Definition
Bluetongue (BT) and epizootic hemorrhagic disease (EHD) are
insect-borne viral diseases of ruminants characterized by acute or subacute clinical
courses in susceptible ruminants. The BT virus (BTV) and EHD virus (EHDV) have also been
associated with congenital disease in sheep and cattle.
Etiology
Bluetongue and epizootic hemorrhagic disease are caused by
orbiviruses in the family Reoviridae. Other orbiviruses include Ibaraki, Palyam,
Eubenangee, and Tilligerry. The viruses are resistant to lipid solvents, which is typical
of nonenveloped viruses. The viruses are relatively acid-labile, and slow freezing at -10
to -20 oC (14 - 4o F) is deleterious to the virus.
Worldwide, 24 serotypes of BTV and 9 serotypes of EHDV have been
identified. Five serotypes of BTV and two serotypes of EHDV have been isolated in the
United States. However, only BTV serotypes 10, 11, 13, and 17 and EHDV serotypes 1 and 2
are currently active. BTV serotype 2, originally isolated from animals imported into
Florida, may not have established itself in the United States; however, epidemiologic
studies will be required to resolve this issue.
Acetic acid is an effective disinfectant.
Host Range
The host range of BTV is very broad and includes all ruminant
species tested to date. However, the expression of clinical disease varies in different
species. Sheep are fully susceptible to BTV. EHDV typically also infects most ruminant
species; however, sheep appear to be a poor host and rarely develop signs of EHDV
infection.
Geographic Distribution
The geographic distribution of the orbiviruses is extensive, but
current knowledge is still incomplete. Virus distribution is based on the presence of
certain Culicoides species, including C. variipennis, C. imicola, C.
brevitaris, and others. Orbivirus infections are common in tropical, subtropical, and
temperate climates. Areas with year- round vector activity could easily maintain the virus
by a continuous vector-host cycle. Virus persistence in areas with severe winters is not
understood. Reintroduction of virus into the area in the warm months by transportation of
infected animals or infected Culicoides being carried on the wind is probably
common. Some research reports suggest that overwintering of the virus in these areas
occurs by mechanisms such as (1) prolonged viremias (up to 3 months) in certain animals,
(2) transplacental transmission of BTV in the late fall and early winter to the late-term
developing fetus with subsequent birth of a viremic calf, and (3) overwintering of the
virus in Culicoides that may survive through the winter at very low population
densities. Virological and serological testing has suggested that BTV exists in North,
Central, and South America; Africa; and parts of Asia; Europe; the Middle East; and the
South Pacific; EHDV is probably similarly distributed.
Transmission
Transmission of orbiviruses is primarily by Culicoides species, which are biological vectors. Limited experimental studies have also demonstrated
that ticks are capable of mechanically or biologically transmitting BTV; however, their
role in the epidemiology of BTV is probably minimal. Virus can also be transferred from
viremic dams (sheep and cattle) to the developing fetus. Although BTV can be found in the
semen of certain rams and bull, it is only isolated at the time of peak viremia; this
presence of virus would appear to be the result of blood cells in the semen. Extensive
field and experimental studies suggest that transmission of BTV via semen is of not
importance in the epidemiology of BTV. The potential for BTV transmission also exists
owing to poor management practices such as using the same needle or infected surgical
equipment on several animals (mechanical transmission).
Incubation Period
The incubation period of BT in sheep is usually 7-10 days;
however, viremia may appear as early as 3 to 4 days after infection. In cattle, viremia
occurs as early as 4 days postinfection, but clinical signs are uncommon. Development of
clinical BT in cattle may be the result of hypersensitization. Under laboratory conditions
such animals develop clinical signs 10 to 12 days following reexposure to the virus. The
incubation of BTV infection in deer is 7 to 12 days. No information is available on the
incubation periods for EHDV.
Clinical Signs of Bluetongue
BT in Sheep
The classic signs of BT in sheep are those of an acute to subacute
infection by a virulent strain of virus in fully susceptible animals belonging to the fine
wool or mutton breeds. However, the signs of BT are variable. Not all strains of BTV that
infect sheep cause clinical disease. In some flocks, no clinical sign is apparent, whereas
in other flocks infected by the same virus up to 30 percent may develop signs of disease.
The first sign of illness which begins 7 to 8 days after
infection, is a rise in temperature to 106-107o F (41.6-41.7o C).
Temperatures may be elevated for 4 to 12 days following the initial rise. Within 24 hours
of the initial rise in temperature, excessive salivation and frothing at the mouth develop
and are associated with hyperemia and swelling of the buccal and nasal mucosa (Fig. 33). If forced to move, sheep may
pant like a dog. During the next 2 to 3 days, erosions and ulcerations may develop in the
buccal mucosa. By 4 to 7 days in severe cases, extensive ulcerations may be covered by
gray necrotic tissue on the dental pad and dorsal surface of the tongue. In addition,
affected animals being fed rough feed (stemmy alfalfa) may have more severe lesions of the
oral mucosa.
Hyperemia is often observed around the coronary bands of the
hooves. Often the hooves are tender and varying degrees of lameness are apparent. In more
severe cases, the animals stand with an arched back (Fig. 34). If the animals are driven during this time, they may
slough their hooves. Animals that recover may have a dark line in the wall of the hoof.
The lesions in the mouth, the reluctance to move, and the necrosis
of striated musculature lead to weakness, depression, and rapid weight loss. These can
result in prostration and eventual death in severely affected animals. Sheep that recover
from severe infections may have a break in the wool 3 to 4 weeks after the fever has
subsided. This can lead to partial or complete shedding of wool.
Bluetongue virus infection of pregnant ewes in the first trimester
can cause fetal death and resorption, abortion, or birth of "dummy" lambs.
Attenuated BTV vaccines can also cause reproductive failure.
BT in Cattle
Bluetongue virus infection in cattle usually does not cause any
clinical sign of disease. Subclincal disease is only evidenced by changes in the leukocyte
and lymphocyte subpopulation counts in the peripheral blood and a mild acute eosinophilic
dermatitis. A consistent fluctuation in rectal temperature is indicative of viremia and a
mild disease. Occasionally, field outbreaks of BT disease occur in which as many as 30
percent of the cattle have clinical signs. Experimental data support the contention that
clinical BT in cattle occurs as result of prior sensitization to a related orbivirus
followed by a later second exposure. After secondary exposure, clinical signs become
apparent in 10-12 days. Clinical signs consist of mild hyperemia in the buccal cavity and
around the coronary band; vesicular lesions, which lead to ulcerations, in the buccal
mucosa; erect hair over the cervical and dorsal thoracic areas; and a definite
hyperesthesia. In addition, the dermis becomes thickened with prominent folds apparent in
the cervical areas, and a dry crusty exudate leads to matting of hair in affected areas.
These lesions may persist for 10 to 20 days. Similar lesions have been reported on teats
of cattle with clinical BT. Hoof lesions may be associated with lameness. In some
instances severe breaks in the hooves occur 40 to 60 days after infection and are usually
followed by foot rot.
Bluetongue virus infection can cause reproductive failure in
cattle. Some infected bulls will become temporarily sterile following acute infections.
After recovery, production of sperm resumes, and the bulls are capable of settling cows.
Certain strains of BTV are capable of causing fetal death,
resorption and or abortion; cell-culture-adapted live virus may be more effective than
field virus in establishing fetal infection. Teratogenic effects of BTV in the bovine
fetus include hydranencephaly and cerebral cysts that result in "dummy" calves.
Critical factors for fetal infection include the stage of
embryonic or fetal development when infection occurs, the immune status of the dam, and
the strain(s) of BTV causing infection. The most susceptible period for fetal infections
occurs between 60 and 140 days gestation in nonimmune dams. Experimental studies suggest
15 to 20 percent of viremic dams will transmit virus to their fetuses. In areas where
strains of BTV are endemic, there is little evidence that BTV has adverse affects on
reproduction.
BT in Goats
Bluetongue infection of goats is typically an inapparent infection
similar to that described for cattle.
Clinical Signs of EHDV Infection
EHD in Sheep
The EHD virus does not appear to cause significant clinical
disease in sheep.
EHD in Cattle
The EHD virus rarely causes disease in cattle. However, Ibaraki
virus (an EHDV serotype) has been associated with sporadic outbreaks of severe disease in
cattle in Japan. Mortality rates have been as high as 10 percent. Clinical signs consist
of fever, erosive and ulcerative lesions of the oral and esophageal mucosa, stiffness,
lameness, and thickened, edematous skin. In addition, there has been a report of a
combined EHDV and BTV disease of cattle. In pregnant cows, EHDV infection can result in
fetal resorption or hydranencephaly if infection occurs between days 70 and 120 of
gestation.
EHD in Deer
An EHD virus infection in white-tailed deer usually follows a
peracute course leading to death. Often, deer are found dead around waterholes which
suggests that they had a high fever and were dehydrated.
Gross Lesions
BT in Sheep
The lesions of BT in sheep vary greatly depending on (1) the
strain of virus, (2) individual animal and breed susceptibility and (3) environmental
(stress) factors. Prominent lesions include facial edema, edematous ears, and dry, crusty
exudate over the nostrils (Fig. 33). Lesions in the oral
cavity include focal petechial (pinhead-size) hemorrhages that progress to gray necrotized
debris over erosions and ulcerations on the lips; on the dorsal, lateral, and ventral
surfaces of the tongue; and on the dental pad. The buccal mucosa may be cyanotic.
Hyperemia and occasional erosions can occur on papillae and laminae in the reticulum and
omasum.
Lesions in the respiratory system include cyanosis and edema of
the nasal mucosa and pharynx, and there may be tracheal hyperemia and congestion. Froth in
the trachea is present only when there is pulmonary congestion and edema.
Lesions in the vascular system cause hyperemia, edema, and
hemorrhages. A characteristic lesion is hemorrhage at the base of the pulmonary artery.
Petechial and ecchymotic (larger than pinhead-size) hemorrhages may be observed at times
in the endocardium. Focal gray-white areas of necrosis are often found in the papillary
muscles and less frequently in other areas of the myocardium.
The most prominent changes in the skin include dermal and
subcutaneous edema of the head and ears. Sometimes an irregular rash (exanthematous
eruptions) may progress into serous and crusty exudates on the skin. Hyperemia is
prominent at the coronet of the hoof. Often, this reddening is accompanied by petechial or
ecchymotic hemorrhages that extend down the horn.
A yellow gelatinous exudate is common in the fascia (connective
tissue) along and between skeletal muscles. On the cut surface of the heavy muscle there
may be focal hemorrhages and areas that appear dry and gray-white.
Newborn lambs with congenital BT have hydranencephaly or
porencephaly. These lesions are characterized by fluid-filled cavities, either occupying
the whole of the cranial vault or as cystic cavities in the gray and white matter of the
cerebral cortex. Cerebellar dysplasia (abnormal development) (Fig. 35) with rudimentary medial and lateral lobes may be present.
The spinal cord may be dysplastic (abnormal development) and lack white matter. Skeletal
deformities may consist of scoliosis (lateral curvature of the spine) and torticollis
(twisted neck).
BT in Cattle
Gross lesions in cattle differ in some respects from those
observed in sheep. The most prominent lesions involve the skin, mouth, and hooves. Skin
lesions are characterized by marked edema that leads to thick folds — particularly in
the cervical areas. Lesions may form in the folds as serous exudate accumulates and dries.
Dry, crusty exudate is present on the skin over the cervical and thoracic areas. The
crusty material results from vesicular eruptions and ulcerations.
The external nares may have erosions covered by crusty exudate
that sloughs. Lesions in the mouth start as vesicles and proceed to ulcers covered with
grayish necrotic debris. These lesions are more common on the buccal mucosa and dental pad
and rarely the tongue. Hyperemia occurs at the coronary band. In some instances, fissures
occur 6 to 8 weeks following infection.
In utero BTV infection may lead to fetal death and resorption,
abortion, hydranencephaly, or cerebral cysts.
BT in Deer
Bluetongue in susceptible deer causes widespread hemorrhages
throughout the body. These lesions are associated with intravascular thromboses and
hemorrhages varying in size from petechial to ecchymotic. In chronic BT, deer may develop
severe fissures and even sloughing of hooves. Ulcers covered with gray necrotic debris are
found in the buccal mucosa, dental pad, and tongue.
EHD in Deer
In susceptible deer EHDV causes lesions very similar to those
caused by BTV. The widespread hemorrhages in mucous membranes, skin, and viscera are the
result of disseminated intravascular clotting. The Ibaraki strain of EHDV can cause
widespread vascular lesions similar to those described for BTV in cattle. Degenerative
changes (focal hemorrhage or dry and gray-white appearance, or both) in striated
musculature are prominent in the esophagus, larynx, tongue, and skeletal muscles.
Morbidity and Mortality
In sheep, BT can range from inapparent to severe, depending on the
breed, strain of virus, and environmental stress on the animals. Morbidity can reach 100
percent; mortality can vary from 0 to 50 percent. Many animals will recover within a few
days to 2 weeks.
In cattle, BTV and EHDV infection is usually subclinical. Although
morbidity can approach 5 percent, cattle typically recover within a few weeks. However,
lameness and unthriftiness may persist for prolonged period.
The morbidity and mortality for BTV infection in other species are
as follows:
- Goats - minimal clinical signs
- White-tailed deer - morbidity approaching 100 percent and a
mortality of 80-90 pecent
- Pronghorn antelope - morbidity approaching 100 percent and a
mortality of 80-90 percent
- Bighorn sheep - morbidity approaching 100 percent and a
mortality of 0 to 50 percent
- North American elk - similar to cattle; the disease is usually
subclinical.
Diagnosis
Field Diagnosis
Tentative diagnosis of BT can be made when (1) clinical signs
appear in populations known to be susceptible, (2) the occurrence of disease coincides
with a prevalence of insect vectors, (3) necropsy of sheep reveals characteristic gross
lesions, and (4) a flock history of recent wasting (loss of weight) and pododermatitis
(foot rot).
Specimens for Laboratory
Preferred samples for confirmatory diagnosis include sterile
heparinized blood samples from animals with clinical signs or spleen or bone marrow, or
both, from dead animals. Samples from aborted and congenitally infected newborn animals
should include heparinized blood and, if possible, spleen, lung, brain, and serum. If
possible, the heparinized whole blood (erythrocytes and white cells) should be washed in
saline containing antibiotics and resuspended in saline prior to shipping. This procedure
will reduce the antibody that may neutralize the virus if blood-cell lysis occurs.
Specimens should be shipped refrigerated, not frozen. Freezing
makes virus isolation difficult.
Laboratory Diagnosis
Confirmatory diagnosis is based on isolation and identification of
virus from blood or tissues. Diagnosis for lambs and calves infected in utero is based on
serology (if no colostrum has been ingested) or virus isolation, or both.
Differential Diagnosis
Differential diagnoses include plant photosensitization,
foot-and-mouth disease, vesicular stomatitis, bovine virus diarrhea, malignant catarrhal
fever, infectious bovine rhinotracheitis, parainfluenza-3, contagious ecthyma, and
actinobacillosis.
Vaccination
Vaccination has been the primary means of controlling BT disease
in sheep. To date, only modified-live (attenuated) virus vaccines have been used. Because
of the multiplicity of BTV serotypes and variable cross-protection between serotypes,
vaccination has resulted in varying degrees of success. The serotypes incorporated into
the vaccine must be the same as those causing infection in the field. The practice of
administering multiple virus serotypes in a single vaccination is argued against by some
scientists because (1) an immune response (virus neutralizing antibody) is typically only
induced to one, or at best two of the serotypes incorporated in the vaccine and (2)
reassortment between the genome segments of the multiple vaccine viruses may occur in the
host of a vector feeding on such a vaccinated animal. Although simultaneous infection of
sheep, cattle, or Culicoides can result in creation of reassortant viruses, there
is no evidence that this process has resulted in generation of new serotypes. However,
such reassortant events may result in altered virulence and biological transmissibility.
No inactivated or subunit vaccines are currently available, though
several experimental vaccine preparations have been studied, including inactivated virus
vaccines, subunit vaccines prepared by purification of natural VP2 (viral protein
responsible for inducing virus neutralizing antibody), and recombinant VP2 expressed in a
baculovirus system.
No vaccine is available for EHDV.
Control and Eradication
Vaccination can be used in endemic areas.
Vector control measures to impede the spread of BTV infection are
not commonly used. However, certain measures have potential effectiveness such as water
management (reduction of Culicoides breeding sites), use of insecticides and
larvacides (spraying breeding areas), and insect repellents in which animals are dipped.
The only applicable treatment available is to minimize animal
stress and administer broad-spectrum antibiotics to combat secondary infection.
Public Health
There is only one documented human infection, and that was in a
laboratory worker
GUIDE TO THE LITERATURE
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J.L. Stott, D.V.M., University of California, School of Veterinary
Medicine, Agricultural Experiment Station, Department of Microbiology and Immunology,
Davis, CA
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