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

鸟分枝杆菌亚种副结核（MAP）是一种难以研究的生物，因为它在培养中生长不可靠，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在包括灵长类动物在内的许多物种中被证实是引起肠道慢性炎症的原因。尽管如此，MAP可以在动物体内存活数年而不会引起明显的疾病。亚临床感染MAP在农场动物中很普遍。在一些地区，大约70%的奶牛群可能受到影响。受感染的动物会在乳汁中分泌MAP。MAP并没有通过巴氏消毒完全灭活，并且已经从英国、捷克共和国和美国的零售巴氏消毒牛奶中分离出来。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。人感染MAP非常难以发现。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的慢性肠道炎症的人都感染了MAP。由于MAP能够在如此多的物种中引起肠道慢性炎症，几乎可以肯定它对人类也有同样的作用。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以百万计的MAP释放到牧场，在那里它们可以长期生存。野生动物被感染。MAP被冲入河流和湖泊。2000年，我们从NERC-MRC环境与健康计划获得了一项为期5年的资助，用于研究环境中的MAP以及人们如何接触到它。在新南威尔士的研究区域，我们在每周两次的塔夫河水样中发现了三分之一的MAP。我们表明，先前描述的克罗恩病病例在卡迪夫的分布与MAP通过气溶胶从受污染的河流传播给人类是一致的。泰威河被广泛抽取供国内使用。我们发现泰威河的污染程度是塔夫河的两倍，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除去了悬浮固体和大部分MAP。将废物处理回土地上形成了另一个环境污染循环。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，该地区MAP分布广泛但不完整。12个主要湖泊中有8个呈阳性。MAP也存在于生活污水处理厂的清洁出水中。如果这些污染物排放到同样供家庭使用的水源中，就有可能使MAP在人群中循环。该研究获得的总体情况是，人类从受污染的环境中接触MAP的广泛机会不断被动物产生的MAP所补充。因此，我们假设“污染环境隔间的鸟分枝杆菌亚种副结核病对人类健康构成了重大的、逐渐增加的威胁。”这一复杂问题只有通过消除动物中的MAP感染才能得到解决。这就需要开发和使用现代抗map疫苗。在NERC-CEH生态和水文学资助计划下，我们希望首先开发一种新的定量测试，测量MAP在我们公布的模型的不同环境区域（例如河水、气溶胶、生物膜和泥浆）中持续存在的程度。我们将开发一种定量PCR方法，专门用于检测MAP，这将是稳健的，适用于我们的环境模型的各个方面。这将得到培养和比较基因组学的支持，这些基因组学描述了来自各种环境来源的分离物。

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.