Vector-borne transmission of lumpy skin disease virus II

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.

This project will use a combination of in vivo experiments and mathematical modelling to characterise and quantify the transmission of LSDV from insect vector groups to bovines, thus addressing a key knowledge gap in our understanding of how LSDV is transmitted. The proposed research builds on the "LIMT" project which focused on the acquisition and retention of LSDV in vector groups. The outputs of LIMT experimental studies were combined with life history parameters of the insects to estimate the basic reproduction number for LSDV (R0). S. calcitrans, C. nubeculosus and Ae. aegypti were all found to have a R0 of >1, indicating they are all potential vectors of the virus, and are therefore the focus of this proposal.

The experimental model developed in LIMT will be used to test two transmission scenarios: 1. Immediate transmission as a consequence of interrupted blood-feeding contributing to in-farm spread, and 2. Retained virus being transmitted on subsequent blood-meals enabling longer distance spread of the virus. The results will be used to assess the risk of LSDV and the impact of control measures, in particular vaccination and culling, at the herd level and at a regional level.

The project utilises the unique and world-class expertise at Pirbright in lumpy skin disease research, multi-scale modelling of viral diseases of livestock, the biology of blood-feeding insects, and in vivo transmission studies of viruses between natural ruminant hosts and vectors. It will benefit from the active integration into the research team of two key end users - our industrial partner MSD Animal Health, and Defra the UK government department responsible for protecting the UK from exotic diseases.

What is the benefit of this research?
Better control of lumpy skin disease. The current LSD situation in Europe is approaching a critical juncture. Region-wide vaccination of millions of cattle in south-east Europe and neighbouring countries in response to the 2015-2018 Eurasian LSDV epidemic has prevented the spread of LSDV into central Europe. The countries currently vaccinating every year with a live attenuated LSD vaccine wish to stop vaccinating in order to obtain LSD freedom and regain lost export markets. However stopping LSD vaccination programmes is risky. LSDV remains endemic in neighbouring regions such as Turkey, and is a very hardy virus, able to survive long periods in the environment and over-winter very effectively. Modelling studies have suggested that LSDV could persist and re-emerge, particularly if initial vaccination campaigns have not been thorough. Control of LSD in Europe for some years to come is therefore likely to require a multifaceted, regionally co-ordinated approach of bovine surveillance programmes supported by targeted vaccination campaigns that are informed by accurate predictions of high risk transmission times and areas. Unfortunately the requisite knowledge about the vector-borne transmission of LSD is currently lacking. The outcomes from this proposed research project will supply knowledge of vector-borne transmission of LSDV that will support regional LSD control programmes as countries in south-eastern Europe exit their vaccination programmes. It will help countries currently free of LSDV, such as the UK, to formulate effective and proportional strategies to prevent incursion of the virus. And, more broadly, it will facilitate development of more effective, evidence-based control plans for LSD in endemic areas.

Who will benefit?
For each beneficiary the timescale of the impact has been estimated as immediate (I, during the time frame of the project), medium term (M, 1-5 years after the project has been completed) or long term (L, >5 years after the project has been completed)
1. Policy makers. This project will provide robust data to support development of more effective LSDV control programmes. This will be of benefit particularly to policy makers in the EU government, and national governments particularly in south-east Europe, the Balkans and Caucasus. Defra, as the UK government department responsible for protecting the UK from exotic diseases such as LSD, will be a key stakeholder of the project. (I and M).
2. Vaccine companies. Knowledge of vector-borne LSD transmission will enable regions at most risk of LSD to be identified resulting in more effective targeted use of available vaccines. The benefit of this research to vaccine companies is highlighted by the industrial partnership with MSD Animal Health. (I, M and L).
3. UK economy. The risk of LSDV reaching the UK will be reduced as a result of this research, therefore avoiding the loss of trade markets. The main trade-related economic consequence of a LSDV outbreak in the UK is loss of semen and embryo markets (there is very little live cattle trade from the UK). (M and L).
4. Rural communities. This research will result in better LSD control and prevention strategies worldwide. Further spread of the virus into Europe and Asia will be inhibited and the impact of the disease in endemic areas reduced. This will result in direct economic and social benefits to rural communities in Africa, Asia and Europe. (M and L).