A MUCOSAL DISEASE VIRUS AS A CAUSE OF ABORTION HAIRY BIRTH COAT AND UNTHRIFTINESS IN SHEEP

A condition resembling border disease has been transmitted by the inoculation of pregnant ewes with material from affected lambs. Forty-nine merino ewes, mated to merino rams 7 to 87 days previously, were inoculated with an homogenate of brain, spinal cord and spleen from affected lambs. Mummified foetuses, abortions and stillbirths were observed, and lambs with hairy birth coats were born to ewes inoculated between days 12 to 70 of gestation. A mucosal disease virus (MDV), present in the original material, was recovered from the aborted foetuses and lambs. Attempts to induce passive protection using bovine anti-serum to the C24V strain of MDV were not successful. The condition was also transmitted by inoculation of pregnant ewes with a cell culture supernatant prepared from tissue cultures that had been inoculated with an organ homogenate pool. MDV was present in the supernatant and was recovered from aborted foetuses and lambs. It is suggested that a condition in sheep in Australia resembling border disease is due to the infection of the pregnant ewe by a mucosal disease virus.     

TRANSMISSION OF A MUCOSAL DISEASE VIRUS INFECTION BETWEEN SHEEP

The transmission of mucosal disease virus (MDV) from infected ewes and their lambs to susceptible sheep was investigated. MDV was recovered from the amniotic fluid of an infected pregnant ewe and from the blood, nasal swabs and urine of hairy lambs. MDV infection was transmitted either at lambing, from infective foetal fluids or lambs, or later as a result of contact with a surviving with a hairy lamb and either aborted or gave birth to an infected hairy lamb. Adult sheep and 12-months-old sheep were less readily infected than were newborn lambs. Pregnant ewes were infected by contact with a hairy lamb and either aborted or gave birth to an infected hairy lamb. A method to minimise spread of the infection in the field is suggested.     

A MUCOSAL DISEASE VIRUS INFECTION OF THE PREGNANT EWE AS A CAUSE OF A BORDER DISEASE-LIKE CONDITION

An experiment was designed to investigate whether a condition in Australian sheep with clinical and pathological similarites to Border Disease was caused by the infection of the pregnant ewe with a Mucosal Disease virus (MDV). Forty ewes, at 58 to 63 days after mating, were inoculated with material from lambs in which all, some or none of the tissues examined contained MDV. The clinical condition was observed only in lambs born to ewes inoculated with MDV-positive material and then only to ewes in the group which had serological evidence of MDV infection. It is concluded that the Border Disease-like condition in Australian sheep is caused by the infection of the pregnant ewe with a Mucosal Disease virus.     

A survey of hairy shaker disease (border disease, hypomyelinogenesis congenita) in sheep

A survey by mail in 1979 of 995 sheep farmers in Victoria enquiring as to the occurrence of hairy shaker disease (HSD) in lambs on their farms resulted in a 48% response. A total of 17 farms reported the presence of HSD. One hundred and eleven ewes produced lambs with HSD representing a small proportion only of the ewes (0.8%) on these farms and an even smaller percentage of the total ewes (0.03%) in the survey. Abortions were not prevalent on the majority of farms reporting HSD. There was no evidence that HSD was more common in any particular area in Victoria. As was anticipated mucosal disease virus/bovine virus diarrhoea (MDV) antibody was often present in serums from affected sheep. It was concluded that at present, the hairy shaker form of border disease did not appear to be an economically important problem in Victoria.     

Clinical variations of border disease in sheep according to the source of the inoculum

Non-cytopathogenic pestivirus obtained from lambs with border disease, with or without nervous signs, was inoculated into pregnant ewes at 57 to 65 days of gestation. Live lambs born to inoculated ewes were clinically identical to the lambs from which virus was obtained, ie, either a hairy birth coat with central nervous system disturbance or a hairy birth coat without central nervous system disturbance.     

A Border Disease-like Syndrome in a Southern Ontario Sheep Flock

An outbreak of nervous disease and abnormally hairy fleece was observed among newborn lambs in a closed flock of sheep in southern Ontario. The outbreak was investigated and found to closely parallel syndromes described in the British Isles and Australia and variously referred to as border disease, hypomyelinogenesis congenita and hairy shaker syndrome. Clinically affected lambs represented only a portion of the animals affected, considerable losses being caused by reproductive failure in the ewes and suboptimal performance in subclinically affected lambs. Sheep from the affected flock showed a strong serological response to the causative agent of bovine virus diarrhea/mucosal disease. The episode appeared to be chronologically related to the introduction of beef heifers from a sales barn. The paper discusses the results of clinico-epidemiological investigation of the outbreak in the light of current knowledge of border disease-like syndromes.     

Pathology in the ovine foetus caused by an ovine pestivirus

Homogenised tissues or tissue culture supernatant fluid containing a noncytopathic pestivirus obtained from a lamb with a neurologic form of border disease, were inoculated into ewes at different stages of pregnancy. Foetal death occurred in 9 ewes of those inoculated between 19 and 47 days of pregnancy while 3 ewes did not lamb. Eight of the foetuses were aborted between 77 and 132 days of pregnancy; of these 6 were autolysed or mummified and one had arthrogryposis. The one full-term dead lamb had a hairy birth coat and lissencephalic micrencephaly. Foetal death occurred in only 7 of 14 ewes inoculated between 57 and 72 days of pregnancy. Four of these ewes aborted between 77 and 108 days of pregnancy and 3 gave birth to full-term, dead, hairy lambs. The remaining 7 ewes gave birth to live hairy lambs with severe inco-ordination. All lambs carried to term and aborted foetuses or lambs that could be examined had a range of intracranial malformations including focal leucomalacia, micrencephaly, hydranencephaly, porencephaly, lissencephaly and cerebellar hypoplasia. Some lambs also had skeletal abnormalities including arthrogryposis, scoliosis and brachygnathia inferior. The pestivirus isolate used in these trials produced more severe effects on the ovine foetus than previously observed in similar inoculation trials using pestivirus isolates from border disease lambs without nervous signs.     

The production and survival of lambs persistently infected with border disease virus.

From 1985 to 1989 lambs persistently infected with border disease virus (BDV) were produced for comparative immunological studies by infecting 57 susceptible pregnant ewes between 50 and 60 days' gestation with Moredun or Oban strains of BDV. Ewes were infected either by injection with virus grown in cell culture or by housing with lambs excreting BDV. There was no significant difference in the outcomes of these different methods of infection. There was a significant difference in the number of viable lambs born to ewes receiving the two viruses. Of 41 ewes infected with Moredun virus 21 produced 32 live lambs of which 17 were reared to 1 month old (53% viability). Of 16 ewes receiving Oban virus 10 gave birth to 17 live lambs of which 15 were reared to 1 month old (88% viability). All the lambs born to ewes infected with Moredun BDV had varying signs of tremor and increased hairiness ("hairy-shakers") while those born to ewes infected with the Oban virus had no obvious clinical signs. Survival of the lambs was poor. Up until February 1991, 14 Moredun and 10 Oban sheep between the ages of 4 months and 5.5 yr had died from a variety of causes. The two commonest causes were a chronic wasting syndrome and a mucosal disease-like syndrome which was associated with the recovery of cytopathic BDV. Mating of unrelated persistently infected sheep was largely unproductive although 2 lambs were reared.     

The effects of bovine viral diarrhoea-mucosal disease (BVD) virus on the ovine foetus

Bovine viral diarrhoea-mucosal disease (BVD) virus has been incriminated as a cause of abortion, hairy birth coat and unthriftiness in sheep. Intravenous inoculation of 40 ewes 34 to 45 days pregnant with the V/TOB strain of virus produced death in two of four foetuses 9 days after inoculation and in all but one of 31 foetuses between 11 and 56 days. The highest levels of virus in placentomes and foetal tissues occurred between 9 and 15 days after inoculation and in foetal fluids between 11 and 18 days. Virus was not detected in any foetus later than 21 days after inoculation. Groups of 10 ewes infected between 59 and 62 days (Group B) and 70 and 76 days (Group C) of gestation had 73% and 62%, respectively, of abortions or perinatal foetal deaths. Birth weights of lambs born to infected ewes in groups B and C were significantly lower than those born to uninfected control ewes. Virus was recovered consistently from the cotyledons of the foetal membranes of live lambs, and irregularly from the tissues of full term foetuses that were dead at birth but on no occasion from mummified foetuses. There were no specific gross or microscopic lesions in tissues selected from aborted foetuses and the results highlight the difficulties associated with the diagnosis of BVD abortions and perinatal death of foetuses under field conditions.     

Intrauterine transmission of ovine progressive pneumonia virus

Ovine fetuses, newborn lambs, and ovine colostrum were examined for ovine progressive pneumonia virus. The lambs and colostrum were also examined for specific antibody. Virus was isolated from 1 fetus, from 2 newborn lambs, and from most samples of colostrum. The fetus was about 100 days old and was carried by a seronegative ewe in contact with seropositive sheep. Both newborn lambs were carried by seropositive ewes. One lamb was dead at birth; the other lamb was normal and had not nursed. Antibody specific for the virus was present in the colostrum of 12 of 14 seropositive ewes and in the serum of 8 of 11 lambs that had nursed seropositive ewes, but not in the serum of lambs that had not nursed.     

Experimental infection of pregnant ewes with bovine viral diarrhea virus type-2 (BVDV-2): effects on the pregnancy and fetus

The reproduction effects of bovine viral diarrhea virus type-2 (BVDV-2) infection were investigated in ewes inoculated with a non-cytopathic BVDV-2 isolate at three stages of gestation. Virus inoculation was followed by a transient viremia, accompanied by a transient and mild hyperthermia and nasal discharge in a few animals. Some ewes were sacrificed at different time-points after virus inoculation to study the kinetics of fetal infection. Infectivity and viral antigens were detected in placentomes from day 7 to 36 post-inoculation (pi) and in fetal fluids and tissues between days 10 and 28 pi. Cardiac petechial hemorrhages and hemoperitoneum accompanied by a severe fibrinous ulcerative placentitis were observed in fetuses examined at days 21, 28 and 36 pi. Inoculation of ewes at days 55-60 of gestation resulted in a prolonged virus replication in placentomes and fetal tissues; ewes that were allowed to proceed with pregnancy had 77% of abortions or fetal and perinatal deaths. Seven stillbirths, unviable and viable lambs born to these ewes were virus-positive at birth. Infectious virus was repeatedly isolated from leukocytes of two lambs up to 2 and 6 months of age, indicating they were persistently infected. Ewes inoculated at days 65-70 of gestation had 66.6% of fetal and perinatal losses. Three viable lambs born to these ewes were healthy, BVDV antibody-positive and virus-negative. A transient viral replication in placentomes and in a few fetal tissues, followed by the rise of fetal neutralizing antibodies and virus clearance was the result of inoculating ewes at days 120-125 of gestation. Lambs born to these ewes were healthy, antibody-positive and virus-negative. These results demonstrate that the biology of BVDV-2 infection in pregnant sheep is essentially similar to that of BVDV-1 in pregnant cattle and sheep. These features make this species an attractive animal model for studying the pathogenesis of congenital BVDV-2 infection.     

Border disease without nervous signs or fleece changes

A natural infection with border disease virus occurred in a flock on low ground in Argyll in the spring of 1984. The outbreak was unusual in that the typical clinical signs of border disease, ie, tremor and, or, fleece changes were not present; manifestations of disease were restricted to abortion and the birth of small weak lambs. The disease was shown to have been introduced to the flock by four healthy ewes persistently infected with border disease virus among a group of 39 purchased in October 1983. Further investigations in late August 1984 detected viraemia in six of seven ill-thriven lambs and four of 24 apparently healthy lambs. Attempted 'natural vaccination' of susceptible sheep by mixing them at grass for three months with groups of ewes and lambs known to contain virus excretors was largely unsuccessful as only four of 22 'sentinel' sheep seroconverted. In October 1984 the persistently infected purchased animals and all that year's lamb crop were removed from the farm. No disease occurred in 1985 when the lambing percentage was 129 per cent compared with 100 per cent in 1984. Two of the four persistently infected purchased ewes were mated at Moredun Research Institute in December 1984 and both produced healthy but persistently infected lambs.     

Repetitive abortion in Neospora-infected ewes.

Pregnant ewes inoculated with cultured Neospora caninum tachyzoites in 1995, 1996, or 1995 and 1996 aborted or delivered weak or clinically normal lambs in 1996. Nine of 11 ewes in the study had previously produced infected lambs or fetuses after being experimentally infected in 1995. Fetuses and lambs produced in 1996 showed histologic lesions and zoites indicative of Neospora. Serologic responses and production of infected fetuses/lambs indicated systemic neosporosis in the ewes during gestation, although tachyzoites could not be cultured from maternal tissues. The repetitive infection of fetuses, and resulting clinical and histopathologic findings in the present study are similar to those reported in naturally infected cattle, adding to the already established similarities of neosporosis between sheep and cattle.     

Bluetongue virus serotype 20 infection in pregnant Merino sheep

Eleven maiden Merino ewes, free of antibody to bluetongue virus serotype 20 (BTV-20) in agar gel immunodiffusion and serum neutralisation tests, were mated once with a ram. Ten ewes were inoculated with BTV-20 35 to 42 days after service, and one ewe was left as an uninoculated control. One of the inoculated ewes and the control ewe remained uninfected throughout the experiment. Eight of the remaining 9 ewes showed clinical signs ranging from mild to moderate, and the other showed no clinical signs of infection. BTV-20 viraemia was detected in ewes between days 3 and 11 post inoculation, and the serum antibody response was followed. The control ewe and 5 of the 9 infected ewes were pregnant when examined 90 to 97 days after service. Each of these animals produced a normal lamb. There was no evidence of abortion in the remaining 5 ewes, and no transplacental transfer of virus was detected in the lambs of the 5 infected ewes. At necropsy, 46 days after the birth of the last lamb, no gross or microscopic lesions were observed in either the ewes or lambs.     

Properties of a respiratory syncytial virus isolated from a sheep with rhinitis

A virus isolated from a yearling cross-bred ewe was identified as respiratory syncytial virus (RSV) by indirect immunofluorescence and by virus neutralization with bovine RSV antisera. The virus caused a mild conjunctivitis in 3-month-old lambs when inoculated alone. Although clinical signs of pneumonia were not observed, there was gross and microscopic evidence of pulmonary inflammation in the lungs of lambs inoculated with either the sheep RSV isolate alone or in conjunction with Pasteurella haemolytica. Lung lesions in the dual infection were more severe, with approximately 10% of the total lung mass affected. Lavage fluids from lambs inoculated with virus and bacteria contained approximately 3 times more inflammatory cells than from control lambs or lambs inoculated with virus only. The sheep RSV isolate was classified as a mild respiratory pathogen in lambs of this age. Speculations on the potential importance of this virus in interspecies transmission to cattle and goats were discussed.     

Prevalence and effect of subclinical ovine progressive pneumonia virus infection on ewe wool and lamb production

The prevalence of infection with ovine progressive pneumonia (OPP) virus and its effects on ewe wool and lamb production were investigated in a flock of 2,976 ewes of 6 breed types (Rambouillet, Targhee, Columbia, Polypay, 1/4 cross Finnsheep, and 1/2 cross Finnsheep). Prevalence of seropositivity was significantly (P less than or equal to 0.01) lower among Rambouillet and Targhee breeds (44 and 42%, respectively), intermediate in Polypay, Columbia, and 1/4 cross Finnsheep (approximately 53%), and higher among 1/2 cross Finnsheep (62%). Seropositivity increased with age in all breed types from 11% at 1 year of age to 93% at greater than or equal to 7 years of age. Lateral disease transmission is indicated by linear increase of seropositivity prevalence with increasing age, including that in sheep greater than 6 years old. Subclinical infection with OPP virus had no apparent detrimental effect on number of lambs born, lamb viability, birth weight, number of lambs weaned, or growth rate of single and twin lambs, compared with findings for noninfected sheep in the same flock. Mature ewe body weight and grease fleece weight did not differ between subclinically infected seropositive and seronegative ewes. Subclinical infection with OPP virus does not appear to have an adverse economic effect on ewe wool and lamb production. Culling rate attributable to clinical manifestation of infection with OPP virus must be accurately determined before the true effects of virus infection on production can be determined and an eradication program can be recommended.     

Mucosal disease-like lesions in sheep infected with Border disease virus

An enteric disease characterised by diarrhoea and ill thrift affected 12 of a flock of 700 six- to 12-month-old ewe lambs in Cornwall between December 1996 and September 1997. The affected lambs were undersized, became thin and suffered an unremitting diarrhoea until they died. The illness lasted for three to 14 days, although, with hindsight, the owner considered that the lambs had been below average size before the enteric signs developed. The outbreak ceased only as a result of the dispersal sale of the flock as breeding ewes. The flock had been purchased from different sources, but 11 of the cases occurred in a group of 40 purchased from one source. Postmortem, the alimentary changes resembled mucosal disease in cattle, and immunostaining of histological sections of the affected tissues revealed pestiviral antigen. Non-cytopathic pestiviruses were isolated from the lesions of two of the affected lambs and from the blood of several clinically normal ewe lambs from the same group. All the pestivirus isolates were typed as Border disease virus.     

The effects of maedi-visna virus infection on productivity in ewes

A total of five data sets obtained from four separate sheep flocks were used to evaluate the effects of subclinical maedi-visna virus infection (as determined by serological procedures) on productivity in ewes. In general, infection with maedi-visna virus had a detrimental effect on productivity. Infection resulted in a reduction in conception rates, with the odds of an infected ewe conceiving being only approximately 0.67 times those of a non-infected ewe. For ewes which did conceive, there was no detrimental effect of infection on the number of lambs born. The birth weights of lambs born to middle-aged (3–4 years) infected ewes were 3–6% lower than the weights of lambs born to non-infected ewes of the same age. There was very little apparent effect of infection in younger (1–2 years) and older (5 + years) ewes: some factors which may have biased these results are discussed. Lamb weights at 25–50 days of age appeared to be reduced by maedi-visna infection in the ewe but the results were not statistically significant.     

Epizootic of ovine congenital malformations associated with Schmallenberg virus infection

Epizootic outbreaks of congenital malformations in sheep are rare and have, to the best of our knowledge, never been reported before in Europe. This paper describes relevant preliminary findings from the first epizootic outbreak of ovine congenital malformations in the Netherlands. Between 25 November and 20 December 2011, congenital malformations in newborn lambs on sheep farms throughout the country were reported to the Animal Health Service in Deventer. Subsequently, small ruminant veterinary specialists visited these farms and collected relevant information from farmers by means of questionnaires. The deformities varied from mild to severe, and ewes were reported to have given birth to both normal and deformed lambs; both male and female lambs were affected. Most of the affected lambs were delivered at term. Besides malformed and normal lambs, dummy lambs, unable to suckle, were born also on these farms. None of the ewes had shown clinical signs during gestation or at parturition. Dystocia was common, because of the lambs' deformities. Lambs were submitted for post-mortem examination, and samples of brain tissue were collected for virus detection. The main macroscopic findings included arthrogryposis, torticollis, scoliosis and kyphosis, brachygnathia inferior, and mild-to-marked hypoplasia of the cerebrum, cerebellum and spinal cord. Preliminary data from the first ten affected farms suggest that nutritional deficiencies, intoxication, and genetic factors are not likely to have caused the malformations. Preliminary diagnostic analyses of precolostral serum samples excluded border disease virus, bovine viral diarrhoea virus, and bluetongue virus. In December 2011, samples of brain tissue from 54 lambs were sent to the Central Veterinary Institute of Wageningen University Research, Lelystad. Real-time PCR detected the presence of a virus, provisionally named the Schmallenberg virus, in brain tissue from 22 of the 54 lambs, which originated from seven of eight farms that had submitted lambs for post-mortem examination. This Schmallenberg virus was first reported in Germany and seems to be related to the Shamonda, Aino, and Akabane viruses, all of which belong to the Simbu serogroup of the genus Orthobunyavirus of the family Bunyaviridae. These preliminary findings suggest that the Schmallenberg virus is the most likely cause of this epizootic of ovine congenital malformations, which is the first such outbreak reported in Europe.     

Experimentally induced ovine border disease: extensive hypomyelination with minimal viral antigen in neonatal spinal cord

Border disease (BD) was experimentally induced in 9 lambs by inoculation of their dams with the BD-31 strain of border disease virus (BDV) at 50 days of gestation. These ewes developed serum-neutralizing antibody titers to BDV. The diagnosis of BD in their lambs was confirmed by hairy birthcoats, intrauterine growth retardation, tremors, and hypomyelination. Three clinically healthy age-matched control lambs, whose dams had been given an inoculum containing only BDV-free cell culture supernatant, were studied in parallel. There were significant differences in birth weights and in the lengths of the right tibiae and radii between the affected and the control lambs. There was a gradient in severity of clinical neurologic signs among the affected lambs, which directly correlated with the severity of hypomyelination in their spinal cords. However, the difference in severity of the neurologic deficits did not correlate with differences either in the precolostral serum-neutralizing antibody titers to BDV in these lambs or in the number of BDV antigen-containing cells in their spinal cords. Only approximately 0.01% to 0.3% of spinal cord cells, both in gray matter and white matter, were BDV antigen positive in the affected lambs. These results indicate that extensive infection of CNS cells with their subsequent destruction or functional alteration may not be a critical part of the pathogenesis of the hypomyelination in BD.