Alonso-Padilla Julio, Tassies Dolors, Cortes-Serra Nuria, Gascon Joaquim, Reverter Joan-Carles, Pinazo María-Jesús
Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
Hemotherapy and Hemostasis Department, Hospital Clínic, Barcelona, Spain.
Methods Mol Biol. 2019;1955:275-286. doi: 10.1007/978-1-4939-9148-8_21.
The most severe clinical symptomatology of Chagas disease affects ~30% of those chronically infected with the Trypanosoma cruzi parasite. The pathogenic mechanisms that lead to life-threatening heart and gut tissue disruptions occur "silently" for a longtime in a majority of cases. As a result, despite there are several serological and molecular methods available to diagnose the infection in its acute and chronic stages, diagnosis is often achieved only after the onset of clinical symptoms in the chronic phase of the disease. Furthermore, although there are two drugs to treat it, the assessment of their performance is impractical with current parasite-derived diagnostics, and therapeutic efficacy cannot be acknowledged in a timely manner.In this chapter we present two procedures to measure host-derived molecules as surrogates of therapeutic response against chronic T. cruzi infection. Their outputs relate to the generation and activity of thrombin, a major component of the blood coagulation cascade. This is due to the fact that a hypercoagulability state has been described to occur in chronic Chagas disease patients and revert after treatment with benznidazole.
恰加斯病最严重的临床症状出现在约30%长期感染克氏锥虫寄生虫的患者身上。在大多数情况下,导致危及生命的心脏和肠道组织破坏的致病机制会在很长一段时间内“悄然”发生。因此,尽管有几种血清学和分子方法可用于诊断急性和慢性阶段的感染,但通常只有在疾病慢性期出现临床症状后才能确诊。此外,虽然有两种药物可用于治疗该病,但用目前基于寄生虫的诊断方法评估其疗效并不实际,且无法及时确认治疗效果。在本章中,我们介绍了两种测量宿主来源分子的方法,作为针对慢性克氏锥虫感染治疗反应的替代指标。其结果与凝血级联反应的主要成分凝血酶的生成和活性有关。这是因为在慢性恰加斯病患者中已发现存在高凝状态,且在用苯硝唑治疗后这种状态会恢复。