Riggs Michael W, Schaefer Deborah A
School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, USA.
Methods Mol Biol. 2020;2052:253-282. doi: 10.1007/978-1-4939-9748-0_15.
Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a moderate-to-severe diarrheal disease now recognized as one of the leading causes of morbidity and mortality in livestock globally, and in humans living in resource-limited parts of the world, particularly those with AIDS or malnourished individuals. This recognition has fueled efforts for the discovery of effective therapeutics. While recent progress in drug discovery has been encouraging, there are presently no acceptably effective parasite-specific drugs for the disease. The urgent need for new drug discovery or drug repurposing has also increased the need for refined animal models of clinical disease for therapeutic efficacy evaluation. Here, we describe an acute model of cryptosporidiosis using newborn calves to evaluate well-defined clinical and parasitological parameter outcomes, including the effect on diarrhea severity and duration, oocyst numbers produced, and multiple measures of clinical health. The model is highly reproducible and provides unequivocal direct measures of treatment efficacy on diarrhea severity and parasite replication.
隐孢子虫病由顶复门寄生虫微小隐孢子虫引起，是一种中度至重度腹泻疾病，目前被认为是全球家畜发病和死亡的主要原因之一，也是生活在世界资源有限地区的人类，特别是艾滋病患者或营养不良者发病和死亡的主要原因之一。这一认识推动了人们对有效治疗方法的探索。虽然最近在药物研发方面取得的进展令人鼓舞，但目前尚无针对该疾病的可接受的有效寄生虫特异性药物。对新药研发或药物重新利用的迫切需求也增加了对用于治疗效果评估的精确临床疾病动物模型的需求。在此，我们描述了一种使用新生小牛的隐孢子虫病急性模型，以评估明确的临床和寄生虫学参数结果，包括对腹泻严重程度和持续时间、产生的卵囊数量以及多种临床健康指标的影响。该模型具有高度可重复性，并能明确直接地衡量治疗对腹泻严重程度和寄生虫复制的效果。
