Bluetongue Virus

Bluetongue is a non-contagious, arthropod-borne viral disease of both domestic and wild ruminants.  Bluetongue virus (BTV) is endemic in some areas with cattle and wild ruminants serving as reservoirs for the virus.  Epizootics of Bluetongue virus killing approximately 179,000 sheep within 4 months have threatened the livestock industry in recent years.  For this reason, regulatory veterinarians have heightened their interest in this devastating disease.

  The threat of decreased trade associated with Bluetongue outbreaks has become an even bigger threat to the livestock industry than the actual disease itself.  According to Kahrs, “bluetongue is a major obstacle to exportation of U.S. ruminants and ruminant products and probably affects the United States more than most countries.”  This is because of the prevalence of BTV in conjunction with competent vectors within the U.S., vague surveillance and reporting policies, and extensive BTV research emanating from U.S. laboratories.

  Bluetongue is an orbivirus which cross-reacts with many antigenically related viruses including Palyam virus and the viruses that cause epizootic hemorrhagic disease of deer and African Horse sickness.  Bluetongue virus replicates in both arthropod and mammalian host cells.  The virulence of BTV varies quite markedly; even strains with matching serotypes have variable virulence.  A  total of 25 serotypes have been identified worldwide with only 5 recognized within the United States.

  Testing diagnostically for BTV can be difficult.  Two types of viral antigen are used for BTV testing.  All Bluetongue serotypes share a common antigenic determinant called antigen protein P7, while the antigen protein Ps is variable and is used to determine the specific serotype of a virus (1-25).  The serum is often tested by complement fixation, AGID, or one of several Elisa techniques.  The AGID test can detect antibodies that have persisted for years in BTV-exposed animals and can cross-react with related orbiviruses, thereby producing high numbers of false negatives (low sensitivity and specificity).  While difficult to perform, complement fixation is still used to determine BTV exposure status for export since it can detect shorter-lived antibodies.  However, because of BTV’s wide pathogenic variability and the fact that cross-reaction may occur between other orbiviruses (especially EHD), a positive result on Bluetongue group test does not mean clinical signs seen were caused by BTV itself.  The competitive ELISA (C-ELISA) has proven to be the best serologic test for BTV antibody detection.  Monoclonal antibody detection is used with ELISA to decrease the chance of cross-reaction.  In any case, the detection of BTV antibodies is poorly correlated with BTV viremia.

  Virus isolation from blood of a viremic animal is the most definitive means of BTV diagnosis.  Virus isolation can be labor intensive, time-consuming, and expensive; however, spleen and brain tissues (often from aborted fetuses) are used to isolate the BTV.  According to James Mechan, “Isolation of BTV has traditionally relied on inoculation of cell cultures, embryonated chicken eggs, or sheep with blood from infected animals or with homogenates of insects collected in endemic areas.”  Currently, PCR is taking over previous methods of virus isolation.  The PCR tests have proven to be very sensitive and specific for BTV RNA.  A positive PCR is not always indicative of infection, however, since viral RNA can be detected in some tissues after viremia has passed.

  BTV can replicate in a variety of mammalian cells.  According to Smith, “Clinically, the BTV seems to present as underlying endothelial cell damage resulting in a vasculitis causing edema and eventually necrosis of epithelial and mucosal surfaces.”  Teratogenesis occurs in the developing fetus due to virally induced disruptions of organogenesis.

  It has recently been hypothesized that development of clinical disease in cattle may be mediated through Type 1 hypersensitivity (aranylaris).  Likewise, clinical disease in sheep appears to be most severe when previous exposure has occurred.

  BTV infection occurs in both wild and domestic ruminants/camelids from the bite of the vector midge of the genus Culicoides.  The Culicoides vector infects most species during mid-summer to early fall when it is most active.  The virus can also be transmitted sexually in infected semen and transplacentally from dam to offspring.  Transmission via embryo transfer may also be a concern if the embryo is not washed at least ten times. Culicoides transmission is by far the most important method of transmission in endemic areas.  BTV is mostly seen in the southern United States where Culicoides are widespread.  In the absence of competent vector populations, animal to animal transmission is not capable of maintaining an endemic state.  The overall seroprevalence of cattle in the United States is >18%.

  Bluetongue is clinically manifested as two syndromes: 1) vascular insult of several organ systems and 2) a reproductive syndrome.  Sheep are commonly seen with clinical disease, but other domestic ruminants such as cattle and goats only rarely show clinical signs.  Differential diagnoses of Bluetongue in sheep include Orf (contagious ecthyma), foot and mouth disease, any vesicular disease, and sheep pox.

  After a prepatent period of 3-8 days, sheep may begin to show clinical signs such as transient fever (up to 106F), edema of the face, lips, muzzle and ears, excessive salivation, and hyperemic oral mucosa.  The disease name stems from the fact that affected sheep begin to develop a mucopurulent nasal discharge after the first few days and the tongue may become cyanotic.  This is actually an infrequently reported sign;  however, the oral lesions may progress to petechial hemorrhages, erosions, and ulcers.  A marked pulmonary edema is often seen.  Late in the disease (7-12 days), lameness characterized by petechial hemorrhages at the coronary band may occur and the hooves may eventually slough.  Fragile wool and diarrhea are commonly seen.  Many affected animals become depressed and die while others make a full recovery.

  The reproductive portion of the disease varies greatly.  Signs include abortions, stillbirths, and weak  “dummy lamb” live births.  BTV can be both abortigenic and teratogenic in cattle experimentally, but neither is commonly seen in field conditions.  Early embryonic loss and decreased reproductive efficiency is a more frequently seen manifestation of the disease in cattle and can be devastating to their calf/milk production.  Clinical signs in cattle also include hyperemia and necrosis of the muzzle (“burnt muzzle”) and patchy dermatitis.  Differentials for BTV in cattle include Bovine Viral Diarrhea virus, Malignant Catarrhal Fever, vesicular diseases, Rinderpest, photosensitization, Bovine Papular Stomatitis and Infectious Bovine Rhinotracheitis.  Regulatory officials should be notified if an outbreak in cattle occurs or is suspected.

  Unfortunately, no single gross or histologic lesion points with certainty towards BTV.  Some animals appear normal at necropsy, while most show hemorrhage in some organ, most frequently the heart.  Petechial and ecchymotic hemorrhages are also seen under the tongue, on the hard palate, esophagus, forestomach, lymph nodes, bladder, and spleen.  Erosions and ulcers can be seen anywhere in the oral cavity.  Gelatinous subcutaneous edema of the head, neck, forelimbs, and trunk is commonly seen.

  Supportive treatment is used since no antibiotic for BTV exists.  Since animals with severe oral lesions are reluctant to eat, they should be fed via stomach tube or encouraged to eat soft feedstuffs.  Muscle and coronary band pain limits mobility and therefore shade and water should be made readily available.  Sulfas may be administered to treat secondary bacterial pneumonia and NSAIDs are commonly used to control pain.

  Environmental elimination is usually not possible so sheep should be kept indoors during peak midge activity, e.g. dusk.  Environmental control using Ivermectin can be attempted, but transmission of BTV can occur before the insect’s demise.  Some modified live vaccines are available and should be based upon the local strains and serotypes.

-by Lisa McDill, Class of 2002

-edited by Dr. Theresa Boulineau, ADDL   Graduate Student

References

Kahrs, Robert: 1998.  The Impact of Bluetongue on International Trade.  Proceedings of the Annual Meeting of the USAHA.

MacLachlan, Pierce and deMattos: 1997.  Evolution of Bluetongue Virus in the Western United States. Proceedings of the Annual Meeting of the USAHA.

Mecham and Wilson: 1994.  Strategies for Improved Bluetongue Diagnostics.  Proceedings of the Annual Meeting of the USAHA.

Monke, Donald R: 1996.  Bluetongue Virus: Review of Regulations and Diagnostic Tests Pertinent to the International Exchange of Bovine Semen.  Proceedings of the Annual Meeting of the USAHA.

Parsonson, Ian M.: 1993.  Bluetongue Virus Infection of Cattle.  Proceedings of the Annual Meeting of the USAHA.

Smith: 2001.  Large Animal Internal Medicine.