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

禽类副结核分枝杆菌(MAP)是一种很难研究的有机体，因为它在培养中不能可靠地生长，可以采用显微镜下看不到的形式，并且可以最大限度地减少免疫系统的识别。MAP已被证实是包括灵长类在内的许多物种的慢性肠道炎症的原因。尽管如此，MAP可以在动物体内生活多年，而不会引起明显的疾病。MAP亚临床感染在家畜中广泛存在。在一些地区，大约70%的奶牛群可能会受到影响。受感染的动物在它们的乳汁中分泌MAP。MAP不是通过巴氏杀菌完全灭活的，已经从英国、捷克共和国和美国的零售巴氏杀菌牛奶中分离出来。在这些国家和其他地方，MAP正在通过零售牛奶供应传播给人们。人类中的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型慢性肠炎的人都感染了MAP。由于MAP能够在如此多的物种中引起慢性肠道炎症，它几乎肯定会对人类造成同样的影响。克罗恩病的发病率正在增加，特别是在儿童中。受感染的农场动物将数百万张地图散落到牧场上，在那里它们可以长期生存。野生动物会被感染。地图被冲进了河流和湖泊。2000年，我们从NERC-MRC E&H倡议获得了一项为期5年的拨款，用于研究环境中的MAP以及人们可能如何接触到MAP。在威尔士南部的研究地区，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，先前描述的克罗恩病病例在加的夫的分布与MAP从受污染的河流通过气雾剂传播给人类的情况是一致的。泰威河被广泛提取以供国内供应。我们发现，Tywi受到的污染是Taff的两倍，可能是因为集水区的动物数量要多得多。对取自河流的水的处理去除了悬浮固体，并随之而来的是地图的大部分。将废物处理回土地上，造成了另一轮环境污染。我们获得了MAP可以进入家庭供水系统的证据。我们还研究了湖区，那里的地图分布广泛，但零星分布。12个主要湖泊中有8个呈阳性反应。住宅污水处理厂的净水流出物中也含有MAP。在这些排放到也来自国内供应的水域的地方，它创造了MAP在人类种群中循环的可能性。这项研究得到的总体情况是，人类从受污染的环境中接触地图的广泛机会不断得到动物地图的产生的补充。因此，我们假设‘污染环境舱的禽分枝杆菌亚种副结核对人类健康构成了重大且日益严重的威胁。’这个复杂的问题只有通过消除动物中的MAP感染才能解决。这就需要开发和使用现代抗MAP疫苗。在NERC-CEH生态和水文学基金倡议下，我们希望首先开发一种新的定量测试方法，衡量在我们已发表的模型的不同环境单元(例如，河水、气溶胶、生物膜和泥浆)中MAP的持久性。我们将开发一种专门用于检测MAP的定量PCR方法，该方法将是稳健的，适用于我们环境模型的所有方面。这将得到培养和MAP的比较基因组学的支持，MAP表征了来自各种环境来源的分离株。

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.