Occurrence

Visna is a disease of sheep and rarely of goats. Visna was originally recorded in Iceland and was a significant cause of death in the epizootic of maedi-visna that occurred in that country. It always occurred in association with maedi and was generally of sporadic occurrence and lesser importance than the pulmonary manifestation of the infection although in some flocks it was the major manifestation of the complex.⁴ Visna has not been seen in Iceland since 1951 and maedi-visna has since been eradicated from Iceland.

Despite the widespread occurrence of maedi-visna or ovine progressive pneumonia in many countries visna is a very uncommon disease and a significant occurrence of clinical disease has seldom been recorded in countries other than Iceland.^4-8 The reason for this is not known but might be due to an increased susceptibility of the Icelandic breed of sheep to the neurological form of the disease, or to differences in maedi-visna virus strain neuroinvasiveness and neurovirulence. Maedi-visna virus was first reported in Britain in the late 1970 and the clinical expression since that time had largely been maedi occasionally with coexistent visna. However, recently there has been the occurrence of visna with no evidence of respiratory disease suggesting that a neurotropic strain might be emerging in that country.⁹

Experimental transmission

Experimental transmission of the infection and the disease is effected by intracerebral inoculation and spread occurs from these to commingled sheep.¹⁰ The incubation period and the course of the disease are very long; clinical signs may not appear for 2 years after experimental inoculation.

Samples for confirmation of diagnosis

Occurrence

Border disease was originally described in the border country between England and Wales. It has subsequently been reported from most of the major sheep-producing countries^2,4-6 and probably occurs in all. The disease occurs naturally primarily in sheep and occasionally in goats. The prevalence of infection is much higher than the incidence of clinical disease as the latter only occurs when there is infection during pregnancy.

Studies on seroprevalence vary in design but suggest that pestivirus infections in sheep and goats are less common than in cattle and that there are considerable differences in seroprevalence between different geographical areas and flocks. Flock seroprevalence in different regions or countries generally falls within the range of 5 to 50%. The prevalence of seropositive females within positive flocks is influenced by age with a lower seroprevalence in sheep 4 to 8 months of age than in older sheep. Seroprevalence is higher in flocks with persistently infected sheep but there can still be a significant proportion of seronegative sheep present in a flock containing persistently infected sheep.⁷

Source of infection

Infection can be introduced into a flock with the purchase of persistently infected replacement sheep. Persistently infected sheep excrete virus in nasal secretions, saliva, urine and feces,^2,6 and provide the major source of infection. A proportion of persistently infected sheep may survive to adulthood and may breed successfully to produce further persistently infected sheep.⁸ However, the breeding efficiency of persistently infected sheep is poor and the probability of establishing lines of persistently infected sheep appears less than with the equivalent infection in cattle.^8,9

Virus is also present in the placenta and fetal fluids at the birth of persistently infected lambs, and in the products of abortions resulting from infection with the virus in early pregnancy. In flocks where there is a long lambing period it is possible that this could provide a source for clinical disease in late lambing ewes. field observations suggest that transmission during the lambing period is limited.

Calves persistently infected with BVDV can infect sheep,¹⁰ and in countries where pregnant sheep and cattle are housed in close proximity during the winter this can be an important source of infection for outbreaks of border disease. In some countries it appears the major source and recent studies in both Northern Ireland and the Republic of Ireland suggest that cattle are the primary source of infection for sheep in those countries.^11,12 In contrast BDV is the predominant ovine pestivirus in Great Britain and New Zealand.¹³

There is also evidence that bovine strains are important in goat infections.^1,14

Free-living deer are also a potential source of infection. Outbreaks of disease are also recorded as the result of vaccinating pregnant goats with a pestivirus contaminated Orf vaccine.¹⁵

Transmission

Transmission is by sheep-to-sheep contact and experimental transmission has been effected with both oral and conjunctival challenge.^2,6

The speed of spread of infection in a susceptible flock will vary with the management, and will be facilitated by factors such as close contact at mating time or gathering for any purpose. There is an increased risk for explosive outbreaks of border disease where animals are housed in early pregnancy.

Host risk factors

Border disease may occur as an outbreak or as a sporadic disease. When infection is introduced into a susceptible flock in early pregnancy, an outbreak with infertility, abortion and congenital disease in lambs from all ages of ewes is likely. Subsequently, older sheep in the flock will have immunity and disease is only common in introduced sheep and maiden ewes. Persistently infected ewes have reduced fertility but will give birth to congenitally affected lambs throughout their breeding life.^8,9 The disproportional occurrence of outbreaks of clinical disease in certain breeds suggests that these breeds have higher rates of persistently infected individuals.

Experimental reproduction

Border disease is readily reproduced by the experimental infection of pregnant ewes prior to 80 days’ gestation and can be effected by oral, conjunctival and parenteral challenge.^6,9 Experimental disease can be produced with both BDV and BVDV strains.

The following have been produced experimentally, although there are strain differences in clinical and pathological manifestations:

Experimental infections of pregnant cows with BDV results in similar defects with placentitis, mummification and abortion of fetuses, intrauterine growth retardation with abnormal osteogenesis, and hypomyelinogenesis.

The disease has also been produced experimentally in goat kids by inoculation of pregnant goats but there are no abnormalities of hair coat, and embryonic mortality and abortion are more common than in the experimental disease in ewes.¹⁶

Economic importance

The effect of infection varies with the immune status of the flock and whether infection occurs during pregnancy. In fully susceptible flocks, abortion and neonatal lamb loss resulting from infection can be 25–75% of the expected lamb crop depending upon the strain of the virus.⁹ An assessment of the economic losses due to infertility, abortion, neonatal losses, and low carcass weight indicate that an outbreak of border disease can result in a potential reduction of income in excess of 20%.¹⁷

Non-pregnant sheep

In adolescent and adult non-pregnant sheep, infection and viremia are subclinical. The IM inoculation of immunocompetent lambs with BDV results in a mild transient disease and a subsequent reduction in growth rate, but no gross or microscopic lesions.

Pregnant sheep

When BDV infects susceptible pregnant ewes the virus infects the placenta to produce an acute necrotizing placentitis and it subsequently invades the fetus. This may result in early embryonic death, abortion and stillbirth, the birth of lambs with malformations and/or neurological abnormalities, the birth of small weak lambs which are immunosuppressed, or the birth of lambs with no clinical abnormality. The ultimate outcome of the infection depends on the age of the fetus, the properties of the strain of the virus, the dose of the virus, the genotype of the host, and the ability of the fetus to respond to the virus. Fetal age at the time if infection is most important, as it is the determinant of the ability of the fetus to mount an immune response to the infection.^2,6,9,18 Immune competence to the virus in sheep develops between approximately 61 and 80 days of gestation.

Enteric disease

Experimental inoculation of a homologous strain of the BDV into persistently infected, but clinically recovered lambs results in a severe clinical syndrome characterized by persistent diarrhea and respiratory distress associated with an inflammatory lymphoproliferative response in the central nervous system, intestines, lungs, heart, and kidney. A similar syndrome is seen at weaning in some persistently infected sheep that survive early life.^2,9 This syndrome resembles certain aspects of mucosal disease in cattle, in which it is postulated that superinfection of persistently viremic immunotolerant cattle with a homologous strain of BVDV results in fatal mucosal disease. In such animals a specific and dynamic equilibrium exists between an attenuated form of the virus and the immunotolerant host. Disturbance of this equilibrium either by injection of the homologous strain of BDV, or some other factor, results in fatal disease.⁹

Conformation

Affected lambs may have a lower birth weight than uninfected lambs, a decreased crown–rump length, and a shorter tibia/radius length so that they have a boxy appearance. The head has a shortened longitudinal axis and the cranium may be slightly domed (goat lambs).

Fleece

The fleece, when dry, appears hairy and rough due to long hairs rising above the fleece to form a halo, especially over the nape, back, flanks and rump.²⁴ This feature is most evident in medium- and fine-wool breeds and is not observed in the coarse kempy-fleeced breeds, such as the Scottish Blackface. The halo kemp fibers are shed with time and are most evident in the first 3 weeks of life. Some lambs have abnormal pigmentation occurring as patches of pigmented fleece or hair, or a totally pigmented fleece. This can occur in white-faced sheep.

Neurological dysfunction

Neurological dysfunction is manifest, with rhythmic tremors of the muscles of the pelvis and upper parts of the hindlimbs, or of the whole body, resulting in a characteristic jerking movement, and of the head and neck with rhythmic bobbing of the head (shaker lambs). In some less severe cases, only fine tremors of the ears and tail are evident. Tremors are most apparent during movement, and are absent while the lamb is sleeping. The tremors usually decline in severity as the lamb matures and may seem to disappear unless the animal is stressed. More severely affected lambs have difficult in rising, and if able to stand with assistance exhibit an erratic gait especially of the hindquarters. Paralysis does not occur. Affected lambs are often unable to nurse the ewe because they cannot hold onto the teat. Affected lambs appear languid and lie around listlessly. They do not suck as they should and bloat continuously, and the ewes’ udders become engorged with milk.

Behavioral and visual defects with circling, head-pressing, nystagmus, and gross incoordination are seen in lambs with the type of infection producing hydranencephaly and cerebellar dysplasia. These lambs are of lighter birth weight but have normal birthcoats.

Growth rate

Growth rate is reduced, affected lambs are unthrifty, and the majority will die before or at weaning time from parasitism, pneumonia, a mucosal disease-like syndrome, or nephritis.^9,20 With good nursing care they can be reared but deaths may occur at any age. Puberty may be delayed and, in males, the testes are flabby and may not develop normally.

Reproductive performance

Impaired reproductive performance of the flock occurs from low fertility, abortion, and poor viability of lambs. Abortions usually are not noticed until lambing when it is evidenced by an unexpected increase in barren ewes. In goats, where there is often closer observation, the aborted fetuses may be reasonably well-developed, small and underdeveloped, or autolyzed and unrecognizable as a fetus in expelled fetal fluid.¹⁶

Detection of persistently infected sheep

For diagnosis of border disease in newborn lambs, precolostral blood samples should be taken from both clinically normal and affected lambs. Persistently infected sheep are seronegative and BDV can be isolated from leukocytes in the blood buffy coat. Lambs infected late in gestation will be seropositive but virus-negative. Persistently infected lambs that have received colostrum from their dam will be seropositive until they lose the maternal passive immunity.

Persistently infected adolescent and adult sheep in a flock can be identified by the detection of virus in blood; however, this is expensive in large flocks and an alternative is test all sheep for antibody and then culture the buffy coat of seronegative sheep. Antigenic differences between laboratory strains and field virus can result in false-negative serologies and serological studies are best done with the homologous virus.^4,26

Abortion

Serological tests are of limited value as an aid to the diagnosis of abortion associated with BDV infection. The infection of the ewe that results in abortion occurs several weeks before clinical disease is apparent, and unless prospective samples can be taken there is little chance of a rise in antibody titers in paired samples. Seropositivity in ewes indicates that the flock has been exposed to pestivirus but does not incriminate it in a disease process. Seronegativity indicates that BDV is not the cause of the abortion, with the exception that aborting ewes, who themselves are persistently infected, will have no antibody titer.

Samples for confirmation of diagnosis

Occurrence

The disease occurs in sheep and goats and causes unthriftiness, varying degrees of pain, and some economic loss. It occurs most commonly in lambs 3–6 months of age when at pasture, although lambs 10–12 days of age and adult animals can be severely affected, and outbreaks involving the lips and face of young lambs and the udders of the ewes also are common. Outbreaks occur at any time but they are most common in dry conditions when the sheep are at pasture, or in penned sheep being fed from feed troughs. The disease has occurred in musk ox in which it causes heavy losses, reindeer, mountain goats and bighorn sheep, chamois, caribou, Dall sheep, buffalo, wild goats, and camels. The virus can be passaged in rabbits if large doses are placed on scarified skin or injected ID. Mild lesions develop on the chorioallantois of the 9 to 12-day chick embryo. Guinea-pigs and mice are not susceptible.

The disease also occurs in humans working among infected sheep. In abattoir workers it is commonest in those handling wool and skins.⁴

Morbidity and case fatality

Outbreaks may occur in sheep and goats, with morbidity rates approaching 100% and case fatality rates from 5 to 15%.^5,6 The deaths that occur are due to the extension of lesions in the respiratory tract, but the case fatality rate may reach 15% if severely affected lambs are not provided with adequate care and support, or if secondary infection and cutaneous myiasis are allowed to occur. In the rare outbreaks where systemic invasion occurs, the case fatality rate averages 25% and may be as high as 75%. Under field conditions recovered animals are immune for 2–3 years, but no antibodies appear to be passed in the colostrum, and newborn lambs of immune ewes are susceptible.⁵

Methods of transmission

Scabs that fall off from healing lesions contain virus and remain highly infective for long periods in dry conditions, but survival of the disease in a flock may be the result of chronic lesions that exist for long periods on individual animals.⁷ Infection can be from environmental persistence of the virus or from infected sheep. Spread in a flock is very rapid and occurs by contact with other affected animals or by contact with contaminated inanimate objects, such as feed troughs, ear-tagging pliers.⁸ An outbreak of lesions on the tails is recorded in association with the use of docking instruments.⁹

It has been assumed that natural infections on pasture are the result of invasion of the virus after skin damage induced by prickly plants or stubble; application of a viral suspension to scarified skin is the established method of inducing orf.¹⁰ However, an outbreak has occurred in a large group of lambs collected from several farms and transported in a vehicle over a period of 23 hours.¹¹ There was no evidence of injury to their mouths.

Experimental reproduction

The disease is readily reproduced by introduction of virus onto scarified areas of skin. Immunity to re-infection is relatively solid at the site of initial infection but shorter duration lesions can be reproduced by re-challenge of these sheep at other sites.^10,12

Risk factors

The primary risk factors are the presence of the virus and the immune status of the sheep.

A simulated shipping exercise has examined these risks.¹³ Initially, the prevalence of scabby mouth on participating sheep farms was determined. The proportion of farms with evidence of the disease in weaner sheep was 23.6%, and on those farms with the disease the overall prevalence was 6.1%. Sheep from different farms are mixed, held at high stocking densities for approximately 3 weeks, and offered pelleted feed that can abrade the lips and mouth to promote development of the lesions. The major risk factor for the prevalence of the disease in sheep arriving in a feedlot after transportation from the farm was immunity to the disease. The arrival and mixing in the feedlot was also important for transmission of the infection to occur. Sheep vaccinated on the farm before road transportation to the feedlot had a lower prevalence at the end of the simulated shipping exercise.¹³

Inter-current infections may exacerbate the occurrence disease on rare occasions.

The disease has spread from clinically normal ewes to susceptible 2–4 years of age which were persistently infected with border disease virus¹⁴ and lambs experimentally infected with Ehrlichia phagocytophilia and subsequently challenged with orf virus developed more severe lesions with a longer course than those in control lambs.¹⁵

Economic importance

The disease produces a minor set back except when it affects young sucking lambs with associated lesions on the teats and udders of their ewes. Loss from lamb mortality and secondary mastitis in these circumstances can be significant.

The disease assumed economic importance for Australia when shipments of sheep exported from Australia in 1989–1990 were rejected at some ports in the Middle East because of the disease¹³ and this problem continues. Litigation is a concern when zoonotic infections occur at petting zoos or fairs.

Zoonotic implications

Orf virus is readily transmitted to humans. In the agricultural environment typical lesions occur at the site of infection, usually an abrasion infected while handling diseased sheep for shearing, crutching or drenching or by accidental means when vaccinating. Lesions progress from macular to papular stages, are usually single and localized on the hands, arm or face. The lesions are self limiting and heal without scaring after 6 to 7 weeks. They are pruritic and respond poorly to local treatment. Orf is also a zoonotic consideration in ‘petting zoos’ and fairs where children allow lambs to suck their fingers or otherwise become infected from handling sheep exhibits. Historically, orf has been a risk for industrial workers handling raw wool.

Sheep

Lesions develop initially as papules and then pustules, stages which are not usually initially observed, and progress to raised moderately proliferative area of granulation, and inflammation covered with a thick, tenacious scab. Time progression from the initial lesions to the formation of scabs is approximately 6 to 7 days. New lesions will develop during the first 10 days of infection. The first lesions develop at the oral mucocutaneous junction, usually at the oral commissures and are accompanied by swelling of the lips. From here they spread on to the muzzle and nostrils, the surrounding haired skin and, to a lesser extent, on to the buccal mucosa. They may appear as discrete, thick scabs 0.5 cm in diameter, or coalesce and be packed close together as a continuous plaque. fissuring occurs and the scabs are sore to the touch. They crumble easily but are difficult to remove from the underlying granulation. Affected lambs suffer a severe setback because of restricted sucking and grazing. In benign cases the scabs dry and fall off, and recovery is complete in about 3 weeks. Affected lambs sucking ewes may cause spread of the disease to the udder where a similar lesion progression is seen. Lesions on the teats predispose to mastitis and secondary infection of the skin lesions by bacteria or fly larvae occurs in some cases. In rams, lesions on the scrotum may be accompanied by fluid accumulation in the scrotal sac and associated temporary infertility. A high incidence of infection can also occur where the dominant lesions are on the feet, occurring around the coronary band, the dew claws and on the volar areas of the intervening skin.

Rarely, systemic invasion occurs and lesions appear on the coronets and ears, around the anus and vulva or prepuce, and on the nasal and buccal mucosae. There is a severe systemic reaction, and extension down the alimentary tract may lead to a severe gastroenteritis, and extension down the trachea may be followed by bronchopneumonia. Lesions may also occur in the mouth involving the tongue, gums, dental pad or a combination of those sites.²¹ These are more commonly seen in outbreaks affecting lambs less than 2 months of age. In the mucosa of the mouth these lesions do not scab but are papular erosive and surrounded by an elevated zone of hyperemia. Extensive painful and proliferative lesions occur on the gingival margins of the incisor teeth.

In some outbreaks the lesions on the skin are highly proliferative and present as raw raised granulating lesions without an overlying scab. This manifestation appears more common in Suffolk sheep and lesions are present on the lips, bridge of the nose and around the eyes. Cases of this proliferative form involving the feet are also recorded.²²

A malignant form of the disease has also been observed in sheep. It begins with an acute episode manifested by oral vesicles, and extension of these lesions down the gastrointestinal tract, followed later by granulomatous lesions and shedding of hooves.

An atypical case of the disease in sheep after extensive cutaneous thermal injury has been described.²³ The virus was present in proliferative verrucous tissue lesions at the periphery of the original thermal injury.²³ The lesions consisted of tightly packed 0.5 mm-diameter papillary projections.

Goats

An unusual case of contagious ecthyma in a group of female goats has been described.²⁴ Multifocal lesions occurred over the head, neck, thorax, and flanks of each animal. The lesions developed approximately 2 weeks after the animals returned from a local summer show at which the does were housed for 3 days in pens previously occupied by sheep. The lesions began as plaques, followed by epidermal proliferation and severe encrustation. Affected areas were discrete and approximately 2–7 cm in diameter. There were no lesions of the muzzle, lips, udder or teats. Recovery occurred uneventfully within 3–6 weeks without treatment. The skin crusts gradually dried and fell off, leaving areas of alopecia and depigmented skin. Regrowth of hair followed.

Persistent orf is recorded in a proportion of Boer goats following an outbreak. The disease in the majority of the animals in the herd was classical and ran a clinical course of 3–4 weeks but in 2% of animals it persisted for several months and lesions disseminated over the body. There were no particular distinguishing differences of the virus genome to those of other orf viruses and the persistence was possibly a result of individual host susceptibility factors.^25,26

Samples for confirmation of diagnosis

Occurrence

Papillomatosis has an international occurrence in all animal species.

Origin of infection and transmission

The method of spread is by direct contact with infected animals, infection gaining entry through cutaneous abrasions. Virus can also persist on inanimate objects in livestock buildings and infect animals rubbing against them.⁸

Crops of warts sometimes occur around ear tags, at branding sites or along scratches made by barbed wire, and can be spread by tattooing implements, dehorning shears, and by procedures such as tuberculin testing.^13-16

An extensive outbreak of perianal warts is recorded in beef heifers, the infection having been spread by rectal examination for pregnancy. A high prevalence of papillomas on the larynx of feedlot steers is ascribed to implantation of the virus in contact ulcers, which are also entry sites for Fusobacterium nodosus (a cause of calf diphtheria), so that the two diseases may occur in the one animal. An outbreak of periorbital papillomatosis in cattle is recorded in association with a heavy periorbital infestation with Haematopinus quadripertusus.¹⁷

Animal risk factors

All species may be affected but the disease is commonest in cattle and horses. With cattle, usually several animals in an age group are affected. Outbreaks have been recorded in sheep and goats,^13,18 but the disease is uncommon in sheep. It is also uncommon in pigs, usually affecting the genitalia. Amongst wildlife, it occurs in white-tailed deer (Odocoileus virginianus) and mule deer (O. hemionus).

Experimental production

The supernatant from a suspension of wart tissue, injected ID, or applied to skin scarifications, is an effective means of experimental production of the disease.^8,19 Lesions are restricted to the site of inoculation. Cutaneous and oral papillomas have been transmitted in cattle, and cutaneous papilloma transmitted in sheep and horses. The incubation period after experimental inoculation in cattle is 3–8 weeks but is usually somewhat longer after natural exposure.

Economic importance

Cutaneous warts are quite common in young cattle, especially when they are housed, but ordinarily they cause little harm and regress spontaneously. In purebred animals they may interfere with sales and shows because of their unsightly appearance. Animals with extensive lesions may lose condition, and secondary bacterial invasion of traumatized warts may cause concern. Warts on the teats of dairy cows often cause interference with milking. In horses, the lesions are usually small and cause little inconvenience, but they are esthetically unattractive. In all species, the development of warts on the genitalia requires immediate treatment.

Cattle

In cattle, warts occur on almost any part of the body, but when a number of animals in a group is affected it is common to find them all affected in the same part of the body. The most common papillomas occur in the skin of cattle under 2 years of age, most commonly on the head, especially around the eyes, and on the neck and shoulders, but may spread to other parts of the body. They vary in size from 1 cm upwards and their dry, horny, cauliflower-like appearance is characteristic. In most animals they regress spontaneously, but the warts may persist for 5–6 months, and in some cases for as long as 18 months, with serious loss of body condition.

Warts on the teats manifest with different forms depending on the papilloma virus type and may show an increasing frequency with age. The frond form have filiform projections on them and appear to have been drawn out into an elongated shape of about 1 cm in length by milking machine action. If sharp traction is used they can often be pulled out by the roots.

Other forms are a flat, round type which is usually multiple, always sessile and up to 2 cm in diameter. The third form has an elongated structure appearing like a rice grain. Teat warts may regress during the dry period and recur with the next lactation.

Perianal warts are esthetically unattractive, but do not appear to reduce activity or productivity. Genital warts on the vulva and penis make mating impracticable because the lesions are of large size, are friable, and bleed easily. They commonly become infected and flyblown. They occur on the shaft or on the glans of the penis in young bulls, may be single or multiple, are pedunculated and they frequently regress spontaneously.

Alimentary tract warts are rarely observed clinically in farm animals in most countries, but are recorded in abattoir cattle at a high incidence in some localities⁹ and have been reproduced experimentally.⁸ Papillomas occur on the lateral and dorsal aspects of the tongue, the soft palate, oropharynx, esophagus, esophageal groove, and rumen. Papillomas occurring in the esophageal groove and in the reticulum are a cause of chronic ruminal tympany.

Less common manifestations of papillomatosis in cattle include lesions in the urinary bladder, which cause no clinical signs but may predispose to enzootic hematuria. BPV-4 papillomas in the upper alimentary tract of cattle being fed bracken fern are the focus for transformation to squamous cell carcinomas. Cattle fed bracken fern are immunosuppressed, which promotes the persistence and spread of the papilloma virus, and mutagens in bracken fern cause neoplastic transformation of papilloma cells.⁴

Goats

Papillomas most commonly occur on the face and ears but may occur on the skin generally, especially on unpigmented skin. Most completely regress, others regress and recur, and occasional lesions progress to carcinomas. Papillomas that occur on the teats are persistent and may spread through the herd.

Horses

Warts are confined to the lower face, the muzzle, nose and lips, and are usually sessile and quite small, rarely exceeding 1 cm in diameter. They may also occur on the penis and vulva, in the mouth, and on the conjunctiva. All ages can be affected. Spontaneous recovery is usual, but the warts may persist for 5–6 months.

Vaccination

For cattle, autogenous vaccines prepared from wart tissues of the affected animal are effective in many cases. Commercially available vaccines are available for cattle but may be less efficacious; an autogenous vaccine prepared for a specific problem has the advantage of including the local virus types. The vaccine is prepared from homogenized wart tissue that is filtered and inactivated with formalin. Because of the different BPV types, care is required in the selection of the tissues. In general terms they can be selected on tumor type, location, and histological composition. The alternative is to use many types of tissue in the vaccine. Animal to animal variation in regression following vaccination of a group of calves with a vaccine prepared from a single calf in the group has been attributed to more than one BPV type producing disease in the group.²⁴ The stage of development is also important, and virus is present in much greater concentration in the epithelial tissue of older warts than young ones.² The vaccine can be administered SC, but better results are claimed for ID injection. Dosing regimes vary, but 2–4 injections 1–2 weeks apart are commonly recommended. Recovery in 3–6 weeks is recorded in 80–85% of cases where the warts are on the body surface or penis of cattle, but in only 33% when the warts are on the teats. The response of low, flat, sessile warts to vaccination is poor.

Other treatments no longer commonly used include the injection into the wart of proprietary preparations containing antimony and bismuth or the intralesional injection of bacille Calmette–Guérin (BCG).²⁵

Occurrence and prevalence

Equine sarcoid is the commonest neoplasm in horses, representing about 20% of all equine tumors diagnosed at necropsy. Horses, donkeys, and mules are affected. Sarcoid tumors occur in 0.7% of Swiss warmblood, and 0.4% of Freiberger horses in Switzerland.¹ Of the horse breeds, Appaloosa, Arabian, and Quarter horses are at more risk than are Standardbreds or Thoroughbreds.⁹

Methods of transmission

Transmission can be by infection of wounds and castration is believed a risk factor, with flies as possible vectors.¹⁰ Close contact may facilitate transmission.² BPV DNA has been detected in face flies (Musca autumnalis) associated with horses with sarcoids.³

Experimental reproduction

The disease has been transmitted with sarcoid tissue and cell free supernatant from minced sarcoid tumors. The disease has also been reproduced with bovine papillomavirus although the experimentally produced tumors subsequently regressed which seldom occurs with natural sarcoid.³

Animal risk factors

There is a genetic-based susceptibility to the disease,⁷ and the predisposition of horses to sarcoid is associated with the type of major histocompatibility complex.¹¹ Approximately 40% of the susceptibility to the disease in Swedish Halfbred horses is attributable to an autosomal, dominant equine leukocyte antigen (ELA)-linked gene.⁷ The prevalence in quarter horses is greater than that in thoroughbreds, and in both is higher than that in standardbreds.⁹ Sarcoids are very rare in horses less than 1 year of age, and the prevalence is highest in horses 1 to 6 years-of-age. Young males appear more at risk, possibly related to castration.¹⁰

Environmental risk factors

Lesions commonly occur on traumatized areas.

Occurrence

The disease used to be confined to sub-Saharan Africa, but it is now enzootic in Egypt, and has occurred in Israel¹ where it was eradicated by slaughter of infected and in-contact animals. Some field outbreaks are associated with severe and generalized infections and a high mortality, while with others there are few obviously affected animals and no deaths but in general outbreaks are more severe with the initial introduction of the infection to a region and then abate, probably associated with the development of widespread immunity. Morbidity rates reach 80% during epizootics, but are nearer 20% in enzootic areas. Morbidity rates of 31% are recorded in Egypt, and a morbidity of 10% in the recent incursion into Israel.¹ In Kenya, the disease is characterized by a much lower morbidity rate and the disease is much milder. Case fatality rates average 2%, but vary with the outbreak. Israel has experienced no direct mortality from the disease. There has been a resurgence of the disease in South Africa in the past decade probably due to higher rainfall and a decrease in the use of vaccination consequent to a previously low incidence.²

Origin of infection and transmission

Cattle can be infected by drinking water, but ingestion and direct contact transmission are not common routes, even though the virus is present in nasal and lacrimal secretions, semen, and milk of infected animals. Most cases are believed to result from transmission by an arthropod vector. Historically, LSD virus has been isolated from Stomoxys calcitrans and Musca confiscata and transmitted experimentally using S. calcitrans but other vectors are also suspect including Biomyia, Culicoides, Glossina and Musca spp. However, in a recent study, despite the detection of virus in mosquitoes (Anopheles stephensi, Culex quinquefascuatus) the stable fly and a biting midge (Culicoides nebeculosis) after they had fed on cattle with lumpy skin disease, the infection did not transmit to susceptible cattle when these arthropods were allowed to re-feed on them.³

Risk factors

Experimental production

Experimental transmission can be accomplished using ground-up nodular tissue and blood, or tissue culture virus. Disease is produced following intranasal, ID or IV challenge.⁵ While lumpy skin disease is characterized by generalized nodular skin lesions, less than 50% of natural or experimental infections develop generalized skin nodules and the length of the viremic period does not correlate with the severity of the clinical disease.

Economic importance

The mortality rate is low, but the economic loss is high. In all cattle there is severe loss of milk production and the occurrence of secondary mastitis predisposed by the development of lesions on the teats. Loss also occurs from damage to hides, the loss of bodily condition during the course of the disease, and the loss of fertility in affected bulls. Cow may abort in the course of the disease. Lumpy skin disease is considered to be one of the high risk diseases for spread out of Africa to the outside world and a potential agent of agroterrorism.

Samples for confirmation of diagnosis

Vaccination

A safe and effective vaccine has been produced by 60 passages of the virus through lamb kidney culture. It is administered to all animals over 6 months of age and is effective, but is associated with considerable local reaction that may persist over 1 month and may predispose fly strike. Local response to the vaccine is usually correlated with good antibody reponse.² A freeze-dried, living attenuated virus vaccine is also available. Vaccination of cattle with sheeppox virus, also attenuated by passage through tissue culture, is effective in preventing infection with the lumpy skin disease virus and is currently the most common method of protection.^11,12 A small percentage of cattle develop granulomatous local reactions but there is no spread of the sheeppox to sheep running with the cattle. Vaccination of a herd at the start of an outbreak has limited efficacy as most animals will already be incubating the disease. Poor needle hygiene in these circumstances may spread the disease.

Cattle vaccinated with a recombinant capripox-rinderpest vaccine are immune to experimental challenge with both viruses but for a different length of time with each agent.¹³

Slaughter of affected and in-contact animals and destruction of contaminated hides, coupled with vaccination of at-risk animals, is used when the disease gains access to a previously free country.

Occurrence

Cowpoxvirus could be considered to be misnamed. Infection with this virus is endemic in wild rodents such as voles (Microtus spp.) in Great Britain, Europe and western Asia, with infection in different rodent species acting as the reservoir host in different geographic areas.^2,3 Domestic cats are commonly infected from hunting rodents, but cowpoxvirus infection can occur in a number of different mammalian species,² one of which is cattle. The clinical syndrome of cowpox in cattle is now extremely rare but it occurs sporadically in Europe. Seroprevalence in British cattle is less than 1%.

Origin of infection and transmission

The origin of infection is most probably from infected farm cats or humans. Transmission from cow to cow within a herd is effected by milkers’ hands or teat cups. Spread from herd to herd is probably effected by the introduction of infected animals, by carriage on milkers’ hands, and in the absence of either of the above methods, transport by biting insects is possible. In a herd in which the disease is enzootic, only heifers and new introductions develop lesions. Milkers recently vaccinated against smallpox may serve as a source of infection for cattle, although the vaccinia virus, the smallpox vaccine virus, is a different virus.

It is generally assumed that the virus gains access to tissues through injuries to teat skin, and extensive outbreaks of cowpox are likely to occur when the environment is conducive to teat injuries. Spread is rapid within a herd and immunity is solid, so that the disease tends to occur in sharp outbreaks of several months’ duration with subsequent immunity protecting the cattle for at least several years.

Economic importance

Losses are due to inconvenience at milking time because of the soreness of the teats and from occasional cases of mastitis, which develop when lesions involve teat sphincters. Milk from affected cows is suitable for human consumption.

Zoonotic implications

Human cowpox is not common and usually consists of one or a few lesions on the hand and face with minimal systemic reaction.⁴ Infection is more likely to come from an infected cat than cattle.^4,5

Occurrence

Pseudocowpox is reported from most countries. In an affected herd the rate of spread is relatively slow and may result in the disease being present in the herd for up to a year. The morbidity rate approximates 100%, but at any given time varies between 5 and 10%, and occasionally up to 50%.

Origin of infection and transmission

The source of infection is infected cattle. The method of transmission includes physical transport by means of contaminated milkers’ hands, wash cloths, and teat cups. The virus cannot penetrate mucosa, and a pre-existing discontinuity of it is necessary for the virus to gain entry. Transmission by biting insects seems likely. The virus can be isolated from the mouths of calves sucking affected calves, and from the semen of bulls.

Animal risk factors

Freshly calved and recently introduced cattle are most susceptible, but all adult cattle in a herd, including dry cows, are likely to be affected. The disease does not appear to occur in animals less than 2 years of age unless they have calved. There is no seasonal variation in incidence. Little immunity develops and the disease is likely to recur in the herd within a short time.¹

Economic importance

Pseudocowpox is relatively benign, most losses occurring as a result of difficulty in milking and an increase in the incidence of mastitis.

Zoonotic implications

The disease is transmissible to humans, infection usually resulting in the development of milkers’ nodule on the hand.

Occurrence

Herpes mammillitis is recorded in North America, Australia, Europe and Africa, but probably has widespread occurrence. Herds infected for the first time have a high morbidity rate. Subsequently, the incidence is low and is limited to fresh heifers. The morbidity rate varies between 18 and 96%, susceptible herds recording more than 30% affected. The mortality rate is negligible.

Origin of infection and transmission

Introduction of bovine ulcerative mammillitis into a herd may occur with the introduction of infected animals, but outbreaks have been observed in self-contained herds. Spread within the herd is probably by direct and fomite-mediated transmission, although experimentally the virus must be deposited in the deep layers of the skin, and even rubbing it into pseudocowpox lesions is not an efficient way of transmitting the disease. Milking machine liners, hands, and udder cloths may act as carriers of virus when a large amount of it is being released.

Seasonal and circumstantial evidence in the United Kingdom and Australia suggest an insect vector, but this has not been confirmed by attempts at transmission with the stable fly (Stomoxys calcitrans), and in the mid-west of the United States, disease is more common in the winter months between November and April.²

Survival of the virus for long periods in carrier animals occurs and it is thought that this may be the means of survival of the virus within a herd that has become immune.³ Infection in some cows is suspected to result in chronic infection at the teat end with the cows becoming ‘hard milkers’ and carriers of the disease.²

Animal and pathogen risk factors

Lesions are most common in animals within the first 2 weeks after calving, particularly in heifers, and the disease is more severe in heifers. Heifers that have udder edema at calving are particularly prone to develop severe lesions. Occasionally, lesions may be seen on the teats of replacement heifers and calves sucking infected dams often develop mouth lesions.

The disease is usually self-limiting, persisting in a herd for 6–15 weeks, the severity of the lesions decreasing as the outbreak progresses. Immunity appears to last about a year, herds infected naturally can suffer recurrences a year later. Large herds may have persisting disease, particularly in heifers.

The virus is relatively resistant to environmental influences and can survive freezing. It is susceptible to iodophor disinfectants and less so to hypochlorites.

Economic importance

Forms of loss include a much higher incidence of mastitis, reduction in milk in affected herds by up to 20%, the culling of some cows because of severe mastitis and of heifers because of intractable ulcers, and a great deal of interference with normal milking procedure.

Zoonotic implications

There are anecdotal reports of herpetic lesions in farmers exposed to infected cattle.⁴

Occurrence and prevalence of infection

Sheeppox and goatpox are prevalent in North and Central Africa, the Indian subcontinent, Middle Eastern countries, China, Southwest Asia and the former Soviet Union. Sporadic outbreaks occur in southern Europe and elsewhere.⁶ The capripoxvirus infections of small ruminants are the most serious of all the pox diseases in animals. In susceptible flocks and herds morbidity is 75–100% with outbreaks often causing death in 10–85% of affected animals depending on the virulence of the infecting strain.^2,6-9

Methods of transmission

Sheeppox and goatpox are highly contagious. The virus enters via the respiratory tract and transmission commonly is by aerosol infection associated with close contact with infected animals. The virus is present in nasal and oral secretions for several weeks after infection and can live in scabs that have fallen off the animal for several months. Spread can also occur from contact with contaminated materials and through skin abrasions produced iatrogenically or by insects. Capripox has been shown to spread via the bites of Stomoxys calcitrans and the tsetse fly.¹⁰

Experimental reproduction

The disease can be transmitted by intradermal, intravenous and subcutaneous inoculation and by virus aerosols.

Risk factors

Economic importance

Loss is from mortality, abortions, mastitis, loss of wool, skin condemnation and loss of exports. In ewes and does, severe losses may occur if the udder is invaded because of the secondary occurrence of acute mastitis. In some outbreaks, adult sheep are affected with the more severe form of the disease.¹¹ Sheeppox is a potent threat to countries that have big sheep populations, and where the disease does not occur, because of its ineradicability and heavy mortality rate.

Zoonotic implications

Human infections in people handling infected animals are not a consideration.⁶

Antigen detection

Diagnosis is based on typical clinical signs combined with laboratory confirmation of the presence of the virus or antigen. Using electron microscopy, large numbers of characteristic ‘sheeppox cells’ containing inclusion bodies and typical capripox virions can be seen in biopsies of the skin. The virus can be cultured in tissue culture but virus isolation as a method of rapid diagnosis is limited by the time it takes for virus cytopathic effects to develop and the need, with some strains, for several blind passages before this develops. Direct fluorescent antibody test is used to detect the presence of pox virus in the edema fluid and the antigen can be detected in biopsies of lymph glands by AGID using specific immune sera. An antigen detection ELISA is also available.

Serology

In India a ‘soluble antigen fraction’, which is non infectious, has replaced infectious virus for serological tests which avoids the risk of accidental spread of the virus from diagnostic laboratories and from the postal supply of diagnostic agents.⁶ However, serological tests such as AGPT, serum neutralization and agar gel diffusion are confounded due to cross reaction with orf virus. A capripox-specific capture-ELISA is reported to have sufficient sensitivity, specificity and speed to have utility in rapid diagnosis using biopsy samples.¹³ Serological testing can be by virus neutralization, which is specific or by an indirect fluorescent antibody test or an agar gel precipitation (AGPT), however both of the latter cross react with antibody to contagious pustular dermatitis virus. Virus-specific analysis of antibody response by Western blot analysis can differentiate the infections.¹⁴

A capripox PCR for detection of antigen is used in some countries which do not have the disease and do not hold live virus.^15,16

Occurrence

Swine pox (pig pox) occurs worldwide where swine are raised and is more common in swine units where there is poor sanitation.

Methods of transmission

Transmission is by contact transmission and mechanically by the pig louse (Haematopinus suis), and possibly by flies and other insects.² Young sucking pigs may have lesions on the face, with similar lesions on the udder of the sow, with spread by direct contact. The virus can survive in scab material for several months.

Animal risk factors

The virus infects only swine and can infect all ages but clinical disease is most commonly seen in young piglets. It is usually a sporadic disease with occasional outbreaks affecting a cluster of litters within a herd and of short duration. Some or all pigs in a litter may show clinical signs.³ The disease may appear apparently spontaneously or may occur only in pigs brought into the contaminated environment of a herd in which the indigenous pigs are immune.

The incidence in individual herds may be high. Mortality is usually low except in very young piglets and congenitally affected piglets where mortality rates can be high.^2,3 Congenital infection presents with a low morbidity but high case fatality.^3-6 Older animals seem to suffer little ill effect.²

Occurrence

The disease is one of the commonest causes of diagnosed abortion in sheep and goats in the United Kingdom, the United States,³ and in other countries. In the UK it accounts for approximately 45% of abortions, and it is particularly common in lowland flocks that are intensively managed at lambing time. However, its importance varies from country to country. It is an uncommon cause of abortion in Northern Ireland,⁴ and the disease does not occur in Norway or New Zealand.⁵

There have been several studies of seroprevalence in Europe which show a high seroprevalence in both domestic and wild ruminants but, until recently, most surveys have used the complement fixation test which is not specific for Cp. abortus and the seroprevalence rates for Cp. abortus in different countries are not well established.⁶

Source of infection and transmission

Infection is introduced into a flock by the purchase of latently infected replacements which usually abort at the end of their first pregnancy.

Within a flock, the major source of infection is the placenta and the uterine discharge of aborting ewes. The main routes of transmission of Cp. abortus are through ingestion of organisms shed in vaginal fluids and placental membranes at the time of abortion or lambing, or through inhalation of aerosols from the environment.⁷ Pasture and the environment are contaminated by vaginal discharges, placenta and aborted fetuses, and infected ewes shed the organism for a week before aborting and for 2 weeks afterwards. The elementary body of Cp. abortus is resistant to both physical and chemical influences as it is metabolically inactive and the rigid cell envelope is osmotically stable and poorly permeable. As a consequence the organism is believed to survive for several days on pasture and longer in cold weather.

Infection of the ewe lamb may occur at birth, shortly following, or at subsequent lambing periods. Infection of pregnant ewes in early or mid gestation results in either abortion in the final 2–3 weeks of gestation, or the birth of stillborn or weak lambs that frequently die in the first few days of their life. Abortion always appears in the last weeks of gestation regardless of the time of infection. Infection of ewes in the last 5–6 weeks of pregnancy usually leads to the development of a latent infection, where ewes appear to be uninfected until the next lambing season, when they abort. Thus, late pregnant sheep may be infected by contact with aborting ewes but usually do not themselves abort until the next lambing season.

The common pattern of infection and disease is the a small number of abortions in year 1 usually resulting from the introduction of infected replacement ewes, followed by an epidemic abortion storm where up to 35% of ewes abort in the last 3 weeks of gestation or give premature birth to weak or dead lambs. After abortion, the ewes develop a protective immunity and, in endemically infected flocks, 5–10% of the ewes abort annually. Surviving lambs born to infected mothers may be affected by EAE in their first pregnancy.^8-10

Sheep that have aborted, subsequently re-breed successfully, do not have further abortions, and the organism is not present in the placenta or vaginal discharge of subsequent pregnancies. However, levels of immunity vary and some may excrete organisms at estrus or seasonally for up to 3 years.¹¹

In chronically infected sheep, persistent infection can be demonstrated in the endometrial cells of the reproductive tract,¹² and the organism is excreted in vaginal fluids during estral periods.

Vaginal challenge of ewes at breeding time will result in infection and subsequent abortion, and venereal or passive venereal transmission is a possible route of infection,^13,14 but it does not appear to be a common or important route. Chronic infection of the male genital tissues has been recorded and infection may impair fertility in both rams and bulls.⁸

The epidemiology of abortion with this agent in cattle is unknown but it may transmit to cattle from infected sheep on the same farm.^2,15

Experimental reproduction

The disease is readily reproduced experimentally.^16,17 Following subcutaneous injection there are no signs of clinical disease other than a modest increase in rectal temperature for two days after infection. There is a systemic antibody response that peaks 2 weeks after infection and then decreases until just before abortion or parturition, when there is a second increase in the antibody levels to Cp. abortus. Experimental infection at 70 to 75 days pregnancy can result in abortion in the last 2 to 3 weeks of pregnancy or the birth of stillborn or live lambs. There is variation in the severity of the placental lesions in experimental infections. Abortion is associated with severe placental lesions but the reason for the variation in severity and fetal manifestations is not known.¹⁷

Economic importance

Enzootic abortion is the most common infectious cause of abortion in lowland flocks that are intensively managed at lambing time, and has a major economic impact on agricultural industries worldwide. There are no recent estimates of economic impact but losses in the UK were estimated in the early 1990s at £15–20 million per annum.¹⁰

Zoonotic implications

There is some risk for shepherds, and those in allied fields such as abattoir workers, to contract respiratory infection with this organism but the major zoonotic risk is to pregnant women because of the ability of Cp. abortus to colonize the human placenta. Human infection in early pregnancy results in abortion whereas later infection can result in stillbirth or pre-term labor.^8,18 Infection is believed by the oral route from infected hands or food following direct handling of infected sheep or goats or infected clothing. Practices at lambing such as mouth to mouth resuscitation of weak lambs or bringing weak lambs into the house to be warmed promote zoonotic spread. Infected placentas and dead lambs should be handled using gloved hands and disposed of by burning or burial.

The organism can be detected in milk both in sheep and in cattle and raw milk could also pose a risk for zoonotic infection.^19,20

Samples for confirmation of diagnosis

Note the zoonotic potential of this organism when handling carcasses or submitting specimens.

Vaccines

Two types of vaccine are currently available but there is yet no vaccine that has excellent efficiency against this disease.

Killed vaccines, composed of egg-grown or tissue culture grown organisms of one or two strains have been used for several decades. They are variably effective and can reduce the frequency of abortion and the shedding of the organism. However, outbreaks have occurred in vaccinated sheep and strain variation is a possible cause of failure of monovalent vaccines.¹

The addition of Freund’s incomplete adjuvant has provided a vaccine that provides better protection²⁶ and it has been recently claimed that specific adjuvants can markedly improve the efficiency of killed vaccines against naturally occurring enzootic abortion.^27,28

A live vaccine containing a temperature-sensitive attenuated strain of C. psittaci has shown to engender excellent, but not complete, protection against challenge; with five different abortigenic strains of Cp. abortus there was a marked reduction in the number of ewes aborting and marked increase in live-born lambs compared to controls.²⁹ It is labeled for sheep but not for goats. Concern has been expressed for the zoonotic potential of an attenuated vaccine.²⁷

Recombinant and DNA vaccines have shown disappointing protection in studies with experimental challenge.^30,31