Towards the strategic control of endemic foot-and-mouth disease in Africa: new techniques for a neglected problem

口蹄疫是一种非常严重的偶蹄动物病毒性疾病，它通过对动物健康、生产力的影响以及随之而来的贸易限制造成巨大的经济损失。虽然对口蹄疫病毒（FMDV）生物学的了解相当充分，因为它发生在发达国家的疫情环境中，但这种了解尚未应用于世界上该病毒长期存在的地区。这是特别不幸的，因为口蹄疫对小农有严重的影响，而以前的研究将口蹄疫列为与贫困有关的最重要的牲畜疾病之一。坦桑尼亚拥有非洲第三大家畜种群，牲畜对生活在坦桑尼亚农村的数百万人的营养和经济福利至关重要。农村社区直接依赖牲畜获取食物、牛奶、在作物生产中使用牲畜，并通过当地销售筹集资金。口蹄疫导致动物体重减轻、产奶量减少、行动不便和经济价值降低，因此，对直接依赖牲畜健康的社区来说，控制口蹄疫尤为重要。口蹄疫病毒经常被发现感染水牛和其他野生有蹄类动物，野生动物经常被怀疑是导致家畜疾病的病毒的直接最终来源。这导致了野生动物管理和家畜之间的冲突，野生动物本身就是坦桑尼亚等国家非常重要的财政资源，有人呼吁建造类似于非洲南部建造的围栏，以减少家畜和野生动物之间的接触。迫切需要了解野生动物作为家畜口蹄疫来源的重要性，并找到更环保的方法来防止病毒从野生动物保护区传播出去。口蹄疫可以通过接种疫苗得到控制，但疫苗并不完美，只能对口蹄疫的症状提供短暂的保护，而不能对感染本身提供保护，而且只能对有限范围的遗传类型的病毒提供保护。为了有效地使用疫苗接种，了解可能在动物中引起感染的病毒的遗传类型是至关重要的，以便可以选择最佳疫苗。不幸的是，尽管很容易获得，但在被认为存在该病毒的非洲非常大的地区，几乎完全缺乏这方面的知识。该项目旨在对坦桑尼亚10个不同地区牲畜和野生动物的口蹄疫进行大规模调查。将从家畜和野生动物身上采集血液样本，并检测以前感染口蹄疫的证据，这将提供目前存在的最重要病毒类型的粗略情况。在实际分离出病毒的地方，我们将对部分基因组进行测序，以获得有关病毒类型的更详细信息。我们还将重点关注坦桑尼亚北部的一个地区，开展一项更详细的长期研究，定期从畜群中收集血液样本，并在口蹄疫暴发期间收集病毒并对其进行测序。利用这些数据，我们将能够确定导致感染的病毒来自何处（是该地区的野生动物或其他家畜，还是在其感染的畜群中进化？）我们还将研究长期感染FMDV的动物的作用，确定与FMDV感染相关的其他养殖方法，并研究由一种菌株感染引起的免疫保护在多大程度上可以保护动物免受其他菌株的感染。

Foot-and-mouth disease (FMD) is a very serious viral disease of cloven-hooved animals, which causes immense economic losses through its impacts on animal health, productivity, and consequent trading constraints. While the biology of foot-and-mouth disease virus (FMDV) is quite well-understood as it occurs in outbreak settings in developed countries, this understanding has not been applied to regions of the world where the virus is permanently present. This is particularly unfortunate, since FMD has serious impacts for small-farmers, and previous studies rank FMD as one of the most important livestock diseases associated with poverty. Tanzania has the third largest population of domestic livestock in Africa, and livestock are critical for the nutrition and economic welfare of the millions of people who live in rural Tanzania. Rural communities depend directly on livestock for food, milk, use of animals in crop production, and in raising money through local sales. FMD causes animals to lose weight, reduce milk production, become immobile, and reduce in financial value, and therefore its control is particularly important for communities who depend directly on the well-being of their livestock. FMDV is often found to infect buffalo and other wild ungulates, and wildlife are often suspected to be either the direct of ultimate source of viruses causing disease in domestic livestock. This has led to conflict between the management of wildlife, which is itself a hugely important financial resource in countries like Tanzania, and domestic livestock, with calls for the construction of fences similar to those constructed in southern Africa that serve to reduce contact between domestic livestock and wildlife. There is an urgent need to understand how important wildlife is as a source of FMD for domestic livestock, and to find more environmentally-friendly ways of preventing the virus from moving out from wildlife sanctuaries. FMD can be controlled through the use of vaccination, but the vaccines are not perfect, providing only short-lived protection from the symptoms of the disease rather than infection itself, and protecting against only a limited range of genetic types of the virus. In order to use vaccination effectively, it is critical to know the genetic types of the virus that are likely to cause infection in animals, so that the best vaccines can be chosen. Unfortunately, although quite easily obtained, this knowledge is almost completely lacking from very large areas of Africa in which the virus is thought to be present. This project aims to conduct a large-scale survey of FMD in livestock and wildlife in 10 different areas across Tanzania. Blood samples will be collected from domestic livestock and wildlife and tested for evidence of previous infection by FMD and this will provide a crude picture of the most important types of virus that are present. Where virus is actually isolated we will sequence parts of the genome to obtain much more detailed information on the virus types. We will also focus on one area in northern Tanzania to carry out a more detailed longer-term study, collecting blood samples from herds at regular time intervals and collecting viruses during FMD outbreaks and sequencing them. Using these data, we will be able to determine where virus that causes infections comes from (is it wildlife or other domestic animals in the region, or does it evolve within the herds that its infecting?). We will also study the role of animals that have long-term infections of FMDV, identify other farming practices that are associated with infection by FMDV, and study just how much immune protection caused by infection with one strain can protect animals from infection with other strains.