Vector-borne transmission of lumpy skin disease virus II

结节性皮肤病是由LSDV引起的牛的一种严重的痘病毒病。此前仅在非洲发现，2015年首次进入东南欧，作为2012-2018年欧亚LSD流行的一部分。2017年，由于对受影响地区的动物和动物产品实行严格的行动限制，数千头牛被扑杀，以及全国性的疫苗接种运动，该病毒的传播速度有所减缓，并在2018年有效停止。受影响的国家仍然每年接种LSDV减毒活毒株，以防止疾病复发。Beard博士（PI）和Gubbins博士（co-I）作为欧洲和邻国应对LSD流行的专家顾问，并经历了缺乏对LSDV传播的知识如何阻碍了流行的控制，特别是在疫情爆发周围设置隔离区和优先接种紧急疫苗的地区时。由于缺乏关于LSDV传播的科学证据，一些国家甚至选择了不明智的控制措施，例如使用针对性不强的空中杀虫剂。这些经验被用来形成一个两阶段的研究计划，调查病媒传播的LSDV。该计划的第一阶段（简称LIMT）提供了关于在载体中获得和保留LSDV的关键信息。本建议描述了研究计划的第二阶段，并将LIMT的研究结果纳入研究昆虫向牛传播LSDV的实验设计中。先前发表的工作（Chihota et al 2001，Chihota et al 2003）报告了在临床受影响的供体动物上饲喂（DPF）后，LSDV在埃及伊蚊中保留6天，并通过Ae成功将LSD从供体牛传播到受体牛。埃及蚊子。然而，这项工作未能证明LSDV在其他载体（包括Stomoxys calcitrans和Culicoides nubeculosus）中的保留时间超过1 DPF，并且使用这些载体组将病毒或疾病从供体传播到受体的尝试失败。Chihota及其同事的工作使用了一个狭窄且不一致的实验设计，特别是没有计算摄食效率，这限制了估计LSDV传播效率的数据价值。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。在S. calcitrans和Ae. aegypti和C. nubeculosus，表明该病毒可被一系列昆虫媒介群体获得和保留。LIMT研究的这些数据与昆虫的生活史参数相结合，以估计R 0（基本繁殖数，即完全易感的种群中典型感染病例产生的继发感染数）。S. calcitrans，C. nubeculosus和Ae.埃及伊蚊的R 0均>1，表明它们都是病毒的潜在载体。为了完成我们对LSDV传播周期的研究，本提案的目标1将使用在LIMT开发的LSDV实验模型进行供体到受体传播研究，以检查昆虫通过S. calcitrans，C. nubeculosus和Ae.埃及人。在目标2中，这些实验的结果将用于更新对LSDV构成的风险的评估以及采用三种方法的不同控制措施的影响：（一）计算LSDV的基本繁殖数（R 0），以估计传播风险;（ii）猪群内LSDV传播的随机模型，以研究控制措施的影响（特别是疫苗接种和扑杀）在牛群水平;和（iii）LSDV在牛群之间传播的随机模型，以扩大和探索控制措施在区域层面的影响。

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.