Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  PCR-based tests are available

  A serological ELISA for LSD was recently released.

  For all commercially available diagnostics: see link (Diagnostics for Animals).

• Commercial diagnostic kits available in Europe

  PCR-based tests are available

  A serological ELISA for LSD was recently released.

  For all commercially available diagnostics: see link (Diagnostics for Animals).

• Diagnostic kits validated by International, European or National Standards

  None.

• Diagnostic method(s) described by International, European or National standards

  Routine methods are described in the OIE Manual of Diagnostic Tests and Vaccines. The most commonly used are:

  1. Identification of the agent

  1. Nucleic acid recognition (PCR)

  2. Serological

  1. Virus neutralisation

• Commercial potential for diagnostic kits in Europe

  High given the recent spread of LSD into Europe.

• DIVA tests required and/or available

  DIVA for both antigen and antibody are required but are not currently available.

• Opportunities for new developments

  Opportunities:

  • Establish a collection of well-characterised samples from experimentally and naturally infected or vaccinated animals to be used in diagnostic test development.
  • Develp diagnostic tests which measure the cell mediated response to LSDV
  • Investigate the opportunities for using nasal or oral swabs for detecting LSDV
  • Validate diagnostic tests in different geographic regions

• Vaccines availability

• Commercial vaccines availability (globally)

  Several live attenuated vaccines are available and have been sequenced.

• Commercial vaccines authorised in Europe

  Live attenuated vaccines against LSD have been used under emergency legislation to good effect in Europe 2015-present.

• Marker vaccines available worldwide

  None available.

• Marker vaccines authorised in Europe

  None available.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Effectiveness:

  • Poxviral diseases are traditionally relatively easy to protect against by using appropriate live attenuated vaccines.
  • Each capripoxvirus-based vaccine needs to be evaluated on an individual vaccine basis to ensure safety and immunogenicity are balanced.
  • “Neethling” based LSD vaccines (LumpyVax by MSD Animal Health and Lumpy Skin Disease vaccine for cattle by Onderstepoort Biological Products) have been shown to be effective both experimentally and in the field. Evidence shows they are >80% effective in prevention of disease.

  Shortcomings:

  • Side effects (commonly a local reaction at the vaccination site and drop in milk production, and rarely a generalized infection).
  • Length of protection provided is unknown.
  • Unknown if vaccine virus can be shed from a vaccinated animal
  • Cannot distinguish between vaccinated and infected animals using serological tests.
  • Vaccines are propagated on primary cells with inherent risk.
  • Correlates of protection are unknown
  • It has not been possible to prove disease freedom in a region following a vaccination campaign.

• Commercial potential for vaccines in Europe

  Depends on whether the disease becomes endemic in Europe.

• Regulatory and/or policy challenges to approval

  None of the available LSD vaccines are produced in an EUGMP site. EU derogations do allow emergency use of non-EUGMP vaccines, but should the disease become endemic then changes to production sites may be required.

• Commercial feasibility (e.g manufacturing)

  Demand in the EU is unclear and there is little transparency. Until this becomes clearer then the commercial feasibility remains low as there is too much risk for large investment by pharmaceutical companies.

• Opportunity for barrier protection

  Seemingly very effective in the recent European outbreaks.

  GAPS:

  • Zoning and compartmentalization requirements for LSD.

• Opportunity for new developments

  GAPS:

  Proving a region is free from LSD following a disease outbreak and vaccination programme is problematic.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  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.

• Future therapy

  Not a priority. Prevention of disease rather than treatment of disease is the aim of control programmes.

• Commercial potential for pharmaceuticals in Europe

  None at present.

• Regulatory and/or policy challenges to approval

  The EU has a policy of compulsory notification and slaughter therefore it is unlikely that regulatory approval for use in the EU would be granted.

• Commercial feasibility (e.g manufacturing)

  Not currently applicable.

• Opportunities for new developments

  Unlikely due to a lack of a profitable market.

• New developments for diagnostic tests

• Requirements for diagnostics development

  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 the other CPPV strains, and the differentiation of wildtype and vaccine strains. Further PCR-based developments are not a priority.

  An antibody detection ELISA based on recombinant antigens has recently been brought to the market by ID-VET. Further developments in detection of immune response to LSDV are required, to enable historical or subclinical infections to be identified on an individual or herd basis and therefore allowing disease surveillance and virus eradication programmes to be carried out.

  GAPS:

  • An understanding of the immune response to LSDV infection

• Time to develop new or improved diagnostics

  In general the development of tests is much faster and less expensive than developing vaccines. Real-time PCR and ELISA-based diagnostic tests for LSD have appeared on the market in recent years and the pace of development of these tests has increased in response to the outbreak of LSD in Europe.

• Cost of developing new or improved diagnostics and their validation

  Potentially significant. The development and validation of new tests is time consuming, labour intensive and costly. Costs cannot be specified as they will depend on the nature of the test and the cost of producing reagents and supplying reading or processing machines if necessary.

• Research requirements for new or improved diagnostics

  Knowledge requirements:

  • The ability to identify infected herds at the population level is required to demonstrate freedom from disease (disease surveillance).
  • A serological test able to detect exposure to the virus in individual animals is required in order to detect subclinically infected cattle.
  • A test to differentiate infected from vaccinated cattle is required to complement virus eradication programmes.

  Research requirements:

  • A more comprehensive understanding of the immune response to LSDV infection, including temporal changes and inter-animal variability.
  • A comparative study of the immune response to vaccinated vs infected cattle.

  GAPS:

  • An understanding of the immune response to LSDV infection

• Technology to determine virus freedom in animals

  A test to differentiate infected from vaccinated cattle is required to complement virus eradication programmes.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  The live-attenuated vaccines currently on the market are effective and have played an important role in controlling the 2012-2017 epidemic. However as live vaccines their use results in loss of trade opportunities which can have substantial financial penalties. It is also difficult to develop a DIVA test for live attenuated vaccines. Inactivated or subunit vaccines would therefore be more suited to LSDV outbreaks in Europe, if they can be shown to be effective.

• Time to develop new or improved vaccines

  This could be significant, especially in view of the need for any new vaccine to be cheap enough for use by subsistence farmers in Africa.

  Depending on when a candidate vaccine could be identified the timescale will be 5-10 years. This will involve development, clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials, the outcome of which will determine the time to commercial availability.

• Cost of developing new or improved vaccines and their validation

  Significant.

  Expensive, with the need to develop and undertake all the relevant tests to provide data to enable the product to be authorised. Field trials will be difficult, as will be evaluation of the results generated.

• Research requirements for new or improved vaccines

  Better understanding of the LSDV immune response in order to facilitate development of DIVA assays, as well as inactivated and subunit vaccines.

  Better understanding of the pathogenesis of LSD in order to limit post-vaccinal reactions.

  Improved heat-stability of vaccines.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  There is unlikely to be any pharmaceutical development that could impact this disease.

• Time to develop new or improved pharmaceuticals

  Significant.

• Cost of developing new or improved pharmaceuticals and their validation

  Expensive.

• Research requirements for new or improved pharmaceuticals

  N/A.

Disease details

• Description and characteristics

• Pathogen

  Lumpy skin disease virus (LSDV) is a member of the genus Capripoxvirinae in the family Poxviridae, subfamily Chordopoxvirinae. It is closely related to the other two capripoxviruses Sheeppox virus (SPPV) and Goatpox virus (GTPV). The three viruses can be distinguished by genome analysis, but cannot be differentiated serologically.

• Variability of the disease

  LSDV causes disease in all breeds of cattle and Asian water buffalo. Lumpy skin disease (LSD) occurs in most African countries, the Middle East, Caucasus, Balkans, Russia and Khazakstan. It is thought to be primarily transmitted by blood feeding arthropods.

  GAPS:

  • The genetic variability of LSDV.
  • The molecular determinants of host range and virulence.
  • The vectors responsible for transmitting LSDV.

• Stability of the agent/pathogen in the environment

  LSDV survives for long periods at ambient temperatures (for up to 6 months if protected from sunlight), especially in dried scabs (40 days), but virus is susceptible to high temperatures (inactivation is achieved by heating at 55ºC for 2 hours) and also to highly alkaline or acidic pH. LSDV is susceptible to sunlight, but survives well at cold temperatures.

  GAPS:

  • The infectiousness of the virus to cattle after weeks/months in the environment (including in insect and arthropod vectors) under different conditions.
  • The survival of LSDV in animal products such as hides and meat.

• Species involved

• Animal infected/carrier/disease

  All cattle are susceptible.

  Clinical disease can vary from inapparent, characterised by virus present in the blood stream but no clinical signs of disease (subclinical infection), to severe resulting in death of the animal.

  No carrier status occurs in cattle following infection with LSDV although live virus can be detected up to 39 days post infection in the skin of infected animal.

  LSDV is highly species specific. Like many other poxviruses it stimulates a protective immune response when inoculated into species other than cattle (such as sheep and goats) but does not cause disease.

  Large serological surveys of wildlife in areas of Africa where LSD is endemic have not found evidence of a wildlife reservoir.

  GAPS:

  • How common is subclinical LSD and what role does it play in the epidemiology of the disease?

• Human infected/disease

  Humans are not susceptible.

• Vector cyclical/non-cyclical

  Very few experimental transmission studies of LSDV by arthropod vectors have been carried out. Epidemiological evidence from LSD outbreaks strongly supports an insect-borne method of spread of the virus.

  GAPS:

  • The competence and capacity of potential vectors of LSD. This is a key knowledge gap which greatly hampers efforts to control the disease. It is suggested to initiate integrated studies to determine the competence and capacity for various potential vectors. This would include distinguishing mechanical and biological transmission, and cover potential vectors present in different climates.

• Reservoir (animal, environment)

  There is no carrier state for LSDV but the virus may survive for prolonged periods in the skin of severely infected animals or environment.

  GAPS:

  • The infectiousness of LSDV to cattle after weeks/months in environment under different conditions.
  • The risk posed by a LSD-affected animal over time.

• Description of infection & disease in natural hosts

• Transmissibility

  Transmission is believed to be mediated primarily by arthropod vectors (insects and ticks).

  Virus is present at high levels in the cutaneous nodules of the skin of affected animals. It is present at lower levels in nasal and oral discharges. It is present at low levels and intermittently in the blood stream (viraemia). LSDV has been detected in the skin of subclinically affected animals, indicating the dermotropic nature of this virus. It has also been detected in semen of affected bulls.

  GAPS:

  • Spread of LSD by subclinically affected cattle
  • Spread of LSD by fomites (vehicles, people, etc)
  • Spread of LSD by carcasses
  • Spread of LSD by semen

• Pathogenic life cycle stages

  Not applicable.

• Signs/Morbidity

  Clinical signs can range from inapparent to severe.

  • Fever may be transitory or last up to 2 weeks.
  • Enlargement of superficial lymph nodes is commonly observed.
  • Multifocal to coalescing, firm, well demarcated cutaneous nodules up to 5 cm in diameter develop, particularly on the head, neck, udder, perineum and limbs. In severe cases they may cover the majority of the animal. The nodules may extend through the dermis into the subcutaneous tissue and underlying musculature, and can develop necrotic centres, called “sitfasts” which form a nidus for secondary bacterial infections and myiasis.
  • Focal to multifocal, well demarcated erosions and ulcers may form in the mucus membranes of the respiratory and gastrointestinal tracts.
  • Animals may be depressed and reluctant to move.
  • Lactating animals may experience a sudden drop in milk yield and pregnant cattle may abort.
  • Bulls can experience temporary or permanent infertility.
  • Marked deterioration in body condition can occur, and recovery may be prolonged.

  It is estimated that up to 50% of infected cattle develop inapparent disease characterised only by a transient mild pyrexia with or without a mild lymphadenopathy.

  GAPS:

  • The host, virus and environmental factors which determine the outcome of LSDV infection.

• Incubation period

  In experimental models of LSD there is an incubation period of 6-7 days before the animal develops a fever, followed 1-2 days later by the appearance of cutaneous nodules. There are reports of longer incubation times in older literature.

  GAPS:

  • The interactions which occur between the virus and the host during the incubation period

• Mortality

  The mortality rates in affected herds in recent outbreaks in the Middle East and Europe have varied from 0.4% in Greece to 6.4% in Turkey. Morbidity varied form 8.7% in Greece to 17.9% in Iran and 26% in Jordan.

  GAPS:

  • Factors which contribute to higher morbidity and mortality rates

• Shedding kinetic patterns

  LSDV is present in cutaneous lesions for up to 39 d post-infection and likely longer. Virus is also shed in saliva, respiratory secretions, blood, milk and semen. Shedding in semen may be prolonged since the virus has been associated with necrotising and granulomatous orchitis and epididymitis in experimentally inoculated bulls, with virus isolated from the semen of one of these animals 42d. after inoculation.

  GAPS:

  • Transmission of LSD via semen and embryos.
  • Shedding of virus from subclinically infected animals.

• Mechanism of pathogenicity

  Pathogenicity of capripoxviruses is largely unstudied. Other poxviruses such as Vaccinia virus and Ectromelia virus have been studied in great detail. Poxviruses are characterised by their large (over 150kb) and complex double-stranded DNA genome, and their entirely cytoplasmic replication cycle, which is very unusual for a DNA virus. Poxviruses replicate initially at the site of infection before travelling to draining lymph nodes and then systemically. Poxviruses encode a wide array of immunomodulatory proteins which enable them to evade the host’s antiviral immune response.

  Poxviruses stimulate a strong immune response, including both cell mediated (T cell-based) and humoral (B cell-based) immunity. This has resulted in them being developed as vaccine vectors for a range of pathogens, and as oncolytic therapies.

  Protective immunity against a subsequent challenge with poxviruses is correlated with a strong and varied antibody response.

  Understanding of the pathogenesis of capripoxvirus disease is in its infancy. Examples of areas which require investigation include:

  • The mechanisms of immune evasion by LSDV
  • Characterisation of a protective immune response against LSDV, including identification of immunodominant epitopes / proteins
  • The mechanisms underlying the narrow host range of LSDV

• Zoonotic potential

• Reported incidence in humans

  LSDV is not zoonotic.

• Risk of occurence in humans, populations at risk, specific risk factors

  N.A

• Symptoms described in humans

  N.A

• Estimated level of under-reporting in humans

  N.A

• Likelihood of spread in humans

  N.A

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  LSD undoubtably causes substantial and long term pain, harm and distress in cattle, particularly those severely affected.

  Control measures include vaccination, movement restrictions, and slaughter campaigns. Vaccination with live-attenuated LSD strains can cause mild LSD-like symptoms. Movement restrictions and slaughter campaigns can result in mild to moderate negative impacts on animal welfare.

  During the recent LSD epidemic in the Balkans widespread and indiscriminate insecticide use was practiced in some areas, likely leading to loss of biodiversity.

  Slaughter campaigns, if extensive, have the propensity to reduce biodiversity.

  GAPS:

  • A better understanding of the pathogenesis and epidemiology of LSD is needed in order to enable focused and targeted control measures such as vector control and vaccination. This will reduce the negative welfare and biodiversity impacts of these measures as currently used. It will also improve control, prevention and eradication of LSD, leading to reductions in the number of cattle suffering from the disease.

• Endangered wild species affected or not (estimation for Europe / worldwide)

  There is no solid data to support the theory that LSDV causes disease in wild species.

• Slaughter necessity according to EU rules or other regions

  Compulsory slaughter is a recommended means of control, particularly in previously disease free countries. Current evidence suggests that if efficient vaccination is implied, culling has only minor additional effect for disease control.

  GAPS:

  • The impact of partial vs complete stamping out in LSD control programmes.

• Geographical distribution and spread

• Current occurence/distribution

  LSD occurs in most African countries with sporadic outbreaks in the Middle East. In 2012, the disease re-appeared in the northern part of Israel and then spread swiftly within the Middle East region and was reported in Lebanon, Palestinian Autonomous Territories and Jordan. It spread further in 2013 into Turkey, Kuwait, Saudi Arabia and Iraq. In 2014 LSD occurred in Iran and northern parts of Cyprus. In 2015 the disease spread into Saudi Arabia, Bahrain, Greece and into the Caucasus region including Azerbaijan, Georgia and Russia. In 2016, LSD continued to spread into Bulgaria, Serbia, Montenegro, Former Yugoslav Republic of Macedonia, Kosovo and Albania and also spread to Iran, Iraq, Azerbaijan, Armenia, Georgia, Kazakhstan and the southern Caucasian parts of the Russian Federation. LSD represents an immediate threat to central parts of Russia, Ukraine, Afghanistan and Pakistan.

  GAPS:

  • The factors contributing to rapid and uncontrolled LSD spread.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Endemic in most African countries. Endemic in Turkey and probably other countries in the Middle East.

• Seasonality

  In tropical climates the incidence of disease is highest in wet warm weather and decreases during the dry season (linked to possible insect vector occurrence/numbers). As LSDV spread into temperate climates, initial evidence suggests there may be several peaks; i.e. during the dry warm season, winter (in Mediterranean climate) and spring.

  GAPS:

  • The correlation of certain climatic conditions with the occurrence of LSD
  • The role of winter in slowing the spread of LSD in countries with different climates where it is spreading (ie Russia)

• Speed of spatial spread during an outbreak

  New foci of disease can occur at distant sites. This may be due to spread by insect vectors or movement of infected cattle.

  GAPS:

  • The main routes of virus transmission: e.g. animal transport/ winds/ birds/carcasses

• Transboundary potential of the disease

  The 2012-2017 epidemic of LSD in the Middle East, Balkans and Caucasus clearly demonstrates the ability of LSDV to spread rapidly through political and geographic boundaries.

• Route of Transmission

• Usual mode of transmission (introduction, means of spread)

  Evidence suggests that transmission of LSDV occurs via arthropod vectors. Direct (cattle to cattle) transmission represents a very low to negligible risk.

  Movement of infected cattle has been linked with spread of LSDV, particularly in epidemic situations.

  GAPS:

  • The risk of transmission of LSDV by different arthropod vectors.
  • The risk of transmission of LSDV by subclinically infected cattle.

• Occasional mode of transmission

  Potential occasional modes of transmission of LSDV include sexual transmission, transmission via fomites, via carcasses or via animal products.

  A presence of live LSDV in semen of infected bulls has been demonstrated, however transmission of disease to naïve animals via infected semen has not been shown to occur. LSDV is present at high levels in the cutaneous nodules of the skin of affected animals. It is present at lower levels in nasal and oral discharges. It is present at low levels and intermittently in the blood stream (viraemia). LSDV has been detected in the skin of subclinically affected animals. In addition to these potential means of virus shedding, LSDV is very resistant to certain environmental conditions (drying, temperature fluctuations etc).

  GAPS:

  • The risk of transmission of LSD by indirect routes (fomites, carcasses, semen and embryos).
  • The risk of transmission of LSD by animal products (hides, meat, milk).

• Conditions that favour spread

  On a local level warm wet weather and animal movement from endemic to non-endemic regions have been identified as risk factors associated with LSD outbreaks.

  On a regional level the spread of LSDV throughout the Middle East, Russia, the Balkans and Causasus in the past 5 years (2012-2017) is unpredecented. This provides a unique opportunity to investigate the factors contributing to this rapid and unexpected spread of the virus.

  GAPS:

  • The influence of risk factors which contribute to the regional spread of LSDV such as:
    • Climatic conditions
    • Abundance of arthropod vectors.
    • Civil unrest
    • Alterations in cattle trading patterns

• Detection and Immune response to infection

• Mechanism of host response

  Experimental and field studies have identified a cell mediated immune response (IFN-gamma production and CD4 T cell proliferation) and humoral immune response in naïve cattle infected with LSDV. Experimental studies indicate that protection against a secondary challenge with LSDV (for example post vaccination) is strongly correlated with rapid production of anti-LSDV antibodies, consistent with other poxviruses.

  GAPS:

  • The protective components of an immune response to LSD
  • Immune evasion mechanisms employed by LSDV.
  • Mechanism/s by which antibodies provide protection against LSD

• Immunological basis of diagnosis

  There are no commercially available tests to measure the cell mediated immune response to LSDV.

  The only validated test for measuring the antibody response to LSDV infection is the virus neutralisation test (VNT), as described in the OIE manual. It has high specificity but low sensitivity, is expensive and time consuming and requires use of live virus.

  A diagnostic ELISA has recently (May 2017) been launched on the market by ID-VET.

  Product gaps:

  • There are few LSD immunology-detection diagnostic tests available. This hampers identification of subclinically infected cattle, tracking outbreaks of the disease, and proving freedom from disease after an outbreak. For example a sensitive and specific diagnostic test to identify antibodies to LSDV is required. Ideally the test should be cheap, simple, and amenable to a high throughput of testing. In addition, it should be able to differentiate between infected and vaccinated animals.

• Main means of prevention, detection and control

• Sanitary measures

  Cleaning and disinfection of contaminated premises and equipment - LSDV is susceptible to highly alkaline or acidic pH, formalin (1%), sodium hypochlorite 3 %, Virkon 2%, some detergents (e.g., sodium dodecyl sulphate) and phenol (2%).

• Mechanical and biological control

  The three key control measures used against LSD are movement restrictions, slaughter campaigns, and vaccination.

  Animal movement restrictions are an important method of restricting spread of LSD, particularly in epidemic situations, however the width of an effective “quarantine” zone is difficult to define given the gap in knowledge over the insect vectors believed to transmit the disease.

  In disease-free countries in the EU complete stamping-out has been mandated for all LSDV-infected herds. Recent scientific evidence has called into question the efficacy of this expensive and often controversial method of control. Partial stamping of only the clinically affected cattle within a herd has been suggested as an effective alternative. Total stamping out was shown to be effective only in very localized outbreaks in Israel in 1989, 2006 and 2007, while modified stamping out produced the same result. A recent EFSA report used mathematical modelling to compare complete and modified stamping out policies. This found that, when combined with an effective vaccination campaign, a complete stamping out programme has only a minor additional effect for disease control, if any, compared to a modified stamping out programme.

  Vaccination with a live attenuated strain of LSDV in the recent outbreaks in Europe has been shown to be very effective at restricting the spread of LSD. Vaccination is often the only method of control available in resource-restricted settings.

  GAPS:

  • The length of time vaccination provides protection.
  • The impact of vector populations, geographic features (mountains, rivers), climatic conditions, and other factors on the required width of an effective “quarantine zone”.

  Methodological gaps:

  • Specific, focused and effective methods of vector control are required.

• Diagnostic tools

  LSD is often suspected based on the characteristic clinical signs and confirmed with a PCR-based assay.

  PCR-based tests which differentiate between LSDV, SPPV and GTPV have been published.

  PCR-based tests which differentiate between wildtype LSDV and the commonly used “Neethling” vaccine strain of LSDV have been published.

  Other methodology which can be used to diagnose LSD are described in the OIE manual.

  As described above there are few immunology-based diagnostic tests available which hampers control, eradication and prevention of LSD.

  Product gaps:

  • A highly sensitive and specific diagnostic test to identify antibodies to LSDV is required. Ideally the test should be cheap, simple, and amenable to a high throughput of testing. In addition, it should be able to differentiate between infected and vaccinated animals

  Methodological gaps:

  • Formal validation of LSD diagnostic tests to the standards set by the OIE.

• Vaccines

  Live-attenuated vaccines are recommended. Homologous (LSDV-based) and heterologous (SPPV or GTPV-based) live attenuated vaccines against LSD are available. Poxviruses exhibit within genus cross-protection. This has been proven experimentally and in the field with SPPV and GTPV – based vaccines as well as attenuated LSDV-based vaccines providing protective for cattle against LSDV.

  There is evidence from the literature of variation in protection afforded by individual capripoxvirus vaccines. There is a very strong body of evidence that the attenuated “Neethling” LSDV strain vaccines are highly effective (around 80% effectiveness) for prevention of LSDV. There is firm evidence that RM-65 administered in sheep dose (2.5 TCID) is not effective for protection against LSDV. Several studies have shown that goat pox vaccines are protective against LSD (Gari et al. 2015, Capstick and Coackley, 1961).

  The side effects of live-attenuated vaccines include necrotic lesions at the site of inoculation, reduction in milk production, and occasionally a mild form of LSD.

  Annual vaccinations with the live attenuated vaccines are recommended, although there is no published evidence to support this.

  There are currently no subunit or virally-vectored vaccines available against LSD.

  GAPS:

  • Correlates of protection for LSD.
  • Length of protection provided by live-attenuated vaccines.

  Methodological gaps:

  • Standardised vaccine testing methodology is required in order to compare the efficacy of available and novel LSD vaccines.

  Product gaps:

  • Vaccines which facilitate differentiating vaccinated from infected cattle are required.

• Therapeutics

  There are no specific therapeutic products available to treat LSDV.

• Biosecurity measures effective as a preventive measure

  Movement restrictions are an important part of LSD control in epidemic situations. For example protection zones and surveillance zones are often recommended to be set up around the infected premises.

  Biosecurity measures alone, however, are often ineffective in a LSD outbreak and need to be combined with vaccination programmes.

  GAPS:

  • The impact of vector populations, geographic features (mountains, rivers), climatic conditions, and other factors on the required width of an effective “quarantine zone”.
  • The length of time LSDV can survive in the environment or vectors requires investigation in order to determine the length of time quarantine bans need to remain in place.
  • The mechanisms by which LSDV over-winters in Europe.

• Border/trade/movement control sufficient for control

  LSD in a region is often a barrier for trade with LSD-free countries.

  Countries free of LSD should consider very carefully the risks associated with importation of livestock, carcases, hides and semen from LSD-affected regions. Rules associated with importing from LSD-affected countries are outlined in the OIE manual.

  GAPS:

  • The risks posed by different animal products from LSD-affected areas
  • The efficacy of “border vaccination” to prevent introduction of LSD into a new areas.
  • Evidence-based regulations governing a declaration of “freedom from LSD”.

• Prevention tools

  In endemic countries minimising mixing of cattle with other herds, minimising buying in of cattle, and vaccination are the most effective means of prevention.

  In disease-free countries, prohibiting the importation of livestock and their products from countries where LSD is endemic reduces the risk of LSD occurring. However in the past 5 years LSD has spread rapidly across the Middle East and into Europe, Asia, and Russia, highlighting the difficulty of preventing the spread of this disease even in the face of movement and trade restrictions.

  Methodological gaps:

  • Additional management actions which may help prevent LSD outbreaks.

• Surveillance

  Lumpy skin disease is classified as notifiable by the World Organization for Animal Health (OIE). A presumptive diagnosis is usually based on characteristic clinical signs, but the diagnosis must be confirmed by laboratory testing.

  Lack of sensitive serological tests hamper efforts at disease surveillance.

  Lack of serological tests which differentiate infected and vaccinated animals hamper post-outbreak disease surveillance.

  Product gaps:

  • A highly sensitive and specific diagnostic test to identify antibodies to LSDV is required. Ideally the test should be cheap, simple, and amenable to a high throughput of testing. In addition, it should be able to differentiate between infected and vaccinated animals.

  Methodological gaps:

  • Scientifically valid, standardised recommendations for effective surveillance for LSD in post-outbreak situations.

• Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

  To date eradication and prevention measures have proved ineffective in Africa and the Middle East. No country has succeeded in eradicating LSD once it has entered the country. New data from the outbreaks in the Balkans and Caucasus supports this observation.

  A slaughter policy combined with strict movement controls was ineffective when LSD was introduced into the Balkans in 2015-6. This finding was supported by subsequent mathematical modelling which showed that stamping out or modified stamping out when combined with effective vaccination has only a minor additional effect for disease control, if any.

  GAPS:

  • A comprehensive retrospective evaluation of the different control measures undertaken in the 2012-2017 epidemic to allow lessons to be learnt.

  Methodological gaps:

  • Improved and novel methods for eradicating LSD from endemic areas

• Costs of above measures

  No thorough analysis of the economic impact of LSD has been reported. Estimates of the cost of the outbreaks in the Balkans are many millions of euros.

  Methodological gaps:

  • A framework enabling a cost-benefit analysis of an outbreak of LSD is urgently required, to enable economically viable control measures.
  • A similar framework to facilitate a cost-benefit analysis of LSD under endemic conditions, for example in Africa, in order to assess the economic consequences of eradication programmes.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  Yes. Full list of notifiable diseases is here.

• WOAH disease card available

  Yes. OIE technical disease card for Lumpy skin disease.

• WOAH Terrestrial Animal Health Code

  Available here.

• WOAH Terrestrial Manual

  Available here.

• Socio-economic impact

• Zoonosis: impact on affected individuals and/or aggregated DALY figures

  Human (Geographic impact)

  LSD is not believed to influence the geography of human settlements or movements.

  LSD is endemic in many low and middle income countries in Africa. On a farm level LSD reduces productivity through reduced milk production, reduced weight gain, loss of body condition, and the death of cattle. These impacts are particularly significant for subsistence famers as their animals provide high quality protein food source (meat and milk), skins for clothing, a means of accumulating capital and a ready source of emergency funds as well as socio-cultural wealth. LSD therefore contributes to instability of income for subsistence farmers and rural poverty.

• Zoonosis: cost of treatment and control of the disease in humans

  N.A.

• Direct impact (a) on production

  Animal (Geographic impact)

  This has not been studied.

  Few studies on the economic impact of LSD have been published. In Ethiopia (doi: 10.1016/j.prevetmed.2011.07.003) the costs arising from milk loss, beef loss, traction power loss, and treatment and vaccination costs were estimated to be USD 6.43 (5.12-8) per head for local zebu and USD 58 (42-73) per head for HF/crossbred cattle.

  GAPS:

  • A thorough study of the economic impact of LSD is required

• Direct impact (b) cost of private and public control measures

  Few studies on the economic impact of LSD have been published. In the same study described above (doi: 10.1016/j.prevetmed.2011.07.003) the financial benefit of an annual vaccination programme in Ethiopia were examined. A vaccination programme was estimated to enable the financial costs due to LSD to be reduced by 17% per head in local zebu herds and 31% per head in HF/crossbred herds.

  The cost of control programmes in the Balkans in 2015-2016 (vaccination, movement control, trade losses, slaughter campaigns) are estimated at many millions of euros.

  GAPS:

  • A thorough study of the economic impact of LSD is required

• Indirect impact

  No studies on the indirect impact of LSD have been published.

  GAPS:

  • A thorough study of the economic impact of LSD is required

• Trade implications

• Impact on international trade/exports from the EU

  High impact. Standards for movement are specified in the OIE Terrestrial Animal Health Code.Trade of live cattle and embryo and semen exports are banned from countries with LSD to countries free of the disease.

• Impact on EU intra-community trade

  High impact. Standards for movement are specified in the OIE Terrestrial Animal Health Code.Trade of live cattle and embryo and semen exports are banned from countries with LSD. This has significantly impacted the EU countries recently affected by LSD including Greece and Bulgaria.

• Impact on national trade

  High impact. Standards for movement are specified in the OIE Terrestrial Animal Health Code.Trade of cattle and specified cattle products are banned from an infected zone to a uninfected zone within a country.

• Main perceived obstacles for effective prevention and control

  Obstacles in applying prevention and control measures:

  • Lack of knowledge of LSD transmission
  • Rapid and accurate serological diagnosis
  • Knowledge of the role of subclinically affected cattle in the epidemiology of the disease
  • Inability to eradicate the disease from a region once it has been infected
  • Ability to differentiate infected and vaccinated animals
  • Lack of understanding of the pathogenesis of the disease
  • Lack of understanding of the protective components of the immune response to LSDV infection
  • Lack of an effective veterinary infrastructure in some developing countries.

• Main perceived facilitators for effective prevention and control

  Facilitators to apply prevention and control measures:

  • Effective and safe live attenuated vaccines
  • Specific and sensitive PCR-based diagnostic tests
  • Beginnings of the development of ELISA-based diagnostic tests
  • Sequencing of full genomes of multiple strains of CPPVs
  • Standardisation of an experimental model of LSD
  • Increased prominence of CPPV disease leading to grant funding opportunities from European sources

• Disease outbreaks reported to OIE in last 18 months

• Number of reports

  LSD outbreaks were reported to the OIE by 41 countries in 2015 (31 in Africa, 7 in the Middle East, 1 in Asia and 2 in Europe), 43 countries in 2016 (29 in Africa, 5 in the Middle East, 2 in Asia and 7 in Europe) and 27 countries in 2017 (to end June; 19 in Africa, 4 in the Middle East, 1 in Asia and 3 in Europe)

• Date

  Outbreaks were reported in all months in 2015, 2016 and 2017

• Delay between first suspicion / first confirmation and OIE first emergency notification

  The delay ranged from a few days to a few months

• Frequency of follow up reports

  For countries reporting in 2016, the the mean number of follow ups was 8 and ranged from 1 (Burundi) to 27 (Greece)

• Level of under-reporting (in relation to prevalence/incidence information under 6 above)

  Not recorded (unknown). In many endemic countries in Africa, a continual low-incidence of the disease is noted, and not reported.

  GAPS:

  • Lack of reporting of LSD in endemic countries contributes to difficulties in assessing the economic cost of LSD, and therefore which control measures are most suitable.

• Links to climate

  Seasonal cycle linked to climate

  Evidence would suggest this is the case.

• Distribution of disease or vector linked to climate

  There is a close correlation, although exceptions do occur.

  GAPS:

  • The correlation of climatic conditions (and associated changes in vector populations) with the incidence of LSD

• Outbreaks linked to extreme weather

  This has not been studied.

  GAPS:

  • Association of LSD with extreme weather

• Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

  This has not been studied in detail.

  GAPS:

  • The role of specific arthropod vectors in transmission of disease, and associated alterations in vector distribution and dynamics caused by climate change.

Risk

• LSD occurs in most African countries with sporadic outbreaks in the Middle East. In 2012, the disease re-appeared in the northern part of Israel and then spread swiftly within the Middle East region and was reported in Lebanon, Palestinian Autonomous Territories and Jordan. It spread further in 2013 into Turkey, Kuwait, Saudi Arabia and Iraq. In 2014 LSD occurred in Iran and northern parts of Cyprus. In 2015 the disease spread into Saudi Arabia, Bahrain, Greece and into the Caucasus region including Azerbaijan, Georgia and Russia. In 2016, LSD continued to spread into Bulgaria, Serbia, Montenegro, Former Yugoslav Republic of Macedonia, Kosovo and Albania and also spread to Iran, Iraq, Azerbaijan, Armenia, Georgia, Kazakhstan and the southern Caucasian parts of the Russian Federation. LSD currently represents an immediate threat to central parts of Russia, Ukraine, Afghanistan and Pakistan.

  Warm wet weather appears to favour outbreaks and therefore spread of the disease. The incubation period of LSD is approximately 6-7 days, during which time infected animals could travel a considerable distance thereby contributing to disease spread.

  LSD virus is a potential agriterrorist agent as it (i) causes morbidity and mortality 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.

Main critical gaps

• Knowledge gaps:

  • Lack of knowledge of LSD transmission
  • Lack of understanding of the pathogenesis of the disease
  • Lack of understanding of the protective components of the immune response to LSDV infection
  • Knowledge of the role of subclinically affected cattle in the epidemiology of the disease

  Methodological gaps:

  • Lack of “roadmap” defining the stages to eradication of the disease from a region
  • Lack of regulations for determining proof of disease freedom
  • Inability to differentiate infected and vaccinated animals
  • Lack of an effective veterinary infrastructure in some developing countries

  Product gaps:

  • Rapid and accurate serological diagnosis on a herd and animal level

Conclusion

• Other information/comments/gaps:

  Much has been learnt from the recent LSD epidemic in the Middle East, Europe and Russia. Most importantly the profile of LSDV has been raised resulting in more funding opportunities and development of new diagnostic and disease control tools. Future research should focus on (i) characterising the vector-borne transmission of LSDV, (ii) developing improved immune-based diagnostic assays to support disease surveillance and eradication activities, and (iii) understanding the fundamental immunology and pathology of LSDV in order to underpin develop of future novel disease control tools.

Sources of information

• Expert group composition

  Pip Beard, The Pirbright Institute, UK - [Leader]

  Simon Gubbins, The Pirbright Institute, UK

  Shawn Babiuk, National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Canada

  Sotiria-Eleni Antoniou, Animal Health Directorate, Hellenic Ministry of Rural Development and Food, Greece

  Eyal Klement, Koret School of Veterinary Medicine, the Hebrew University of Jerusalem, Israel

  Alasdair King, Intergovernmental Veterinary Health, Merck Animal Health

  Kris De Clercq, Sciensano, Belgium

  David B. Wallace, Agricultural Research Council – Onderstepoort Veterinary Institute, South-Africa

  Jonathan Rushton, University of Liverpool, UK

  Loic Comtet, IDVET

• Reviewed by

  Project Management Board.

• Date of submission by expert group

  18 April 2018

• References