Toledo M J O, Bahia M T, Veloso V M, Carneiro C M, Machado-Coelho G L L, Alves C F, Martins H R, Cruz R E, Tafuri W L, Lana M
Departamento de Análises Clínicas, Centro de Ciências da Saúde, Bloco I-90, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900, Maringá, PR.
J Antimicrob Chemother. 2004 Jun;53(6):1045-53. doi: 10.1093/jac/dkh224. Epub 2004 Apr 21.
The goal of this study was to verify the effect of specific treatment on parasitological and histopathological parameters in mice experimentally infected with different Trypanosoma cruzi clonal genotypes. Twenty cloned stocks were selected, representative of the whole phylogenetic diversity of the protozoan and belonging to the clonal genotypes 19 and 20 (T. cruzi I) and 39 and 32 (T. cruzi II). The stocks were inoculated in 40 BALB/c mice divided into four groups: (i) treated with benznidazole, (ii) treated with itraconazole and (iii and iv) untreated control groups (NT) for each drug, respectively. Seven parameters related to parasitaemia curves and histopathological lesions were analysed. Four during the acute phase (AP) and three during both the AP and chronic phase (CP) of infection. Statistical comparison between benznidazole-treated and NT groups for the biological parameters showed significant differences for all genotypes. Benznidazole treatment led to lower patent period, maximum of parasitaemia, day of maximum parasitaemia and area under the parasitaemia curve for all genotypes analysed. Percentage of positive haemoculture during AP and CP was lower for genotypes 19 and 32. Tissue parasitism (TP) and inflammatory process (IP) during AP were lower for genotypes 19 and 32, respectively. In general, itraconazole treatment induced a smaller reduction in these same parameters between treated and NT animals in relation to benznidazole treatment. Our results indicate that phylogenetic divergence among T. cruzi clonal genotypes must be taken in account in chemotherapy and studies dealing with all aspects of the parasite and the disease.
本研究的目的是验证特定治疗对实验感染不同克氏锥虫克隆基因型小鼠的寄生虫学和组织病理学参数的影响。选择了20个克隆株,它们代表了原生动物的整个系统发育多样性,属于克隆基因型19和20(克氏锥虫I)以及39和32(克氏锥虫II)。将这些菌株接种到40只BALB/c小鼠中,分为四组:(i)用苯硝唑治疗,(ii)用伊曲康唑治疗,(iii)和(iv)分别为每种药物的未治疗对照组(NT)。分析了与寄生虫血症曲线和组织病理学损伤相关的七个参数。感染急性期(AP)分析四个参数,感染急性期和慢性期(CP)均分析三个参数。苯硝唑治疗组和NT组之间生物学参数的统计比较显示,所有基因型均存在显著差异。苯硝唑治疗使所有分析基因型的寄生虫血症期缩短、寄生虫血症峰值降低、寄生虫血症峰值出现天数减少以及寄生虫血症曲线下面积减小。基因型19和32在急性期和慢性期的血培养阳性率较低。基因型19和32在急性期的组织寄生虫感染(TP)和炎症过程(IP)分别较低。总体而言,与苯硝唑治疗相比,伊曲康唑治疗在治疗动物和NT动物之间对这些相同参数的降低幅度较小。我们的结果表明,在化疗以及涉及寄生虫和疾病各个方面的研究中,必须考虑克氏锥虫克隆基因型之间的系统发育差异。