Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
Clin Infect Dis. 2010 Sep 1;51(5):485-95. doi: 10.1086/655680.
One hundred years after the discovery of Chagas disease, it remains a major neglected tropical disease. Chronic Chagas heart disease (cChHD) is the most severe manifestation. Heart transplantation is the proper treatment for end-stage heart failure, although reactivation of disease may result after receipt of immunosuppressive therapy. T. cruzi strains cluster into 6 discrete typing units (DTUs; I-VI) associated with different geographical distribution, transmission cycles and varying disease symptoms. In the southern cone of South America, T. cruzi II, V, and VI populations appear to be associated with Chagas disease and T. cruzi I with sylvatic cycles.
Molecular characterization of DTUs, T. cruzi I genotypes (on the basis of spliced-leader gene polymorphisms), and minicircle signatures was conducted using cardiac explant specimens and blood samples obtained from a cohort of 16 Argentinean patients with cChHD who underwent heart transplantation and from lesion samples obtained from 6 of these patients who presented with clinical reactivation of Chagas disease.
Parasite persistence was associated with myocarditis progression, revealing T. cruzi I (genotype Id) in 3 explant samples and T. cruzi II, V, or VI in 5 explant samples. Post-heart transplantation follow-up examination of bloodstream DTUs identified T. cruzi I in 5 patients (genotypes Ia or Id) and T. cruzi II, V, or VI in 7 patients. T. cruzi I, V, and VI were detected in skin chagoma specimens, and T. cruzi V and VI were detected in samples obtained from patients with myocarditis reactivations. Multiple DTUs or genotypes at diverse body sites and polymorphic minicircle signatures at different cardiac regions revealed parasite histotropism. T. cruzi I infections clustered in northern Argentina (latitude, 23 degrees S-27 degrees S), whereas T. cruzi II, V, or VI DTUs were more ubiquitous.
Multiple DTUs coexist in patients with Chagas disease. The frequent finding of T. cruzi I associated with cardiac damage was astounding, revealing its pathogenic role in cChHD at the southern cone.
在查加斯病发现 100 年后，它仍然是一种主要的被忽视的热带病。慢性恰加斯心脏病（cChHD）是最严重的表现。心脏移植是治疗终末期心力衰竭的恰当方法，尽管在接受免疫抑制治疗后可能会导致疾病复发。克氏锥虫菌株聚类为 6 个离散的分型单元（DTU；I-VI），与不同的地理分布、传播周期和不同的疾病症状相关。在南美洲南部锥体，T. cruzi II、V 和 VI 种群似乎与查加斯病有关，而 T. cruzi I 与森林循环有关。
使用心脏移植患者的心脏标本和血液样本以及来自 6 名出现恰加斯病临床复发的患者的病变样本，对来自 16 名患有 cChHD 的阿根廷患者的 DTU、T. cruzi I 基因型（基于拼接领导基因多态性）和微环特征进行分子特征分析。
寄生虫持续存在与心肌炎进展有关，在 3 个标本中发现 T. cruzi I（基因型 Id），在 5 个标本中发现 T. cruzi II、V 或 VI。心脏移植后的血液 DTU 随访检查发现 5 名患者（基因型 Ia 或 Id）存在 T. cruzi I，7 名患者存在 T. cruzi II、V 或 VI。皮肤 chagoma 标本中检测到 T. cruzi I、V 和 VI，心肌炎复发患者的标本中检测到 T. cruzi V 和 VI。不同部位的多个 DTU 或基因型以及不同心脏区域的多态性微环特征显示寄生虫组织嗜性。T. cruzi I 感染集中在阿根廷北部（纬度，23 度 S-27 度 S），而 T. cruzi II、V 或 VI DTU 则更为普遍。
多种 DTU 共存于患有恰加斯病的患者中。令人惊讶的是，经常发现与心脏损伤相关的 T. cruzi I，这揭示了它在南部锥体 cChHD 中的致病作用。
