PCR-based tests are available
A serological ELISA for LSD was recently released.
For all commercially available diagnostics: see link (Diagnostics for Animals).
PCR-based tests are available
A serological ELISA for LSD was recently released.
For all commercially available diagnostics: see link (Diagnostics for Animals).
Routine methods are described in the OIE Manual of Diagnostic Tests and Vaccines. The most commonly used are:
1. Identification of the agent
High given the recent spread of LSD into Europe.
DIVA for both antigen and antibody are required but are not currently available.
Several live attenuated vaccines are available and have been sequenced.
Live attenuated vaccines against LSD have been used under emergency legislation to good effect in Europe 2015-present.
Depends on whether the disease becomes endemic in Europe.
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.
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.
Seemingly very effective in the recent European outbreaks.
Proving a region is free from LSD following a disease outbreak and vaccination programme is problematic.
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.
Not a priority. Prevention of disease rather than treatment of disease is the aim of control programmes.
None at present.
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.
Not currently applicable.
Unlikely due to a lack of a profitable market.
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.
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.
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.
A test to differentiate infected from vaccinated cattle is required to complement virus eradication programmes.
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.
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.
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.
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.
There is unlikely to be any pharmaceutical development that could impact this disease.
Obstacles in applying prevention and control measures:
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.
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.
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.
Facilitators to apply prevention and control measures:
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.
Humans are not susceptible.
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.
There is no carrier state for LSDV but the virus may survive for prolonged periods in the skin of severely infected animals or environment.
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.
Clinical signs can range from inapparent to severe.
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.
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.
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.
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.
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:
LSDV is not zoonotic.
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.
There is no solid data to support the theory that LSDV causes disease in wild species.
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.
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.
Endemic in most African countries. Endemic in Turkey and probably other countries in the Middle East.
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.
New foci of disease can occur at distant sites. This may be due to spread by insect vectors or movement of infected cattle.
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.
Evidence would suggest this is the case.
There is a close correlation, although exceptions do occur.
This has not been studied.
This has not been studied in detail.
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.
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).
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.
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.
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.
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%).
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.
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.
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.
There are no specific therapeutic products available to treat LSDV.
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.
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.
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.
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.
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.
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.
Yes. Full list of notifiable diseases is here.
Yes. OIE technical disease card for Lumpy skin disease.
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)
Outbreaks were reported in all months in 2015, 2016 and 2017
The delay ranged from a few days to a few months
For countries reporting in 2016, the the mean number of follow ups was 8 and ranged from 1 (Burundi) to 27 (Greece)
Not recorded (unknown). In many endemic countries in Africa, a continual low-incidence of the disease is noted, and not reported.
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.
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.
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.
No studies on the indirect impact of LSD have been published.
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.
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.
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.
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.
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.
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
Project Management Board.
18 April 2018