Summary sheet

Lumpy Skin Disease.SummaryIntroduction1. This note provides a brief summary of an analysis undertaken by a DISCONTOOLS group of experts on Lumpy skin disease (LSD). They reviewed the current knowledge on the disease, considered the existing disease control tools, identified current gaps in the availability and quality of the control tools and finally determined the research necessary to develop new or improved tools. Full details of the analysis can be downloaded from the web site at http://www.discontools.eu/ by selecting Disease Database, then the specific disease and highlighting the variables of interest. This is completed by selecting create a report which can then be downloaded as either a PDF or Excel spread sheet.

Disease profile2. Lumpy skin disease virus (LSDV) is a member of the genus Capripoxvirinae. All breeds of cattle are considered to be at risk, while Asian water buffalo are also reported to be susceptible. Bos taurus breeds of cattle are more susceptible than Bos indicus breeds, and young calves often experience more severe disease than adults. The impact on production, particularly in affected dairy herds, can be considerable. Mortality can reach 12%. In addition losses incurred due to export bans can be significant. 3. Transmission is mediated primarily by biting and blood feeding arthropods probably acting as mechanical rather than biological vectors. Transmission may occur directly or indirectly via infected saliva and nasal discharges but is considered to be inefficient in the absence of an insect vector. Spread of the disease is also related to movement of cattle.

Risk4. LSD is primarily a problem in developing countries and occurs in most African countries and Madagascar. Sporadic outbreaks have occurred also in the Middle East region (Egypt, Israel, Oman and Bahrain). It may be present in other Middle Eastern countries which are lacking active surveillance. In the 1989 Egyptian outbreak LSD spread thousands of kilometres throughout the whole country in one summer and also spread into Israel. Recent outbreaks of LSD in Egypt, Israel (2006 and 2007), Oman and Bahrain (2009) raise the possibility that LSDV might become established in the Middle East, and spread to Asia and Europe. 5. Warm wet weather appears to favour outbreaks and therefore spread of the disease. With the anticipated increase in global warming it is conceivable that the disease will be spread by insect vectors to the extent that it becomes a threat to European agriculture. In addition Capripoxviruses have a long incubation period and infected animals could travel a considerable distance before showing disease thereby spreading infection from endemic to non-endemic regions.6. LSDV virus is a potential agriterrorist agent as it (i) causes high morbidity in susceptible animals,(ii) has potential for rapid or silent spread,(iii) has potential to cause serious economic losses and(iv) is of major importance in the international trade of cattle and cattle products

Diagnostics7. There are several reports on the development of diagnostic tests for LSD such as indirect ELISA and conventional or real-time PCR, but none is available commercially. Formal validation of most of these tests has not been undertaken (particularly to the level required by the OIE). 8. Improved reliable high-throughput serological tests are required. The ability to identify infected herds at the population level may be suitable to demonstrate freedom from disease. A serological test sensitive enough to detect exposure to the disease in individual animals would be ideal. An antibody detection ELISA based on recombinant antigens, with no requirement for infectious reagents, could be a desirable test format. The identification of immune dominant antigens should facilitate the development of improved antibody detection tests. 9. Several conventional and real-time PCR methods have been developed and further refined for the detection of virus in different types of specimens such as skin biopsies, EDTA blood, semen and insects. Primers have also been published for the differentiation of LSDV from sheep pox virus. An antigen detecting pen-side test needs to be developed and validated.

Vaccines10. An efficacious vaccine is needed to reduce the incidence of disease in cattle and reduce economic losses. Several live attenuated vaccines are currently available in Africa. Whilst effective, there are occasionally serious side effects which can include local reaction at the vaccination site and rarely a generalized infection. Annual booster vaccinations are recommended. Inactivated vaccines do not provide long term immunity. Immunity to capripoxviruses is considered to be mainly cell mediated, which is better stimulated by the use of live vaccines. Due to the mainly cell mediated immunity low antibody responses are common after the vaccination with attenuated live LSDV vaccines although the animals would be fully protected against the disease 11. The mechanism of attenuation is unknown for live vaccines. Sequencing whole genomes of vaccine and field isolates would help to identify the potential LSDV virulent factors. This would help in designing a strategy for the development of safer and potent attenuated live vaccines12. Poxviruses are ideal vaccine vectors that can be used for vaccinating against several diseases using multiple antigens. Recombinant vaccines have been developed based on capripoxvirus as the vector and including antigens from other viruses of concern such as Rift Valley fever, rabies and bovine ephemeral fever and shown to be effective against multiple agents. There is little research currently on-going in developing a marker vaccine which is likely due to the lack of a commercial market.

Pharmaceuticals13. Apart from the use of antibiotics to control secondary infections there are no pharmaceutical products currently available for use directly against LSDV. Insecticides to reduce the abundance of vectors are available for use as aerial sprays or for topical/systemic application to cattle.14. Several candidate antiviral therapeutics have been developed for use against smallpox virus in the event of a possible pandemic arising through an act of bioterrorism. These might contribute to the identification of candidate drugs for use against capripoxviruses in cattle although this seems unlikely as their use would be prohibited due to the risk of resistance.

Knowledge15. There are significant areas of uncertainty in the understanding and knowledge about LSD especially in relation to pathogenesis, immunology, vaccinology, epidemiology and control. Of particular importance is the understanding of the relative importance of the different types of potential arthropod vectors in the spread of LSDV, identification of these vectors, whether vector borne biological transmission of LSDV can occur, and how long the LSDV can survive on/in the vector. The correlation of the climate changes and the changes in vector populations with the occurrence of the LSD needs to be investigated. It is not understood where or how the virus persist in the host animal nor is there any understanding of the reasons for the wide variation in clinical signs in different individuals. 16. Research is needed to fill these gaps in knowledge as many of these are closely linked to the research requirements to develop more effective tools for the control of the disease. Full details of the gaps are shown in the Disease and Product Analysis for Lumpy Skin Disease on the DISCONTOOLS web site.

Conclusions17. There does not appear to be sufficient information about the way in which LSD spreads or the potential vectors which may be involved. Mass vaccination does not seem a possibility and the commercially available vaccines are all attenuated live vaccines which are not recommended to be used in disease free countries. Efficacious vaccines are needed to reduce the incidence of the disease in cattle, and the associated economic losses.18. Current research should focus on (i) development of improved assays, particularly to support disease surveillance and control activities (ii) developing improved vaccination regimes with live attenuated vaccines, and (iii) finding improved methods for educating farmers, through extension activities.