Rev. sei. tech. Off. int. Epiz., 1990, 9 (1), 131-150. Pestivirus infections in ruminants other than cattle P.F. NETTLETON * Summary: Pestiviruses infect a wide range of domestic, captive and free-living ruminants. Among domestic livestock, Border disease virus is a well recognised cause of an important congenital disease of sheep in virtually all sheep-rearing countries of the world. The clinical signs, pathogenesis, diagnosis, epidemiology and control of this disease are described in detail. One natural outbreak of Border disease in domestic goats has been described and there is serological and virological evidence that pestiviruses occur widely in this species. A pestivirus has been isolated from a farmed red deer (Cervus elaphus) and there is serological evidence of a widespread low prevalence of infection among this new domestic species. Pestiviruses have been associated also with outbreaks of disease among captive ruminants in zoological collections. Among free-living ruminants, pestiviruses have been recovered from dead roe deer (Capreolus capreolus), fallow deer (Dama dama), African buffalo (Syncerus caffer), giraffe (Giraffa camelopardalis) and wildebeest (Connochaetes spp.) but in all these instances the contribution of the virus to the cause of the disease was uncertain. Serological surveys have shown that many species of freeliving ruminants in North America, Europe and Africa have varying prevalence rates of antibodies to pestiviruses. KEYWORDS: Border disease - Border disease virus - Bovine virus diarrhoea virus - Control - Deer - Epidemiology - Free-living ruminants - Goats Pathogenesis - Pestivirus - Ruminants - Sheep. INTRODUCTION The three pestiviruses, h o g cholera (classical swine fever) virus (HCV), bovine virus diarrhoea (mucosal disease) virus (BVDV) and Border disease virus (BDV) were named after t h e important diseases they cause. T h e recognition of a serological relationship between viruses causing a systemic haemorrhagic disease of pigs, a n enteric disease of cattle and a congenital disease of sheep remains a tribute to those responsible (19, 53, 58). Pestiviruses appear t o infect naturally only the even-toed ungulates belonging t o the order Artiodactyla, within which there are 11 species of pig a n d 173 species of ruminant (80). Despite attempts t o adapt pestiviruses t o grow in a variety of other * Moredun Research Institute, 408 Gilmerton Road, Edinburgh EH17 7JH, Scotland, United Kingdom. 132 hosts, only rabbits appear to support virus replication (22). Recent reports of antibodies to pestiviruses in h u m a n sera (28, 59, 81) and pestivirus antigen in h u m a n stools (83) require further substantiation, but raise the possibility of h u m a n infection with a serologically related virus. The success of pestiviruses, particularly in ruminants, is due to their ability to cross the placenta, invade the fetus and set u p a persistent infection which continues into post-natal life. These persistently infected animals excrete virus continuously and spread infection wherever they go, sometimes for years (31, 49, 73). This paper will address pestivirus infections in all ruminants, except cattle. After a brief consideration of the relationship between ruminant pestiviruses, the main features of Border disease (BD) in sheep will be described, followed by sections on BD in goats a n d pestivirus infections in other farmed, captive and free-living ruminants. RELATIONSHIPS BETWEEN A N D AMONG R U M I N A N T PESTIVIRUSES Traditionally, pestiviruses isolated from pigs have been termed H C V , those from cattle BVDV and those from sheep and goats BDV, but as new information emerges the picture becomes more complex. Nevertheless, nearly all studies of the antigenic relationship between representative isolates of the three pestiviruses have readily differentiated H C V from the ruminant pestiviruses (31). The differentiation of bovine virus diarrhoea (BVD) and BD viruses is less clear-cut. Serological comparisons of more t h a n 110 British isolates using polyclonal and monoclonal antisera indicate the presence of at least two antigenic groups of pestivirus, one of which predominates in cattle and one in sheep (21, 47). There is limited information on the antigenic relatedness between pestiviruses from other ruminants, although isolates from a giraffe and a fallow deer have been shown to be substantially different (16), and the fallow deer isolate is different from BVDV and BDV isolates (21). T h e probability exists, therefore, that pestiviruses have evolved along with their own host species. Interspecies transmission is achieved easily experimentally (31) and it is prudent to believe that it will occur readily in domestic and free-living ruminants when permitted to do so by new husbandry practices or changes in population dynamics. BORDER DISEASE OF SHEEP Introduction Border disease is a congenital disease of sheep first reported from the Border region between England and Wales (33). Since then BD has been recorded in Scotland (6), New Zealand (46), Ireland (30), Australia (1), USA (34), Switzerland (18), Greece (66), Netherlands (68), C a n a d a (57), Norway (43), Federal Republic of Germany (41), Syria (82), France (15) and Sweden (2). In addition, there is serological evidence that 133 BD is present in sheep in Nigeria (67) and the G e r m a n Democratic Republic (39) and there is a strong likelihood that sheep flocks in other countries will be shown to be infected by future investigators. Virtually all field isolates of BDV are non-cytopathic in cell cultures, although cytopathic strains have been described (37, 74). While the non-cytopathic biotypes cause congenital disease and persistent infection, cytopathic isolates have been recovered from sheep dying of a 'mucosal disease-like' syndrome (7, 27). Review articles on BD include a m o n o g r a p h (8), a general review (70), an u p d a t e on clinical disease (48) and chapters in two books (4, 31). Clinical disease One or m o r e of the following signs m a y indicate the presence of BD in a flock: 1. A n excessive number of abortions and barren ewes and the birth of small weak lambs (Fig. 1). FIG. 1 A group of hand-reared one-week-old lambs affected with Border disease All were small and only one was able to stand unaided. At one month old, 3 of the 4 lambs were sufficiently recovered to move about freely 134 2. A number of lambs being b o r n with abnormal b o d y conformation, tremor a n d / o r fleece changes sometimes with abnormal pigmentation (Fig. 2). T h e fleece changes are due to long hairs rising above the fleece to form a ' h a l o ' effect especially along the neck and back (Fig. 3). This effect is most evident in smooth-coated breeds and is much less obvious in the coarse-fleeced breeds such as the Scottish Blackface. Affected lambs have been termed 'hairy-shaker' or 'fuzzy lambs' in English-speaking countries, and 'pellous' or ' b o u r r u s ' in France. FIG. 2 Characteristic stance of a B D affected lamb Hind legs splayed to reduce swaying of hindquarters. Tail swinging from side to side 135 FIG. 3 Border disease lamb with hairy fleece Long hairs rising above the rest of the fleece form a 'halo' effect, especially over the back of the neck 3. A group of older lambs, especially a r o u n d weaning time, in which some have died and others are scouring a n d / o r ill-thriven. 4. Occasionally other unusual clinical signs are associated with infection. In one outbreak in France, lambs showed an unusual atrophic lesion of the diaphragm which resulted in constriction between the thorax and a b d o m e n (64). Pathogenesis Infection of non-pregnant sheep Infection of n o r m a l healthy sheep with virtually all BDV isolates is short-lived and mostly sub-clinical. Mild pyrexia and transient lymphopaenia coincide with viraemia, but with the production of neutralising antibodies 2 to 3 weeks after infection these signs disappear. O n e French isolate of BDV, however, has been shown t o produce profound leucopaenia and death in 5 0 % of 3- to 5-month-old lambs. This unusually pathogenic 136 strain of BDV was recovered from a case of Syndrome ' X ' [also called Aveyron disease, ovine leucopaenic enterocolitis or petega ovina (sheep plague)] first reported in December 1983 in the Aveyron region of France a m o n g sheep reared intensively for the production of milk used in the manufacture of Roquefort cheese. This new disease killed 1,500 ewes a n d 24,000 lambs in 1984. T h e principal symptoms were severe depression, pyrexia and diarrhoea and at post-mortem examination haemorrhages were seen at m a n y sites and were consistently present in the caecum, colon and mesenteric lymph nodes. Some recovered ewes later aborted or gave birth to weak shaking lambs with p o o r viability. The incidence of the disease fell sharply in 1985 and has remained low and although its cause was never determined conclusively, characteristics of the syndrome suggested it had a viral aetiology. Of t h e 5 viral agents recovered, only t h e B D virus isolate (AV2 strain) has a strong claim for having m a d e a major contribution to causing syndrome ' X ' (17). One other pestivirus isolate has been shown to cause disease in 4- to 5-month-old lambs. This isolate, recovered in the Netherlands, was a pestivirus contaminant of a live H C V vaccine. The contaminant was probably of sheep origin since its most likely source was the secondary lamb kidney cells used to prepare the vaccine. Lambs given the contaminated vaccine developed fever, prolonged leucopaenia, anorexia, conjunctivitis, nasal discharge, pale conjunctivae, dyspnoea and diarrhoea and 4 of 8 lambs died (78). Infection of pregnant ewes The most serious consequences of BDV infection occur when the virus infects susceptible ewes during pregnancy. The ewes show no clinical signs but virus spreads rapidly t o the placenta and crosses t o the fetus within one week of infection. T h e immune response of the ewe quickly eliminates all virus from the maternal tissues but it has n o effect in the fetus where virus can persist. Fetal infection The outcome of the fetal infection depends on the strain and dose of virus, the breed of the fetus and its ability to repair damage but most important is the stage of fetal development at which infection occurs. The age at which the fetus gains immunological competence is critical in determining the distribution and persistence of virus, which in turn influences the extent of fetal damage. The ovine fetus can first respond to an antigenic stimulus between approximately 60 and 80 days of gestation. T h e possible fates of fetuses before, during or after this crucial period are summarised in Figure 4. T h e most dangerous time for a fetus t o become infected is in the first 60 days of gestation. Virus replication is uncontrolled and the death of the fetus is likely. Death may occur rapidly leading to resorption or the unnoticed abortion of small fetuses or may not occur until weeks or m o n t h s after infection when the subsequent abortion or stillbirths are obvious. It is also possible for one fetus to die in early gestation and be found mummified at the birth of its surviving twin. In lambs surviving infection in early gestation virus is widespread in virtually all organs. Typically there is n o evidence of any inflammatory reaction. T h e principal pathological findings are myelin deficiency in the CNS which accounts for the tremor and an increase in the number of primary hair follicles causing 'hairiness'. The low pathogenicity of some virus strains, however, means that some lambs can be b o r n persistently infected with virus without showing any clinical signs and with only minimal pathological 137 Conception. 20 Early Gestation 40 60 Days 80 of gestation Onset of |foetal immune response Mid Gestation 100 Late Gestation 120 140 Birth "Hairy-Shaker", weak or normal PERSISTENTLY INFECTED VIRAEMIC LAMBS Weak or normal or late lambs w i t h gestation. antibody to B D V Also severe C N S defects LAMB STATUS As for early VIRUS VIRUS + + ANTIBODY ANTIBODY + FIG. VIRUS o r _ o r _ ANTIBODY + 4 Diagram showing the likely virological and serological status of lambs at birth following in utero infection with BDV during early, mid or late gestation 138 lesions ( 1 4 ) . Precolostral blood samples from 'hairy-shaker' and other persistently infected lambs contain readily detectable amounts of infectious BDV. Such lambs are tolerant to the virus and have a persistent infection usually for life (69). If fetal infection occurs when the i m m u n e system is beginning to develop (60-80 days) the outcome is unpredictable. Some lambs will be born viraemic and persistently infected without detectable antibody in precolostral blood. Others will be b o r n virus negative and antibody positive. Infection at this stage can result also in widespread inflammatory lesions in the CNS leading to cerebral cavitation and cerebellar dysplasia; the alternative pathology of BD (5). Lambs thus affected frequently have severe nervous symptoms and major locomotor disturbances and have a high concentration of serum antibody to BDV (61). Fetal infection after 80 days gestation is met by an i m m u n e system capable of eliminating the virus. Fetal death is rare and virtually all lambs will be born apparently n o r m a l . They will be free of virus but have demonstrable antibody. Persistently infected (PI) lambs Persistent infections with BDV can be established only if lambs are infected during their first 80 days of intra-uterine life. At birth, clinically affected lambs have a low chance of survival. M a n y die early in life while survivors have a poor growth rate and an increased susceptibility to other diseases. Less severely affected lambs can be reared with careful nursing but death may occur at any age. As lambs mature, the nervous signs gradually diminish but may recur at times of stress. ' H a l o ' hairs are soon lost from the birth-coat which is replaced by a coarse fleece. Whilst some affected lambs grow poorly and die young, others mature normally and can survive as persistent excretors of virus for years. Most P I lambs will receive colostral antibody to BDV and for the first three months of life can be serum antibody positive and viraemic. The virus can be difficult to detect in serum during this time but can be recovered readily from leucocytes. Lambs become seronegative as the colostral antibody concentration wanes. Virus persists in most tissues and the lambs remain a potent source of infection. Within groups of P I lambs some animals can suffer from chronic wasting, others can develop excessive ocular and nasal discharges sometimes with respiratory distress, while others develop an intractable scour and die within 2 to 4 weeks. Necropsy of these scouring lambs often reveals gross thickening of the distal ileum, caecum and colon resulting from focal hyperplastic enteropathy. Cytopathic BDV can be recovered from the gut of these lambs and this syndrome has several similarities with bovine mucosal disease (7, 27). P I sheep surviving t o breeding age often have reduced fertility but P I ewes have produced infected lambs in successive pregnancies (10, 79). Also virus-containing semen from a P I r a m can produce P I offspring, with the early embryo becoming infected from virus replicating in the uterine epithelium (26). Diagnosis The diagnosis of BD on clinical grounds will present little difficulty if typical 'hairyshaker' lambs are b o r n . Often however, laboratory confirmation will be necessary since swayback, 'daft' lamb disease, bacterial meningo-encephalitis, focal symmetrical encephalomalacia and hypothermia m a y have to be considered in the differential 139 diagnosis of affected lambs. The specimens required by the laboratory to confirm BD are summarised in Table I. As placentas and fetuses aborted due to BDV infection have n o distinguishing characteristics, laboratory confirmation will be required to differentiate BD from the other known infectious causes of ovine abortion. All animals in suspected groups should be blood sampled in order to detect the antibody negative, virus positive persistently infected sheep, whereas to determine the presence and extent of BDV infection in a flock, 10% of animals from different age groups should be tested for antibody. The most commonly used laboratory methods for demonstration of virus are detection of viral antigen in cryostat sections of tissues using immunofluorescence (IF), and virus isolation in susceptible ovine cell cultures, e.g. fetal lamb kidney or muscle cells, with detection of the non-cytopathic virus by I F or immunoperoxidase (IP) tests. Serum neutralisation or E L I S A methods are used for detecting specific antibody. Histopathology on brain and spinal cord is also useful if skilled interpretation is available. TABLE I Specimens to be collected for the laboratory confirmation of BD Clinical manifestation Live animal Dead animal 'Hairy-shaker' or weak lambs; also poorly thriving or scouring lambs Whole blood (clotted and heparinised) for virus isolation and serology from both the lamb and its dam Thyroid, kidney, brain, spleen, gut and lymph nodes: fresh for antigen detection and in virus transport medium for virus isolation. Heart blood for serology. Brain and spinal cord in calcium formol saline for histopathology Abortion Blood from dam for serology and virus isolation Tissues as above plus placenta for antigen detection and virus isolation. Brain and spinal cord in calcium formol saline for histopathology Epidemiology Sheep-to-sheep contact is the principal way in which BDV is spread, and the most potent source of virus is the persistent excretor. Bought-in P I sheep have been shown to introduce BDV into a susceptible flock and cause a serious outbreak of B D , and many other outbreaks of BD have a history of introduction of new stock at the beginning of the breeding season (14, 76). M o r e intensive husbandry, particularly housing during early pregnancy, increases the risk of an explosive outbreak of B D . Under experimental conditions pestiviruses from other species can also cause BD in sheep so that, among domestic animals, cattle in particular but also goats and possibly pigs represent potential sources of infection. A m o n g free-living ruminants pestiviruses have been isolated from red, roe and fallow deer and serological surveys in E u r o p e , N o r t h America and Africa have shown that m a n y species have detectable antibodies t o pestiviruses (see section below). Therefore, where sheep are grazed extensively in contact with free-living ruminants the possibility of infection from these other species cannot be excluded. 140 One other possible source of BDV infection which cannot be ignored is a modified live vaccine (MLV) contaminated with a pestivirus. All M L V ' s produced in ovine, bovine or porcine cell cultures, or in medium supplemented with serum from these species run the risk of being contaminated with a pestivirus (72). Screening techniques must include I F or I P tests to detect non-cytopathic viruses. Both sheep pox and orf virus vaccines administered to sheep have been incriminated as vectors of BDV infection (41, 66). Control Countries importing high quality breeding stock should ensure that they originate from flocks with no serological evidence of B D . Seronegativity of individual animals from infected flocks is not acceptable since such sheep could be seronegative, virus positive carriers. In countries where the disease is endemic, the introduction of replacement breeding stock onto farms with no history of BD needs careful consideration. Ideally, replacement females should be home-bred and purchased rams tested to ensure they are not persistently infected. Where females are bought-in the feasibility of testing t h e m should also be considered. Newly purchased females should always be mated and kept separate from the rest of the flock until lambing time. In a flock which has recently had a sporadic outbreak of BD, the entire lamb crop and the sheep suspected of or shown by blood tests to have introduced infection must be removed from the farm before the start of the next breeding season. Disposal by slaughter is the only way of preventing further spread of disease. Control of infection in endemically infected flocks by the identification and disposal of persistently infected sheep m a y not be practicable. In such a flock, control of disease can be achieved by deliberately exposing all breeding stock t o k n o w n persistently infected lambs. This natural exposure of breeding stock should be done when they are not pregnant and at least two months before they are mated. The rate of virus spread will depend on the ratio of P I to susceptible animals and the closeness of their contact. Close herding indoors for at least 3 weeks is recommended for effective spread of BDV. It is very likely that the vaccination of female breeding stock several months before tupping will ultimately play a major role in the control of B D . There are currently n o vaccines available against BD and there is a need to develop one to protect sheep against b o t h the BD virus which predominates in them and the antigenically distinguishable viruses which have been recovered from sheep but which are more closely related to BVD virus isolates from cattle (21, 47, 75). In the meantime, in countries where BVDV vaccines are licensed for use in cattle, their use in sheep could be considered. Such vaccines, however, should be critically evaluated to see if they afford protection against local isolates of BDV. BORDER DISEASE OF GOATS There is serological evidence that BD occurs in goats in Africa (12, 67), North America (25, 36), Australia (24) and E u r o p e (44). There appears to have been only a single case of spontaneous clinical BD (44), although pestiviruses have been isolated from aborted goat fetuses (52, 56) and the lung of a kid which died at 4 m o n t h s of age (23). 141 Experimental infections of pregnant goats with BDV produces severe placentitis and clinical and pathological signs in the offspring similar to severe BD in sheep (9, 32, 42). Goats also appear very susceptible to H C V : intravenous inoculation of 13 pregnant goats with virulent H C V between 64 a n d 84 days of gestation resulted in all their offspring becoming infected. Six goats kept until parturition produced 6 normal and H C V antibody positive, one apparently normal but dead, one mummified and 3 oedematous kids (65). PESTIVIRUS INFECTION IN F A R M E D RED DEER The only other domestic r u m i n a n t from which a pestivirus has been recovered is a penned red deer calf which died approximately 24 hours after first being seen unwell. It was considered that the non-cytopathic virus was unlikely to have been responsible for the symptoms and fatal outcome of this illness but that it may have been a contributory factor (50). The experimental infection of healthy red deer calves with BVD and BD viruses results in seroconversion without obvious disease (45; Nettleton, unpublished findings). A serological survey of 371 British farmed deer revealed 6% had antibodies to pestiviruses (Nettleton, unpublished findings). PESTIVIRUS INFECTION OF R U M I N A N T S IN ZOOLOGICAL COLLECTIONS Outbreaks of disease with similarities to mucosal disease in cattle have been described in captive ruminants in zoological collections in the H a n o v e r Z o o and four zoos in the U S A . L a c k of virological c o n f i r m a t i o n m e a n s t h a t the o u t b r e a k in t h e H a n o v e r Z o o cannot be attributed with certainty t o a pestivirus infection (35). A l t h o u g h extensive virological a n d serological investigations were carried o u t in t h e A m e r i c a n o u t b r e a k s , i n t e r p r e t a t i o n of t h e results w a s c o m p l i c a t e d b y t h e diagnosis of malignant c a t a r r h a l fever ( M C F ) in s o m e of t h e a n i m a l s a n d b y a d m i n i s t r a t i o n of B V D V vaccines t o in-contact a n i m a l s . Nevertheless, pestiviruses were isolated from t w o wildebeest (Connochaetes s p p . ) , a nilgai {Bosalephus tragocamelus), an axis deer (Cervus axis) a b a r a s i n g h a deer (Cervus duvauceli), muntjac {Muntiacus reevesi), serow (Capricornis sumatraensis), p i g m y goats (Capra hirus) and a Waterhuck (Kobus ellipsiprymnus). T h e r e w a s also serological evidence of pestivirus infection in 49 species of r u m i n a n t b u t m a n y of these h a d been vaccinated (20). T h e species with a n t i b o d i e s a p p a r e n t l y d u e t o n a t u r a l infection a r e included in T a b l e I I . Veterinarians in charge of valuable zoological collections should be aware of the dangers of pestivirus infection in r u m i n a n t s , and the possibility of enhanced pathogenicity of isolates crossing species barriers. A policy of quarantine and testing to prevent the introduction of P I animals should be followed. 142 TABLE II Captive or free-living ruminants with evidence of pestivirus infection Continent [Captive (C) or free-living (FL)] Species Evidence for infection Antibody (AB) or virus isolation (VI) Reference Camelidae Dromedary (Camelus dromedarius) Llama (Lama guanicoe) America (C) America (C) AB AB 20 20 America (C) VI 20 America (C) VI 20 Europe (FL) Europe (FL) Australasia (FL) America (FL) AB 38 VI/AB AB AB 21,38,40,51,78 35, 64 72 America (FL) AB 35 America (C) VI 20 Europe (FL) AB 13, 38, 40, 45 Europe (FL) VI/AB 3, 40, 63 Europe (FL) AB 38 America (FL) Australasia (?) AB VI 35 64 Africa (C) Africa (FL) VI AB 59 29, 35 America (C/FL) AB 11, 20 Africa (FL) America (C) AB AB 29, 35, 59 20 AB AB 29 20 VI 20 AB 29 Cervidae Axis deer (Cervus axis) Barasingha deer (Cervus duvauceli) Chinese water deer (Hydropotes inermis) Fallow deer (Dama dama) Moose (Alces alces) Mule deer (Odocoileus hemionus) Muntjac (Muntiacus reevesi) Red deer (Cervus elaphus) Roe deer (Capreolus capreolus) Sika deer (Cervus nippon) White-tailed deer (Odocoileus virginianus) Deer - unspecified Giraffidae Giraffe (Giraffa camelopardalis) Antilocapridae Pronghorn antelope (Antilocapra americana) Bovidae Eland (Taurotragus spp.) Kudu (Tragelaphus strepsiceros) Africa (FL) America (C) Nilgai (Boselaphus tragocamelus) America (C) Nyala (Tragelaphus angasi) Africa (FL) 143 TABLE II (contd.) Species Continent [Captive (C) or free-living (FL)] Evidence for infection Antibody (AB) or virus isolation (VI) Reference Oryx/gemsbok (Oryx gazella) Africa (FL) America (C) AB AB 29 20 Africa (FL) AB 29 Africa (FL) AB 29 Africa (FL) America (C) AB VI/AB 29 20 Africa (FL) AB 29 Africa (FL) AB 29, 61 Africa (FL) AB 29, 61 Africa (FL) AB 29 America (C) AB 20 Africa (FL) America (C) VI/AB VI/AB 29, 55 20 Africa (FL) AB 29 Africa (FL) AB 61 Africa (FL) America (C) AB AB 29 20 Africa (FL) America (C) AB AB 29 20 (Capra aegagrus aegagrus) America (C) Europe (FL) Ibex (Capra ibex) Pygmy goat (Capra hircus) America (C) AB AB VI 20 3 20 Europe (FL) AB 3 (Capricornis sumatraensis) America (C) America (C) Urial (Ovis vignei) VI AB 20 20 America (FL) AB 54 America (C) AB 20 America (C) AB 20 Africa (FL) VI/AB 29, 59 America (C) AB 20 Sable antelope (Hippotragus niger) Defassa Waterhuck (Kobus defassa) Waterhuck (Kobus ellipsiprymnus) Lechwe (Kobus leche) Reedbuck (Redunca arundinum) Hartebeest (Alcelaphus buselaphus) Tsessebe (Damaliscus lunatus) Bontebok/blesbok (Damaliscus dorcas) Wildebeest (Connochaetes spp.) Impala (Aepyceros melampus) Korin/red-fronted gazelle (Gazella rufifrons) Springbuck (Antidorcas marsupialis) Duiker (Sylvicapra grimmia) Dik-dik (Madoqua kirki) Bezoar Chamois (Rupicapra rupicapra) Serow American bighorn (Ovis canadensis) Barbary sheep/Aoudad (Ammotragus lervia) Mountain goat (Oreamnos americanus) African buffalo (Syncerus caffer) Gaur (Bos gaurus) 144 PESTIVIRUS INFECTION OF FREE-LIVING RUMINANTS Pestiviruses have been recovered from dead roe deer (Capreolus capreolus) (62), fallow deer (Dama dama) (77), African buffalo (Syncerus coffer), giraffe (Giraffa camelopardalis) (29, citing W . Plowright) and wildebeest (Connochaetes spp.) (55). The role of the viruses in causing diseases in these free-living ruminants is uncertain. Similar uncertainty relates to outbreaks of disease resembling mucosal disease in white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) in the U S A (35). Serological surveys have revealed t h e presence of antibodies to pestiviruses in the sera of several species of free-living ruminants (Table II). In E u r o p e , low seroprevalence rates of 5 t o 1 0 % have been detected in red deer (Cervus elaphus), sika deer (C. nippon), roe deer (Capreolus capreolus), fallow deer (Dama dama), chamois (Rupicapra rupicapra) and ibex (Capra ibex) (3, 38, 40). In N o r t h America, antibody to B V D virus has been demonstrated in white-tailed a n d mule deer, p r o n g h o r n antelope (Antilocapra americana) a n d moose (Alces alces) (35, 71). A n outstanding study on 3,359 sera from ruminants a n d other species in nine African countries by H a m b l i n a n d Hedger (29) detected antibody t o BVDV (NADL strain) in 17 of 29 species of ruminants. Seroprevalence rates of between 30 a n d 87% were detected in African buffalo, kudu (Tragelaphus strepsiceros), eland (Taurotragus oryx), Waterhuck, defassa Waterbuck (Kobus defassa), reedbuck (Redunca arundinum), sable antelope (Hippotragus niger) a n d oryx (Oryx gazella). It is reasonable t o believe that disease due t o pestiviruses is occurring in these 8 species at least, since seroprevalence rates of this order are associated with a widespread low incidence of disease in sheep a n d cattle. It is also reasonable t o suppose that many other species of ruminants h a r b o u r pestiviruses. CONCLUSION A m o n g ruminants other than cattle, pestiviruses are known to be serious pathogens of sheep in which they cause B D . Studies on this important congenital disease have helped t o demonstrate the pivotal role of fetal infection in pestivirus infections. Of t h e other domestic ruminants, goats are very susceptible t o experimental infections with pestiviruses b u t natural disease is rare and although pestiviruses have been isolated from red deer there is no evidence that they cause disease in this species. Similarly, the role of pestiviruses in other ruminant populations is largely unknown although there is some evidence that they m a y be significant: infection has been demonstrated serologically in more t h a n forty species. Outbreaks of disease similar to those caused by pestiviruses in domestic ruminants have been described in captive and free-living ruminants, with pestiviruses being isolated from some such cases. The elucidation of t h e epidemiology of pestiviruses in free-living ruminants and the antigenic relationship of isolates from various species would make an important contribution t o further understanding of the biology of these fascinating viruses. * * * 145 LES INFECTIONS PROVOQUÉES PAR LES PESTIVIRUS CHEZ LES RUMINANTS AUTRES QUE LES BOVINS. - P.F. Nettleton. Résumé: Les pestivirus peuvent infecter un grand nombre de ruminants, domestiques, vivant en captivité ou en liberté. Le virus de la maladie de la frontière (border disease) est responsable d'une maladie congénitale dont l'importance est bien connue. On l'observe pratiquement dans tous les pays d'élevage ovin. L'auteur expose en détail les signes cliniques, la pathogenèse, le diagnostic, l'épidémiologie et la prophylaxie de cette maladie. On a décrit un foyer de maladie de la frontière apparu dans les conditions naturelles chez des chèvres domestiques. On a également la preuve sérologique et virologique de la fréquence des pestivirus dans cette espèce. Un pestivirus a été isolé chez un cerf d'élevage (Cervus elaphus) et on a la preuve sérologique que l'infection se rencontre chez cette nouvelle espèce domestique, dans de nombreux pays, avec une faible prévalence. Les pestivirus ont aussi été responsables de foyers de maladie chez des ruminants en captivité dans des jardins zoologiques. Parmi les ruminants vivant en liberté, des pestivirus ont été identifiés chez le chevreuil européen (Capreolus capreolus), le daim (Dama dama), le buffle (Syncerus caffer), la girafe (Giraffa camelopardalis) et le gnou (Connochaetes spp.), mais dans aucun de ces cas la responsabilité du virus dans le développement de la maladie n'a été établie avec certitude. Des enquêtes sérologiques ont montré que beaucoup d'espèces de ruminants, vivant en liberté en Amérique du Nord, en Europe et en Afrique, présentent des anticorps dirigés contre les pestivirus, avec une prévalence variable. MOTS-CLÉS : Cerfs - Chèvres - Epidémiologie - Maladie de la frontière Moutons - Pathogenèse - Pestivirus - Prophylaxie - Ruminants - Ruminants vivant en liberté - Virus de la diarrhée virale bovine - Virus de la maladie de la frontière. * * * LAS INFECCIONES PROVOCADAS POR PESTIVIRUS EN RUMIANTES DISTINTOS DE LOS BÓVIDOS. - P.F. Nettleton. Resumen: Los pestivirus pueden infectar gran cantidad de rumiantes, tanto domésticos como en cautividad o en libertad. El virus de la enfermedad de la frontera (border disease) es responsable de una enfermedad congénita cuya importancia es bien conocida. Se lo observa en prácticamente todos los países de explotación ganadera ovina. El autor expone detalladamente los síntomas clínicos, la patogénesis, el diagnóstico, la epidemiología y la profilaxis de esta enfermedad. Se ha descrito un foco de enfermedad de la frontera que apareció en cabras domésticas en condiciones naturales. Se cuenta asimismo con las pruebas serológica y virológica que confirman la frecuencia de pestivirus en esta especie. Un pestivirus fue aislado en un ciervo de cría (Cervus elaphus) y se tiene la prueba serológica de que la infección puede hallarse en esta nueva especie doméstica, en varios países, con baja prevalencia. Los pestivirus han sido también causa de focos de enfermedad en rumiantes cautivos en jardines zoológicos. 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