Northern climates. Adult lactating dairy cows, usually during winter months when housed. Immunity develops and lasts variable periods. High morbidity with outbreaks; no mortality. Transmitted by fecal–oral route
Sudden onset of diarrhea affecting almost entire herd within several days. Mild fever, decline in milk production, inappetence. Recover in few days. Some coughing
No specific control measures available. Hygiene. Minimize overcrowding in dairy housing
Winter dysentery is a highly contagious disease of adult cattle characterized by an acute onset of a short course of severe diarrhea and sometimes dysentery. Mild respiratory signs, accompanied by decreased milk production and variable depression and anorexia are also characteristic of the disease. Recovery is spontaneous within a few days
The disease is associated with a bovine coronavirus (BCV) which is a member of family Coronaviridae, order Nidovirales.1 The virus can be found in the feces of affected cows along with a serological response to the virus. The disease can be reproduced in bovine coronavirus seronegative lactating cows.2
Several studies have found a close serological relationship between the coronavirus causing winter dysentery and the coronavirus causing diarrhea in calves but there are antigenic differences between the different isolates.1,3 The oral and intranasal inoculation of gnotobiotic and colostrum-deprived calves with the virus of winter dysentery results in diarrhea in the calves indistinguishable from that seen in calves inoculated with the calf diarrhea coronavirus.4 The BCV has also been isolated from the diarrheic feces of adult wild ruminants (sambar deer, one waterbuck and white-tailed deer) affected with diarrhea in both England and the United States.5 The BCV has tropism for both the intestinal and respiratory tracts.6 The virus also causes respiratory tract infections in calves and feedlot cattle.7,8
The disease occurs primarily in mature dairy cattle and has been reported in many countries including the United States, Canada, Sweden, Germany, France, Israel, Australia, and New Zealand. It is common in dairy cattle in Sweden.2,9 A nationwide survey of antibodies to BCV in bulk tank milk in Swedish dairy herds found that 89% of samples were positive and 52% had very high levels of antibodies.9 There were also higher antibody levels in larger herds.
Winter dysentery is most common in recently calved adult lactating dairy cows. Young cattle may be affected but with only mild clinical signs. The disease is most common in cattle in northern climates when they are housed from November to April. A moderate immunity, which persists for about 6 months, develops after clinical disease, and recurrent clinical disease seldom occurs in less than 2–3 years. In France, the frequency of epidemics in a herd vary from a few months to 10 years. In herds regularly exposed to the infection, epidemics are mild; when the intervals between recurrences are more than 3 years, the epidemics are more severe. Serological examination of paired serum samples from affected herds reveal that almost all cows seroconvert to bovine coronavirus and the BVDV.2 The titers to the bovine coronavirus are still high 1 year after the outbreak and antibody is transferred to colostrum and to the calves in which it persists for up to 4–6 months of age.2
The disease has also occurred in adult beef cattle and in feedlot cattle 6 to 9 months of age.8
A coronavirus indistinguishable from BCV has been isolated from wild ruminants with diarrhea similar to winter dysentery in cattle.10 The virus was isolated from the feces of sambar deer, waterbuck in a wild animal habitat, and from a white-tailed deer on a wildlife farm in Ohio. In a serological survey of coronaviruses among wild deer, 8.7% and 6.6% of sera from mule deer in Wyoming and from white-tailed deer in Ohio, respectively, were seropositive against the wildlife isolates and selected bovine coronaviruses. Thus coronaviruses exist in wild ruminants which may be a source of infection transmissible to cattle.
The morbidity rate may be as high as 30–50% within a few days after the first case is encountered, and up to 100% after 1 week. The case–fatality rate is less than 1%. A typical outbreak may last for 1–2 weeks and in Sweden, 75% occur between November and January.2 The disease is important in dairy herds because, although few animals die of the disease, it may cause serious loss of body condition and milk flow. In mild epidemics, the maximum decrease in milk production compared to a theoretical lactation curve ranges from 6–11%. The overall decrease in milk production may persist for 8–15 d, after which time milk production levels are regained. In severe epidemics, the maximum decrease in milk production may be as high as 30% and may last for up to 28 d.
Outbreaks of the disease diagnosed by farmers exhibit space–time clustering within a 30-day time and a 5.5 km radius. Large herds with more than 60 cows and a history of an outbreak in the previous year were at increased risk of an outbreak. In Sweden, one-third of the affected herds had experienced an outbreak within the previous 4 years and 18% had a least one further outbreak during the following 2 years.
Feces from clinical cases or clinically normal carriers are the source of infection, and contamination of feed or drinking water is the method of spread. In France, the disease occurs on small dairy farms where the surface area is smaller than 2.3 m2/cow. The disease is highly contagious and is introduced to farms by human visitors, carrier animals and fomites. Infection of the respiratory tract with the bovine coronavirus may enhance the transmission of the infection in addition to the usual fecal–oral route of transmission of enteric pathogens.
Both winter dysentery and calf diarrhea can be reproduced using the same strain of BCV.2 Calf diarrhea and winter dysentery strains of the virus can cause diarrhea in adult cows in conjunction with host or environmental factors.3 Winter dysentery can be reproduced in seronegative lactating dairy cows by direct contact with an experimentally infected calf. All experimental cattle shed the virus in the feces at the onset of profuse watery diarrhea with small amounts of blood in the feces of the most severely affected animals including both cows and calves. The cows are commonly more depressed, and their appetites are decreased which is associated with a marked decrease in milk yield. Following infection all cattle will produce early interferon type 1 in serum and in nasal secretions and milk. All cattle develop high IgM antibody responses and long-lasting IgA antibody responses both systemically and locally. Prolonged IgM antibody responses occur in all infected cattle. The IgA antibody response in serum may be detectable for up to 17 months after infection. Bovine-specific IgG can be detected in all cattle during the experimental period of up to 22 months.
The cow-level risk factors for the development of winter dysentery in dairy cattle have been examined.11 The likelihood of developing disease increased as the ELISA value for bovine coronavirus (BCV) antigen detectable in feces increased. Pregnant cattle were less likely to develop the disease compared with nonpregnant animals. Cows with high acute antibody titers to BCV which seroresponded had greater odds of developing disease, compared with cows with lower titers.
Some herd-level risk factors have been identified in dairy herds which have been exposed to the BCV and have experienced outbreaks of the disease.12 The factors which appeared to increase a herd’s risk for the disease include: an increase in herd prevalence of adult cows that had a four-fold or more increase in BCV serum IgG antibody titer; increase in herd prevalence of adult cows that had a fourfold or more increase in bovine viral diarrhea titer; housing cattle in tie-stall or stanchion barns rather than free-stall facilities; and use of equipment to handle manure and subsequently handle feed. The adjusted population-attributable risk for these variables was 71, 43, 53, and 31$, respectively, and 99% overall, indicating that these variables had considerable effect on winter dysentery outbreaks.
Coronaviruses are divided into at least three antigenic groups, and antigenic cross-reactivity exists within an antigenic group.10 Bovine coronavirus, mouse hepatitis virus, murine enteric coronavirus, rat coronavirus, human coronavirus, porcine hemagglutinating encephalomyelitis virus belong to the same group. Bovine coronavirus is an important cause of neonatal calf diarrhea, and winter dysentery. BCV also possesses tropism for the respiratory tract of young cattle.
Some BCV strains isolated from the respiratory tract of cattle had different biological, antigenic, and genetic properties compared with enteric strains of the virus. Strains isolated from feedlot cattle and compared to those with the originally described Mebus prototype (from neonatal diarrheic calves) reveal that the respiratory strains of BCV may differ genetically from the classical calf enteric and adult winter dysentery strains.13
Cross-protection studies between respiratory and calf diarrhea and winter dysentery coronavirus strains in calves have been examined using RT-PCR and nested PCR for their detection.7 Calves inoculated with bovine respiratory coronavirus (BRCV), calf diarrhea coronavirus (CD), winter dysentery (WD) coronavirus strains of BCV and the challenged 3 to 4 weeks later with either BRCV, CD, or WD strains of BCV developed diarrhea, then recovered and were protected from BCV-associated diarrhea after challenge exposure with either homologous or heterologous BCV strains. Nasal and fecal shedding of BCV, which were detectable only by nested PCR, after challenge exposure confirmed field and experimental data documenting reinfection of the respiratory and enteric tracts of cattle, indicating that in closed herds, respiratory or enteric tract infections may constitute a source of BCV transmission to cows or young calves. The biological, serological and genome properties of cytopathogenic RBCV strains isolated in Quebec and Ontario, Canada, have been compared to the original Mebus strain. RBCV strains have also been compared to previously characterized enteric bovine coronavirus strains in order to identify specific strain markers which should be considered for diagnosis and development of vaccines.1
The disease is a mild enteritis affecting the small intestine. The virus also has a tropism for the respiratory tract and has been associated with respiratory disease in adult cattle and pneumonia in calves.
After an incubation period of 3–7 d there is an explosive outbreak of diarrhea which, in the course of the next 4–7 d, affects the majority of adult cattle. The youngest animals of the mature group may have only mild signs. A fever (39.5–40.5°C; 103–105°F) may precede the onset of diarrhea but when clinical signs are evident, the temperature is usually normal. There is a marked fall in milk yield which lasts for up to 1 week, anorexia of short duration, and some loss of body condition. The feces are liquid and homogeneous without much odor, and with no mucous or epithelial shreds; the color is dark green to almost black. Feces are often passed with little warning and considerable velocity. A nasolacrimal discharge and cough may precede or accompany the epidemic. The frequency of coughing may be higher in those herds which have not experienced a more recent outbreak. In most animals the course is short and the feces return to normal consistency in 2–3 d. In occasional cases the syndrome is more severe, dehydration and weakness are apparent, and dysentery – either with feces flecked with blood or the passage of whole blood – occurs. The disease in the herd usually subsides in 1–2 weeks but in some cases production may not return to normal for several weeks or a few months.2
In feedlot cattle, 6 to 9 months of age, the disease has been characterized by an acute onset of diarrhea with high morbidity and low mortality, dyspnea, coughing, and nasal discharge, and high body temperature (40 to 41°C in most severe cases.8 The diarrhea is characterized by fluid dark (brown-black) feces sometimes containing frank blood.
The laboratory diagnosis is dependent on detection of the virus in feces and serology. Fecal and blood samples should be submitted from both affected and normal cows.
Fecal samples can be examined for the presence of bovine coronavirus using the ELISA test and by electron microscopy for viral particles. For routine purposes, direct electron microscopy viral identification and/or ELISA is sufficient. This can be complemented by protein A gold immune electron microscopy because of its high sensitivity and specificity in the detection of viral particles. A reverse transcriptase PCR (RT-PCR) can be used to detect the BCV in the feces of experimentally inoculated cattle.3 The 1-step RT-PCR and nested PCR assays were highly sensitive to detect BCV in nasal and fecal specimens and are useful for the etiological diagnosis of BCV in calves and adult cows.7
In addition to detection of the virus in feces, an increase in the antibody titer to coronavirus based on acute and convalescent sera collected 8 weeks apart is supportive evidence that the virus is the causative agent.14 Attempts at diagnosing these infections serologically are often problematic because in adult cattle high BCV-specific IgG levels are often encountered in the acute samples, presumably due to reinfections with the virus, obscuring the detection of a possible increase in titer in paired samples.14 In addition, adult cattle are usually seropositive and maternal antibodies frequently obliterate the detection of infection in calves. There is a need for serologic tests that do not require the cumbersome and expensive paired samples necessary for an Ig-G based diagnosis.
A capture ELISA test for BCV-specific IgA and IgM in milk and sera has been developed and is useful for discriminating between primary infection and reinfection.14 In adult cattle, testing of paired serum samples using the antibody-capture ELISA may be a better indicator of recent BCV exposure than testing of serum samples with virus neutralizing assays.15 Antigen–antibody binding in feces may interfere with results of the antigen-capture ELISA for BCV.
In the rare fatalities available for necropsy, there is severe hemorrhage and hyperemia of the colonic and cecal mucosa. Frank blood may be present in the lumen of the large intestine.8 Microscopically there is widespread necrosis and degeneration of the epithelium of the large bowel. Similar but less severe gross and microscopic changes have been observed in experimentally infected cattle.
Winter dysentery must be differentiated from:
BVD/MD affects cattle 8–24 months of age in small outbreaks. Erosions of the oral cavity are present and the diarrhea and systemic effects are much more severe. The more recently recognized Type II BVD affects cattle of all ages including adult cattle and is a severe, highly fatal disease.
Coccidiosis affects cattle from 3–12 months of age and is characterized by frank blood in the feces and tenesmus, and the fecal sample is usually diagnostic.
Enteric salmonellosis is a severe toxemic enteritis with diarrhea and dysentery, fibrinous casts in the feces, a high fever, severe depression and rapid death. Culture of the feces is important.
A chronic intractable diarrhea in mature cattle with loss of body weight and eventual emaciation.
Rare cases of diarrhea in mature lactating dairy cows associated with Group B rotavirus have been described.16 The onset of diarrhea is sudden, milk production decreased, the feces were liquid, and recovery occurred in 3 to 5 days.
Treatment is of doubtful value because affected cattle usually respond spontaneously in 24–36 h. Occasionally dehydration will become severe and is best treated with fluids and balanced electrolytes as indicated.
Because of the explosive nature of the disease and the lack of information on possible precipitating causes, effective control measures cannot be recommended. Every effort must be made to avoid the spread of infection on inanimate objects such as boots, feeding utensils and bedding, but even the greatest care does not appear to prevent the spread of the disease within a herd.
Some preliminary studies have tested the potency of bovine coronavirus vaccine to induce serum antibodies but randomized controlled trials to test the efficacy of the vaccine have not been done.17
1 Gelinas A-M, et al. Virus Res. 2001;76:43.
2 Traven M, et al. Vet Microbiol. 2001;81:127.
3 Tsunemistu H, et al. Arch Virol. 1999;144:167.
4 Tsunemitsu H, Saif LJ. Arch Virol. 1995;140:1303.
5 Tsunemitsu H, et al. J Clin Microbiol. 1995;33:1995.
6 Clark MA. Br Vet J. 1993;149:51.
7 Cho K-O, et al. Arch Virol. 2001;146:2401.
8 Cho KO, et al. J Am Vet Med Assoc. 2003;217:1191.
9 Traven M, et al. Vet Rec. 1999;144:527.
10 Tsunemitsu H, et al. J Clin Microbiol. 1995;33:3264.
11 Smith DR, et al. Am J Vet Res. 1998;59:986.
12 Smith DR, et al. Am J Vet Res. 1998;59:994.
13 Hasoksuz M, et al. Virus Res. 2002;84:101.
14 Naslund K, et al. Vet Microbiol. 2000;72:183.
15 Smith DR, et al. Am J Vet Res. 1998;59:956.
Bluetongue virus, an orbivirus with several serotypes and considerable genetic heterogeneity
An infectious, non-contagious disease of sheep and occasionally cattle, transmitted by Culicoides spp. Cattle are the reservoir and amplification hosts. Severe disease is restricted to fine wool and mutton breeds of sheep. Infection, but not disease is endemic in tropical and subtropical regions. Disease occurs in epidemic and incursive areas when climatic conditions allow the expansion of vector occurrence
Fever, catarrhal stomatitis, rhinitis, enteritis and lameness due to coronitis and myositis
Virus isolation, agar gel immunodiffusion and competitive or blocking enzyme-linked immunosorbent assay (cELISA) serological tests. Detection of nucleic acid
Mucosal lesions, hemorrhage and necrosis of skeletal and cardiac muscles, hemorrhagic lesion at base of pulmonary artery
Bluetongue virus (BTV) is an arthropod-borne Orbivirus in the family Reoviridae. Within the BTV serogroup there are at least 24 serotypes of BTV worldwide. There is considerable genetic variability within the serogroup. This arises by genetic drift of individual gene segments as well as by reassortment of gene segments when ruminants or the vectors are infected with more than one strain. There is also debate of the biological validity of the classification of BTV into strict types.1-3 All serotypes do not exist in any one infected area.
Bluetongue virus infects domestic livestock populations in all tropical and subtropical countries and occurs on the continents of Africa, Asia, North America, South America, Australia and several islands in the tropics and subtropics, primarily between latitudes 40°N and 35°S.4 Incursive disease has occurred in Portugal, Spain and Greece but until very recently bluetongue was not considered an endemic infection in Europe. However, in an epidemic beginning in 1998, and persisting to date (2005), five serotypes have spread across and persisted in 12 countries in southern Europe occurring 800 km further north than ever previously recorded.5 This persistence indicates over-wintering of these infections in these new regions and is believed the result of climate change from global warming.
The distribution and intensity of infection in regions of the continents is determined by the climate, geography and altitude, as they affect the occurrence and activity of the Culicoides vectors, and by the presence of susceptible mammalian hosts. There is a gradation from continuous BTV activity in tropical areas to absence of virus transmission in colder areas. In large countries that span different lattitudes, such as the United States and Australia, there are areas that are free of infection.
In endemic areas, the infection is always present but clinical disease of the indigenous species is unusual. It can occur with new BTV strains and when non-indigenous susceptible species are introduced to the area.
Epidemic zones also exist, where infection and clinical disease occur every few years. Infection in these areas is highly focal and outbreaks occur when climatic conditions allow the vector to spread beyond its usual boundaries and to infect susceptible ruminants.
Incursive disease can occur in regions which do not normally experience infection and may occur when the virus is introduced by windborne movement of infected Culicoides with subsequent insect breeding in the summer before ‘die out’ in the autumn and winter. This method of spread is believed to have been the genesis of several serious outbreaks of bluetongue in countries normally free of the disease and of the outbreaks in Portugal in 1956, in Cyprus in 1977, in Turkey and Greece in 1979–1980 and in Israel in 1960–1980.4-6 Polymerase chain reaction-based procedures can be used to determine the serotypic and geographic origin of infection with BTV.7
In the United States, the prevalence of seropositive cattle varies from high in the southern and western states to low in the northern states, especially the northeastern states. In the northwest region, there are epidemics of infection in the summer and fall every few years, associated with movement of infected vectors from the south. Canada is free of infection except for periodic incursions into the Okanagan Valley in British Columbia from windborne infected Culicoides from south of the border.8 In Australia, there has been a sequential introduction of bluetongue serotypes from Indonesia by windborne Culicoides spp. but endemic infection is limited to northern cattle areas with extension down the east coast.7, 9-11
Infection occurs in a number of animals but significant disease occurs only in sheep. Cattle are the major reservoir host for sheep. Under natural conditions infection occurs in sheep and cattle, but it is also recorded in elk, white-tailed deer, pronghorn antelope, camels and other wild ruminants. Natural infection rarely occurs in goats but the infection can be transmitted experimentally.12
The disease is not contagious and is transmitted biologically by certain species of Culicoides. There are over 1400 species of Culicoides worldwide but only a limited number have been associated with BTV.10,13-15 Female Culicoides feed on cattle and horses and also sheep, deer, and goats, requiring at least one blood meal for the completion of the ovarian cycle. They feed nocturnally on animals in open pens and fields and the optimal temperatures for activity lie between 13°C and 35°C.
Virus in ingested blood infects cells of the midgut by a receptor-mediated process,16 replicates and subsequently is released to the salivary gland. Once infected, they are infected for life – a period of several weeks.14 They may feed twice or more and on different hosts, and achieve their greatest transmission potential 6–14 d after feeding on a viremic animal. BTV is maintained in nature by alternating cycles of infection between the midge and ruminant species. In many areas the disease is seasonal because Culicoides are killed by the first hard frost.
Culicoides breed in damp, wet areas including streams, irrigation channels, muddy areas and fecal runoff areas around farms, and habitats for them exist on the majority of farm environments. Species that are cattle associated, such as C. brevitarsis, breed in cattle dung. The generation time in the summer is about 14 d. Different species have different geographic occurrence and their distribution in a country is determined by climatic factors and the presence of a preferred host.
In the United States, C. variipennis var sonorensis is the vector except in the southeast where it is C. insignis. This species and C. pucillus, C. insignis, C. pusillus and C. filarifer are also important in transmission in the Caribbean and Central and South America. There are other subtypes of C. variipennis in the United States which have different distributions to C. variipennis var. sonorensis. In Africa, C. imicola (pallidipennis) is a major vector and in the Middle East and Asia C. fulvis, C. imicola, C. obsoletus, C. nudipalpis and C. orientalis. In Australia, C. wadai, C. actoni, C. brevitarsis, C. peregrinus, C. oxystoma, C. brevipalpis and C. fulvus are vectors or potential vectors. They have different distribution in the country which oscillates, depending on climate. C. brevitarsis, C. brevipalpis and C. wadai are obligate parasites of cattle (dung breeders), but the others can complete their lifecycle in the absence of cattle. C. brevitarsis is the most extensively dispersed vector.10 C. imicola has been involved in the recent expansion of bluetongue in southern Europe, but C. obsoletus and C. pulicaris have been implicated as new vectors in these regions.5,17
Other vectors may transmit the disease mechanically but are unlikely to be of major significance in disease epizootics. The argasid tick Ornithodoros coriaceus has been shown experimentally to be capable of transmitting the virus and be a potential vector. The sheep ked (Melophagus ovinus) ingests the virus when sucking the blood of infected sheep and can transmit the infection in a mechanical manner. Mosquitoes may play a role in transmission and Aedes lineatopennis and Anopheles vagus have been suspect.
The life span of an adult culicoides is usually less than 10 days and at the most a few weeks. Cold winters kill virtually all of the adult vectors and there can be no transmission during these cold periods. Despite this there is an annual recrudescence of bluetongue in several temperate areas. The reason for the persistence of the infection from season to season is not fully understood. There is the possibility of the virus over-wintering in the insect vector but there is little evidence in support of this. Culicoides survive winter periods as larvae but there is no evidence of transovarial transmission of BTV in these insects.5,18
With infected animals bluetongue viruses can be isolated after initial infection for only a short period of time in infected sheep and only slightly longer in cattle. Infection of Culicoides sonorensis that were allowed to feed on infected animals occurred for only 11 days after initial infection in sheep and 49 days following infection of cattle although bluetongue virus nucleic acid can be detected for longer periods.19 An analysis, in 2001, of published data indicated that the duration of viremia in cattle ceased by 63 days after infection in adult cattle and a slightly longer period in infected colostrum-deprived calves.20 Infection, as detected by routine isolation if virus, can also persist in wild ruminants.
However, none of these periods adequately explain the recrudescence and apparent over-wintering of infection in some areas. It has been recently shown that infectious BTV can be recovered from ovine skin biopsies for more than 9 weeks after infection and it is postulated that infection can be covertly present in seropositive and aviremic ruminants as a result of a persistent infection established in γδ T-cells. This covert but persistent infection is believed to allow perpetuation of BTV through the winter.21 It is suggested that the occurrence of new vectors in the following spring with biting activity results in skin inflammation with recruitment of inflammatory cells including γδ T-cells and that interaction of these infected cells with skin fibroblasts results in a conversion of a persistent infection of the γδ T-cells to a productive lytic infection that allows subsequent infection of biting vectors.5,21
Bluetongue virus has been found in the semen of infected bulls during the initial viremic period, and infection has been transmitted through bull semen to susceptible cows,22 but it is unlikely that this is a significant mechanism of transmission. Transplanted embryos from infected services are free of the virus and this is regarded as a minimal risk technique for obtaining offspring from cattle and sheep in infected areas.23,24
The geographical occurrence of bluetongue serotypes varies and is changing with time. There are differences in virulence between serotypes and between strains within serotypes and virulence is also related to virus dose and dependent on vector species, distribution and competence. Different Culicoides species vary in susceptibility to infection and some known vectors are resistant to infection with some serotypes, which in part explains regional differences in serotype occurrence.10 Different Culicoides species have different host preferences and some have a distinct preference for cattle and little host preference for sheep.10
Climate is a major risk factor as culicoides require warmth and moisture for breeding and calm, warm, humid weather for feeding. A cold winter or a dry summer can markedly reduce vector numbers and risk for disease. Moisture may be in the form of rivers and streams or irrigation but rainfall is the predominant influence and rainfall in the preceding months is a major determinant of infection.26-29
Precipitation affects the size and persistence of breeding sites and the availability of humid microhabitats to allow shelter from desiccation during hot summer and autumn periods. Optimal temperature is also essential and in endemic areas temperatures for survival of the adults and larvae require temperatures sustained above a mean of 12.5°C for the cooler months and temperatures in the range of 18 to 30°C in the summer and autumn for optimum recruitment to adults and for optimal adult activity.30,31 Temperature also affects the rate of virus production in culicoides.32 Geographic information systems (GIS) can be used to predict area risk.28
Genetic studies indicate that BTV tends to exist in discrete, stable ecosystems and that BTV serotypes that circulate in one region of the world are largely different from those in other regions. In the United States, five serotypes – 2, 10, 11, 13, and 17 – have been isolated. Serotype 2 is a relatively recent isolate and is restricted to the habitat of C. insignis, but the latter four are endemic throughout much of the south and west. Serotype 13 is probably a reassortment virus with a gene segment derived from a vaccine virus parent33 and other reassortments between live vaccine virus and wild-type virus are a concern for the emergence of virus types that could posses enhanced virulence characteristics or novel antigenic properties.34 In the Caribbean Region and South and Central America, serotypes 1–4, 6, 8, 12, 14, and 17 are reported.4,13,35 In Australia, eight serotypes – 1, 3, 9, 15, 16, 20, 21, and 23 – have been isolated. Six of these (3, 9, 15, 16, 20, and 23) have only been found in the north of the Northern Territory, while two serotypes (1 and 21) are widely distributed across the northern and eastern coast of Australia. The introduction appears to have been sequential and five have been introduced since 1981. The virus has been isolated from infected Culicoides and sentinel animals and although there is serological evidence of infection in Queensland and New South Wales, there has been no clinical disease. In Africa, serotypes 1, 16, 18, 19, and 24 are the major serotypes isolated and in Asia, serotypes 1, 4, 7, 9, 10, 12, 16, 17, 20, 21, and 23.4,36 Serotypes 1, 2, 4, 9, and 16 are associated with disease in the current expansion in southern Europe.5
The bluetongue viruses are stable and resistant to decomposition and to some standard virucidal agents, including sodium carbonate. They are sensitive to acid, inactivated below pH 6.0, and susceptible to 3% sodium hydroxide solution and organic iodides.
Cattle are the reservoir and amplifying host and have a high titer viremia. Cattle appear to be much more attractive to Culicoides spp. and this may enhance the importance of cattle as carriers. A critical density of cattle in a region may be required to sustain bluetongue in regions where the Culicoides vector is strongly cattle associated.10
Bos taurus breeds are more likely to be seropositive than Bos indicus and bulls have a greater risk for infection than females or castrated males. Seroprevalence increases with age, probably a reflection of increased duration of exposure.
All breeds of sheep are susceptible but to varying degrees. Merinos and British breeds are more susceptible than native African sheep. There are also differences in age susceptibility to clinical disease which, inexplicably, vary with different outbreaks. With Australian serotypes, disease occurs only in sheep 3 years of age or older.11 Exposure to solar radiation can increase the severity of the disease, as can excessive droving, shearing, poor nutrition and other forms of stress.
When the disease occurs in a flock for the first time the incidence of clinical disease may reach 50–75% and the mortality 20–50%. Outbreaks in Cyprus and Spain were accompanied by mortality rates of 70% in affected flocks2 but most outbreaks result in much lower mortality. Mortality rates of 2–30% are reported under field conditions in South Africa and from 0–14% in field outbreaks in the United States. High mortality can occur when a new strain of BTV emerges in an area.
Immunity to BTV tends to be strain specific and in epizootics, more than one strain may be introduced into an area. Infections caused by different serotypes may follow one another in quick succession in a sheep population. The serotypes vary widely in their virulence with a corresponding variation in the severity of the disease produced. However, sequential infection with more than one type of BTV results in the development of heterotypic antibody and may result in protection against heterologous serotypes not previously encountered.
Infection is readily produced by experimental infection of sheep and cattle but it is common for the clinical presentation of the experimental disease to be very mild despite the fact that the isolate might have been associated with severe disease in the field.12,37 In many cases experimental infection produces viremia, fever, leukopenia and an antibody response but the localizing, identifying lesions are often minimal, with erythema of the coronary bands as the only visible abnormality in some cases.38
Congenital defects of the nervous system of lambs occur when pregnant ewes are vaccinated with attenuated vaccine virus, and when calves and lambs are inoculated experimentally before midgestation, but occur rarely with natural infection. Unadapted virus does not readily cross the placenta.39 Experimental inoculation of pregnant ewes is more likely to lead to fetal death with a generalized hepatic necrosis and suppressed hepatic hematopoiesis. Infection of the ewe in mid-pregnancy can result in infection of the lamb which is unaffected and born normally, but viremic so that it may remain as a source of infection for a further 2 months.40 However, such lambs are not expected to have a major role in the spread of the disease.
The location and the nature of the lesions in the lambs of ewes injected with attenuated vaccine virus is related to the level of maturation and migration of nerve cells at the time infection occurs. The degenerative nature of the lesions results from the presence of immature neural cells with enhanced viral susceptibility combined with an inability to mobilize an effective immunological response.22 In older fetuses, a typical inflammatory response develops and there is also a generalized retardation of growth and lymphoreticular activity.41
Experimental inoculation of cows at 60–120 d of pregnancy with virulent viruses can cause congenital defects, including excessive gingival tissue, agnathia (tilted mandible), arthrogryposis, ataxia and head pressing. Hydranencephaly or porencephaly may also be a sequel to infection with more virulent strains. The severity of the brain lesions decreases with increasing fetal age and infection at 243 d results in a mild encephalitis and the premature birth of calves which are still viremic but poorly viable.
Mortality varies with the serotype but can be significant and it is estimated that the incursion of the disease in Europe since 1998 has caused has death of over 1 million sheep.5,34 However, production loss is also of great importance. Adults either lose their fleece from a break in the growth of the staple or develop a weakness (tender wool) that causes breaks in processing and markedly reduces the value of the fleece. Pregnant ewes commonly abort. There is a severe loss of condition and convalescence is prolonged, particularly in lambs. The loss from clinical disease and from reduced wool quality and suboptimal production following infection in sheep are significant.
A further major indirect cost of the disease is the restriction in international trade. The severe disease that occurred in the outbreaks in Cyprus and the Iberian peninsula in the 1940s and 1950s resulted in bluetongue being placed on list A of veterinary diseases by the Office International Des Epizooties (OIE). As a result there are restrictions on the international movement of cattle and sheep and their products from countries that have this infection to those that do not. The validity of these restrictions imposed by countries where bluetongue is unlikely to transmit is questionable. It is estimated that the United States has an annual loss of $144 million because of the inability to trade with BTV-free countries.42
Movement restrictions within an affected country, even though having limited scientific reason for imposition with bluetongue, can have a significant economic effect on a country’s tourist-related income. In the year 2005 movement restrictions for cattle in Spain threaten the quality of bullfights and functions such as the running of the bulls in the Pamplona festival.
The pathology of bluetongue can be attributed to vascular endothelial damage resulting in changes to capillary permeability and fragility, with subsequent disseminated intravascular coagulation and necrosis of tissues supplied by damaged capillaries. These changes result in edema, congestion, hemorrhage, inflammation and necrosis. Following infection into the skin, there is replication in the local draining lymph node and dissemination in mononuclear cells to secondary sites of replication in lymphoid tissue and lung. Viremia is detectable by day 3 and peak viremia, associated with fever and leukopenia, usually occurs 6–7 d after infection. Circulating virus concentrations subsequently fall with the appearance of circulating interferon and specific neutralizing antibodies.38,43 With the viremia, there is localization of the virus in vascular endothelium which causes endothelial cell degeneration and necrosis with thrombosis and hemorrhage. There is also the development of a hemorrhagic diathesis and coagulation changes consistent with disseminated intravascular coagulation.44 The distribution of the lesions is believed to be influenced by mechanical stress and the lower temperatures of these areas in relation to the rest of the body.12
With infection in cattle and wild ruminants, infection of endothelial cells is minimal. The viremia in cattle is highly cell associated, particularly with erythrocytes and platelets.38,44,45 Although the virus does not replicate in the erythrocytes, it is protected from circulating neutralizing antibody and infected erythrocytes are likely to circulate for their lifespan. BTV antigen can be detected in erythrocytes of cattle 140 d after infection.45 The severe clinical disease that occurs in only a few infected cattle is possibly a type 1 hypersensitivity reaction dependent upon virus-specific IgE from repeated exposure.44
The presence of the bluetongue virus in the semen of bulls is accompanied by structural abnormalities of the spermatozoa and by the presence of virus particles in them.
Naturally occurring, florid bluetongue in sheep has the following clinical characteristics. After an incubation period of less than a week, a severe febrile reaction with a maximum temperature of 40.5–41°C (105–106°F) is usual, although afebrile cases may occur. The fever continues for 5 or 6 d. About 48 h after the temperature rise, nasal discharge and salivation, with reddening of the buccal and nasal mucosae, are apparent. The nasal discharge is mucopurulent and often blood stained and the saliva is frothy. Swelling and edema of the lips, gums, dental pad and tongue occur and there may be involuntary movement of the lips. Excoriation of the buccal mucosa follows, the saliva becomes blood stained and the mouth has an offensive odor.
Lenticular, necrotic ulcers develop, particularly on the lateral aspects of the tongue, which may be swollen and purple in color, but more commonly is not. Hyperemia and ulceration are also common at the commissures of the lips, on the buccal papillae and around the anus and vulva. Swallowing is often difficult for the animal. Respiration is obstructed and stertorous and is increased in rate up to 100/min. Diarrhea and dysentery may occur.
Foot lesions, including laminitis and coronitis and manifested by lameness and recumbency, appear only in some animals, usually when the mouth lesions begin to heal. The appearance of a dark red to purple band in the skin just above the coronet, due to coronitis, is an important diagnostic sign. Wryneck, with twisting of the head and neck to one side, occurs in a few cases, appearing suddenly around day 12. This is apparently due to the direct action of the virus on muscle tissue as is the pronounced muscle stiffness and weakness which is severe enough to prevent eating. There is a marked, rapid loss of condition. There is facial swelling with extensive swelling and drooping of the ears and hyperemia of the non-wooled skin may be present. Some affected sheep show severe conjunctivitis, accompanied by profuse lacrimation. A break occurs in the staple of the fleece. Vomiting and secondary aspiration pneumonia may also occur. Death in most fatal cases occurs about 6 d after the appearance of signs.
In animals that recover, there is a long convalescence and a return to normal may take several months. Partial or complete loss of the fleece is common and causes great financial loss for the farmer. Other signs during convalescence include separation or cracking of the hooves and wrinkling and cracking of the skin around the lips and muzzle. Although the subsequent birth of lambs with porencephaly and cerebral necrosis is usually recorded after vaccination with attenuated virus, it also occurs rarely after natural infections.
In sheep in enzootic areas, the disease is much less severe and often inapparent. Two syndromes occur: (i) an abortive form in which the febrile reaction is not followed by local lesions and (ii) a subacute type in which the local lesions are minimal, but emaciation, weakness and extended convalescence are severe. A similar syndrome occurs in lambs which become infected when colostral immunity is on the wane.
Most infections are inapparent, although a few animals may develop a clinical syndrome not unlike that seen in severely affected sheep. Clinical signs which have been recorded include:
Many affected cattle also have ulcerative lesions on the tongue, lips, dental pad, and muzzle. A severe coronitis, sometimes with sloughing of the hoof, may occur. Some cows have photodermatitis and lesions on the teats. Serosanguineous exudate may appear in the nostrils and a discharge from the eyes. Contraction of the infection during early pregnancy may cause abortion or congenital deformities including hydranencephaly, microcephaly, curvature of the limbs, blindness and deformity of the jaw.
Infected goats show very little clinically. There is a mild to moderate fever, and hyperemia of the mucosae and conjunctivae. BTV infections in deer produce an acute disease that is clinically and pathologically identical to epizootic hemorrhagic disease of deer and characterized by multiple hemorrhages throughout the body.
There is a fall in packed cell volume and an initial leukopenia followed by a leukocytosis. In severe disease there is a marked leukopenia, due largely to lymphopenia. Infected cattle show a similar leukopenia. The skeletal myopathy which occurs in this disease is reflected by a rise in creatine phosphokinase.
Specific diagnosis is either by isolation of the virus, detection of viral antigen or nucleic acid, or detection of specific antibodies in serum. Serological assays can detect prior exposure to BTV but cannot establish if the animal is viremic, which is currently still important for movement decisions concerning cattle.
Virus isolation commonly is carried out by tissue culture or culture in developing chick embryos. The virus can be isolated from blood during the febrile period and it, or detection of viral nucleic acid, is the most reliable confirmation of BTV infection because there are difficulties with the interpretation of serological test results. However, traditional isolation methods require 2–4 weeks.
Less commonly, diagnosis is by inoculation of blood into susceptible sheep. A positive test depends on the appearance of diagnostic clinical signs and resistance to subsequent challenge with the bluetongue virus, or a significant increase in virus-neutralizing antibodies in the recipient sheep.
Immunohistochemical tests including immunofluorescence, immunoperoxidase and immunoelectron microscopic techniques using monoclonal antibody can be used for rapid sensitive and specific detection of antigen.46,47 In situ nucleic acid hybridization and PCR can be used for detection of the virus and have the advantage of speed over tissue culture virus isolation and can also differentiate between wild-type isolaytes and vaccine strains.19,46,48,49 Tests that detect viral RNA do not necessarily indicate that an infectious virus is still present.
A number of serological tests are available based on the detection of group-reactive antibody or serotype-specific antibody. Bluetongue diagnosis by serology is imprecise, unless a rising titer is demonstrated in acute and convalescent serum samples. The commonly available tests include complement fixation, the AGID, a number of different ELISA tests and virus neutralization.46 In most laboratories the complement fixation test has been replaced by the AGID test. The AGID test is easy to perform and inexpensive. Antibody appears 5–15 d after infection and persists for 2 or more years.50 The test is relatively insensitive and detects cross-reacting antibodies to other orbiviruses. Also, in epizootics a significant proportion of antibody-negative animals may be viremic.
There are a number of ELISA tests that have been developed using group-specific monoclonal antibodies and that have been suggested as alternates to the AGID for routine diagnosis and international trade.42,46,51 The competitive ELISA appears more sensitive than most and is highly specific and may replace the AGID test as the preferred test for serodiagnosis of bluetongue.42,46,52
The mucosal and skin lesions have already been described. Other consistent lesions include generalized edema, hyperemia and hemorrhage and necrosis of skeletal and cardiac muscles. There is a most distinctive hemorrhage at the base of the pulmonary artery. Animals with damage to esophageal or pharyngeal musculature may have lung consolidation due to aspiration pneumonia. Hyperemia and edema of the abomasal mucosa are sometimes accompanied by ecchymoses and ulceration. Microscopically there is thrombosis and widespread microvascular damage leading to myodegeneration and necrosis. Aborted bovine fetuses should be examined for evidence of hydranencephaly or porencephaly. As previously discussed, there are numerous tests available to confirm the presence of BTV in blood and tissue samples.
• Histology – fixed oral and mucocutaneous lesions, abomasum, pulmonary artery, skeletal muscle from a variety of sites, left ventricular papillary muscle. Brain from aborted fetus. (LM, IHC)
• Virology – chilled lung, spleen. CNS tissues, thoracic fluid from aborted fetus (ISO, PCR, in situ HYBRID, ELISA, etc.)
Local irrigations with mild disinfectant solutions may afford some relief. Affected sheep should be housed and protected from weather, particularly hot sun, and fluid and electrolyte therapy and treatment to control secondary infection may be desirable.
Attempts to control bluetongue through a reduction of infection consist of reducing the risk of exposure to infected Culicoides and reduction in Culicoides numbers. Neither are particularly effective.
Reducing the risk of exposure is attempted by spraying cattle and sheep with repellents and insecticides and housing sheep at night. Biweekly application of permethrin was found not to be effective in preventing infection.53
During transmission periods avoidance of low, marshy areas or moving sheep to higher altitudes may reduce risk. Because of the preference of some Culicoides for cattle as a host, cattle have been run in close proximity to sheep to act as vector decoys.54 Widespread spraying for Culicoides control is not usually practical and has only a short-term effect.
There is a high mortality in Culicoides that fed on cattle that have been treated with a standard anthelmintic dose of ivermectin and also a larvicidal effect in manure passed for the next 28 d for Culicoides that breed in dung.55
Vaccination is the only satisfactory control procedure once the disease has been introduced into an area. Vaccination will not prevent or eliminate infection but it is successful in keeping losses to a very low level provided immunity to all local strains of the virus is attained.56,57 Current vaccines are usually polyvalent attenuated virus vaccines and are in use in South Africa and Israel and available in other countries. These vaccines have been used in South Africa for more than 50 years and they are known to induce effective and long lasting immunity. Currently they are produced in cell culture and freeze-dried. The present Onderstepoort Bluetongue Vaccine comprises three bottles (Vaccines A, B, and C) and includes the following serotypes of BTV:
The three bluetongue vaccines are administered separately at 3-week intervals.
Reactions to vaccination are slight but ewes should not be vaccinated within 3 weeks of mating as anestrus often results. Annual revaccination 1 month before the expected occurrence of the disease is recommended. Immunity is present 10 d after vaccination so that early vaccination during an outbreak may substantially reduce losses. Lambs from immune mothers may be able to neutralize the attenuated virus and fail to be immunized, whereas field strains may overcome their passive immunity. In enzootic areas, it may therefore be necessary to postpone lambing until major danger from the disease is passed and lambs should not be vaccinated until 2 weeks after weaning. Rams should be vaccinated before mating time.
Live attenuated vaccines should not be used in pregnant ewes because of the risk of deformity in the lambs or embryonic death.54 The danger period is between the 4th and 8th weeks of pregnancy with the greatest incidence of deformities occurring when vaccination is carried out in ewes pregnant for 5–6 weeks. The incidence of deformities may be as high as 13%, with an average of 5%. Abortions do not occur although some lambs are stillborn.
The preparation and use of attenuated vaccines against BTV is problematic. The neutralizing epitopes are highly conserved on some serotypes but they are highly plastic on others1. It is therefore necessary to continually monitor the identity and prevalence of the serotypes that need to be in the vaccine.
There are also concerns for the use of live vaccines to control insect-borne diseases because of the risk of the vaccine strain being transmitted, of being exalted in virulence by passage, and of recombinants resulting in the development of new virus strains with unwanted characteristics. There is evidence for the emergence of a reassortment strain from a vaccine virus in the United States33 and suspicion of occurrence elsewhere.5 However, living vaccines are used for practical reasons, including the fact that inactivated vaccines do not provide protection against infection.58 The difficulty in obtaining safe vaccines may be overcome by the use of recombinant DNA technologies. There is also good reason to suggest that cattle should be a major target of vaccination for bluetongue control.
Countries that are free of BTV infection have traditionally erected barriers to avoid its introduction by prohibiting the importation of any ruminant animals from countries where the disease occurs. Others have less severe restrictions and several procedures aimed at permitting limited movement are in force; their stringency varies with the importing country. Some countries only require a negative serological test or series of tests prior to movement. Others require a negative test in conjunction with a period of quarantine. The introduction of bovine semen from low-risk areas after suitable tests of donors and a prolonged storage period is accepted by most countries. Most countries allow the importation of embryos.
A more enlightened understanding of the epidemiology of bluetongue will probably result in a re-evaluation of these requirements in the future including regionalization within a country to allow exports from areas where there is no prevalence or transmission.42
Gibbs EPJ. Bluetongue: an analysis of current problems with particular reference to importation of ruminants to the USA. J Am Vet Med Assoc. 1983;182:1190-1194.
Osburn BI, et al. A review of bovine bluetongue. Proc Am Assoc Bovine Pract. 1983;15:23-28.
Roberts DH. Bluetongue: a review. State Vet J. 1990;44:66-80.
Roy P, Gorman BM. Bluetongue viruses. Curr Top Microbiol Immunol. 1990;162:1-200.
Walton TE, Osburn BI. Bluetongue African horse sickness and related orbiviruses. Boca Raton FL: CRC Press, 1992;1042.
Osburn BI. Bluetongue virus. Vet Clin North Am Food Anim Pract. 1994;103:547-560.
Ward NP. The epidemiology of bluetongue virus in Australia. Aust Vet J. 1994;71:3-7.
Barratt-Boyes SM, MacLachlan NJ. Pathogenesis of bluetongue virus infection of cattle. J Am Vet Med Assoc. 1995;206:1322-1329.
Mellor PS, Boorman J, Baylis M. Culicoides biting midges: their role as arbovirus vectors. Ann Rev Entomol. 2000;45:307-340.
Purse BV, et al. Climate change and the recent emergence of bluetongue in Europe. Nature Rev Microbial. 2005;3:171-181.
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4 Gibbs EPJ, Greiner EC. Comp Immunol Microbiol Infect Dis. 1994;17:207.
5 Purse BV, et al. Nature Rev Microbiol. 2005;3:171.
6 Braverman Y, Chechnik F. Rev Sci Tech Off Interntl Epiz. 1996;15:1037.
7 McColl KA, et al. Aust Vet J. 1994;71:102.
8 Sellers RF, Maarouf AR. Am J Vet Res. 1991;55:367.
9 St George TD. Aust Vet J. 1989;66:393.
10 Ward MP. Aust Vet J. 1994;71:3.
11 Bishop AL, et al. Aust Vet J. 1996;73:174.
12 Parsonson IM. Curr Top Microbiol Immunol. 1990;162:119.
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14 Mellor PS. Curr Top Microbiol Immunol. 1990;162:143.
15 Osburn BI. Vet Clin North Am Food Anim Pract. 1994;103:547.
16 Xu G, et al. J Gen Virol. 1997;78:1671.
17 Torina A, et al. Med Vet Entomol. 2004;18:81.
18 Mellor PS, et al. Ann Rev Entomol. 2000;45:307.
19 Bonneau KR, et al. Vet Microbiol. 2002;88:115.
20 Singer RS, et al. J Vet Diag Invest. 2001;13:43.
21 Takamatsu H, et al. J Gen Virol. 2003;84:227.
22 Osburn BI. Comp Immun Microbiol Infect Dis. 1994;17:189.
23 Sutmoller P, Wrathall AE. Prev Vet Med. 1997;32:111.
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25 Parsonson IM. Proc US Anim Hlth Ass. 1993;97:120.
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Epizootic hemorrhagic disease virus (EHDV) is a serogroup of Orbivirus closely related to bluetongue virus. There are at least 10 serotypes and some have antigenic relations with serotypes of bluetongue virus.1 The serotypes infect deer and cattle naturally; sheep can be infected experimentally but not goats or pigs. In deer, the serotypes produce clinical disease. The pathogenesis of epizootic hemorrhagic disease is similar to that of bluetongue and infection of ruminants with either virus is characterized by extensive vascular injury, disseminated intravascular necrosis and tissue necrosis.2
The geographic occurrence of epizootic hemorrhagic disease viruses is similar to that of bluetongue virus. The virus, or serological evidence of infection, occurs on the North American, Australian, Asian and African continents.3 In North America, there are two serotypes (EHDV-1, EHDV-2) and infection occurs in all areas of the United States, except the northeast and the arid southwest, and in southern Canada. In Australia, five serotypes are identified and the virus has been predominantly isolated from sentinel cattle in the north.4 Transmission is by species of Culicoides and some species of gnats and mosquitoes.3 There are also geographic differences in the severity of disease following EHDV infection with clinical disease in cattle being of rare occurrence in the United States but capable of causing outbreak of disease in cattle in Asia.
In North America, epizootic hemorrhagic disease is considered one of the most important diseases of deer, particularly of white-tailed deer (Odocoileus virginianus) but also mule deer (O. hemionus, and pronghorn antelope (Antiocarpa americanna).5 There are areas of enzootic stability, where seroprevalance in deer is high but clinical disease rare, and areas with low seroprevalance where clinical disease is severe.6,7 All ages are susceptible, morbidity can be as high as 90% and mortality as high as 60% in some deer herds. The virus infects endothelial cells and the pathogenesis, clinical signs and postmortem lesions are similar to those of acute bluetongue in sheep with fever, hemorrhage and death.
Seroprevalence studies suggest that infection of cattle is common but clinical disease is very rare. An exception is infection with a genetically distinct strain of EHD-2, which was initially associated with an epizootic of disease of cattle in Japan in 1959, called Ibaraki disease, and which resulted in 39 000 sick cattle and 4000 deaths.8 Disease with this agent was subsequently observed in other Asian countries. Clinically, the disease was characterized by fever, hyperemia and edema of the mucosae, a hemorrhages ulcerative stomatitis with laryngeal and pharyngeal paralysis salivation and dysphagia. At postmortem there were hemorrhages in the pharynx and esophagus and animals commonly died with aspiration pneumonia. Infection of pregnant cattle with Ibiraki virus can also result in abortion and stillbirths and currently this seems a more common clinical manifestation. There is evidence of genetic change in isolates from different outbreaks and the clinical manifestations of infection with different strains can vary.9,10
Occasional disease associated with infection with EHDV is recorded in cattle in the late summer in the United States and is also recorded in a recent outbreak on the island of Reunion.11 It is similar to bluetongue and manifest with fever, lameness, reddening and swelling of the oral mucosa with necrotic ulceration of the dental pad and behind the incisor teeth, cracking and sloughing of the skin of the muzzle and hyperemia of the skin of the teats and udder.3 Morbidity has ranged from 1–20%.
Diagnosis of infection is by virus isolation, nucleic acid identification and serology. AGID will detect antibody but will also detect cross-reacting antibodies with bluetongue. The c-ELISA is specific and sensitive.12
1 Gorman BM. Curr Top Microbiol Immunol. 1990;162:1.
2 McLaughlin BE, et al. Am J Vet Res. 2003;64:860.
3 Metcalf HE, et al. Walton TE, Osburn BI, editors. Bluetongue African horse sickness and related orbiviruses. Boca Raton: CRC Press. 1992:222.
4 Weir RP, et al. Vet Microbiol. 1997;58:135.
5 Osburn BI, et al. Bov Practit. 1995;29:106.
6 Flacke GL, et al. J Wildlife Dis. 2004;40:288.
7 Gaydos JK, et al. J Wildlife Dis. 2004;40:383.
8 Inaba Y. Aust Vet J. 1975;51:178.
9 Uchinuno Y, et al. J Vet Med Sci. 2003;65:1257.
10 Ohashi S, et al. J Clin Microbiol. 2002;40:3684.