Bluetongue in Ruminants

Bluetongue virus is the type species of the genus Orbivirus in the family Reoviridae. The virion is a nonenveloped double-layered particle with an outer capsid that encloses a core containing a segmented double-stranded RNA genome.

Hosts typically become infected from the saliva of a biting midge. The virus spreads locally and replicates in regional lymph nodes, leading to viremia and systemic spread with virus replication in hematopoietic cells and endothelial cells, resulting in endothelial damage, hemorrhage, vascular occlusion, tissue edema, and epithelial sloughing due to loss of microvasculature.

There are at least 29 serotypes of BTV worldwide, although not all serotypes exist in any one geographic area. Distribution of BTV throughout the world parallels the spatial and temporal distribution of vector species of Culicoides biting midges (the only important natural transmitters of the virus) as well as the temperatures at which BTV will replicate in and be transmitted by these vectors. Continued cycling of the virus among competent Culicoides vectors and susceptible ruminants is critical to viral ecology. In the US, the principal vectors are C sonorensis and C insignis, which limit the distribution of BTV to southern and western regions. In northern and eastern Australia, the principal vector is C brevitarsis, whereas in Africa, southern Europe, and the Middle East, it is C imicola. In northern Europe, the major vectors are species within the C obsoletus-dewulfi complex. In each geographic region, secondary vector species may attain local importance.

Vectors become infected with BTV by imbibing blood from infected vertebrates; transovarial transmission has not been reported. The high affinity of the virus to blood cells, especially the sequestering of viral particles in invaginations of RBC membranes, contributes to prolonged viremia in the presence of neutralizing antibody. The extended viremia in cattle (occasionally up to 11 weeks), as well as the host preference for cattle that some vector species of Culicoides display, provides a mechanism for year-round transmission in domestic ruminants in locations where the vector-free period (ie, winter) is relatively short. Mechanical transmission by other bloodsucking insects is of minor importance.

Vector-borne transmission through Culicoides spp is the primary way that BTV is transmitted. Virus concentrations in secretions and excretions are minimal, making direct, indirect, or aerosol transmission unlikely. However, in-contact transmission of BTV serotype 26 has been demonstrated in goats. The importance of this form of transmission in the ecology of this serotype is not known. Semen from viremic bulls can serve as a source of infection for cows through natural service or artificial insemination. Embryo transfer is regarded as safe, provided that donors are not viremic and an appropriate washing procedure for embryos is used. Transplacental transmission of field strains of BTV from dam to fetus, leading to the birth of viremic calves, is reported in cattle; however, the epidemiological importance of this mechanism is unclear. Bluetongue is listed by the World Organisation for Animal Health (OIE) as a notifiable disease. Bluetongue virus is not zoonotic.

The course of bluetongue in sheep can vary from peracute to chronic, with a mortality rate of 2%–90%. Peracute cases die within 7–9 days of infection, mostly as a result of severe pulmonary edema leading to dyspnea, frothing from the nostrils, and death by asphyxiation. In chronic cases, sheep may die 3–5 weeks after infection, mainly because of bacterial complications (especially pasteurellosis) and exhaustion. Animals with mild cases usually recover rapidly and completely. The major production losses include deaths, unthriftiness during prolonged convalescence, wool breaks, and reproductive losses.

In sheep, BTV causes vascular endothelial damage, resulting in changes to capillary permeability and subsequent intravascular coagulation, leading to edema, congestion, hemorrhage, inflammation, and necrosis. The clinical signs in sheep are typical. After an incubation period of 4–6 days, a fever of 40.5°–42°C (105°–107.5°F) develops. Affected animals are listless and reluctant to move. Clinical signs in young lambs are more apparent, and the mortality rate can be high (up to 30%). Approximately 2 days after onset of fever, additional clinical signs may be evident, such as edema of the lips, nose, face, submandibular area, eyelids, and sometimes ears; congestion of mouth, nose, nasal cavities, conjunctiva, and coronary bands; and lameness and depression. A serous nasal discharge is common, later becoming mucopurulent. The congestion of nose and nasal cavities produces a “sore muzzle” effect, the term used to describe the disease in sheep in the US.

Sheep eat less because of oral soreness and will hold food in their mouths to soften before chewing. They may champ to produce a frothy oral discharge at the corners of the lips. On close examination, small hemorrhages are visible on the mucous membranes of the nose and mouth. Ulceration develops where the teeth come in contact with lips and tongue, especially in the areas of most friction. Some affected sheep have severe swelling of the tongue, which may become cyanotic (hence the term "blue tongue”) and even protrude from the mouth. Animals walk with difficulty as a result of inflammation of the hoof coronets. A purple-red color is obvious as a band at the junction of the skin and the hoof. Later in the course of disease, lameness or torticollis develops due to skeletal muscle damage. In most affected animals, abnormal wool growth results from dermatitis.

Clinical signs of bluetongue in cattle are rare but may be similar to those that occur in sheep. They are usually limited to fever, increased respiratory rate, lacrimation, salivation, stiffness, oral vesicles and ulcers, hyperesthesia, and a vesicular and ulcerative dermatitis. Susceptible cattle and sheep infected during pregnancy may abort or deliver malformed calves or lambs. The malformations include hydranencephaly or porencephaly, which results in ataxia and blindness at birth. White-tailed deer and pronghorn antelope develop severe hemorrhagic disease leading to sudden death.

In many areas of the world, BTV infection in sheep, and especially in other ruminants, is subclinical. Although clinical signs in cattle are rare and limited, exposure to BTV can influence international trade and movement of serologically positive animals.

• Clinical evaluation

• Postmortem examination

• Virus identification

• Serologic testing

The typical clinical signs of bluetongue enable a presumptive diagnosis, especially in areas where the disease is endemic.

Suspicion is confirmed by the presence of petechiae, ecchymoses, or hemorrhages in the wall of the base of the pulmonary artery and focal necrosis of the papillary muscle of the left ventricle. These highly characteristic lesions are usually obvious in severe clinical infections; in mild or convalescent cases, however, they may be barely visible. These lesions are often described as pathognomonic for bluetongue, but they also occur occasionally in other ovine diseases, such as heartwater, pulpy kidney disease, and Rift Valley fever. Hemorrhages and necrosis are usually found where mechanical abrasion damages fragile capillaries, such as on the buccal surface of the cheek opposite the molar teeth and the mucosa of the esophageal groove and omasal folds. Other necropsy findings include subcutaneous and intermuscular edema and hemorrhages, skeletal myonecrosis, myocardial and intestinal hemorrhages, hydrothorax, hydropericardium, pericarditis, and pneumonia.

Laboratory confirmation of bluetongue is based on virus isolation in embryonated chicken eggs or mammalian and insect cell cultures, or on identification of viral RNA by PCR assay. The identity of isolates may be confirmed by group-specific antigen-capture ELISA, group-specific PCR assay, immunofluorescence, immunoperoxidase technique, serotype-specific virus neutralization tests, serotype-specific PCR assay, or hybridization with complementary gene sequences of group- or serotype-specific genes. For virus isolation, blood (10–20 mL) is collected as early as possible from febrile animals into an anticoagulant such as heparin, sodium citrate, or ethylenediaminetetraacetic acid (EDTA) and transported at 4°C (39.2°F) to the laboratory. For long-term storage when refrigeration is not possible, blood is collected in oxalate-phenol-glycerin (OPG). Blood to be frozen should be collected in buffered lactose peptone and stored at or below −70°C (−94°F). Blood collected later during the viremic period should not be frozen because lysing of the RBCs on thawing releases the cell-associated virus, which may then be neutralized by early humoral antibody. The virus does not remain stable very long at −20°C (−4°F). In fatal cases, specimens of spleen, lymph nodes, or red bone marrow are collected and transported to the laboratory at 4°C (39.2°F) as soon as possible after death.

A serologic response in ruminants can be detected 7–14 days after infection by BTV and is generally lifelong after a field infection. Current recommended serologic techniques for detection of BTV antibody include agar gel immunodiffusion (AGID) and competitive ELISA. The latter is the test of choice and does not detect cross-reacting antibody to other orbiviruses, especially anti-EHDV (epizootic hemorrhagic disease virus) antibody. Various forms of the serum neutralization test, including plaque reduction, plaque inhibition, and microtiter neutralization, can be used to detect type-specific antibody.

• Supportive care

• Prevention

There is no specific treatment for animals with bluetongue apart from rest, provision of soft food, and good husbandry. Complicating and secondary infections should be treated appropriately during the recovery period.

Prophylactic immunization of sheep remains the most effective and practical control measure against bluetongue in endemic regions. Attenuated and inactivated vaccines against BTV are commercially available in some countries. Three polyvalent vaccines, each comprising five BTV serotypes, are widely used in southern Africa and elsewhere. A monovalent (BTV type 10) modified live virus vaccine is available for use in sheep in the US. Use of vaccines with different serotypes does not provide consistent cross-protection. Live, attenuated virus vaccines should not be used during Culicoides vector seasons because these insects may transmit the vaccine viruses from vaccinated to nonvaccinated animals (eg, other ruminant species). The result may be reassortment of genetic material, giving rise to new viral strains. Passive immunity in lambs usually lasts 2–4 months.

Control of bluetongue is different in areas where the disease is not endemic. During an outbreak, when one or a limited number of serotypes may be involved, vaccination strategy depends on the serotypes causing infection. Use of vaccine strains other than those causing infection affords little or no protection and is not recommended. The potential risk from vaccine virus reassortment with wild-type viral strains, virus transmission by the vectors to other susceptible ruminants, and reversion to virulence of vaccine virus strains or even the production of new BTV strains of uncertain virulence should also be considered. The use of inactivated vaccines in BTV incursions into northern Europe has played a major part in controlling virus transmission in those regions where extensive vaccination rates (>80%) have been achieved.

Control of vectors by the use of insecticides or protection from vectors may lower the number of Culicoides bites and subsequently the risk of exposure to BTV infection. However, these measures alone are unlikely to effectively halt a bluetongue epidemic and should be regarded as mitigation measures to be used alongside a comprehensive and vigorous vaccination program.

• World Organisation for Animal Health (OIE). Bluetongue.

• USDA Animal and Plant Health Inspection Service. Bluetongue.

• Spickler AR. Bluetongue. Center for Food Security and Public Health. 2015.