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Lumpy skin disease
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Lumpy skin disease
Previous authors: J A W COETZER
J A W COETZER - Professor Emeritus, BVSc, BVSc (Hons), M Med Vet (Path), Faculty of Veterinary Science, University of Pretoria, Private, Bag X04, Onderstepoort, Gauteng, South Africa, 0081
E TUPPURAINEN - Self Employed, DMV, MSc, PhD, 20 Wolseley Road, Aldershot, GU11 1NE, Hampshire, United Kingdom
S BABIUK - Research Scientific, PhD, National Centre for Foreign Animal Disease, 1015 Arlington Street, Manitoba, Canada, R3E 3MA
D B WALLACE - Senior Researcher, PhD, Agricultural Research Council, Onderstepoort Veterinary Research, Old Soutpan Road, Gauteng, South Africa, 0110
Lumpy skin disease (LSD) is a viral disease of cattle and possibly Asian domestic buffaloes (Bubalus bubalis) caused by lumpy skin disease virus (LSDV). It is characterized by fever and multiple firm, well-circumscribed and deep-seated skin nodules and necrotic plaques in the mucous membranes, chiefly of the upper respiratory tract and oral cavity. Mastitis, orchitis and swelling of peripheral lymph nodes are also common. Lumpy skin disease virus is a capripoxvirus first isolated in the 1940s; however, the first widespread outbreak was reported from Zambia in 1929.5, 15
Despite the fact that its origins are obscure LSD was until recently believed to be a disease confined to Africa. The disease that was initially termed pseudo-urticaria, but now presumed to have been LSD,81, 82 was thought to be the result of insect bites and later ascribed to plant poisoning.81 Lumpy skin disease was first recognized as an infectious condition in 1943 following an outbreak in Ngamiland (northern Botswana).119 Towards the end of 1944 LSD was reported from South Africa105 where it spread rapidly throughout the country despite enforcement of control measures. The disease subsequently spread northwards and was reported from Central and East Africa in 1956; since then it has occurred widely in Africa and in Madagascar.39, 52, 91, 92 It was first reported from Ethiopia in 198383 and in Egypt in 1988.64 Lumpy skin disease was recorded for the first time outside Africa/Madagascar in 1989 in Israel,37, 123 followed by outbreaks in Bahrain and Reunion in 1993, although those outbreaks were not confirmed by virus isolation.10
In 2006 and 2007 LSD was reported again in Egypt98 and Israel and in 2009 occurred in Oman.25 The disease reappeared in northern Israel in 201220 and then spread swiftly in the Middle East, being reported in Lebanon, the Palestinian Autonomous Territories and Jordan.1 The disease also spread into Turkey,106 Kuwait, Saudi Arabia and Iraq in 2013.4 In 2014 outbreaks of LSD were reported in Iran99 and the northern part of Cyprus as well as in Saudi Arabia and Bahrain.103 It then spread northeast through the Caucasus, affecting Azerbaijan (2014), Armenia and the Russian Federation (2015) and Georgia and Kazakhstan (2016).
Lumpy skin disease was reported for the first time in the European Union from Greece in 2015; it probably originated in Thrace (Turkey). The Greek outbreak occurred in two beef herds situated in the Evros River Delta from August 2015 to December 2015, i.e. within 15 km of the closest confirmed LSD outbreak in Turkey. The Evros River Delta is a National Park and a wetland with high temperatures and humidity. The disease emerged again in Greece from April to November 2016.3, 49
In 2016 LSD spread to Bulgaria, the former Yugoslav Republic of Macedonia (FYROM), Serbia, Montenegro, Kosovo and Albania49 in the same year was reported again in Iran and Iraq as well as Azerbaijan.126
The number of reported LSD outbreaks in Balkan countries was substantially less in 2017 (385) than in 2016 (7,483) and most occurred in Albania (379) in areas where vaccination was not applied in all cattle herds, indicating that the virus is still present in the environment and/or in the cattle population and may re-emerge again.49 In contrast, Bulgaria, Serbia, Montenegro and Kosovo reported no outbreaks, providing field evidence of the effectiveness of mass vaccination campaigns conducted at regional levels.49
Since the beginning of the LSD epidemic in south Eastern Europe (excluding Turkey) in 2015 more than 7900 outbreaks and approximately 13 650 cases have been reported.49
It appears that LSD spread rapidly and more or less unpredictably during the recent outbreaks in Greece and the Balkan countries. Current information on its distribution can be obtained from the OIE (World Organisation for Animal Health) website (www.oie.int) under the WAHIS interface’s disease distribution maps and the Food and Agriculture Organization of the United Nations (FAO EMPRES-I website, www.fao.org). Information is also provided by FAO on the incursion risk of LSD to Central Asia and Europe51 and distribution maps of recent outbreaks (2013-2017) in the Middle East, Turkey, the Balkans and Eastern Europe/ Central Asia.51
Lumpy skin disease can be considered a ‘neglected disease’ because since it was first confirmed as a poxvirus infection in South Africa in 1944, research has been limited. Until recently, LSD was not a research priority for developed countries because it was exotic. Consequently, there are still gaps in information about the disease including:
- the role of different potential insect vectors, including ticks, in different epidemiological settings and the persistence of LSDV in some of these potential vectors in interepidemic periods;
- the susceptibility of different wildlife species to LSDV and their role in the epidemiology of the disease;
- the proportion of animals that develop subclinical infections and their role in transmitting disease and infecting potential vectors;
- the importance of fomites such as saliva-contaminated feed and water troughs in the transmission of the disease;
- the level and duration of virus excretion in milk, semen, saliva and nasal secretions and their role in transmission of LSD;
- the level and duration of viraemia in animals vaccinated with attenuated LSD viruses and the potential for transmission;
- determinants of immunity and its duration following vaccination with attenuated LSD viruses; and
- the usefulness of improved serological tests, including ELISAs.
Because LSD is ‘listed’ by the OIE, member countries are obliged to report its occurrence promptly. Although the disease does not incur high mortality (usually less than 10 per cent), it is economically important because of its prolonged debilitating effects in severely afflicted animals including reduced weight-gain, temporary or permanent cessation of milk production, sometimes accompanied by mastitis, temporary or permanent infertility or even sterility in bulls as a consequence of orchitis, as well as permanent skin damage. Abortion may follow infection in approximately 10 per cent of pregnant cows.58, 63
In the outbreak reported in Albania in 2017, the morbidity had a median value of 0.8 per cent with values up to 7.2 per cent while mortality median value was 0.3 per cent with values up to 2.9 per cent. Similar ranges were reported in 2016 in Albania, when morbidity median value was 0.7 per cent up to 4.8 per cent and the mortality upper values was 0.7 per cent.49
During the outbreaks of LSD in the Balkans in 2016 the disease resulted in severe socio-economic consequences for small-scale farmers whose livelihoods are highly dependent on the production of their few dairy cows. In addition to the above-mentioned impacts, losses were also ascribed to costly control measures such as total or partial stamping-out (see Control) and the resultant need for compensation, cleaning and disinfection measures on affected farms, vaccination, supportive medical treatments and nursing of affected animals, vector control and increased laboratory activity (e.g. diagnostic kits, reagents and equipment) as well as more intensive monitoring and surveillance costs.
In African countries where cattle are often used for other purposes, such as for draught power and social and religious ceremonies, restrictions of such traditional practices result in economic and social disruption.
The most dramatic effects of LSD in endemic as well as newly infected areas are often indirect, resulting from market exclusion due to bans on movement and sale of cattle and commodities derived from them. That is particularly so if trade restrictions are unreasonable, i.e. do not accord with international trade standards set out in the OIE’s Terrestrial Animal Health Code chapter on LSD (i.e. Chapter 11.9 – www.oie.int), according to which meat (beef), hooves, horns, casings, tallow, gelatine and collagen are not considered a significant trade risk.51 Infection through milk and semen is possible.8, 9, 51 Hides are more likely to be contaminated with virus than meat or milk and the OIE Terrestrial Animal Health Code made certain recommendations for the importation of hides from LSD-infected countries.
Lumpy skin disease virus is a member of the genus Capripoxvirus within the family Poxviridae (subfamily Chordopoxvirinae); see Introduction to the Poxviridae for a more general overview of poxviruses.
Mature capripox virions (Figure 1) have a similar morphology to those of orthopoxviruses (prototype, vaccinia virus) when viewed using transmission electron microscopy, although capripox virions tend to be less symmetrical in shape,120 with average dimensions of 320 × 260 nm, giving an axis ratio of approximately 1:2.88 A cross-sectional analysis of the virions reveals a pair of lateral bodies (Figure 2) common to all poxviruses.88
Compared to other poxviruses, the double-stranded DNA genomes of capripoxviruses are relatively small, averaging around 150 kilo-base pairs (kbp) (compare with avipoxvirus genomes of around 300 kbp). Their genomes are highly conserved between the three genus members, with LSDV containing two unique genes compared to sheeppox or goatpox viruses.109 The viruses share around 97 per cent sequence identity.108, 109 Centrally located “house-keeping” genes (coding for structural proteins, proteins involved in replication, transcription etc.) are the most highly conserved, in line with other poxviruses, with inclusion of less conserved “virulence” genes (coding for proteins involved in pathogenesis) towards the termini, a number of which have putative immunomodulatory functionality for host immune response.70, 108
Available evidence suggests that there is only one serotype of LSDV. Virus isolates collected over an extended period from a large number of natural cases originating from outbreaks of the disease in South Africa, Kenya and Malawi,96, 120 showed reciprocal cross-neutralization with the prototype Neethling strain.40-42, 73 Complete genome sequencing of recent LSDV isolates SERBIA/Bujanovac/2016 and Evros/GR/15 demonstrated 99.5 per cent and 99.8 per cent homology respectively with the LSDV field isolate Neethling Warmbaths LW isolated in South Africa in 2000, indicating genetic stability of LSDV as well as providing genetic evidence in support of a single serotype.2, 107
Existence of only one serotype is further supported by studies in which cross-neutralisation of capripoxviruses is possible using sera containing neutralising antibodies generated in animals inoculated with a different capripoxvirus. This fact has been utilized to demonstrate that capripoxviruses can afford varying degrees of cross-protection.10, 22, 74 For example, the Kenyan sheep- and goatpox (KSGP) O-240 vaccine strain has been successfully used for the immunization and protection of sheep and goats against sheeppox and goatpox and cattle against LSD in many regions in Africa.30, 38 This vaccine strain was originally believed to be a SPPV but was later shown to be LSDV using DNA sequencing.116 This error in the original classification of the vaccine as a sheeppox virus illustrates the need to use DNA sequencing to properly identify capripoxviruses as all other identification methods are insufficiently specific (see Diagnosis).
Culturing capripoxviruses in cell cultures is relatively simple, although they replicate more slowly and grow to lower titres (up to 106 TCID50/ml) in permissive cells than the orthopoxvirus vaccinia virus, and thus for new LSDV isolations in cell cultures up to 11 days, and more than one passage may be required before cytopathic effects (cpe) become evident (www.oie.int Lumpy skin disease chapter). The highest titres are achievable in a variety of primary cell cultures of ovine or bovine origin, most commonly kidney or testes cells, but cells from other organs, including adrenal, thyroid, muscle, lung and skin, may also be utilized.5, 10, 96 Additionally, there are several transformed cell lines that are permissive to LSDV propagation, including Madin-Darby bovine kidney (MDBK) and ovine testes (OA3.Ts) cells.16, 21 The development of cpe may be observed as early as three days after culture inoculation but it usually requires longer incubation in the case of primary isolation.5, 94-96, 120, 121 The virus induces discrete viral plaques in cell monolayers derived from primary cells, characterized by early appearance of discrete foci of rounded cells, followed by formation of irregular holes in the monolayer as the cells die.88 Virus replication is accompanied by the formation of intracytoplasmic inclusion bodies similar to those which occur in a variety of cells in the epidermis and dermis in skin lesions (see Clinical signs and pathology) of affected cattle.26, 43, 95
As is the case with other poxviruses, LSDV is highly stable (see General Introduction: Poxviridae). Virus is recoverable for at least 18 days from air-dried hides kept at room temperature and from infected tissue culture fluid stored at 4 °C for six months.120 The virus was reported to persist in necrotic skin nodules for up to 33 days but this period may be much longer.110, 120, 121
Between pH 6.6 and 8.6 virus preparations showed no significant reduction in titre after exposure to a temperature of 37 °C for five days. The resistance to physical and chemical actions are summarized in the OIE manual (http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/Disease_cards/LUMPY_SKIN_DISEASE_FINAL.pdf).
The range of animal species that may be infected and develop clinical disease is uncertain but it is probably wider than cattle and Asian water buffaloes (Bubalus bubalis); there are conflicting reports concerning the latter species.46
All ages of cattle and both sexes are susceptible to infection120 although on occasion cows have been only mildly affected while their calves developed more typical and severe lesions 24 to 48 hours earlier than their dams.79 More severe disease has been reported in breeds of cattle exotic to Africa, especially those with thin skins such as Friesians and in other high-producing European dairy breeds. Cows in peak lactation seem also to be more severely affected.54, 79, 101, 102
Involvement of wildlife in the maintenance and transmission of LSD is uncertain. Disease resembling LSD clinically has been reported in Arabian oryx (Oryx leucoryx) in Saudi Arabia,12 springbok (Antidorcas marsupialis) in Namibia75 and oryx (Oryx gazella) in South Africa, although there is no record of isolation of LSDV from these species. According to Hedger and Hamblin61 wildlife play no significant part in the epidemiology of the disease. Birds have been postulated as possible vectors27, 63 but there is likewise no objective evidence for that.
Serological studies on wildlife have provided inconsistent results. Sera from 440 culled African buffalo (Syncerus caffer), 1-20 years of age, in the Kruger National Park (KNP) in South Africa were all found to be negative in serum virus neutralizing tests against the prototype Neethling strain and a more recent field isolate.65 Conversely, antibodies to LSDV were demonstrated in African buffalo in an area of Kenya where the disease is believed to be endemic.39 In South Africa, blue wildebeest (Connochaetes taurinus), black wildebeest (Connochaetes gnou), springbok and eland (Taurotragus oryx) have been reported to show serological evidence of infection.18
Experimental studies have provided equally equivocal results. Giraffe (Giraffa camelopardalis) and impala (Aepyceros melampus) were found to be highly susceptible to experimental infection125 but two African buffalo calves infected during the same study did not develop disease.125 In a subsequent study a group of nine sero-negative African buffalo comprising five adults and four calves were experimentally infected by subcutaneous inoculation with increasing doses (103 to 106 TCID50) of cell culture-passaged virus derived from a virulent field isolate.65 No skin nodules appeared at the site of inoculation or elsewhere on the skin or mucosae of the animals. Furthermore, seroconversion did not occur within 42 days of infection, while two susceptible control cattle that received 103 and 105 TCID50 respectively, developed skin nodules 12 days later. Both cattle also seroconverted.
In southern Africa LSD is usually more prevalent during the wet summer and autumn months, particularly in low-lying areas and along water courses,6, 7, 33, 44, 60, 63, 81, 87, 90, 119, 122 but outbreaks have also occurred during dry seasons and winter months.60, 90 In this regard, in Albania and other Balkan countries, outbreaks were reported from high mountainous areas where arthropods are not as abundant as in low-lying areas and also during the winter months. According to OIE’s WAHIS database, Albania reported 580 outbreaks in December 2016, 104 outbreaks in January and 17 in February 2017. Greece reported an outbreak in late February 2017 in Corfu and the former Yugoslav Republic of Macedonia (FYROM) one outbreak in early January 2017. Most outbreaks were, however, reported between May and August, in common with the typical seasonality of LSD.49
In African countries, spread of LSD apparently follows road, rail or cattle migration routes.7, 60, 82 In Sudan, for example, it covered a distance of more than 1 000 km across the country in 35 days.7 In Israel, air-borne spread of disease by vectors over more than 100 km has been suggested.123 Although there is as yet no clear evidence of the role of Culicoides midges in the transmission of LSD it is known that these midgescan be carried for long distances by wind currents.
A mathematical model fitted to Albanian data suggested that LSD spreads mostly up to 4 km (i.e. via vectors), but some transmission occurred over much longer distances (i.e. Through animal movement).49
Lumpy skin disease’s mode of transmission has not clearly been established although there is circumstantial evidence suggesting that haematophagous arthropods are largely responsible for mechanical transmission of the infection. Carn and Kitching32 concluded that the low levels of viraemia that occur in infected cattle would be insufficient to support mechanical transmission by biting flies feeding on blood alone and it would therefore be necessary for biting flies to feed on skin lesions to enable ingestion of sufficient virus for transmission to occur. Subclinical infection is common (possibly around 50 per cent of infected animals),111 but the role of sub-clinically infected animals in transmission is uncertain.
Attempts to isolate LSDV from insects, including Culex and Aedes spp., Culicoides spp., and flies belonging to the Muscidae, have mostly been unsuccessful. However, the virus was recovered from Stomoxys spp. and Musca confiscata,45 although attempts to transmit the infection with those flies were unsuccessful.45 In this respect, Stomoxys spp. (stable flies) (Figure 3) have been shown to be capable of transmitting related sheeppox virus.84 An abundance of the Stomoxys flies was associated with outbreaks of LSD in Israel.69 Experimentally, female Aedes aegypti (L.) mosquitoes were shown to transmit the infection from infected to susceptible cattle.35 Lumpy skin disease viral DNA was detected in non-engorged female midges (Culicoides punctatus) from affected areas within a radius of two km from LSDV-infected herds in Turkey.101 Further indirect evidence that a vector(s) is involved in the transmission of LSD was the failure of control measures such as quarantine to halt the spread of the disease in South Africa120 and Kenya.90
Recently, transmission studies have been conducted on the potential of some common African tick species to transmit LSDV. Interrupted feeding is a natural behaviour pattern in male Rhipicephalus appendiculatus (brown ear tick) and Amblyomma hebraeum (African bont tick). Experimentally, R. appendiculatus males were shown to transmit LSDV mechanically from infected to naïve cattle.112 There is less evidence that A. hebraeum males80, 114 behave similarly but it is likely they do. Infected African blue ticks, R. (Boophilus) decoloratus), females were shown to transmit the virus via their eggs to larvae that, in turn, were able to infect naïve cattle.113 Sexual transmission, i.e. in addition to vertical transmission, is also possible although not yet demonstrated. Further work is required to establish whether multiplication of the virus (i.e. virogenesis) occurs in these tick species as well as precise long-term persistence/transmission in ticks. No work has yet been done on closely related tick species in the Middle East such as R. (Boophilus) annulatus, R. praetextatus and Hyalomma extravatum or European tick species to establish their potential vector competence.
Potential arthropod vectors of LSDV probably vary amongst affected regions, depending on the season, environmental temperature and humidity as well as type of vegetation that favour the breeding and survival of different species. For example, in most of sub-Saharan Africa where LSD is endemic, high densities and prevalence of many tick species may be more important as vectors of LSD than in the Middle East and European and Balkan countries where there is a lower variety of ticks, usually at lower densities. In Albania, most dairy cattle are kept indoors in a small confined space and up to four animals may share the same feeding and water troughs. In this setting, ticks would seem to play a minor if any role in the transmission of the disease while saliva and nasal secretions that contaminate hay and drinking water may be more important in transmission of the disease.
In Greece it has been shown that the risk of contracting LSD was six times higher where cattle were kept outdoors than where animals were housed indoors, independent of vaccination status, possibly because of higher exposure to arthropod vectors.49
Lumpy skin disease may spread in the absence of insects although direct transmission by contact between animals would seem to be inefficient in most instances.60, 63 Deliberate attempts to infect susceptible animals by handling them immediately after handling infected animals were unsuccessful.120 However, transmission did occur when common drinking and feeding troughs were used, thus confirming the suspicion that infected saliva may contribute to the spread of the disease.60, 63 Particularly in severely affected animals numerous necrotic lesions are present in the oral and nasal cavities and it is known that high levels of virus are found in lesions. Although more work needs to be done, LSDV can be found in saliva and nasal discharges for up to 18 days in clinically affected animals.15
The disease is transmissible to suckling calves through infected milk and infected cows have been reported to give birth to calves with skin lesions.97
Iatrogenic transmission via contaminated needles during vaccination or other injections may also occur.51
In a study by Weiss (1968)120 LSDV was isolated from the semen of experimentally infected bulls for 22 days after infection. A more recent study by Irons et al.(2005) 68 demonstrated the persistence of live virus in bovine semen for up to 42 days after infection and viral DNA was detected for up to 159 days. In both studies the virus was isolated from the semen of bulls without apparent disease. The epididymis and testis were identified as the sites of persistence of LSDV, viral DNA being detected in all fractions of semen.9 Vaccination of bulls with the South African live attenuated Neethling strain prevented shedding of LSDV in the semen of animals subsequently challenged with wild-type LSDV, and vaccinated animals did not shed vaccine virus in their semen.93 Transmission of LSDV via artificial insemination has also been shown experimentally.8
Lumpy skin disease virus was shown to replicate in sheep by recovery of LSDV from animals inoculated intradermally or subcutaneously with different field isolates of LSDV. The inoculated animals developed localized erythematous swellings at the site of inoculation, as well as enlarged regional lymph nodes from which LSDV was isolated.17
Subcutaneous or intradermal inoculation of cattle with LSDV usually results in the development of a localized swelling at the site of inoculation after four to seven days and enlargement of the regional lymph nodes while generalized eruption of skin nodules usually occurs seven to 19 days after inoculation.120 Animals inoculated intravenously are more inclined to develop generalized lesions and more severe disease.17, 33, 120 However, clinical signs and pathology are variable following both natural and experimental infection; obtaining consistent experimental results is therefore problematic.
Initial experimental investigation indicated that viraemia persisted for about four days.120 However, in more recent studies that employed more sensitive diagnostic methods, viral genomic material could be detected by PCR for up to eight days.115
After experimental infection LSDV was present in skin nodules, lymph nodes, liver, kidneys, saliva, nasal mucosa and semen of infected animals.15, 28, 60, 95, 105, 120 Skin nodules contain high levels of virus (up to 106 TCID50/ml). High levels and shedding of virus were also found in the nasal mucosa of affected animals. The virus has been demonstrated electron microscopically in keratinocytes in the epidermis, and fibroblasts and endothelial cells and pericytes of blood vessels in the dermis in affected parts of the skin.95 Immunohistochemistry revealed that several different cell types may contain LSDV antigen, including keratinocytes, hair follicle epithelium, and fibroblasts and macrophages in the dermis, subcutis and lymph nodes.13, 15
Clinical signs and pathology
The clinical signs and pathology of LSD in naturally and artificially infected cattle are well documented.27, 32, 39, 42, 63, 81, 104, 115, 119 Morbidity rates of five to 45 per cent on affected farms is usual while mortality rates may be as high as 10 per cent even among indigenous cattle.60, 104
Typically, cattle develop a febrile response one to two weeks after exposure to the virus.15, 32, 60, 115 Animals remain febrile for four to 14 days, during which time excessive salivation, lachrymation and a mucoid nasal discharge are evident. The nasal discharge later becomes mucopurulent. Lachrymation may be followed by conjunctivitis, and in a few cases erosions are present in the mucosae of the conjunctivae, ultimately resulting in corneal opacity and blindness (Figure 4). In the majority of affected cattle the superficial lymph nodes are enlarged.
Skin nodules, the characteristic feature of the disease, usually appear two to five days after the initial febrile response (Figures 5 to 8). The nodules, which are randomly distributed and range in diameter from 10 to 30 mm, involve both the skin and subcutaneous tissues and sometimes even the underlying musculature. The size of the nodules is usually fairly uniform but several nodules may fuse to form large, irregularly circumscribed nodules or plaques. The number of nodules may range from a few to several thousand in severely affected animals. The nodules are well-circumscribed, firm, round and raised (Figure 9) and are particularly conspicuous in short-haired animals. In long-haired cattle the nodules are often only recognized when the skin is palpated or moistened.63 In most cases, nodules are particularly noticeable on the perineum and the vulva.120 On cross-section, in the skin nodules in acute or subacute stages of infection are reddish-grey and the dermis and subcutaneous tissues oedematous.104 The subcutis is often infiltrated with a reddish-grey serous fluid.120 Skin lesions either resolve, become indurated (in which case they persist as hard lumps or ‘sitfasts’ for 12 months or longer) (Figure 9) or sequestrate to leave deep ulcers (Figure 10), partly filled with granulation tissue that often suppurates.
In severe acute cases, the ventral parts of the body, for example the dewlap, brisket and the legs (Figure 11) may be slightly too severely oedematous one to two days before the appearance of the nodules and remain so for a week or more.
Figure 5 Severe case of subacute lumpy skin disease: randomly distributed nodules in the skin (Courtesy of Dr Massimo Scacchia, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise "G.Caporale" Via Campo Boario, 64100 Teramo, Italia)
Figure 6 Severe case of subacute lumpy skin disease: numerous nodules in the skin (Courtesy of Dr Massimo Scacchia, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise "G.Caporale" Via Campo Boario, 64100 Teramo, Italia)
Figure 8 Mild case of lumpy skin disease: few nodules randomly distributed over the body (Courtesy of Dr Massimo Scacchia, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise "G.Caporale" Via Campo Boario, 64100 Teramo, Italia)
Figure 9 Chronic lumpy skin disease: fibrotic and indurated skin lesions (Courtesy of Dr Massimo Scacchia, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise "G.Caporale" Via Campo Boario, 64100 Teramo, Italia)
Figure 11 Acute lumpy skin disease: note severe oedematous swelling of the dewlap, brisket, ventral abdomen and thorax and legs
Figure 12 Desquamating lesions on coronary band of the hoof (Courtesy of Dr Massimo Scacchia, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise "G.Caporale" Via Campo Boario, 64100 Teramo, Italia)
Nodular skin lesions may extend into underlying tissue such as tendons and tendon sheaths resulting in lameness in one or more legs (Figure 12). Most affected animals have multifocal, roughly circular, necrotic areas 10-20mm in diameter on the muzzle (Figure 13) and in the respiratory tract (nasal cavity, larynx, trachea and bronchi) and buccal cavity (the inside of the lips, gingivae and dental pad); these lesions may also be present in the fore-stomachs, abomasum, uterus, vagina, teats (Figures 14 and 15), udder, and testes (Figure 16).
In the upper respiratory tract (e.g. larynx and trachea) multiple, well-circumscribed, necrotic areas of about 10-20mm in diameter are common in severe clinical cases (Figures 17 to 19). These necrotic tissues may dislodge and be inhaled, resulting in pneumonia. Stenosis of the trachea may follow healing of these lesions (Figure 19) with scar tissue formation some weeks or months after the acute stage of the disease.42
In bulls, lesions may occur on the scrotum, prepuce, preputial mucosa, the glans penis and in the parenchyma of the testes (Figure 16).63 Acute orchitis may progress to fibrosis and atrophy of the testes, resulting in temporary or permanent infertility or more rarely, sterility. Similarly, lesions in the reproductive tract of cows may result in infertility.
Nodules, necrotic plaques or scabs, 10-20mm in diameter, are commonly present in the skin of the udder and teats (Figures 14 and 15), and, when the parenchyma of the udder is involved, as it frequently is, the gland becomes swollen and tender due to mastitis. Secondary bacterial mastitis may be severe and complicate the udder lesions. Occasionally, parts of the udder may become sequestrated and slough. Involution of the udder as a result of mastitis often causes severe economic losses on dairy farms. Lesions on and in the teats may cause distortions of the teat canal, leading to ascending bacterial infections.
Figure 14 Subacute lumpy skin disease: Numerous ulcerative lesions on the teats and the skin of the udder (Courtesy of Dr Massimo Scacchia, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise "G.Caporale" Via Campo Boario, 64100 Teramo, Italia)
Microscopically the lesions vary considerably depending on the stage of development. In the acute stage of the disease, vasculitis is sometimes accompanied by thrombosis and infarction, as well as perivascular fibroplasia and infiltration by macrophages, some lymphocytes and eosinophils in the dermis and subcutis particularly. The keratinocytes in the epidermis reveal ballooning degeneration and may show evidence of lysis, intra- and intercellular oedema with vesicle formation, as well as some degree of acanthosis, parakeratosis and hyperkeratosis.
During the acute and subacute stages of the disease eosinophilic intracytoplasmic inclusions (Figure 23) that range in size from 1 µm to almost the size of the nucleus may be present, particularly in macrophages and keratinocytes in the skin, but may also be seen in endothelial cells, pericytes, and the acinar and ductal epithelial cells of mucus and serous glands. Ultrastructurally, the viroplasms (inclusions), appear as well-delineated areas of finely granular to fibrillar deposits that contain developing virions, mature viral particles and, occasionally, groups of tubular structures.95 Mature viral particles are apparently randomly distributed in the cytoplasm of affected cells (Figures 20 and 21).95
A presumptive diagnosis of LSD can be made on the characteristic clinical signs but it is advisable to confirm the diagnosis by submitting appropriate samples to a suitably equipped laboratory to confirm the diagnosis.
Classical methods for laboratory diagnosis include serology using the gold standard serum/virus neutralization test, virus isolation on cell culture or histopathology. However, these tests have certain shortcomings including being relatively insensitive, time-consuming and expensive to perform. Thus, more modern molecular-based tests such as polymerase chain reaction (PCR) assays have been introduced to most diagnostic laboratories and are well described in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, Chapters 13/14 on LSD) (www.oie.int).
A detailed history including vaccination status of the herd should accompany the specimens. Biopsies of nodules or scabs on ice, as well as in 10% buffered formalin, are the preferred samples for histopathology, immunohistochemistry (IHC) and transmission electron microscopy (TEM). Fresh skin biopsies or scabs or in virus transport medium, both kept on ice, are preferred samples for molecular studies and virus isolation. Although blood in ethylenediaminetetraacetic acid (EDTA) can be used for virus detection by polymerase chain reaction (PCR) and collected in heparin for virus isolation, detection of viraemia is unreliable because it is frequently of short duration. Oral and nasal swabs can also be taken for PCR or virus isolation. Sera should be collected for serum or virus neutralization testing (the current gold standard assays) and enzyme-linked immunosorbent assay (ELISA) two to three weeks after the first appearance of skin lesions.
The diagnosis of LSD can be confirmed by isolation of LSDV on different cell cultures (see Aetiology). Confirmation is obtained by subjecting the virus to techniques such as PCR and sequencing or fixing and staining the cell monolayer for immunohistochemical analysis.
Serum or virus neutralisation testing (SNT or VNT): The SNT and VNT are essentially the same test, with minor differences, and are used to measure the levels of neutralising antibodies in a serum sample, as an indicator of prior exposure to the virus, either through natural infection or vaccination. However, in general, the immune status of a previously infected or vaccinated animal doesn’t directly correlate to the levels of serum neutralizing antibodies. For example, some animals following natural infection or vaccination may remain seronegative, even though fully protected. In those animals that do develop neutralizing antibodies, levels start to rise approximately one week after detection of fever and reach the highest levels approximately two to three weeks later and then start to decline, eventually dropping below detectable levels. The interpretation of serological results may thus sometimes be difficult.10, 72
Enzyme-linked immunosorbent assay (ELISA): After many attempts to develop an indirect antibody ELISA24, 34 the first validated ELISA has recently become commercially available, facilitating large-scale sero-surveillance for LSD in unvaccinated cattle populations. This ELISA (manufactured by IDVet) is able to detect antibodies against capripoxviruses (LSDV, SPPV and GTPV) from approximately 20 days until seven months post-vaccination. Its sensitivity is therefore better than the SNT and its specificity is 99.7 per cent. Individual animals with low antibody levels such as those in the early stage of infection or with mild disease or a low antibody response to vaccine may not be identified.49 In addition, another serological assay, the immunoperoxidase monolayer assay (IPMA)59 has been developed for LSDV. This assay is comparable to the SNT, but it is labour-intensive and requires experienced personnel to interpret the result. Live virus is used and therefore the assay should be performed in high bio-containment laboratories in areas where the disease is non-endemic. The assay is not suitable for large scale testing.
It is not possible to distinguish antibody responses resulting from infection with wild-type LSDV from those following vaccination with currently available attenuated LSDV vaccines (DIVA testing).
An antigen-trapping ELISA has been developed to detect viral antigen in skin lesions.10, 31 However, the molecular methods described have made this assay obsolete.
The macroscopic lesions of a typical severe case of LSD will leave little doubt that you are dealing with the disease, but less typical and milder cases should be differentiated from other conditions (see Differential diagnosis). Although the intracytoplasmic inclusion bodies in keratinocytes in haematoxylin and eosin-stained sections of acute skin nodules may support a diagnosis of LSD, these inclusions are not always present in all acute cases (see Pathology) and are not discernible in subacute and chronic skin lesions.
More specific immunohistochemical methods, for example immunoperoxidase staining of tissue sections, can be used to demonstrate the virus in formalin-fixed skin lesions and tissues. Immunohistochemistry using a monoclonal antibody was used to detect LSDV antigen in skin nodules from animals with acute LSD, as well as in some subacute or chronic cases of the disease. The sensitivity of this assay was comparable to PCR.13
Transmission electron microscopy (TEM)
In specialized laboratories the diagnosis can be confirmed within a few hours of receipt of specimens by TEM demonstration of virus in negatively-stained preparations of biopsies or scabs taken from affected skin.40
Polymerase chain reaction (PCR)
As stated previously (see Aetiology), members of the genus Capripoxvirus (SPPV, GTPV and LSDV) are genetically similar with nucleotide homology greater than 96 per cent.109 This genetic similarity has enabled rapid, sensitive and validated conventional10, 62, 67 and real-time group-specific PCR23 assays to be developed that are gaining acceptance in an ever increasing number of national reference laboratories. There are also several PCR-based commercial diagnostic kits available for the detection of capripoxviruses (e.g. Techne quantitative PCR [qPCR] test, Genesi Standard and Advanced Kit, Tetracore, Biosellal).49 Some assays are also able to differentiate between SPPV, GTPV and LSDV75-78 and a one-step multiplex RT-qPCR assay has recently become available for simultaneous detection of peste des petits ruminants virus, capripoxviruses, Pasteurella multocida and Mycoplasma capricolum subspecies capripneumoniae.100
Polymerase chain reaction assays are also available to differentiate between wild-type LSDV and attenuated vaccine LSDV when clinical signs are detected in animals following vaccination.2, 3, 49, 71, 85, 86, 118
Sometimes during an outbreak of LSD, characteristic clinical signs may be detected in cattle vaccinated with attenuated SPPV or GTPV-containing vaccines. Species-specific genotyping PCR methods can be used to determine if the vaccine virus or wild-type LSDV is the cause of disease in these cases.56, 57 These same PCR assays are suitable to confirm the presence of SPPV or GTPV in certain wild antelope species that are susceptible to these viruses.
Four loop-mediated isothermal amplification (LAMP) assays36, 89, 117, 127 are available for diagnostic purposes. The advantage of these LAMP assays is that they can be performed inexpensively compared to real-time PCR and do not require expensive equipment. Recently the first PCR assay utilizing a portable thermocycler has been described.11
As the price for sequencing is continually being reduced, sequencing of whole viral genomes is now relatively cheap, fast and simple and provides a wealth of information. Sequencing of virulent and vaccine isolates of LSDV revealed a number of differences between the isolates,55, 70 with the field isolates being more highly conserved, as expected, compared to the multiple cell-passaged vaccine strains.
The skin lesions of LSD can be confused with pseudo-lumpy skin disease caused by bovine herpesvirus-2 infection. Generally, the latter causes more superficial lesions affecting only the epidermis while in LSD the lesions are deep-seated, involving the epidermis, dermis and other subcutaneous tissues as well as other tissues and organs. Pseudo-lumpy skin disease is a mild disease and apart from a brief febrile reaction, affected animals show no signs of systemic illness and full recovery is usual. In LSD on the other hand, the disease is characterized by prominent signs of systemic disease in severely affected animals (see Clinical signs and pathology). Molecular and other appropriate diagnostic methods should be applied to confirm the diagnosis (see Diagnosis). In contrast to the intracytoplasmic inclusions in LSD, intranuclear inclusion bodies (Figure 22) are found in keratinocytes in pseudo-lumpy skin disease caused by BHV-2 infection.120
Skin lesions caused by allergic reactions, nodular lesions resulting from arthropod bites such as ticks as well as Demodex infection, dermatophilosis, onchocercosis and besnoitiosis also need to be differentiated from LSD skin lesions.
Control of LSD in endemic countries in Africa
In most African countries, LSD control has relied mainly on vaccination, with no movement control or stamping-out. Vaccination is voluntary and aimed at clinical protection rather than decreasing and eventually eliminating the circulating virus. In endemic situations, outbreaks of LSD occur intermittently, consequently vaccination is often neglected in interepidemic periods. Although preventative vaccination (see below) should be conducted annually, that is usually only carried out in relatively few commercial dairy and beef herds. Most subsistence or small-scale farmers do not routinely vaccinate their cattle against LSD and may only do so in the face of an outbreak.
In most instances mildly affected animals with only a few skin nodules will recover without any treatment while those that are severely affected should be provided with quality palatable feed and should be well cared for. Prolonged supportive treatment with antibiotics and anti-inflammatory drugs should also be given to combat secondary infections, pneumonia, mastitis and orchitis. The prognosis of severely affected animals is grave as they will most probably not recover fully and will die or remain unthrifty notwithstanding proper care and therapy and should preferably be culled to avoid ongoing losses.
Control of LSD in non-endemic countries (epidemic situations)
During the widespread outbreaks of LSD in 2015/16 in Greece, western Balkan and Caucasus countries, it became evident that vaccination, in combination with cattle movement control, were crucial in halting the spread of the virus and that a range of other interventions were also required to diagnose and control the disease.51 Lumpy skin disease was a “new” disease for this region and it was considered a regional problem, involving many countries, and consequently it could best be dealt with through a coordinated multi-national effort.51 The following actions were taken in these countries in an attempt to combat the devastating consequences of the disease:
All of the Balkan countries affected by LSD in 2016 used the attenuated Neethling strain LSDV vaccine, either obtained from the European Commission vaccine bank or directly sourced from the manufacturers. In the early stages of the outbreaks, some of the countries experienced severe delays in acquiring LSD vaccines due to lack of financial resources, legal or bureaucratic obstacles and cumbersome tender procedures.
The live attenuated LSD vaccines are not registered for use within the European Union. In order to use these vaccines, a Member State must provide a detailed vaccination plan to the European Commission to obtain authorization to apply vaccination. Also preemptive vaccination affects the official disease-free status of the country, resulting in restrictions to trade in live cattle and their products. For this reason, competent veterinary authorities and farmers of those countries neighbouring the infected areas were unwilling to adopt vaccination. Later, the Commission Implementing Decision (EU) 2016/2008 was changed to allow the movement of vaccinated animals, under specified conditions and under bi-lateral agreements that reduced some of these drawbacks. The European Union also provided specific rules for movement of cattle products, such as dairy products, semen, ova and hides that were considered to be risks for transmitting LSD. A distinction was made between zones where animals were vaccinated preventively, i.e. in the absence of disease (free zones with vaccination) and zones where disease had been reported (infected zones with vaccination). Milk and dairy products from free zones with vaccination were not restricted with specific conditions but certain restrictions were implemented in infected zones with vaccination. In both free and infected zones, it was required that at least 28 days should lapse after vaccination before any movement of animals or their products could take place. The aim was to attain 100 per cent vaccination coverage and to carry out clinical surveillance in these zones.
In Balkan countries it became evident that vaccination of the entire cattle population, including pregnant animals and calves, was the most effective measure to prevent the spread of LSD, especially if it was applied before the virus entered the region or a country. It has been shown that if vaccination is properly done, the additional benefits derived from stamping-out are limited.47 Achieving the highest vaccination coverage in the shortest period of time is therefore recommended for the control of LSD outbreaks, coupled with good clinical surveillance for detection of clinical cases caused by wild-type virus from cases resulting from vaccine virus.49
The following vaccines are currently commercially available for the control of LSD:
Attenuated LSDV vaccines: In 1963 Weiss produced the first attenuated LSDV vaccine by 60 serial passages of the LSDV prototype Neethling strain in lamb kidney cells, followed by 20 serial passages in the chorio-allantoic membranes of eight day-old embryonated hen’s eggs. According to Weiss, this attenuated LSDV was safe when inoculated into cattle of all ages and was more effective when applied subcutaneously rather than intradermally. A local swelling (nodule) developed at the inoculation site in 50 per cent of cattle but did not generalize or cause ill-health of vaccinated animals. The local nodules disappeared within four to six weeks without complications.120
According to the recommendations of Onderstepoort Biological Products (OBP, South Africa), susceptible adult cattle should be vaccinated annually to ensure adequate protection. Under field conditions approximately 50 per cent of cattle may develop a swelling 10 to 20 mm in diameter at the point of inoculation and this may be accompanied by a temporary drop in milk yield in dairy cows. The swelling disappears within a few weeks. Calves whose dams were either naturally infected or immunized should be vaccinated at four to six months of age to preclude interference by maternal antibody. However, calves born to non-vaccinated cows are highly susceptible and should be vaccinated irrespective of age in the face of an outbreak.
In Israel a low percentage (0.5 per cent) of animals vaccinated with the attenuated Neethling strain of LSDV showed a vaccine reaction referred to as “Neethling disease”.20 In Balkan countries, following vaccination of cattle with attenuated Neethling strain LSDV vaccine, adverse reactions were apparently more frequent and severe compared with the potential adverse effects described by the manufacturer on the information leaflet that accompanied the vaccine namely “swelling at vaccine injection site” and “temporary decrease in daily milk yield”. In Greece, a decreased daily milk yield, lasting for more than two weeks, was reported by farmers. Most of the reactions occurred 10-14 days after vaccination and were characterized by a fever lasting a couple of days and a small nodule at the injection site, lasting sometimes for more than 15 days. Some animals developed a few to many nodules all over the body. In some of these cases PCR assays were done and these confirmed that the “LSD-like signs” were indeed caused by attenuated LSDV vaccine. Occasionally a big oedematous swelling occurred at the injection site that gravitated to the ventral parts of the neck and abdomen that lasted up to 30 days.71, 103 Although no explanation for these swellings was given, they could have been due to the use of contaminated needles.
So-called “Neethling disease” is a rare condition for a short period after vaccination and is clinically much milder than LSD. Its true occurrence is difficult to estimate with accuracy as in most instances vaccination campaigns were initiated when outbreaks were already ongoing. However, data collected from Croatia, which was the first non-affected country that applied preventive vaccination campaigns against LSDV in high-risk regions showed that only 0.09 per cent of vaccinated cattle developed adverse reactions.48 A recent study claimed that the incidence of side effects following vaccination was underestimated.19
Table 1 lists currently available commercial vaccines.
Table 1 Commercially available attenuated LSDV vaccines
Lumpy skin disease vaccine for cattle
Live attenuated Neethling strain of LSDV
Onderstepoort Biological Products, (OBP), South Africa
Live attenuated LSDV field strain(SIS)
MSD Animal Health, South Africa
Live attenuated LSDV
MCI Sante Animale, Morocco
Attenuated LSDV vaccine
Live attenuated LSDV
National Veterinary Institute of Ethiopia
Live attenuated LSDV vaccine
Kenya Veterinary Vaccines Production Institute-KEVEVAPI
Attenuated sheeppox- and goatpoxvirus vaccines: Several SPPV and GTPV vaccines have been used to protect cattle against LSDV in countries where these diseases overlap.20, 53 The so-called Kenyan sheep and goat pox O-240 and O-180 strains have been used as vaccine strains in Kenya and elsewhere to control LSD.28-30, 82, 124 Recently, this vaccine strain was shown to have been derived from LSDV.116
Attenuated SPPV or GTPV vaccines have often been used at increased dosages compared to the doses that are recommended for small ruminants to vaccinate cattle against LSD. For example, in Israel in 2013 the attenuated Neethling strain LSDV vaccine was shown to be more effective in preventing LSD than the RM65 SPPV vaccine used at ten times the small ruminant dose.20 Yugoslavian RM65 SPPV vaccine has been used in cattle in the Middle East at 10 times the dose that is prescribed in sheep. Romanian SPPV vaccine has been used to control LSD in Egypt, Bakirköy SPPV was used in cattle in Turkey at 3 or 10 times the dose in sheep and in Russia a local SPPV strain was used to control LSD.
Immunity after recovery from natural infection is believed to be lifelong in most cattle.120 After vaccination, antibodies appear within 15 days and reach the highest level in 30 days, dropping gradually to below detectable levels. Some vaccinated animals did not seroconvert although they are fully protected.120 Annual revaccination is recommended by vaccine manufacturers. By 28 days after vaccination, animals will have a protective immunity.14, 66
In Greece and most affected Balkan countries, total stamping-out was carried out before vaccination with live attenuated vaccines was approved for use. Greece and Bulgaria applied total stamping-out of all infected and in-contact animals throughout the epidemics. The negative impact of total stamping-out on peoples’ livelihoods, food security and welfare should not be underestimated, particularly as it concerns the most vulnerable producers whose few animals are often their main source of income. According to the European Food Safety Authority (EFSA) Urgent Advice on LSD, vaccination has a greater impact in reducing LSDV spread than stamping-out and that when vaccination was properly done, the additional benefits of stamping-out were limited.47
In some affected countries, culling of severely affected animals (modified or partial stamping-out) from the herd was recommended as they were regarded as a more important source of virus for haematophagous insects than subclinically infected animals and a full recovery of the former was unlikely (Figure 24). In order for farmers to cooperate, compensation was paid for those cattle that died or were culled due to LSD.
Culling of animals should be done in a humane and safe manner with prompt and appropriate disposal of carcasses, which should be sprayed with disinfectant and insect repellent prior to disposal to prevent insects feeding on them. Cleansing and disinfection of holdings are important measures to prevent spreading of the virus by indirect means. FAO has provided practical recommendations for decontamination of premises, equipment and the environment in the Animal Health Manual on Procedures for Disease Eradication by Stamping Out.50
Although not precisely specified, LSDV like other poxviruses can survive for prolonged periods in the environment and therefore restocking should be done after a minimum waiting period of 21 days, as specified in the current EU legislation (Council Directive 92/119/EEC), and the restocked animals vaccinated at least 28 days before introduction into formerly infected locations.
Movement of unvaccinated cattle for trade, slaughter or communal or seasonal grazing is the major risk for spreading the disease. Implementing effective movement control is challenging and not always successful.
The guidelines by OIE specify that protection (3 km), surveillance (20 km) and restriction (at least 50 km) zones need to be established around outbreaks. Commission Implementing Decision (EU) 2016/2008 requires the establishment of an increased surveillance area of at least 20 km around the area where vaccination is practised, in which intensified surveillance is conducted and the movement of cattle is subject to official controls. A recent recommendation is to establish a vaccination zone of at least 50 km radius around the infected area, with at least 90 per cent vaccination cover.51
Efforts should be made to institute vector control on the animals or in the barns and stables where the animals are kept. Spot-on products, dipping or spraying of cattle with acaricides and insect repellents can be used in an attempt to reduce transmission by vectors.
Other measures: Large-scale awareness campaigns on the importance and other aspects of LSD to all stakeholders are crucial to ensure success in the implementation of effective surveillance, monitoring, control and eradication of LSD. Particular effort should be made to detect and report LSD as early as possible through active clinical surveillance, followed by sample collection from infected and suspected animals. Diagnostic capacities of local laboratories should be capable of dealing with the large number of specimens received.
- ABUTARBUSH, S.M., ABABNEH, M.M., AL ZOUBI, I.G., AL SHEYAB, O.M., AL ZOUBI, M.G., ALEKISH, M.O. & AL GHARABAT, R.J., 2015. Lumpy skin disease in Jordan: disease emergence, clinical signs, complications and preliminary-associated economic losses. Transboundary and Emerging Diseases 62, 549-554.
- AGIANNIOTAKI, E.I., MATHIJS, E., VAN DEN BUSSCHE, F., TASIOUDI, K.E., HAEGEMAN, A., ILIADOU, P., CHAINTOUTIS, S.C., DOVAS, C.I., VAN BORM, S., CHONDROKOUKI, E.D. & DE CLERCQ, K., 2017. Complete genome sequence of the lumpy skin disease virus isolated from the first reported case in Greece in 2015. Genome Announcements, 5(29). pii: e00550-17.
- AGIANNIOTAKI, E.I., TASIOUDI, K.E., CHAINTOUTIS, S.C., ILIADOU, P., MANGANA-VOUGIOUKA, O., KIRTZALIDOU, A. & CHONDROKOUKI, E., 2017. Lumpy skin disease outbreaks in Greece during 2015-16, implementation of emergency immunization and genetic differentiation between field isolates and vaccine virus strains. Veterinary Microbiology, 201, 78–84. https://doi.org/10.1016/j.vetmic.2016.12.037.
- AL-SALIHI, K.A. & HASSAN, I.Q., 2015. Lumpy skin disease in Iraq: Study of the disease emergence. Transboundary and Emerging Diseases, e pub March 17, 2015. DOI: 10.1111/tbed.12386.
- ALEXANDER, R.A., PLOWRIGHT, W. & HAIG, D.A., 1957. Cytopathogenic agents associated with lumpy skin disease of cattle. Bulletin of Epizootic Diseases of Africa, 5, 489–492.
- ALI, A.A., ESMAT, M., ATTA, H., SELIM, A. & ABDEL-HAMID, Y.M., 1990. Clinical and pathological studies on lumpy skin disease in Egypt. The Veterinary Record, 127, 549–550.
- ALI, B.H. & OBEID, H.M., 1977. Investigation of the first outbreak of lumpy skin disease in the Sudan. British Veterinary Journal, 133, 184–189.
- ANNANDALE, C.H., HOLM, D.E., EBERSOHN K. & VENTER E.H., 2013. Seminal transmission of lumpy skin disease virus in heifers. Transboundary Emerging Disease, 61 (5), 443–448. doi:10.1111/tbed.12045.
- ANNANDALE, C.H., IRONS, P.C., BAGLA, V.P., OSUAGWUH, U.I. & VENTER E.H., 2010. Sites of persistence of lumpy skin disease virus in the genital tract of experimentally infected bulls. Reproduction in Domestic Animals, 45 (2), 250-255. doi:10.1111/j.1439-0531.2008.01274.x.
- ANON, 1996. Manual of Standards for Diagnostic Tests and Vaccines. 4th Edition. Office International des Epizooties, World Health Organization.
- ARMSON, B., FOWLER, V., TUPPURAINEN, E., HOWSON, E.L.A., MADI, M., SALLU, R., KASANGA, C. J., PEARSON, C., WOOD, J., MARTIN, P., MIOULET, V. & KING, D.P., 2015. Detection of Capripoxvirus DNA Using a field-ready nucleic acid extraction and real-time PCR platform. Transboundary and Emerging Diseases, Online: 25 NOV 2015. doi: 10.1111/tbed.12447.
- ARNAUD, G., GOURREAU, J.M., VASSART, M., NGUYEN-BA-VY, WYERS, M. & LEFEVRE, P.C., 1992. Capripoxvirus disease in an Arabian oryx (Oryx leucoryx) from Saudi Arabia. Journal of Wildlife Diseases, 28, 295–300.
- AWADIN, W., HUSSEIN, H., ELSEADY, Y., BABIUK, S. & FURUOKA, H., 2011. Detection of lumpy skin disease virus antigen and genomic DNA in formalin-fixed paraffin-embedded tissues from an Egyptian outbreak in 2006. Transboundary and Emerging Disease, 58, 451-457.
- AYELET, G., ABATE, Y., SISAY, T., NIGUSSIE, H., GELAYE, E., JEMBERIE, S. & ASMARE, K., 2013. Lumpy skin disease: preliminary vaccine efficacy assessment and overview on outbreak impact in dairy cattle at Debre Zeit, central Ethiopia. Antiviral Research, 98, 261– 265.
- BABIUK, S., BOWDEN, T.R., PARKYN, G., DALMAN, B., MANNING, L., NEUFELD, J., EMBURY-HYATT, C., COPPS, J. & BOYLE, D.B., 2008. Quantification of lumpy skin disease virus following experimental infection in cattle. Transboundary and Emerging Disease, 55, 299-307.
- BABIUK, S., PARKYN, G., COPPS, J., LARENCE, J.E., SABARA, M.I., BOWDEN, T.R., BOYLE, D.B. & KITCHING, R.P., 2007. Evaluation of an ovine testis cell line (OA3.Ts) for propagation of capripoxvirus isolates and development of an immunostaining technique for viral plaque visualization. Journal of Veterinary Diagnostic Investigation, 19, 486-491.
- BARNARD, B.J.H., 1981–1987. Onderstepoort Veterinary Institute, South Africa. Personal observation.
- BARNARD, B.J.H., 1997. Antibodies against some viruses of domestic animals in South African wild animals. Onderstepoort Journal of Veterinary Research, 64, 95–110.
- BEDEKOVIC´, T., SˇIMIC´, I., KRESˇIC´, N., & LOJKIC´, I., 2017. Detection of lumpy skin disease virus in skin lesions, blood, nasal swabs and milk following preventive vaccination. Transboundary and Emerging Diseases, (July), 6–11. https://doi.org/10.1111/tbed.12730).
- BEN-GERA, J., KLEMENT, E., KHINICH, E., STRAM, Y. & SHPIGEL, N.Y., 2015. Comparison of the efficacy of Neethling lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease - The results of a randomized controlled field study. Vaccine, 33, 4837-4842.
- BINEPAL, Y. S., ONGADI, F. A. & CHEPKWONY, J. C., 2001. Alternative cell lines for the propagation of lumpy skin disease virus. Onderstepoort Journal of Veterinary Research, 68, 151-153.
- BLACK, D.N., HAMOND, J.M. & KITCHING, R.P., 1986. Genomic relationship between capripoxviruses. Virus Research, 5, 277–292.
- BOWDEN, T.R., BABIUK, S.L., PARKYN, G.R., COPPS, J.S. & BOYLE, D.B., 2008. Capripoxvirus tissue tropism and shedding: A quantitative study in experimentally infected sheep and goats. Virology, 371, 380-393.
- BOWDEN, T.R., COUPAR, B.E., BABIUK, S.L., WHITE, J.R., BOYD, V., DUCH, C.J., SHIELL, B.J., UEDA, N., PARKYN, G.R., COPPS, J.S. & BOYLE, D.B., 2009. Detection of antibodies specific for sheeppox and goatpox viruses using recombinant capripoxvirus antigens in an indirect enzyme-linked immunosorbent assay. Journal of Virological Methods, 161, 19-29.
- BRENNER, J., BELLAICHE, M., GROSS, E., ELAD, D., OVED, Z., HAIMOVITZ, M., WASSERMAN, A., FRIEDGUT, O., STRAM, Y., BUMBAROV, V. & YADIN, H., 2009. Appearance of skin lesions in cattle populations vaccinated against lumpy skin disease: Statutory challenge. Vaccine, 27, 1500-1503.
- BURDIN, M.L., 1959. The use of histopathological examination of skin material for the diagnosis of lumpy skin disease in Kenya. Bulletin of Epizootic Diseases of Africa, 7, 27–36.
- BURDIN, M.L. & PRYDIE, J., 1959. Observations on the first outbreak of lumpy skin disease in Kenya. Bulletin of Epizootic Diseases of Africa, 7, 21.
- CAPSTICK, P.B., 1959. Lumpy skin disease: Experimental infection. Bulletin of Epizootic Diseases of Africa, 7, 51–62.
- CAPSTICK, P.B. & COACKLEY, W., 1961. Protection of cattle against lumpy skin disease. I. Trials with a vaccine against Neethling type infection. Research in Veterinary Science, 2, 362.
- CAPSTICK, P.B., PRYDIE, J., COACKLEY, W. & BURDIN, M.L., 1959. Protection of cattle against ‘Neethling’ type virus of lumpy skin disease. The Veterinary Record, 71, 422.
- CARN, V.M., 1995. An antigen trapping ELISA for the detection of capripoxviruses in tissue culture supernatant and biopsy samples. Journal of Virological Methods, 51, 95–102.
- CARN, V.M. & KITCHING, R.P., 1995. The clinical response of cattle experimentally infected with lumpy skin disease (Neethling) virus. Archives of Virology, 140, 503–513.
- CARN, V.M. & KITCHING, R.P., 1995. An investigation of possible routes of transmission of lumpy skin disease virus (Neethling). Epidemiology and Infection, 114, 219–226.
- CARN, V.M., KITCHING, R.P., HAMMOND, J.M. & CHAND, P., 1994. Use of a recombinant antigen in an indirect ELISA for detecting bovine antibody to capripoxvirus. Journal of Virological Methods, 49, 285–294.
- CHIHOTA, C.M., RENNIE, L.F., KITCHING, R.P. & MELLOR, P.S., 2001. Mechanical transmission of lumpy skin disease virus by Aedes aegypti (Diptera : Culicidae). Epidemiology & Infection, 126 (2), 317–321.
- DAS, A., BABIUK, S. & MCINTOSH, M.T., 2012. Development of a loop-mediated isothermal amplification assay for rapid detection of capripoxviruses. Journal of Clinical Microbiology, 50, 1613-1620.
- DAVIDSON, M., 1990. State Veterinary Service, Ministry of Agriculture, Tel Aviv, Israel. Personal communication.
- DAVIES, F.G., 1982. Observations on the epidemiology of lumpy skin disease in Kenya. Journal of Hygiene, 88, 95–102.
- DAVIES, F.G., 1991. Lumpy skin disease of cattle: A growing problem in Africa and the Near East. World Animal Review, 68, 37–42.
- DAVIES, F.G., KRAUSS, H., LUND, L.J., & TAYLOR, M., 1971. The laboratory diagnosis of lumpy skin disease. Research in Veterinary Science, 12, 123–127.
- DAVIES, F.G. & OTEMA, C., 1981. Relationship of capripox viruses found in Kenya with two Middle Eastern strains and some orthopox viruses. Research in Veterinary Science, 31, 253–255.
- DE BOOM, H.P.A., 1948. Knopvelsiekte. South African Scientific Bulletin, 1, 44–46.
- DE LANGE, M., 1959. The histopathology of the cytopathogenic changes produced in monolayer epithelial cultures by viruses associated with lumpy skin disease. Onderstepoort Journal of Veterinary Research, 28, 245.
- DIESEL, A.M., 1949. The epizootiology of lumpy skin disease in South Africa. Proceedings of the 14th International Veterinary Congress, London, 2, 492–500.
- DU TOIT, R.M. & WEISS, K.E., 1960. Onderstepoort Veterinary Institute, South Africa. Unpublished observations.
- EL-NAHAS, E.M., EL-HABBAA, A.S., EL-BAGOURY, G.F. & RADWAN, M.E.I., 2011. Isolation and identification of lumpy skin disease virus from naturally infected buffaloes at Kaluobia, Egypt. Global Veterinaria, 7, 234-237
- EUROPEAN FOOD SAFETY AUTHORITY (EFSA)., 2016. Strengthening regional cooperation in South East Europe and Middle East for prevention and control of Lumpy Skin Disease (LSD). 13, EFSA supporting publication, 1059, 2019.
- EUROPEAN FOOD SAFETY AUTHORITY (EFSA)., 2017. Lumpy skin disease: I. Data collection and analysis, European Food Safety Authority Journal, 15(4), 4773.
- EUROPEAN FOOD SAFETY AUTHORITY (EFSA)., 2018. Scientific report on lumpy skin disease II. Data collection and analysis. European Food Safety Authority Journal, 16(2), 5176, 33. https://doi.org/10.2903/j.efsa.2018.5176.
- FAO., 2001. Animal Health Manual on Procedures for Disease Eradication by Stamping Out, Rome, Italy.
- FAO., 2017. Sustainable prevention, control and elimination of lumpy skin disease – Eastern Europe and the Balkans. FAO Animal Production and Health Position Paper. No. 2. Rome, Italy.
- FENNER, F., BACHMANN, P.A., GIBBS, E.P.J., MURPHY, F.A., STUDDERT, M.J. & WHITE, W.O., 1987. Veterinary Virology. New York, London, Sydney, Tokyo, Toronto: Academic Press.
- GARI, G., ABIE, G., GIZAW, D., WUBETE, A., KIDANE, M., ASGEDOM, H., BAYISSA, B., AYELET, G., OURA, C.A., ROGER, F. & TUPPURAINEN, E.S., 2015. Evaluation of the safety, immunogenicity and efficacy of three capripoxvirus vaccine strains against lumpy skin disease virus. Vaccine, 33, 3256-61.
- GARI, G., BONNET, P., ROGER, F. & WARET-SZKUTA, A., 2011, Epidemiological aspects and financial impact of lumpy skin disease in Ethiopia. Preventive Veterinary Medicine, 102, 274-283.
- GELAYE, E., BELAY, A., AYELET, G., JENBERIE, S., YAMI, M., LOITSCH, A., TUPPURANEN, E., GRABHERR, R., DIALLO, A. & LAMIEN, C., 2015. Capripox disease in Ethiopia: Genetic differences between field isolates and vaccine strain, and implications for vaccination failure. Antiviral Research, 119, 28–35.
- GELAYE, E., LAMIEN, C.E., SILBER, R., TUPPURAINEN, E.S., GRABHERR, R. & DIALLO, A., 2013. Development of a cost-effective method for capripoxvirus genotyping using snapback primer and dsDNA intercalating dye. PLoS One, 8, e75971.
- GELAYE, E., MACH, L., KOLODZIEJEK, J., GRABHERR, R., LOITSCH, A., ACHENBACH, J.E., NOWOTNY, N., DIALLO, A. & LAMIEN, C.E., 2017. A novel HRM assay for the simultaneous detection and differentiation of eight poxviruses of medical and veterinary importance. Scientific Reports, 7, 42892.
- GREEN, H.F., 1959. Lumpy skin disease: Its effect on hides and leather and a comparison in this respect with some other skin diseases. Bulletin of Epizootic Diseases of Africa, 7, 63.
- HAEGEMAN, A., ZRO, K., SAMMIN, D., VAN DEN BUSSCHE, F., ENNAJI, M.M. & DE CLERCQ, K., 2015. Investigation of a possible link between vaccination and the 2010 sheep pox epizootic in Morocco. Transboundary Emerging Disease. Epub March 9. doi:10.1111/tbed.12342.
- HAIG, D.A., 1957. Lumpy skin disease. Bulletin of Epizootic Diseases of Africa, 5, 421–430.
- HEDGER, R.S. & HAMBLIN, C., 1983. Neutralizing antibodies to lumpy skin disease virus in African wildlife. Comparative Immunology and Microbiology of Infectious Diseases, 6, 209–213.
- HEINE, H.E., STEVENS, M.P., FORD, A.G. & BOYLE, D.B., 1999. A capripoxvirus detection PCR and antibody ELISA based on the major antigen P32, homologue of the vaccinia virus H3L gene. Journal of Immunological Methods, 227, 187–196.
- HENNING, M.W., 1956. Animal Diseases in South Africa. 3rd Edition. Cape Town: Central News Agency.
- HOUSE, J.A., WILSON, T.M., EL NAKASHLY, S., KARIM, I.A., ISMAIL, I., EL DANAF, N., MOUSSA, A M. & AYOUB, N.N., 1990. The isolation of lumpy skin disease virus and bovine herpesvirus-4 from cattle in Egypt. Journal of Veterinary Diagnostic Investigation, 2, 111–115.
- HOWELL, P.G. & COETZER, J.A.W., 1998. Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, South Africa. Unpublished data.
- HUNTER, P. & WALLACE, D., 2001. Lumpy skin disease in southern Africa: a review of the disease and aspects of control. Journal of the South African Veterinary Association, 72, 68–71.
- IRELAND, D.C. & BINEPAL, Y.S., 1998. Improved detection of capripoxvirus in biopsy samples by PCR. Journal of Virological Methods, 74, 1–7.
- IRONS, P.C., TUPPURAINEN, E.S.M. & VENTER, E. H., 2005. Excretion of lumpy skin disease virus in bull semen. Theriogenology, 63, 1290-1297.
- KAHANA-SUTIN, E., KLEMENT, E., LENSKY, I. & GOTTLIEB, Y., 2017. High relative abundance of the stable fly Stomoxys calcitrans is associated with lumpy skin disease outbreaks in Israeli dairy farms. Medical and Veterinary Entomology, 31 (2), 150–160. doi:10.1111/mve.12217.
- KARA P.D., AFONSO C.L., WALLACE D.B., KUTISH G.F., ABOLNIK C., LU Z., VREEDE F.T., TALJAARD L.C., ZSAK A., VILJOEN G.J. & ROCK D.L., 2003.Comparative sequence analysis of the South African vaccine strain and two virulent field isolates of lumpy skin disease virus. Archives of Virology, 148, 1335-1356.
- KATSOULOS, P.D., CHAINTOUTIS, S.C., DOVAS, C.I., POLIZOPOULOU, Z.S., BRELLOU, G.D., AGIANNIOTAKI, E.I., TASIOUDI, K.E., CHONDROKOUKI, E., PAPADOPOULOS, O., KARATZIAS, H. & BOSCOS, C., 2017. Investigation on the incidence of adverse reactions, viraemia and haematological changes following field immunization of cattle using a live attenuated vaccine against lumpy skin disease. Transboundary and Emerging Diseases. doi:10.1111/tbed.12646.
- KITCHING, R.P. & HAMOND, J.M., 1991. Poxvirus, infection and immunity. In: ROITT, I.M. & DELVES, P.J., (eds). Encyclopaedia of Immunology, London: Academic Press, 3, 1261–1264.
- KITCHING, R.P. & TAYLOR, W.P., 1985. Transmission of capripoxviruses. Research in Veterinary Science, 39, 196–199.
- KITCHING, R.P., HAMOND, J.M. & BLACK, D.N., 1986. Studies on the major common precipitating antigen of capripoxvirus. Journal of General Virology, 67, 139–148.
- LAMIEN, C.E., LE GOFF, C., SILBER, R., WALLACE, D.B., GULYAZ, V., TUPPURAINEN, E., MADANI, H., CAUFOUR, P., ADAM, T., EL HARRAK, M., LUCKINS, A.G., ALBINA, E. & DIALLO, A., 2011. Use of the Capripoxvirus homologue of Vaccinia virus 30 kDa RNA polymerase subunit (RPO30) gene as a novel diagnostic and genotyping target: Development of a classical PCR method to differentiate goat poxvirus from sheep poxvirus. Veterinary Microbiology, 149, 30-39.
- LAMIEN, C.E., LELENTA, M., GOGER, W., SILBER, R., TUPPURAINEN, E., MATIJEVIC, M., LUCKINS, A. G. & DIALLO, A., 2011. Real time PCR method for simultaneous detection, quantitation and differentiation of capripoxviruses. Journal of Virological Methods, 171 (1), 134-140.
- LE GOFF, C., FAKHFAKH, E., CHADEYRAS, A., ABA-ADULUGBA, E., LIBEAU, G., HAMMAMI, S., DIALLO, A. & ALBINA, E., 2005. Host-range phylogenetic grouping of capripoxviruses: genetic typing of CaPVs. In Applications of Gene-based Technologies for Improving Animal Production and Health in Developing Countries, MAKKAR, H.P.S. & VILJOEN, G.J. (eds). IAEA, The Netherlands, 727-733.
- LE GOFF, C., LAMIEN, C.E., FAKHFAKH, E., CHADEYRAS, A., ABA-ADULUGBA, E., LIBEAU, G., TUPPURAINEN, E., WALLACE, D. B., ADAM, T., SILBER, R., GULYAZ, V., MADANI, H., CAUFOUR, P. HAMMAMI, S., DIALLO A. & ALBINA, E., 2009. Capripoxvirus G-protein-coupled chemokine receptor: a host-range gene suitable for virus animal origin discrimination. Journal of General Virology, 90, 1967-1977.
- LE ROUX, P.L., 1945. Notes on the probable cause, prevention and treatments of pseudo urticaria and associated septic conditions in cattle. Northern Rhodesian Department of Animal Health News Letter, 1–4.
- LUBINGA, J.C., TUPPURAINEN, E.S.M., MAHLARE, R., COETZER, J.A.W., STOLTSZ, W.H. & VENTER, E.H., 2015. Evidence of trans-stadial and mechanical transmission of lumpy skin disease virus by Amblyomma hebraeum ticks. Transboundary Emerging Diseases, 62(2), 174–82.
- MACDONALD, R.A.S., 1931. Pseudo urticaria of cattle. Northern Rhodesian Department of Animal Health, Annual Report 1930, 20–21.
- MACOWEN, K.D.S., 1959. Observations on the epizootiology of lumpy skin disease during the first year of its occurrence in Kenya. Bulletin of Epizootic Diseases of Africa, 7, 7–20.
- MEBRATU, G.Y., KASSA, B., FIKRE, Y. & BERHANU, B., 1984. Observation on the outbreak of lumpy skin disease in Ethiopia. Revue d'élevage et de médecine vétérinaire des pays tropicaux, 37 (4), 395-399.
- MELLOR, P.S., KITCHING, R.P. & WILKINSON, P.J., 1987. Mechanical transmission of capripox virus and African swine fever virus by Stomoxys calcitrans. Research in Veterinary Science, 43 (1), 109–112.
- MENASHEROW, S., ERSTER, O., RUBINSTEIN-GIUNI, M., KOVTUNENKO, A., EYNGOR, E., GELMAN, B., KHINICH, E., & STRAM, Y., 2016. A high-resolution melting (HRM) assay for the differentiation between Israeli field and Neethling vaccine lumpy skin disease viruses. Journal of Virological Methods, 232, 12-15.
- MENASHEROW, S., RUBINSTEIN-GIUNI, M., KOVTUNENKO, A., EYNGOR, Y., FRIDGUT, O., ROTENBERG, D., KHINICH, Y. & STRAM, Y., 2014. Development of an assay to differentiate between virulent and vaccine strains of lumpy skin disease virus (LSDV). Journal of Virological Methods, 199, 95-101.
- MORRIS, J.P.A., 1931. Pseudo-urticaria. Northern Rhodesia Department of Animal Health, Annual Report, 1930, 12.
- MUNZ, E.K. & OWEN, N.C., 1966. Electron microscopic studies on lumpy skin disease virus type ‘Neethling’. Onderstepoort Journal of Veterinary Research, 33, 3–8.
- MURRAY, L., EDWARDS, L., TUPPURAINEN, E.S.M., BACHANEK-BANKOWSKA, K., OURA, C.A.L., MIOULET, V. & KING, D.P., 2013. Detection of capripoxvirus DNA using a novel loop-mediated isothermal amplification assay. BMC Veterinary Research, 9.
- NAWATHE, D.R., ASAGBA, M.O., ABEGUNDE, A., AJAYI, S.A. & DURKWA, L., 1982. Some observations on the occurrence of lumpy skin disease in Nigeria. Zentaralblatt für Veterinärmedizin B, 29, 31–36.
- NAWATHE, D.R., GIBBS, E.P.J., ASAGBA, M.O. & LAWMAN, M.J.P., 1978. Lumpy skin disease in Nigeria. Tropical Animal Health and Production, 10, 49–54.
- ODEND’HAL, S., 1983. The Geographical Distribution of Animal Viral Diseases. New York, London: Academic Press.
- OSUAGWUH, U.I., BAGLA, V., VENTER, E.H., ANNANDALE, C.H. & IRONS, P.C., 2007. Absence of lumpy skin disease virus in semen of vaccinated bulls following vaccination and subsequent experimental infection. Vaccine, 25 (12), 2238–2243. doi:10.1016/j.vaccine.2006.12.010.
- PLOWRIGHT, W. & WITCOMB, M.A., 1959. The growth in tissue cultures of a virus derived from lumpy skin disease of cattle. Journal of Pathology and Bacteriology, 78, 397–407.
- PROZESKY, L. & BARNARD, B.J.H., 1982. A study of the pathology of lumpy skin disease in cattle. Onderstepoort Journal of Veterinary Research, 49, 167–175.
- PRYDIE, J. & COACKLEY, W., 1959. Lumpy skin disease: Tissue culture studies. Bulletin of Epizootic Diseases of Africa, 7, 37–49.
- ROUBY, S. & ABOULSOUD, E., 2016. Evidence of intrauterine transmission of lumpy skin disease virus. Veterinary Journal, 209, 193–195. doi:10.1016/j.tvjl.2015.11.010.
- SALIB, F.A. & OSMAN, A.H., 2011. Incidence of lumpy skin disease among Egyptian cattle in Giza Governorate, Egypt. Veterinary World, 4 (4), 162–167.
- SAMEEA YOUSEFI, P., MARDANI, K., DALIR-NAGHADEH, B. & JALILZADEH-AMIN, G., 2016. Epidemiological Study of Lumpy Skin Disease Outbreaks in North-western Iran e pub May 2016, Transboundary and Emerging Diseases, doi:10.1111/tbed.12565.
- SETTYPALLI, T.B.K., LAMIEN, C.E., SPERGSER, J., LELENTA, M., WADE, A., GELAYE, E., LOITSCH, A., MINOUNGOU, G., THIAUCOURT, F. & DIALLO A., 2016. One-step multiplex RT-qPCR assay for the detection of Peste des petits ruminants’ virus, Capripoxvirus, Pasteurella multocida and Mycoplasma capricolum subspecies (ssp.) capripneumoniae. PLoS One, 11(4), e015368.
- ŞEVIK, M. & DOĞAN, M., 2017. Epidemiological and Molecular Studies on Lumpy Skin Disease Outbreaks in Turkey during 2014–2015. Transboundary and Emerging Diseases, 64(4), 1268–1279. https://doi.org/10.1111/tbed.12501.
- TAGELDIN, M.H., WALLACE, D.B., GERDES, G.H., PUTTERILL, J.F., GREYLING, R.R., PHOSIWA, M.N., AL BUSAIDY, R.M. & AL ISMAAILY, S.I., 2014. Lumpy skin disease of cattle: an emerging problem in the Sultanate of Oman. Tropical Animal Health and Production, 46, 241-246.
- TASIOUDI, K.E., ANTONIOU, S.E., ILIADOU, P., SACHPATZIDIS, A., PLEVRAKI, E., AGIANNIOTAKI, E.I., FOUKI, C., MANGANA-VOUGIOUKA, O., CHONDROKOUKI, E. & DILE, C., 2015. Emergence of Lumpy Skin Disease in Greece. Transboundary and Emerging Diseases, 63(3), 260-265.
- THOMAS, A.D. & MARÉ, C.V.E., 1945. Knopvelsiekte. Journal of the South African Veterinary Medical Association, 16, 36–43.
- THOMAS, A.D., ROBINSON, E.M. & ALEXANDER, R.A., 1945. Lumpy skin disease — knopvelsiekte. Onderstepoort Division of Veterinary Services, Veterinary Newsletter, 10.
- TIMURKAN, M.Ö., ÖZKARACA, M., AYDIN, H. & SAĞLAM, Y.S., 2016. The detection and molecular characterization of lumpy skin disease virus, northeast Turkey. International Journal of Veterinary Science, 5(1), 44-47.
- TOPLAK, I., PETROVIĆ, T., VIDANOVIĆ, D., LAZIĆ, S., ŠEKLER, M., MANIĆ, M., PETROVIĆ, M. & KUHAR, U., 2017. Complete Genome Sequence of Lumpy Skin Disease Virus Isolate SERBIA/Bujanovac/2016, Detected during an Outbreak in the Balkan Area. Genome Announcements, 5, 35.
- TULMAN, E.R., AFONSO, C.L., LU, Z., ZSAK, L., KUTISH, G.F. & ROCK, D.L., 2001. Genome of Lumpy Skin Disease Virus. Journal of Virology, 75, 7122-7130.
- TULMAN, E.R., AFONSO, C.L., LU, Z., ZSAK, L., SUR, J.H., SANDYBAEV, N.T., KEREMBEKOVA, U.Z., ZAITSEV, V.L., KUTISH, G.F., ROCK, D.L., 2002. The genomes of sheeppox and goatpox viruses. Journal of Virology, 76, 6054-6061.
- TUPPURAINEN, E., COETZER, J.A.W. & VENTER, E., 2003. Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, South Africa. Unpublished data.
- TUPPURAINEN, E.S. & OURA, C., 2014. Lumpy skin disease: an African cattle disease getting closer to the EU. Veterinary Record, 175 (12), 300-301. doi: 10.1136/vr.g5808.
- TUPPURAINEN, E.S.M., LUBINGA, J.C., STOLTSZ, W.H., TROSKIE, M., CARPENTER, S.T., COETZER, J.A.W., VENTER, E.H. & OURA, C.A.L., 2013a. Mechanical transmission of lumpy skin disease virus by Rhipicephalus appendiculatus male ticks. Epidemiology and Infection, 141, 425–430.
- TUPPURAINEN, E.S.M., LUBINGA, J.C., STOLTSZ, W.H., TROSKIE, M., CARPENTER, S.T., COETZER J.A.W., VENTER E.H. & OURA, C.A.L., 2013b. Evidence of vertical transmission of lumpy skin disease virus in Rhipicephalus (Boophilus) decoloratus ticks. Ticks and Tick-borne Diseases, 4, 329-333.
- TUPPURAINEN, E.S.M., STOLTSZ, W.H., TROSKIE, M., WALLACE, D.B., OURA, C.A.L., MELLOR, P.S., COETZER, J.A.W. & VENTER, E.H., 2011. A potential role for ixodid (hard) tick vectors in the transmission of lumpy skin disease virus in cattle. Transboundary and Emerging Diseases, 58(2), 93–104.
- TUPPURAINEN, E.S.M., VENTER, E.H. & COETZER, J.A.W., 2005. The detection of lumpy skin disease virus in samples of experimentally infected cattle using different diagnostic techniques. Onderstepoort Journal of Veterinary Research, 72 (2) 153-164.
- TUPPURAINEN, E.S., PEARSON, C.R., BACHANEK-BANKOWSKA, K., KNOWLES, N.J., AMAREEN, S., FROST, L., HENSTOCK, M.R., LAMIEN, C.E., DIALLO, A. & MERTENS, P.P., 2014. Characterization of sheep pox virus vaccine for cattle against lumpy skin disease virus. Antiviral Research, 109, 1-6.
- VENKATESAN, G., BALAMURUGAN, V., BHANUPRAKASH, V., SINGH, R.K., PANDEY, A.B., 2016. Loop-mediated isothermal amplification assay for rapid and sensitive detection of sheep pox and goat pox viruses in clinical samples. Molecular and Cellular Probes, 30, 174e177.
- VIDANOVIC, D., SEKLER, M., PETROVIC, T., DEBELJAK, Z., VASKOVIC, N., MATOVIC, K. & HOFFMANN, B., 2016. Real-time PCR assays for the specific detection of field Balkan strains of lumpy skin disease virus. Acta Veterinaria-Beograd, 66, 444–454.
- VON BACKSTRÖMM, U., 1945. Ngamiland cattle disease: Preliminary report on a new disease, the aetiological agent being probably of an infectious nature. Journal of the South African Veterinary Medical Association, 16, 29–35.
- WEISS K.E., 1968. Lumpy skin disease virus. Virology Monographs, 3, 111–131.
- WEISS, K.E. & GEYER, S.M., 1959. The effect of lactalbumin hydrolysate on the cytopathogenesis of lumpy skin disease virus in tissue culture. Bulletin of Epizootic Diseases of Africa, 7, 243.
- WOODS, J.A., 1988. Lumpy skin disease - a review. Tropical Animal Health and Production, 20, 11–17.
- YERUHAM, I., NIR, O., BRAVERMAN, Y., DAVIDSON, M., GRINSTEIN, H., HYMOVITCH, M. & ZAMIR, O., 1995. Spread of lumpy skin disease in Israel dairy herds. The Veterinary Record, 137, 91–93.
- YERUHAM, I., PERL, S., NYSKA, A., ABRAHAM, A., DAVIDSON, M., HAYMOVITCH, M., ZAMIR, O. & GRINSTEIN, H., 1994. Adverse reactions in cattle to a capripox vaccine. Veterinary Record, 135, 330-332.
- YOUNG, E., BASSON, P.A. & WEISS, K.E., 1970. Experimental infection of the giraffe [Giraffa cameleopardis (Linnaeus, 1962)], Impala [Aepyceros melampus (Lichtenstein, 1812)] and the Cape Buffalo [Syncerus caffer (Sparmann, 1779)] with lumpy skin disease virus. Onderstepoort Journal of Veterinary Research, 37, 79–88.
- ZEYNALOVA, S., ASADOV, K., GULIYEV, F., VATANI, M. & ALIYEV, V., 2016. Epizootology and Molecular Diagnosis of Lumpy Skin Disease among Livestock in Azerbaijan. Frontiers in Microbiology, 7, 1022. doi: 10.3389/fmicb.2016.01022.
- ZHAO, Z., FAN, B., WU, G., YAN, X., LI, Y., ZHOU, X., YUE, H., DAI, X., ZHU, H., TIAN, B., LI, J. & ZHANG, Q., 2014. Development of loop-mediated isothermal amplification assay for specific and rapid detection of differential goat pox virus and sheep pox virus. BMC Microbiology, 14, 10. doi:10.1186/1471-2180-14-10.