征和致病性相关,目前仍不清楚。因此,我们检验了这样一个假设,即寄生虫负荷可能是病因性化疗的一个有限靶点,以预防感染不同克氏锥虫菌株的犬类发生慢性心肌病。用对苯硝唑敏感(贝雷尼斯 - 78)和耐药(VL - 10和AAS)的克氏锥虫菌株感染动物。开发了一种定量实时PCR策略,以使用单一标准曲线比较定量三种不同菌株的寄生虫负荷。对于感染VL - 10菌株的犬类,苯硝唑治疗在感染急性期降低了心脏寄生虫感染。然而,在感染慢性期,在治疗和未治疗动物的心肌中检测到相似的寄生虫负荷和胶原沉积。在感染AAS菌株的动物中,苯硝唑在急性期降低了寄生虫负荷、心肌炎和III型胶原沉积。然而,在慢性期证实III型胶原沉积增加。感染贝雷尼斯 - 78菌株的犬类显示寄生虫学治愈且无心肌纤维化证据。在克氏锥虫感染的急性或慢性期,寄生虫负荷与心脏纤维化均无相关性。我们在查加斯病犬模型中的研究结果表明,寄生虫负担是治疗后疾病进展的一个有限预测指标,并表明苯硝唑虽然不能诱导寄生虫学治愈,但能够在感染早期预防完全纤维化,以及在感染开始时消除寄生虫时完全预防心脏损伤。