Epidemiological study of FMDV in East Africa: the development on unbiased molecular tools to assess the burden of infection in endemic settings

为不断增长的世界人口提供可持续的粮食生产是农业部门面临的一个关键挑战。关键因素是控制影响动物生产力的疾病，改善动物健康，作为安全，高效和高质量生产的基础。准确的监测和诊断是旨在改善动物健康和生产力的疾病控制方案的重要组成部分。分子技术为提高诊断能力提供了巨大的希望。然而，在动物疾病对粮食安全影响最大的发展中国家，这些技术的应用仍然有限，主要原因是需要与这些国家现有基础设施不相适应的技术。口蹄疫（FMD）使这些问题更加严重。口蹄疫是由一种高度传染性病毒（FMDV）引起的具有重要经济意义的家畜疾病。该病在全球77%的牲畜中传播，造成50亿美元的生产损失和控制措施。非洲的直接经济影响最大，估计损失为8.15亿美元。坦桑尼亚拥有非洲第三大牲畜种群，但由于存在六种已知的非洲病毒类型中的四种，贸易机会很少。在牲畜是生计关键的系统中，口蹄疫对牛奶生产和牲畜牵引能力的影响也很大，增加了本已贫困的社区的脆弱性。通过疫苗接种控制口蹄疫在减轻非洲口蹄疫负担方面具有巨大潜力。然而，缺乏关于FMDV的真实的时间分子数据影响了诸如坦桑尼亚等国家通过疫苗接种控制FMD的能力，因为疫苗应答的功效完全取决于疫苗株与田间流行的株的匹配。如果没有这种知识，只能进行大规模的疫苗接种，这是非常昂贵的。如果有可能在疫情发生时消除造成疫情的当地流行菌株，这将允许有针对性的疫苗接种，提高疫苗接种的可负担性。粮农组织/国际兽疫局制定的口蹄疫逐步控制途径概述了指导各国控制和根除口蹄疫的六个基本步骤。第一步是确定风险和控制方案。东非目前的实验室基础设施缺乏进行口蹄疫病毒检测和定性的必要设备和专门知识，这限制了在东非建立口蹄疫参考实验室，使坦桑尼亚等国无法独立进入五氯苯酚第一阶段。坦桑尼亚唯一一项关于口蹄疫病毒的综合研究是基于档案（1967-2009年）样本。因此，在我们对目前流行的病毒的了解方面仍然存在差距，突出表明迫切需要对该地区最近的病毒进行分析，阻碍坦桑尼亚进行高质量监测的主要障碍是缺乏适当的诊断技术。如果能开发出这种化验方法并加以调整，使之适用于负担得起的自动化平台，这将成为提高东非实验室检测的诊断能力和质量的先决条件。该应用程序解决了BBSRC的职权范围，即通过产生知识和提供工具来提高动物生产的效率和可持续性，使东非等地区能够管理他们面临的疾病挑战，如影响市场机会的口蹄疫，以及粮食安全。以坦桑尼亚北方为重点，我们将i）更好地了解流行病毒，这将直接为疫苗选择提供信息，ii）开发试剂、方案和平台，使新建立的分子检测方法能够转移到适合部署到坦桑尼亚实验室的自动化平台上。

Sustainable food production for the growing world population is a key challenge faced by the agricultural sector. Crucial factors are the control of diseases compromising animal productivity, and the improvement of animal health as a basis for safe, efficient, and high-quality production. Accurate surveillance and diagnosis are essential components of disease control programmes aimed at improving animal health and productivity. Molecular techniques offer great promise for enhancing diagnostic capacity. However, their application in developing countries, where animal diseases have the greatest impacts on food security, is still limited, primarily due to the need for technologies which are incompatible with current infrastructure in these countries. Foot-and-mouth disease (FMD) exemplifies these issues. FMD is a livestock disease of great economic importance, caused by a highly contagious virus (FMDV). The disease circulates in 77% of the global livestock population, costing 5 billion USD in production losses and control measures. Direct financial impacts are greatest in Africa with an estimated loss of 815 million USD. Tanzania has the third largest livestock population in Africa, but trading opportunities are poor due to the presence of four of the six known African virus types. In systems where livestock are key to livelihoods, FMD impacts on milk production and animal traction capacity are also considerable, increasing vulnerability of already impoverished communities. FMD control through vaccination has great potential to reduce the burden of FMD in Africa. However, the lack of real time molecular data on FMDV impacts the ability of countries such as Tanzania to control FMD through vaccination since the efficacy of the vaccine response is wholly dependent on matching the vaccine strain with strains circulating in the field. Without this knowledge only mass vaccination can be employed which is prohibitively expensive. If it was possible to characterise locally circulating strains responsible for outbreaks as they occur this would permit targeted vaccination, increasing affordability of vaccination as an option. The progressive control pathway (PCP) for FMD developed by FAO/OIE outlines six fundamental steps to guide countries through FMD control and eradication. The first step is the identification of risk and control options. Current laboratory infrastructure in East Africa lacks the necessary equipment and expertise to perform FMDV detection and characterisation.This has constrained the creation of an FMD reference laboratory in East Africa, preventing countries such as Tanzania from independently entering into stage one of the PCP. The only comprehensive study on FMD viruses in Tanzania is based on archival (1967-2009) samples. Hence, gaps still exist in our understanding of currently circulating viruses, highlighting the urgent need for analyses of recent viruses from the area.The major stumbling block preventing Tanzania from undertaking high quality surveillance is the absence of suitable diagnostic technologies. If such assays could be developed and adapted for use on affordable automated platforms this would serve as a prerequisite for the improvement in diagnostic capacity and quality of laboratory testing in East Africa. This application addresses the BBSRC's remit to increase the efficiency and sustainability of animal production by generating knowledge and delivering tools which willenable regions such as East Africa to manage the challenges they face with diseases such as FMD that compromise market opportunities, as well as food security. Focusing on northern Tanzania, we will i) provide a better understanding of circulating viruses that will directly inform vaccine selection and ii) develop reagents, protocols and platforms to enable newly established molecular assays to be transferred onto automated platforms suitable for deployment to laboratories in Tanzania.