Pathogenic factors for the development of chronic Chagas disease in Latin America

为了研究拉丁美洲慢性恰加斯病的发病机制，我们分析了墨西哥、危地马拉、秘鲁、玻利维亚和巴拉圭的克氏锥虫野外分离株和典型慢性恰加斯病个体的遗传结构。在墨西哥，我们与墨西哥城国家心脏病研究所的研究人员合作。我们在两个流行地区，普韦布洛和恰帕斯进行了大规模的实地研究。该地区血清阳性率约为10%，恰帕斯略高。当我们计算心电图异常阳性占血清阳性的百分比时，两个区域显示相同，尽管地方性不同。这表明感染后的预后可能主要由宿主遗传决定。在危地马拉，我们通过与圣卡洛斯大学研究人员的合作研究，从流行地区的人类和锥蝽病媒中收集了许多分离株。利用这些分离株，…More Higo发现了存在的证据，表明来自同一地区的不同分离株之间发生了遗传交换。Sone开发了一种新的方法，通过比较培养的强洗涤剂提取的染毛马鞭毛蛋白溶液的二维电泳图谱来分析单个分离物之间的遗传距离。根据他的分析，在进化树中至少确定了4个主要树干。在玻利维亚，我们与当地热带病中心和日本医院的研究人员和医生一起发起了一项大规模和严格临床界定的慢性恰加斯病研究。该研究方案已经得到了当地和日本机构的伦理委员会的批准。我们从三个临床组，无症状（不确定），心脏无消化改变和消化形式（巨型结肠）中收集了计划数量的30%的样本。我们计划通过常规的靶向基因分析和全基因组扫描来寻找易感基因。在巴拉圭，恰加斯病在原始美洲印第安人居住的西部保留区非常流行。亚松森大学的合作研究人员调查了这些地区的血清患病率，发现约70-90%的血清呈阳性。我们注意到一些居民对锥虫抗原表现出独特的血清反应，它们只与反式唾液酸酶反应。我们计划利用与这种特殊性状相关的许多家族进行连锁研究。一位一起工作的心脏病专家通过对同一村庄的心电图研究发现，这些人有成为心脏恰加斯的倾向。少

To investigate the pathogenesis of chronic Chagas disease in Latin America, we have analyzed genetic structure of the field isolates of Trypanosoma cruzi and of the individuals who developed typical chronic Chagas disease in Mexico, Guatemala, Peru, Bolivia and Paraguay.In Mexico, we have collaborated with researchers of National Institute of Cardiac Diseases in Mexico City. We performed a large scale field study in two endemic areas, Pueblo and Chiapaz. Seropositivity of the areas was around 10%, though Chiapaz was a little higher. When we calculated the percentage of the electrocardiogram abnormality positives in the seropositives, both areas showed the same though the endemicity was different. This indicated the prognosis after the infection may be determined by mainly host genetics.In Guatemala, we have collected many isolates from both humans and from triatomine vectors in the endemic areas by the collaborative study with researchers at San Carlos University. Using those isolates, … More Higo found the existence of evidences that genetic exchange occurred between different isolates from the same field. Sone developed a novel method to analyze the genetic distance between individual isolates by the comparison of the two dimensional electrophoresis patterns of the cultured epimastigote protein solutions extracted by strong detergent. According to his analysis, at least 4 major trunks were identified in the evolution tree.In Bolivia, we have initiated a large scaled and a strictly clinically defined chronic Chagas Disease study with local researchers and doctors at Center for Tropical diseases (CENETROP), and Hospital Japones. The research protocol has already approved by the ethical committee at the local and Japanese institutions. We have collected 30% of the planned number of samples from three clinical groups, asymptomatic (indeterminate), cardiac without digestive changes, and digestive form (mega colon). We are planning to search for the susceptible genes by conventional targeted gene analysis and by the genome wide scanning.In Paraguay, Chagas disease is so much endemic in the western reserved areas where original Amerindians are living. Collaborative researcher at Universidad Asuncion have surveyed the seroprevalence in those areas and found around 70-90% were seropositive. We noticed several inhabitants showed unique sero-reactivity to the trypanosome antigens that they reacted with only trans-sialidase. We have planned to do a linkage study using many families related to such special trait. One cardiologist who worked together found such persons have tendency to become cardiac Chagas by ECG study in the same villages. Less