Bluetongue is an infectious arthropod-borne viral disease primarily of domestic and wild ruminants. Infection with bluetongue virus (BTV) is common in a broad band across the world, which until recently stretched from ~35°S to 40°–50°N. Since the 1990s, BTV has extended considerably north of the 40th and even the 50th parallel in some parts of the world (eg, Europe). The geographic restriction is in part related to the climatic and environmental conditions necessary to support the Culicoides vectors. Most infections with BTV in wild ruminants and cattle are subclinical. Bluetongue (the disease caused by BTV) is usually considered to be a disease of improved breeds of sheep, particularly the fine-wool and mutton breeds, although it has also been recorded in cattle and some wild ruminant species, including white-tailed deer (Odocoileus virginianus), pronghorn antelope (Antilocapra americana), and desert bighorn sheep (Ovis canadensis) in North America, and European bison (Bison bonasus) and captive yak (Bos grunniens grunniens) in Europe.
Bluetongue virus is the type-species of the genus Orbivirus in the family Reoviridae. There are at least 24 serotypes worldwide, although not all serotypes exist in any one geographic area; eg, 13 serotypes (1, 2, 3, 5, 6, 10, 11, 13, 14, 17, 19, 22, and 24) have been reported in the USA and 8 serotypes (1, 2, 4, 6, 8, 9, 11, and 16) in Europe. Distribution of BTV throughout the world parallels the spatial and temporal distribution of vector species of Culicoides biting midges, which are the only significant natural transmitters of the virus, as well as the temperatures at which BTV will replicate in and be transmitted by these vectors. Of more than 1,400 Culicoides species worldwide, fewer than 30 have been identified as actual or potential vectors of BTV to date. Continued cycling of the virus among competent Culicoides vectors and susceptible ruminants is critical to viral ecology. In the USA, 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. 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 wk), and the host preference of some vector species of Culicoides for cattle, provide a mechanism for year-round transmission in domestic ruminants in locations where the vector-free (winter) period is relatively short. Mechanical transmission by other bloodsucking insects is of minor significance.
Vector-borne transmission through Culicoides spp is the primary way BTV spreads. 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 significance 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, but the epidemiologic significance of this mechanism is unclear. Accidental infection has been reported in dogs in the USA after administration of a modified-live canine virus vaccine that was contaminated with BTV. Serologic evidence of infection with BTV has been found in wild and captive carnivores in Africa and Europe, perhaps as a result of ingesting virus-infected viscera. The epidemiologic importance of this oral infection mechanism is at present uncertain. Serologic evidence of BTV exposure has been demonstrated in domestic dogs fed commercial diets.
The course of the disease 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 wk after infection, mainly as a result of bacterial complications, especially pasteurellosis, and exhaustion. 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. This results in edema, congestion, hemorrhage, inflammation, and necrosis. The clinical signs in sheep are typical. After an incubation period of 4–6 days, a fever of 105°–107.5°F (40.5°–42°C) develops. The 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 seen, such as edema of 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 USA. 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 can be seen on the mucous membranes of the nose and mouth. Ulceration develops where the teeth come in contact with lips and tongue, especially in areas of most friction. Some affected sheep have severe swelling of the tongue, which may become cyanotic (‘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 easily seen as a band at the junction of the skin and the hoof. Later in the course of disease, lameness or torticollis is due to skeletal muscle damage. In most affected animals, abnormal wool growth resulting from dermatitis may be seen.
Clinical signs in cattle are rare but may be similar to those seen 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. Pregnant dogs abort or give birth to stillborn pups and then die in 3–7 days.
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 but may be barely visible in mild or convalescent cases. These lesions are often described as pathognomonic for bluetongue, but they have also been seen 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 autopsy findings include subcutaneous and intermuscular edema and hemorrhages, skeletal myonecrosis, myocardial and intestinal hemorrhages, hydrothorax, hydropericardium, pericarditis, and pneumonia.
In many areas of the world, BTV infection in sheep, and especially in other ruminants, is subclinical. Laboratory confirmation is based on virus isolation in embryonated chicken eggs or mammalian and insect cell cultures, or on identification of viral RNA by PCR. The identity of isolates may be confirmed by the group-specific antigen-capture ELISA, group-specific PCR, immunofluorescence, immunoperoxidase, serotype-specific virus neutralization tests, serotype-specific PCR, 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 EDTA and transported at 4°C (39.2°F) to the laboratory. For longterm storage when refrigeration is not possible, blood is collected in oxalate-phenolglycerin (OPG). Blood to be frozen should be collected in buffered lactose peptone and stored at or below −70°C (−94°F). Blood collected at later times 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 for 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 and is generally lifelong after a field infection. Current recommended serologic techniques for detection of BTV antibody include agar gel immunodiffusion 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.
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 different BTV serotypes attenuated by serial passage in embryonated hens’ eggs followed by growth and plaque selection in cell culture, are widely used in southern Africa and elsewhere, should epizootics of bluetongue occur. A monovalent (BTV type 10) modified-live virus vaccine propagated in cell culture is available for use in sheep in the USA. Use of vaccines with different serotypes does not provide consistent cross-protection. Live-attenuated vaccines should not be used during Culicoides vector seasons, because these insects may transmit the vaccine virus(es) from vaccinated to nonvaccinated animals, eg, other ruminant species. This may result in reassortment of genetic material and give rise to new viral strains. Abortion or malformation, particularly of the CNS, of fetuses may follow vaccination of ewes and cows with attenuated live vaccines during the first half and the first trimester of pregnancy, respectively. Passive immunity in lambs usually lasts 2–4 mo.
The 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 serotype(s) causing infection. Use of vaccine strains other than the one(s) causing infection affords little or no protection and is not recommended. The potential risk from vaccine virus reassortment with wild-type viral strains, virus spread 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 spread in those regions where significant cover (>80%) has been achieved.
Control of vectors by using 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.