Jones E M, Colley D G, Tostes S, Lopes E R, Vnencak-Jones C L, McCurley T L
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
Am J Trop Med Hyg. 1993 Mar;48(3):348-57. doi: 10.4269/ajtmh.1993.48.348.
The major cause of morbidity and mortality in Chagas' disease is a chronic inflammatory cardiomyopathy, which presents ten or more years following initial infection. Demonstration of Trypanosoma cruzi in cardiac tissue by routine microscopy or culture is difficult in these patients, which has suggested that persistent organisms are not required for chronic disease. Consequently, studies have focused on elucidating an autoimmune pathogenesis of chronic injury. To further assess the persistence of T. cruzi in host tissue, DNA extracted from formalin-fixed, paraffin-embedded autopsy specimens from seronegative or seropositive patients was amplified by the polymerase chain reaction using T. cruzi-specific primers. Trypanosoma cruzi DNA sequences were not consistently amplified from four seropositive patients who lacked evidence of fatal chronic chagasic cardiomyopathy (CCC) (0 positive of 12 heart samples, 0 positive of four gonadal samples, and 0 positive of four adrenal samples) or nine seronegative patients (0 positive of 27 heart samples, 0 positive of nine gonadal samples and 0 positive of nine adrenal samples). In seven seropositive patients with severe CCC, cardiac tissue adjacent to inflammatory infiltrates yielded amplified T. cruzi DNA sequences in 18 of 21 heart samples. Parallel testing of gonadal and adrenal tissues from these same patients produced detectable T. cruzi DNA in none of the gonadal tissue samples and one of the seven adrenals. Our studies demonstrate that T. cruzi, or a portion of its genome, is present in the inflammatory lesion of chronic cardiac Chagas' disease.
恰加斯病发病和死亡的主要原因是慢性炎症性心肌病,该病在初次感染后十年或更久才会出现。在这些患者中,通过常规显微镜检查或培养在心脏组织中检测克氏锥虫很困难,这表明慢性病并不需要持续存在的病原体。因此,研究集中在阐明慢性损伤的自身免疫发病机制上。为了进一步评估克氏锥虫在宿主组织中的持续存在情况,使用克氏锥虫特异性引物通过聚合酶链反应扩增从血清阴性或血清阳性患者的福尔马林固定、石蜡包埋尸检标本中提取的DNA。在四名缺乏致命性慢性恰加斯心肌病(CCC)证据的血清阳性患者(12份心脏样本中0份阳性,4份性腺样本中0份阳性,4份肾上腺样本中0份阳性)或九名血清阴性患者(27份心脏样本中0份阳性,9份性腺样本中0份阳性,9份肾上腺样本中0份阳性)中,未持续扩增出克氏锥虫DNA序列。在七名患有严重CCC的血清阳性患者中,在炎症浸润附近的心脏组织中,21份心脏样本中有18份扩增出了克氏锥虫DNA序列。对这些相同患者的性腺和肾上腺组织进行平行检测,性腺组织样本均未检测到可检测到的克氏锥虫DNA,七份肾上腺样本中有一份检测到。我们的研究表明,克氏锥虫或其基因组的一部分存在于慢性心脏恰加斯病的炎症病变中。