Vector-borne transmission of lumpy skin disease virus II

牛肿块性皮肤病是由LSDV引起的一种严重痘病毒病。以前只在非洲发现，2015年作为2012-2018年欧亚LSD流行病的一部分，它首次进入东南欧。由于受影响地区严格限制动物和动物产品的流动，成千上万头牛被扑杀，以及国家疫苗接种运动，该病毒的传播在2017年放缓，并在2018年得到有效遏制。在受影响国家，每年仍采用LSDV减毒活株疫苗接种，以防止疾病复发。作为应对欧洲和邻国LSDV流行的专家顾问，向Beard博士（PI）和Gubbins博士（共同i）进行了咨询，并体验到缺乏对LSDV传播的了解如何阻碍了对流行病的控制，特别是在疫情周围设置隔离区和优先考虑紧急接种疫苗的地区时。缺乏关于LSDV传播的科学证据，甚至导致一些国家采取了不明智的控制措施，例如使用目标不明确的空中杀虫剂。这些经验被用来制定一个分两阶段的研究计划，以调查LSDV的病媒传播。该方案的第一阶段（简称LIMT）提供了关于在载体中获取和保留LSDV的关键信息。该提案描述了研究计划的第二阶段，并将LIMT的发现纳入研究LSDV昆虫向牛传播的实验设计中。先前发表的工作（Chihota等人2001年，Chihota等人2003年）报告了LSDV在埃及伊蚊对临床受影响的供体动物喂食后（DPF）在埃及伊蚊体内停留6天，并成功地通过伊蚊将LSD从供体传播给受体牛。蚊。然而，这项工作未能证明LSDV在其他载体（包括钙化口蚊和库蠓）中的滞留时间超过1 DPF，并且使用这些载体群将病毒或疾病从供体传播到受体的尝试失败了。Chihota及其同事的工作采用了狭窄且不一致的实验设计，特别是没有计算摄食效率，这限制了数据在按病媒群体估计LSDV传播效率方面的价值。为了解决这个问题，LIMT研究使用了更多的昆虫，更强大和彻底的协议，以及更灵敏的检测方法。LSDV在钙化斑蚊和伊蚊中检测到8个DPF。这表明该病毒可通过一系列昆虫媒介群获得和保留。这些来自LIMT研究的数据与昆虫的生活史参数相结合，以估计R0（基本繁殖数，即完全易感人群中典型感染病例产生的继发感染数）。白斑棘球绦虫和白斑棘球绦虫。埃及伊蚊的R0均为bb101，表明它们都是该病毒的潜在媒介。为了完成我们对LSDV传播周期的研究，本提案的目标1将使用LIMT开发的LSDV实验模型进行供体到受体的传播研究，以检验S. calcitrans、C. nubecullosus和Ae. LSDV在昆虫到牛的传播。蚊。在目标2中，这些实验的结果将用于更新对LSDV构成的风险和不同控制措施影响的评估，采用三种方法：(i)计算LSDV的基本繁殖数（R0）以估计传播风险；（ii） LSDV在畜群内传播的随机模型，以调查控制措施（特别是疫苗接种和扑杀）在畜群水平上的影响；（iii）建立LSDV在畜群之间传播的随机模型，以扩大规模并探索区域一级控制措施的影响。

Lumpy skin disease is a severe poxviral disease of cattle caused by LSDV. Previously found only in Africa, it entered southeast Europe for the first time in 2015 as part of the 2012-2018 Eurasian LSD epidemic. The spread of the virus slowed in 2017 and effectively halted in 2018 as a result of strict movement restrictions on animals and animal products in affected areas, thousands of cattle culled, and national vaccination campaigns. Annual vaccination with a live attenuated LSDV strain is still practiced in affected countries in order to prevent recurrence of disease.Dr Beard (PI) and Dr Gubbins (co-I) were consulted as expert advisors on the response to the LSD epidemic in Europe and neighbouring countries, and experienced how lack of knowledge of LSDV transmission hampered control of the epidemic, especially when setting quarantine zones around an outbreak and prioritising areas for urgent vaccination. Lack of scientific evidence regarding the transmission of LSDV even led some countries to implement unwise choices of control measures such as poorly-targeted aerial insecticide use. These experiences were used to shape a two-stage research programme to investigate the vector-borne transmission of LSDV. The first stage of the programme (short name LIMT) has provided key information about the acquisition and retention of LSDV in the vector. This proposal describes the second stage of the research programme, and incorporates the findings of LIMT into the design of experiments to study insect to bovine transmission of LSDV. Previously published work (Chihota et al 2001, Chihota et al 2003) reported retention of LSDV in Aedes aegypti for 6 days post feeding (DPF) on a clinically affected donor animal and successful transmission of LSD from donor to recipient bovine via Ae. aegypti mosquitoes. However the work failed to demonstrate retention of LSDV in other vectors (including Stomoxys calcitrans and Culicoides nubeculosus) for longer than 1 DPF, and attempts to transmit the virus or disease from donor to recipient using these vector groups failed. The work by Chihota and colleagues used a narrow and inconsistent experimental design, and in particular did not calculate feeding efficiency which limits the value of the data for estimating transmission efficacy of LSDV by vector groups. In order to address this the LIMT study used a greater number of insects, more robust and thorough protocols, and more sensitive detection methods. LSDV was detected up to 8 DPF in S. calcitrans and Ae. aegypti, and 4 DPF in C. nubeculosus, indicating that the virus can be acquired and retained by a range of insect vector groups. These data from the LIMT studies were combined with life history parameters of the insects to estimate R0 (the basic reproduction number, which is the number of secondary infections produced by a typical case of an infection in a population that is totally susceptible). S. calcitrans, C. nubeculosus and Ae. aegypti all had a R0 of >1, indicating they are all potential vectors of the virus. In order to complete our studies of the LSDV transmission cycle objective 1 of this proposal will use the experimental model of LSDV developed in LIMT to carry out donor to recipient transmission studies to examine insect to bovine transmission of LSDV by S. calcitrans, C. nubeculosus and Ae. aegypti. In objective 2 the outputs of these experiments will be used to update assessments of the risk posed by LSDV and the impact of different control measures using three approaches: (i) computation of the basic reproduction number for LSDV (R0) to estimate the risk of transmission; (ii) a stochastic model for the within-herd transmission of LSDV to investigate the impact of control measures (in particular, vaccination and culling) at the herd level; and (iii) a stochastic model for the spread of LSDV between herds to scale up and explore the impact of control measures at a regional level.