Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringá, Avenida Colombo, 5790, Jardim Universitário, Maringá, Paraná, 87020-900, Brazil; Departament of Pharmacy, Uningá University Center Ingá, Rodovia PR317, Maringá, Paraná, 87035-510, Brazil.
Postgraduate Program in Biological Sciences, Biological Sciences Center, State University of Maringá, Avenida Colombo, 5790, Jardim Universitário, Maringá, Paraná, 87020-900, Brazil.
Exp Parasitol. 2021 Sep;228:108136. doi: 10.1016/j.exppara.2021.108136. Epub 2021 Jul 17.
Strains of Trypanosoma cruzi, etiological agent of Chagas disease, are classified into different discrete typing units that may present distinct dynamics of infection and susceptibility to benznidazole (BZ) treatment. Mice that were orally inoculated with T. cruzi IV strains exhibited a more intense course of infection compared with intraperitoneally inoculated mice, reflected by higher parasite loads. We evaluated the efficacy of BZ treatment in Swiss mice that were inoculated with T. cruzi IV strains from the Western Brazilian Amazon. The mice were orally (OR) or intraperitoneally (IP) inoculated with 2 × 10 culture-derived metacyclic trypomastigotes of the AM14, AM16, AM64, and AM69 strains of T. cruzi that were obtained from two outbreaks of orally acquired acute Chagas disease in the state of Amazonas, Brazil. The animals were treated with BZ (100 mg/kg/day for 20 days). Fresh blood examination, hemoculture, conventional and quantitative real-time polymerase chain reaction were performed to monitor the therapeutic effects of BZ. Significant reductions in five of 24 parameters of parasitemia and parasite load were found in different tissues in the OR group, indicating worse response to BZ treatment compared with the IP group, in which significant reductions in nine of those 24 parameters were observed. The cure rates in the OR groups ranged from 18.2% (1/11) to 75.0% (9/12) and in the IP groups from 58.3% (7/12) to 91.7% (11/12), for the AM14 and AM69 strains, respectively. These findings indicate that treatment with BZ had fewer beneficial effects with regard to reducing parasitemia and parasite load in different tissues of mice that were OR inoculated with four TcIV strains compared with IP inoculation. Therefore, the route of infection with T. cruzi should be considered when evaluating the therapeutic efficacy of BZ in patients with Chagas disease.
克氏锥虫（Trypanosoma cruzi）菌株，恰加斯病的病因，被分为不同的离散型单位，可能具有不同的感染动力学和对苯并咪唑（BZ）治疗的敏感性。与经腹腔接种的小鼠相比，经口接种 T. cruzi IV 株的小鼠表现出更严重的感染过程，这反映在更高的寄生虫负荷上。我们评估了 BZ 治疗在经口接种来自巴西亚马逊西部 IV 型锥虫（Trypanosoma cruzi）株的瑞士小鼠中的疗效。将 2×10 个经培养衍生的 AM14、AM16、AM64 和 AM69 株 T. cruzi 型循环型动基体接种于经口接种或经腹腔接种的瑞士小鼠。从巴西亚马逊州两次经口获得性急性恰加斯病暴发中获得的 AM14、AM16、AM64 和 AM69 株 T. cruzi 型。动物用 BZ（100mg/kg/天，共 20 天）治疗。新鲜血液检查、血培养、常规和定量实时聚合酶链反应用于监测 BZ 的治疗效果。在 OR 组中，五个组织中有 24 个寄生虫血症和寄生虫负荷参数显著降低，表明与 IP 组相比，BZ 治疗的反应较差，在 IP 组中观察到 24 个参数中有九个显著降低。OR 组的治愈率为 18.2%（1/11）至 75.0%（9/12），IP 组的治愈率为 58.3%（7/12）至 91.7%（11/12），分别用于 AM14 和 AM69 株。这些发现表明，与经腹腔接种相比，用 BZ 治疗经口接种的四株 TcIV 株感染的小鼠不同组织中的寄生虫血症和寄生虫负荷减少的有益效果较少。因此，在评估苯并咪唑治疗恰加斯病患者的疗效时，应考虑锥虫感染途径。
