History of lumpy skin disease
Morbidity, mortality and the economic significance of LSD
Diagnosis of LSD
Epidemiology and transmission
Importance of LSD
F. G. Davies
Dr F. Glyn Davies is head of the ODA Virology Project, Veterinary Research Laboratories, PO Box Kabete, Kenya.
Lumpy skin disease (LSD) is an economically important disease of cattle and can produce a chronic debility in infected cattle comparable to that caused by foot-and-mouth disease (FMD). Mortality rates as high as 40 percent or more have been encountered but they are usually lower. Severe and permanent damage to hides results from the skin lesions. Lesions in the mouth, pharynx and respiratory tract commonly occur, resulting in a rapid deterioration in condition and sometimes severe emaciation, which can persist for months. Serious economic losses can follow outbreaks that have a high morbidity.
There is no specific antiviral treatment available for LSD-infected cattle. Two vaccines, however, Neethling and Kenya sheep and goat pox virus, have been used widely in Africa with success.
The clinical syndrome of lumpy skin disease (LSD) was first described in Zambia (formerly Northern Rhodesia) in 1929. Initially, it was considered to be the result either of poisoning or a hypersensitivity to insect bites. Between 1943 and 1945, cases occurred in Botswana (Bechuanaland), Zimbabwe (Southern Rhodesia) and the Republic of South Africa. The infectious nature of the disease was recognized at this time. A panzootic in South Africa, which lasted until 1949, affected some eight million cattle and consequently incurred enormous economic losses (Thomas and Mare, 1945; von Backstrom, 1945; Diesel, 1949).
LSD was first identified in East Africa in Kenya in 1957 and the Sudan in 1972, and in West Africa in 1974, spreading into Somalia in 1983. From 1929 to 1986 the disease was restricted to countries in sub-Saharan Africa, although its potential to extend beyond this range had been suggested (Davies, 1981).
In May 1988, LSD was recognized clinically in the Suez Governorate of Egypt, where it was thought to have arrived at the local quarantine station with cattle imported from-Africa. The disease spread locally in the summer of 1988 and apparently overwintered with little or no manifestation of clinical disease. It reappeared in the summer of 1989 and, in a period of five to six months, spread to 22 of the 26 governorates of Egypt. A rapid reaction to the problem led to the vaccination of nearly two million cattle with a sheep pox vaccine. Morbidity in this epizootic was low, being 2 percent of the whole cattle population. Approximately 1449 animals died.
In 1989, a focus of LSD was identified in Israel and subsequently eliminated by the slaughter of all infected cattle as well as contacts. Ring vaccination with a sheep pox strain was carried out around the focus area and no further clinical cases have occurred.
In sub-Saharan Africa, LSD is now enzootic in all the countries in which it has occurred and has proved impossible to eradicate. Restrictions on cattle movements have not prevented its spread within countries and today LSD is liable to extend its range eastward from northeastern Africa and Egypt into the highly receptive Tigris-Euphrates delta. Further extension westward from Egypt into North Africa is possible and creates a danger of the coexistence of LSD with the screwworm infestation. This is of considerable significance as LSD creates multiple necrotic foci in the skin, which are suitable for oviposition by Cochliomyia hominivorax.
LSD is an acute infectious disease of cattle of all ages. There have been five instances of clinical cases of LSD in Bubalus bubalis, the Asian water buffalo (All et al., 1990). No other domestic ruminant species becomes infected naturally during field outbreaks. There can be a pyrexia of 40 to 41.5 °C, with lachrymation, possible anorexia, some depression and a reluctance to move. Shortly afterwards, the characteristic skin lumps develop; they may cover the whole body or be restricted to the head, neck, perineum, udder, genitalia or limbs. The lesions first manifest themselves as round circumscribed areas of erect hair, measuring 5 to 50 mm in diameter. They are firm and slightly raised above the surrounding normal skin from which they are often separated by a narrow ring of haemorrhage. The lesions are of full skin thickness involving the epidermis, dermis and adjacent subcutis. The regional superficial lymph nodes are enlarged and oedematous.
There is an increase in nasal and oropharyngeal secretions, which may be associated with the development of lesions on the muzzle and in the mouth. They may be found anywhere in the oropharynx and the upper respiratory tract. Lesions can occur throughout the alimentary tract in the subcutis, muscle fascia and in the muscle itself. The lesions on the mucous epithelium are round (usually 4 to 40 mm in diameter) and have a ring shape where separation from the normal tissue has occurred. Necrosis follows quickly and the ulcers become infected. There are mucopurulent discharges from the mouth and nostrils, persistent dribbling of saliva, coughing and often stertorous respiration. Conjunctivitis and keratitis may be seen.
Infected cattle may develop oedematous and inflammatory swellings of the brisket and of one or more limbs. The sheath of bulls can be similarly affected. Secondary infection can develop as the lesions become hard and necrotic. Lesions may harden and remain in situ. They may also slough away to leave a hole of full skin thickness, known as "sitfast". Extensive sloughing of necrotic skin from the udder or limbs can occur when they have become enlarged and oedematous. It is at this stage that the lesions constitute prime sites for oviposition by the screwworm fly.
Severely infected animals become emaciated and may require euthanasia. The debility persists for one to three months and occasionally for up to six months. The mouth lesions interfere with feeding; milk production ceases and udder and teat lesions may result in serious infections with the sloughing of necrotic tissue. Limb lesions can severely restrict movement. Painful lesions on the genitalia of bulls interfere with their ability to serve for many weeks. Oestrus is suppressed during the periods of severe debility.
Lesions in the skin, subcutaneous connective tissue, and muscles of the limbs, together with the severe skin inflammation caused by secondary infection of the lesions, greatly reduce mobility. Under nomadic pastoral conditions, animals affected in this manner may rapidly succumb to dehydration and starvation, thus increasing losses.
Pneumonia is a common sequel in animals with lesions in the mouth and respiratory tract. Nodular lesions may have quite extensive surrounding areas of interstitial pneumonia in the lung, and inhalation pneumonia frequently occurs. The responses to antibiotic therapy are poor. Abortions often follow outbreaks of LSD and calves have been born with extensive skin lesions, presumably acquired by intra-uterine infection.
The morbidity rates in LSD epidemics vary enormously and the disease occurs in many different biotypes, from the temperate high altitude grasslands through to the various wet and dry savannah ecotypes and the very dry semi-desert and thorn scrub. It can also spread extensively in irrigated lands in the Sudan and Egypt. The differences in morbidity rates are thought to reflect the distribution and relative abundance of insect vectors in the various habitats.
Morbidity rates of 1 to 2 percent may be contrasted with those of 80 to 90 percent in different situations. In southern, West and East Africa and the Sudan, the higher rates have been encountered in epizootics, yet much lower rates may occur during the same epizootic. In general, the breeds of Bos taurus, imported into Africa from Europe, are far more susceptible than the indigenous Bos indicus cattle. Channel Island breeds are particularly severely affected by LSD. Mortality rates of 10 to 40 percent and even higher have been reported on occasion but the much lower range of 1 to 5 percent is more usual.
Generalized LSD infection - Dermatose nodulaire généralisée - Infección generalizada de dermatosis nodular contagiosa
LSD lesions on the tail - Lésions sur la queue - Lesiones debidas a la dermatosis nodular contagiosa en la cola
Severe LSD skin lesions - Graves lésions de la peau - Lesiones cutáneas graves de la dermatosis nodular contagiosa
In any epizootic, economic losses clearly depend on the morbidity rates and are brought about by mortality, the loss of production, the depression of growth rates and hide damage. The full skin thickness lesions of LSD punch holes right through the hide, thereby causing permanent damage (Green, 1959).
Treatment and control
There is no specific antiviral treatment available for LSD infected cattle. Sick animals may be removed from the herd and given supportive treatment consisting of local wound dressing to discourage fly worry and prevent secondary infections. Systemic antibiotics may be given for skin infections, cellulitis or pneumonia, and food and water should be made readily available. Local applications of insecticides to infected cattle have been made in an attempt to reduce further transmission, but to no apparent benefit.
Should LSD appear in cattle in another country beyond its previous range, it is recommended that all infected and contact cattle be slaughtered immediately and the carcasses destroyed in an attempt to eliminate the focus of infection. A vaccination cover with a 25 to 50 km radius may then be established around the focus and all cattle movements stopped within that zone. Alternatively, it might be decided to leave all cattle in the zone unvaccinated, allowing the manifestation of any- residual infection. The vaccination policy may allow the virus to persist in some cattle.
When an epizootic occurs in an enzootic area and LSD has already spread extensively, slaughter policies- are inappropriate and extensive vaccination campaigns are recommended. The imposition of strict movement controls are suggested because, although these do not contain outbreaks of LSD, they do prevent new foci from becoming established at a certain distance. Vaccination will greatly reduce the morbidity and economic effects of an epizootic but may not completely limit the extension of-LSD. Follow-up vaccination of calves and re-vaccination programmes over a period-of two to three years will greatly reduce the incidence of clinical disease. No country in sub-Saharan Africa, however, has succeeded in eradicating LSD once it has occurred.
Vaccines for LSD control
Two different vaccines have been widely and successfully used for the prevention of LSD in cattle populations in Africa. In southern Africa, the Neethling strain of LSD was passaged 50 times in tissue cultures of lamb kidney cells and then 20 times in embryonated eggs. The strain proved to be innocuous and immunogenic for cattle, although local reactions do occur in a high proportion of animals at the vaccination site. No generalization of infection has ever followed its use. It is produced in tissue culture and issued as a freeze-dried product (Weiss, 1968).
In Kenya, an effective vaccine has been produced from a local strain of sheep and goat pox virus (SGPV). This was shown to immunize cattle against LSD (Capstick and Coackley, 1961). The SGPV was passaged 16 times in pre-pubertal lamb testes or foetal muscle cell cultures and used for vaccination at this level. Local reactions have not been seen, but some Bos taurus breeds have shown lymphadenitis with signs of mild, generalized LSD-like lesions following vaccination (approximately 0.02 percent). These reactions were not reproduced in the laboratory, when up to 1 000 times the field dose was used, and there is a possibility that they represent needle transmission of the field virus. No such reactions have ever been observed in Bos indicus cattle so the use of the vaccine in the face of epizootics should not be prevented.
Two other strains of sheep pox vaccine have recently been used as a prophylaxis against LSD. The Romanian strain, prepared in the skin of lambs for use against sheep pox, was used in several million cattle in Egypt and appeared to be immunogenic. Another sheep pox strain, the RM 65 prepared in tissue culture, was used in Israel. No complications have followed the use of these strains in cattle.
Studies with both the Neethling and the Kenya SGPV strains show that an immunizing dose of 103.5 TCID50 is desirable for field vaccination campaigns. Good protection has been obtained with 102 in the face of an epizootic, although there is some suggestion that this may not be the case with all strains.
Serological studies with vaccinated cattle have shown that many animals resist challenge with virulent LSD when they have no detectable fluorescent or neutralizing antibody to the virus. Most animals do show a serological response after field infections with LSD, however. There is an important cellular component of the immune response to LSD in cattle, as there is to other pox viruses. This formed the basis for a hypersensitivity test, developed by Capstick and Coackley (1962), to determine the susceptibility of cattle to LSD for use in vaccination studies. This test can be used to determine the responses to vaccination.
LSD, Kenya SGPV, Romanian sheep pox and Gorgon goat pox (from Iraq) have all been shown to be serologically identical by fluorescent antibody and serum virus neutralization tests (Davies and Atema, 1981). Therefore, it is likely that many of the sheep or goat pox vaccine strains available in different parts of the world would prove suitable for the prophylaxis of LSD. It is suggested that ten to 50 times the sheep immunizing dose be used for this purpose, however.
Recent restriction enzyme analyses of the genome of these virus strains have shown that the Kenya SGPV and LSD appear to be identical. The other strains of sheep or goat pox do show differences in their DNA from that of LSD (Gershon and Black, 1988), but this is not reflected in their serological and immunological properties.
The rapid and precise identification of LSD is essential to mobilize resources quickly and effectively should it appear in new non-enzootic areas outside Africa. The clinical diagnosis of LSD is not difficult for those familiar with the disease, but those who are not so experienced can readily confuse the lesions with many other conditions: for instance, bovine herpes virus 2 (Allerton) infections; delayed hypersensitivity reactions following foot-and-mouth disease vaccinations; insect bites; streptothricosis, globidiosis, or demodicosis. Laboratory confirmation is desirable.
The early skin lesions contain large numbers of virus particles which can be readily seen with an electron microscope. Simple negative staining of a few small skin fragments taken from the lesions with phosphotungstic acid will show large numbers of the roughly brick-shaped pox virus particles. Herpes virus particles may also be seen in such skin fragments, and they may be of the bovine herpes type 2 or 3. The latter are termed orphan viruses and are often seen in normal and LSD-infected tissue. They may be present in such numbers that they mask the larger pox viruses, which may also be present. Diagnostic errors may therefore arise from this method. Parapox virus particles of an oval shape and with a spiral matrix may also be seen in an electron microscopy of bovine skin.
Histopathological sections of the skin lesions show changes peculiar to LSD. There is a vasculitis and perivascular infiltration with white cells which causes a thrombosis of the vessels in the dermis and subcutis. The cells infiltrating the lesion are of a predominantly epithelioid type, known as the celles claveleuses, which Borrel (1903) described in sheep pox. There are also eosinophilic intracytoplasmic inclusions in the epidermal elements of the lesion and the inflammatory cells (Burdin, 1959). The lesions gradually become necrotic as a result of the thrombosis. The differential diagnosis from some of the conditions mentioned above can readily be made by a histopathological examination of the lesions.
Virus isolation may be attempted and is best carried out in primary or secondary prepubertal lamb testis cell cultures. They are more sensitive than kidney, muscle, lung, skin, thymus or endothelial cells, although these can be used. Cultures are infected with suspensions of the early skin lesions, preferably in tubes or wells with cover slips. These can then be stained at 48 to 56 hours to show the eosinophilic intracytoplasmic inclusions, or the viral antigen may be identified by immunological methods with fluorescent or peroxidase conjugated antibodies. This may be possible as early as 24 hours after inoculation of the cultures (Davies et al., 1971). There is a cross-relationship with the cowpox virus which may be detected by this method, but it is only demonstrable at low titres. The presence of BHV 2 or 3 in the specimen may result in their rapid growth to mask the simultaneous presence of the Capripox virus. Early fluorescent or immunoperoxidase staining may allow the diagnosis to be made. It is suggested that lesions be collected from several animals and processed separately to reduce the possibilities of such a complication. Cytopathic effects resulting from the LSD virus develop at five to 14 days in most primary cultures, but it is recommended that they be frozen and thawed and that one blind passage be carried out. This process will detect LSD strains that adapt slowly to the cultures or that were present only in very small amounts in the original sample.
The virus of LSD does not spread readily among animals held in insect-proof pens. While infection by contact can occur, this is thought to occur only at a low rate and is not considered a major component of transmission during epizootics. Most infection is thought to be the result of insect transmission of the virus (von Backstrom, 1945; Thomas and Mare, 1945; Diesel, 1949; MacOwan, 1959; Weiss, 1968). Pox viruses are highly resistant and may remain viable in infected tissue for at least four months, and probably longer. Virus is also present in blood, nasal and lachrymal secretions, semen and saliva, which may be sources for transmission.
There is little hard data incriminating any particular insect species as a vector of LSD. Virus has been isolated from Stomoxys spp., commonly associated with cattle, and from the Biomyia fasciata mosquito species, found in large numbers and associated with LSD-infected cattle. Tabanidae, Glossina and Culicoides spp. have all been found in situations where there has been ongoing LSD transmission and have been suspected to be involved. Stomoxys spp. have been shown to transmit SGPV successfully (Kitching and Mellor, 1986). The role of all these insects in the transmission of LSD remains to be evaluated in the laboratory and under field conditions. Transmission is likely to be mechanical, as was found to occur with Rift Valley fever and many of the above insect genera. Fowl pox is transmitted mechanically by mosquitoes and it is likely that many insects could transmit LSD in this manner. Plant pox viruses are frequently involved in biological cycles within insect vectors. This is a possibility, but it would be remarkable for a mammalian pox virus.
LSD is a Capripox virus and these differ from Orthopox viruses by having a narrow vertebrate host range, infecting only sheep, goats and cattle. Some wild species (giraffe, impala and Thomson's gazelle) have been infected by parenteral inoculation with LSD virus and have developed characteristic lesions. Lesions of LSD have not been seen on these animals when they have been present during epizootics of the disease. Sheep and goats do not become infected during outbreaks of LSD even when held in close contact with infected cattle. African buffaloes (Syncerus caffer) do not show lesions in the field during epizootics of LSD, and nor did the majority of Asian water buffaloes, Bubalus bubalis, exposed during the Egyptian LSD epizootic. Five cases of LSD-like lesions in buffaloes were reported in Egypt. Both buffalo types may suffer an inapparent infection and seroconvert, however. This point has not been examined. In an enzootic area for LSD in Kenya, many African buffaloes had high titres of antibody to Capripox virus; in another area, no antibody was found. This may have been specific for LSD or the result of infection with another unknown Capripox virus. The same sera were screened against cowpox virus and no neutralization of this virus occurred, suggesting that the antibody detected was specific.
Sheep were found to be infected with Kenya SGPV on the farm where the first outbreak of LSD occurred in Kenya. The DNA of these viruses is identical according to restriction endonuclease analysis. It was suggested that the cases originated from a strain of Kenya SGPV which had an altered level of host adaptation for cattle. The virus strains are identical in every way in the laboratory, differing only in their ability to produce LSD in one host and sheep and goat pox in the other. In the alternate host, the viruses produce a local lesion at the inoculation site with some regional lymph node enlargement. No sheep pox has ever occurred in southern Africa during the LSD epizootics there, despite the presence of 40 million sheep.
Economically, LSD is a significant cattle disease and high mortality rates of 40 percent or more have been encountered. Skin lesions result in severe and permanent damage to hides, while lesions in the mouth, pharynx and respiratory tract cause a rapid deterioration in condition and sometimes severe emaciation, which may persist for months.
LSD has occurred in a wide range of ecotypes in Africa where, in the last 20 years, it appears to have spread to virtually all countries on the continent. It has recently extended its range to include Egypt where, in one summer, it spread thousands of kilometres throughout the whole of the country and also into Israel. Movement restrictions do not control the disease. Insect movement in air currents is uncontrollable, so there is little way of preventing further extension into the Near East and North Africa. LSD, furthermore, has the potential to spread throughout the Mediterranean region.
The basic scientific studies necessary to define the transmission mechanisms for LSD have not been carried out. This is an embarrassing gap in our knowledge of the disease and calls for a serious research effort. Information is required on the prevalence of the different biting flies associated with cattle in the various biotypes of countries that are potentially receptive to LSD. Subsequently, a judgement may then be made regarding the likelihood of an LSD epizootic.
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