Farm Animal Health, Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Camden, Australia.
Farm Animal Health, Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Camden, Australia.
Vet Microbiol. 2018 Jun;219:53-62. doi: 10.1016/j.vetmic.2018.03.029. Epub 2018 Mar 29.
Johne's disease (JD) or paratuberculosis is an economically significant, chronic enteropathy of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Experimental models of JD in cattle are logistically challenging due to the need for long term monitoring, because the clinical disease can take years to manifest. Three trials were undertaken, the largest involving 20 cattle exposed orally to a low dose of C strain MAP and 10 controls studied for 4.75 years. Frequent blood and faecal sampling was used to monitor immunological and infection parameters, and intestinal biopsies were performed at two time points during the subclinical disease phase. Although clinical disease was not seen, there was evidence of infection in 35% of the animals and at necropsy 10% had histopathological lesions consistent with JD, similar to the proportions expected in naturally infected herds. Faecal shedding occurred in two distinct phases: firstly there was intermittent shedding <∼9 months post-exposure that did not correlate with disease outcomes; secondly, in a smaller cohort of animals, this was followed by more consistent shedding of increasing quantities of MAP, associated with intestinal pathology. There was evidence of regression of histopathological lesions in the ileum of one animal, which therefore had apparently recovered from the disease. Both cattle with histopathological lesions of paratuberculosis at necropsy had low MAP-specific interferon-gamma responses at 4 months post-exposure and later had consistently shed viable MAP; they also had the highest loads of MAP DNA in faeces 4.75 year s post-exposure. In a trial using a higher dose of MAP, a higher proportion of cattle developed paratuberculosis. The information derived from these trials provides greater understanding of the changes that occur during the course of paratuberculosis in cattle.
约翰氏病（JD）或副结核病是一种具有重要经济意义的反刍动物慢性肠病，由鸟分枝杆菌副结核亚种（MAP）引起。由于需要长期监测，JD 在牛中的实验模型在后勤方面具有挑战性，因为临床疾病可能需要数年时间才能显现。进行了三项试验，其中最大的一项试验涉及 20 头经口暴露于低剂量 C 株 MAP 的牛和 10 头对照牛，研究时间为 4.75 年。频繁的血液和粪便采样用于监测免疫和感染参数，并在亚临床疾病阶段进行了两次肠道活检。尽管没有观察到临床疾病，但 35%的动物有感染证据，10%的动物在尸检时具有与 JD 一致的组织病理学病变，与自然感染牛群的预期比例相似。粪便脱落发生在两个不同阶段：首先是暴露后<∼9 个月间歇性脱落，与疾病结果无关；其次，在较小的动物队列中，随后是更一致的脱落，数量不断增加的 MAP 与肠道病理学有关。有证据表明，一头动物的回肠组织病理学病变出现了消退，因此该动物显然已经从疾病中恢复。尸检时具有副结核病组织病理学病变的两头牛在暴露后 4 个月和以后的时间具有低水平的 MAP 特异性干扰素-γ反应，并且随后持续排出有活力的 MAP；它们在暴露后 4.75 年的粪便中也具有最高的 MAP DNA 载量。在使用更高剂量 MAP 的试验中，更高比例的牛发生了副结核病。这些试验获得的信息提供了对牛副结核病过程中发生的变化的更深入了解。
