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Crohn's Disease and Mycobacterium avium subsp paratuberculosis, a Public Health tragedy whose resolution is long overdue: quantifying human exposure

克罗恩病和鸟分枝杆菌副结核亚种是一场早就应该得到解决的公共卫生悲剧：量化人类暴露

基本信息

批准号：
NE/F014791/1
负责人：
Roger Pickup
金额：
$ 24.92万
依托单位：
NERC CEH (Up to 30.11.2019)
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FF014791%2F1
关键词：
Crohn Disease Mycobacterium avium subsp

项目摘要

Mycobacterium avium subspecies paratuberculosis (MAP) is a difficult organism to study because it does not grow reliably in culture, can adopt a form which cannot be seen down a microscope, and can minimize recognition by the immune system. MAP is a proven cause of chronic inflammation of the intestine in many species including primates. Despite this, MAP can live in animals for years without causing visible disease. Subclinical infection with MAP is widespread in farm animals. In some areas about 70% of dairy herds may be affected. Infected animals secrete MAP in their milk. MAP is not completely inactivated by pasteurisation and has been isolated from retail pasteurized milk in Britain, the Czech Republic and the USA. In these countries and by implication elsewhere, MAP is being transmitted to people in retail milk supplies. MAP infection in humans is very difficult to detect. Recent research by us and others has confirmed that almost everybody with chronic inflammation of the intestine of the Crohn's disease type is infected with MAP. With MAP able to cause chronic inflammation of the intestine in so many species it is almost certainly doing the same thing to people. Crohn's disease is increasing in frequency especially in children. Infected farm animals shed millions of MAP onto pastures where they survive for long periods. Wildlife becomes infected. MAP is washed into rivers and lakes. In 2000 we obtained a 5 year grant from the NERC-MRC E&H Initiative to study MAP in the environment and how people might be exposed to it. In the study region of S. Wales we found MAP in one third of twice weekly water samples from the river Taff. We showed that the previously described distribution of Crohn's disease cases within Cardiff was consistent with the transmission of MAP from the contaminated river to humans via aerosols. The River Tywi is extensively abstracted for domestic supply. We found that the Tywi is twice as contaminated as the Taff probably because of the much larger number of animals in the catchment. The treatment of water taken from the river removed suspended solids and with it most of the MAP. Disposal of the waste back onto the land established another cycle of environmental contamination. We obtained evidence that MAP could get through to domestic water systems. We also studied the Lake District where the distribution of MAP was widespread but patchy. Eight of 12 major Lakes were positive. MAP was also present in the clean water effluent of domestic sewage treatment works. Where this discharges into waters also sourced for domestic supply it creates the potential for MAP to cycle in human populations. The overall picture obtained by the research was of the widespread opportunity for human exposure to MAP from a contaminated environment continually being replenished by the production of MAP from animals. Consequently we hypothesise 'that Mycobacterium avium subspecies paratuberculosis contaminating environmental compartments constitutes a significant and incremental threat to human health.' This complex problem will only be solved by eliminating MAP infection in animals. This requires the development and use of modern anti-MAP vaccines. Under the NERC-CEH Ecology and Hydrology Funding Initiative we wish to begin by developing a new quantitative test measure how much MAP persists in different environmental compartments of our published model (e.g. river water, aerosols, biofilms and slurry). We will develop a quantitative PCR method specifically for the detection of MAP which will be robust and applicable to all aspects of our environmental model. This will be supported by culture and the comparative genomics of MAP characterising isolates from a variety of environmental sources.

鸟分枝杆菌副结核亚种 (MAP) 是一种难以研究的生物体，因为它在培养物中不能可靠生长，可以采用显微镜下无法看到的形式，并且可以最大限度地减少免疫系统的识别。 MAP 已被证实是许多物种（包括灵长类动物）肠道慢性炎症的原因。尽管如此，MAP 可以在动物体内存活多年而不会引起明显的疾病。 MAP 亚临床感染在农场动物中广泛存在。在一些地区，大约 70% 的奶牛群可能受到影响。受感染的动物在乳汁中分泌 MAP。巴氏灭菌不会完全灭活 MAP，并且已在英国、捷克共和国和美国从零售巴氏灭菌牛奶中分离出来。在这些国家以及其他地方，MAP 正在通过零售牛奶供应传播给人们。人类的 MAP 感染很难检测到。我们和其他人最近的研究证实，几乎所有患有克罗恩病类型肠道慢性炎症的人都感染了 MAP。由于 MAP 能够在许多物种中引起肠道慢性炎症，因此几乎肯定会对人类产生同样的作用。克罗恩病的发病率正在增加，尤其是在儿童中。受感染的农场动物将数百万 MAP 排放到牧场上，并在那里长期生存。野生动物被感染。 MAP 被冲入河流和湖泊。 2000 年，我们从 NERC-MRC E&H Initiative 获得了为期 5 年的资助，用于研究环境中的 MAP 以及人们如何接触它。在南威尔士的研究地区，我们在塔夫河每周两次的水样中发现了三分之一的 MAP。我们发现，先前描述的卡迪夫克罗恩病病例的分布与 MAP 通过气溶胶从受污染的河流传播给人类是一致的。泰维河被广泛抽取用于国内供应。我们发现泰维河的污染程度是塔夫河的两倍，这可能是因为流域内动物数量多得多。对河水的处理去除了悬浮固体以及大部分 MAP。将废物处理回土地造成了另一个环境污染循环。我们获得的证据表明 MAP 可以进入生活用水系统。我们还研究了湖区，那里的 MAP 分布广泛但不完整。 12 个主要湖泊中有 8 个呈阳性。生活污水处理厂的清水中也存在MAP。如果这些物质排放到也用于国内供应的水域，则可能会产生 MAP 在人群中循环的可能性。该研究获得的总体情况是，人类有广泛的机会接触来自受污染环境的 MAP，而动物生产的 MAP 不断补充。因此，我们假设“污染环境的鸟分枝杆菌副结核亚种对人类健康构成了重大且渐进的威胁。”这个复杂的问题只有通过消除动物体内的 MAP 感染才能解决。这需要开发和使用现代抗 MAP 疫苗。根据 NERC-CEH 生态和水文学资助计划，我们希望首先开发一种新的定量测试，测量 MAP 在我们发布的模型的不同环境部分（例如河水、气溶胶、生物膜和泥浆）中持续存在的程度。我们将开发一种专门用于检测 MAP 的定量 PCR 方法，该方法稳健且适用于我们环境模型的各个方面。这将得到来自各种环境来源的培养和 MAP 特征分离株的比较基因组学的支持。