I.    Background on Bluetongue

Bluetongue disease (BLU) is an OIE List A disease that causes substantial economic losses due to its effect on animals, e.g. sheep, and impacts cattle industries due to international regulations restricting movement of livestock and livestock germplasm from the U.S. BLU-endemic areas to BLU-free areas such as the European Union. U.S. losses due to BLU have been ca. $120 million annually, and world-wide losses are estimated at $3 billion annually (Walton and Osburn 1992). This is a prominent non-tariff trade barrier throughout the world.

Bluetongue disease was first reported in South African sheep (Hutcheon 1902). BLU virus was isolated from sheep in California in 1952 (McKercher et al. 1953). Thereafter, the biting midge Culicoides sonorensis was identified as a U.S. vector (Price and Hardy 1954). The BLU viruses may infect several domestic and wild ruminant species. Clinical signs in sheep and cattle are described elsewhere (Parsonon 1992, MacLachlan et al. 1992). The disease in sheep is characterized by inflammation and congestion leading to hemorrhages, cyanosis and ulceration of the mucous membranes. There may be laminitis, myositis and edema of the head and neck. Fetal abnormalities may occur when animals are infected early in pregnancy. The severity of the disease may vary, with a mortality rate in sheep between 5-50 percent. Clinical BLU disease in cattle is rare (<5% of infected animals): the virus has little if any effect on reproduction, but cattle may show a prolonged viremia. Prenatal infection early in utero may lead to embryonic death. Fetuses infected at later stages of gestation survive but are not persistently infected, and infected animals develop antibodies. (Parsonson 1992). The disease may range from sub-clinical infection (North American elk) to an acute hemorrhagic disease with high mortality (white-tailed deer).

Bluetongue viruses are double-stranded RNA viruses (genus Orbivirus, family Reoviridae). The BLU genome consists of 10 genes which encode mRNAs for seven structural and three nonstructural proteins. The RNA genome is encapsidated in a double-layered protein coat (Roy et al. 1990). The outer coat contains two major proteins, VP2 and VP5. There are 24 serotypes of BLU virus throughout the world, with serotype specificity residing in VP2 (Mecham et al. 1996). The inner coat is composed of two proteins, VP3 and VP7. VP7 contains group-specific epitopes and has been shown to be the virus attachment protein (Xu et al. 1997). When VP2 is cleaved from the outer capsid an infectious subparticle is produced. An inner core particle results from further enzyme treatment (Mertens et al. 1987).

There are genetic similarities among BLU serotypes and related orbiviruses, e.g. African horse sickness and epizootic hemorrhagic disease (EHD) viruses (Gould et al. 1992). Nucleotide sequences for BLU and EHD genes show close relationships between BLU and EHD viruses from the same geographic region (Pritchard et al. 1995, Cheney et al. 1996). The relationships between viral diversity and the different Culicoides vectors present in different regions are unknown. Culicoides vectors influence BLU virus biology (Tabachnick et al. 1992) and modern tests have been applied to Culicoides vectors to provide an ecological perspective (Nunamaker et al. 1997).

Bluetongue viruses are distributed worldwide, wherever there are Culicoides vectors (St. George and Kegao 1996). There are regional differences in the viruses, species of Culicoides vectors and clinical signs in animals, i.e. clinical BLU disease is generally not seen in the Central American-Caribbean Basin where the vector is C. insignis. The potential for BLU in Europe has resulted in animal health requirements to ensure BLU-free animal imports. C. obsoletus and C. pulicaris, BLU capable vectors in the laboratory (Jennings and Mellor 1987), are very common in northern Europe (Mellor 1993). Since there are no data on mechanisms controlling vector ability, BLU incursions remain a concern.

II.    Epidemiology of BLU

United States BLU serotypes are 2, 10, 11, 13 and 17 (Barber 1979, Gibbs and Greiner 1988). A survey for BLU antibody in U.S. cattle ranged from 0-79% in different states (Metcalf et al. 1981). The lowest prevalence was in northern states (6) and was confirmed during the next two decades (Pearson et al. 1992). A large portion of the U.S. is considered endemic for BLU viruses.

Bluetongue 11 occurred in Canada only in the Okanagan Valley, British Columbia in 1976 and 1987 (Dulac et al. 1989, Dulac et al. 1992, Sterritt and Dulac 1993). The mechanisms responsible for BLU epidemiology are unknown, although the presence of these viruses is dependant on the presence of suitable Culiciodes populations.

The principle BLU vector in North America is considered to be the subspecies C. sonorensis (Tabachnick 1996). The northeastern U.S. is generally considered to be BLU free based on the absence of C. sonorensis, failure to isolate BLU antibodies from animals and the consistent low prevalence of BLU antibody in cattle (Tabachnick and Holbrook 1992). Regions of the U.S. have been declared BLU free based on results of the lab's studies (Walton et al. 1992, Tabachnick and Holbrook 1992, Tabachnick 1996).

Other regions in the world maintain different BLU serotypes and different Culicoides vectors. Australia has BLU serotypes 1, 3, 9, 15, 16, 20, 21 and 23 vectored by C. wadai, C. brevitarsis, C. fulvus and C. actoni. Bluetongue serotypes are found in Asia and the Middle East. Africa has serotypes 1-19, 22 and 24 vectored by C. imicola. The Central American-Caribbean Basin has BLU serotypes 1, 3, 4, 6, 8, 12 and 17.

III.    Partnerships Addressing BLU Disease Issues in the U.S.

Due to the serious effect of BLU disease on U.S. livestock and livestock trade, several groups are involved in BLU disease research to characterize BLU epidemiology, define disease-free regions and develop strategies to reduce the impact of domestic BLU viruses on U.S. exports while protecting the U.S. from incursions of exotic BLU viruses. Knowledge of factors controlling BLU pathogenesis in cattle is essential to assess the risk of an exotic BLU being pathogenic in U.S. cattle. This would pose a substantial risk to large areas of the U.S. where 30-50% of cattle may be seropositive for BLU.

Surveillance for BLU in the U.S. is conducted annually using a serosurvey of cattle bloods by the USDA, APHIS National Veterinary Services Laboratories. The USDA, Agricultural Research Service, Arthropod-borne Animal Diseases Research Laboratory conducts research to develop information on BLU viruses, interactions with Culicoides vectors and pathogenesis in animal hosts designed to develop novel control strategies and provide risk assessment to protect the U.S. from emerging BLU serotypes. University collaborators in California and Florida provide information on BLU epidemiology, vector ecology and host-virus interactions. Biochemical markers for BLU virulence are being developed in cooperation with university cooperators in Wisconsin. The ABADRL has provided numerous diagnostic strategies for BLU and EHD viruses (Mecham and Wilson, 1994). In situ hybridization tests for BLU and EHD viral nucleic acids are being developed by university cooperators in Georgia.

IV. Key Points Concerning Bluetongue Disease

1. Bluetongue is a List A disease with serious consequences for sheep and other livestock. Introduction into BLU-free regions or countries such as those in the European Union is considered dangerous and has resulted in non-tariff trade barriers and specific phytosanitary regulations. Importation of exotic BLU viruses into new ecosystems risks changes in the pathogenesis of these viruses.
2. Bluetongue is considered endemic in the U.S. although 17 states in the north-northeastern region (ME, NH, VT, RI, MA, CT, NY, PA, NJ, DE, MD, WV, IN, OH, MI, WI, IL) may be considered BLU free due to the absence of a suitable vector. Transmission of BLU is totally dependant on the presence of a suitable vector, which is Culicoides sonorensis in the U.S.
3. Livestock may be moved from regions of the U.S. if tested to be BLU seronegative using internationally accepted tests (immunodiffusion, linked immunosorbant assay). Animals may be moved without testing to Canada during the vector-free season from the BLU-free north-northeastern U.S.
4. Only BLU 2, 10, 11, 13 and 17 have been found in the U.S. The risk of exotic BLU serotypes in U.S. vectors leading to changes in BLU pathogenesis in U.S. livestock is unknown.
5. BLU viruses may be isolated using several methods, e.g. intravenous innoculation of embryonating chicken eggs, susceptible sheep or directly in cell culture. BLU viruses may be detected using molecular methods such as Polymerase Chain Reaction (PCR) with high sensitivity. Remnants of BLU virus nucleic acid have been detected in cattle with no evidence of infectious virions.
6. Serological tests include group and serotype specific tests, e.g. immunodiffusion, complement fixation and Enzyme-Linked Immunosorbant Assays (ELISAs).
7. Live attenuated BLU virus vaccines are available for different serotypes. Vaccines should only be used in sheep, and should not be used during the first half of pregnancy. Although multivalent vaccines are available these are not recommended due to the potential for recombination and reassortment between serotypes. Live attenuated vaccines also pose the risk of reversion to virulence in the vector.
8. The severe restrictions on the movement of livestock due to BLU virus are based on fear that carrier cattle lacking BLU virus antibody provide a source of infection, and the fear that entry of exotic serotypes could pose great risk in new environments. Evidence is available that seronegative BLU carrier cattle are unlikely to exist and such animals are not a factor in BLU epidemiology. The danger of exotic BLU serotypes is unknown.

V.    References

Barber TL. 1979. Temporal appearance, geographic distribution and species of origin of bluetongue virus serotypes in the United States. Am. J. Vet. Res. 40:1654-1656

Cheney IW, Yamakawa M, Roy P, Mecham JO, Wilson WC. 1996. Molecular characterization of the segment 2 gene of epizootic hemorrhagic disease serotype 2: Gene sequence and genetic diversity. Virology 224:555-560.

Dulac GC, Duboc C, Meyers DJ, Taylor EA, Ward D, Sterritt WG. 1989. Incursion of bluetongue virus type 11 and epizootic hemorrhagic disease of deer type 2 for two consecutive years in the Okanagen Valley. Can. Vet. J. 30:351-354.

Dulac GC, Sterritt WG, Dubuc C, Afshar A, Myers EA, et al. 1992. Incursions of orbiviruses in Canada and their serologic monitering in the native animal population between 1962 and 1991. See Walton and Osburn, pp. 120-127.