<em>Trypanosoma cruzi</em> I and IV Stocks from Brazilian Amazon Are Divergent in Terms of Biological and Medical Properties in Mice

Background In the Brazilian Amazon, clinical and epidemiological frameworks of Chagas disease are very dissimilar in relation to the endemic classical areas of transmission, possibly due to genetic and biological characteristics of the circulating Trypanosoma cruzi stocks. Twenty six T. cruzi stocks from Western Amazon Region attributed to the TcI and TcIV DTUs were comparatively studied in Swiss mice to test the hypothesis that T. cruzi clonal structure has a major impact on its biological and medical properties. Methodology/Principal Findings Seventeen parameters were assayed in mice infected with 14 T. cruzi strains belonging to DTU TcI and 11 strains typed as TcIV. In comparison with TcI, TcIV stocks promoted a significantly shorter pre-patent period (p<0.001), a longer patent period (p<0.001), higher values of mean daily parasitemia (p = 0.009) and maximum of parasitemia (p = 0.015), earlier days of maximum parasitemia (p<0.001) and mortality (p = 0.018), higher mortality rates in the acute phase (p = 0.047), higher infectivity rates (p = 0.002), higher positivity in the fresh blood examination (p<0.001), higher positivity in the ELISA at the early chronic phase (p = 0.022), and a higher positivity in the ELISA at the late chronic phase (p = 0.003). On the other hand TcI showed higher values of mortality rates in the early chronic phase (p = 0.014), higher frequency of mice with inflammatory process in any organ (p = 0.005), higher frequency of mice with tissue parasitism in any organ (p = 0.027) and a higher susceptibility to benznidazole (p = 0.002) than TcIV. Survival analysis showing the time elapsed from the day of inoculation to the beginning of the patent period was significantly shorter for TcIV strains and the death episodes triggered following the infection with TcI occurred significantly later in relation to TcIV. The notable exceptions come from positivity in the hemocultures and PCR, for which the results were similar. Conclusion/Significance T. cruzi stocks belonging to TcI and TcIV DTUs from Brazilian Amazon are divergent in terms of biological and medical properties in mice.背景 在巴西亚马逊地区，恰加斯病（Chagas disease）的临床与流行病学框架与经典地方性流行传播区域存在显著差异，该差异可能源于循环传播的克氏锥虫（Trypanosoma cruzi）虫株的遗传与生物学特性差异。本研究针对西亚马逊地区的26株克氏锥虫虫株（分别归属于TcI与TcIV离散分型单位（Discrete Typing Units, DTU）），以瑞士小鼠为模型开展对比研究，以验证“克氏锥虫的克隆结构对其生物学与医学特性具有核心影响”这一假说。 方法/主要结果 本研究对感染14株TcI DTU克氏锥虫菌株、11株TcIV DTU克氏锥虫菌株的小鼠，共检测17项参数。与TcI组相比，TcIV组虫株可显著缩短潜隐期（p<0.001）、延长虫血症检出期（p<0.001），提升平均每日虫血症载量（p=0.009）与最高虫血症载量（p=0.015），提前出现最高虫血症的天数（p<0.001）与首次死亡时间（p=0.018），升高急性期死亡率（p=0.047）、感染率（p=0.002），提升新鲜血涂片检测阳性率（p<0.001）、早期慢性阶段酶联免疫吸附试验（Enzyme-Linked Immunosorbent Assay, ELISA）阳性率（p=0.022）以及晚期慢性阶段ELISA阳性率（p=0.003）。反之，TcI组小鼠的早期慢性阶段死亡率更高（p=0.014），任一器官出现炎性病变的小鼠占比更高（p=0.005），任一器官存在组织寄生现象的小鼠占比更高（p=0.027），且对苄硝唑（benznidazole）的敏感性更强（p=0.002）。生存分析显示，从接种日至虫血症检出期开始的时长，TcIV组显著短于TcI组；而TcI组感染小鼠的死亡事件发生时间，相较TcIV组显著延后。仅血培养与聚合酶链式反应（Polymerase Chain Reaction, PCR）检测的阳性结果无显著组间差异。 结论与意义 巴西亚马逊地区来源的、归属于TcI与TcIV DTU的克氏锥虫虫株，在小鼠模型中展现出显著分化的生物学与医学特性。