Bovine malignant catarrhal fever
Encyclopedia
Bovine malignant catarrhal fever (BMCF) is a fatal lymphoproliferative disease caused by a group of ruminant gamma herpes viruses including Alcelaphine Herpes Virus 1 (AlHV-1) and Ovine Herpes Virus 2 (OvHV-2) These viruses cause inapparent infection in their reservoir hosts, (sheep with OvHV-2 and wildebeest with AlHV-1) but are usually fatal in cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

 and other ungulate
Ungulate
Ungulates are several groups of mammals, most of which use the tips of their toes, usually hoofed, to sustain their whole body weight while moving. They make up several orders of mammals, of which six to eight survive...

s such as deer
Deer
Deer are the ruminant mammals forming the family Cervidae. Species in the Cervidae family include white-tailed deer, elk, moose, red deer, reindeer, fallow deer, roe deer and chital. Male deer of all species and female reindeer grow and shed new antlers each year...

, antelope
Antelope
Antelope is a term referring to many even-toed ungulate species indigenous to various regions in Africa and Eurasia. Antelopes comprise a miscellaneous group within the family Bovidae, encompassing those old-world species that are neither cattle, sheep, buffalo, bison, nor goats...

, and buffalo.

BMCF is an important disease where reservoir and susceptible animals mix. There is a particular problem with Bali cattle in Indonesia, bison in the USA and in pastoralist herds in Eastern and Southern Africa.

Disease outbreaks in cattle are usually sporadic although infection of up to 40% of a herd has been reported. The reasons for this are unknown. Some species appear to be particularly susceptible, for example Pére Davids deer, Bali cattle and bison, with many deer dying within 48 hours of the appearance of the first symptoms and bison within three days. In contrast, post infection cattle will usually survive a week or more.

Epidemiology

The term bovine malignant catarrhal fever has been applied to three different patterns of disease:
  • In Africa
    Africa
    Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...

    , wildebeest
    Wildebeest
    The wildebeest , also called the gnu is an antelope of the genus Connochaetes. It is a hooved mammal...

    s carry a lifelong infection of AlHV-1 but are not affected by the disease. The virus is passed from mother to offspring and shed mostly in the nasal secretions of wildebeest calves under one year old. Wildebeest associated MCF is transmitted from wildebeest to cattle normally following the wildebeest calving period. Cattle of all ages are susceptible to the disease, with a higher infection rate in adults, particularly in peripartuent females. Cattle are infected by contact with the secretions, but do not spread the disease to other cattle. Because no commercial treatment or vaccine is available for this disease, livestock management is the only method of control. This involves keeping cattle away from wildebeest during the critical calving period. This results in Massai pastoralists in Tanzania and Kenya being excluded from prime pasture grazing land during the wet season leading to a loss in productivity. In Eastern and Southern Africa MCF is classed as one of the five most important problems affecting pastoralists along with East coast fever
    East Coast fever
    -Introduction:East Coast fever is a disease of cattle, sheep and goats caused by the protozoan parasite Theileria parva. The term excludes diseases caused by other Theileria, such as tropical theileriosis , caused by T. annulata, and human theileriosis, caused by T...

    , contagious bovine pleuropneumonia
    Contagious bovine pleuropneumonia
    Contagious bovine pleuropneumonia , is a contagious bacterial disease that afflicts the lungs of cattle, buffalo, zebu, and yaks....

    , foot and mouth disease and anthrax
    Anthrax
    Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...

    .Hartebeest
    Hartebeest
    The hartebeest is a grassland antelope found in West Africa, East Africa and Southern Africa. It is one of the three species classified in the genus Alcelaphus....

    s and topi
    Topi
    The Tsessebe , is one of five subspecies in the binomial class D. lunatus. The other subspecies include Korrigum , Tiang , Coastal Topi , and Topi . Tesessebe are found primarily in Zambia, Namibia, Botswana, Zimbabwe, and South Africa...

     also may carry the disease. However, hartebeests and other antelopes are infected by a variant, Alcelaphine herpesvirus 2
    Alcelaphine herpesvirus 2
    Alcelaphine herpesvirus 2 is a type of rhadinovirus that is believed to be responsible for causing hartebeest infections of malignant catarrhal fever.-Clinical Definition:...

    .
  • Throughout the rest of the world, cattle and deer contract BMCF by close contact with sheep or goats during lambing. The natural host reservoir for Ovine herpesvirus 2 is the subfamily Caprinae (sheep and goats) whilst MCF affected animals are from the families Bovidae, Cervidae and suidae. Susceptibility to OHV-2 varies by species, with domestic cattle and zebu
    Zebu
    Zebu , sometimes known as humped cattle, indicus cattle, Cebu or Brahmin cattle are a type of domestic cattle originating in South Asia, particularly the Indian subcontinent. They are characterised by a fatty hump on their shoulders, drooping ears and a large dewlap...

    s somewhat resistant, water buffalo and most deer somewhat susceptible, and bison
    Bison
    Members of the genus Bison are large, even-toed ungulates within the subfamily Bovinae. Two extant and four extinct species are recognized...

    , Bali cattle, and Pere David's deer
    Père David's Deer
    Père David's Deer, Elaphurus davidianus, also known as the Milu , is a species of deer known only in captivity. It prefers marshland, and is believed to be native to the subtropics of China. It grazes on a mixture of grass and water plants. It is the only extant member of the genus Elaphurus...

     very susceptible. OHV-2 viral DNA has been detected in the alimentary, respiratory and urino-genital tracts of sheep all of which could be possible transmission routes. Antibody
    Antibody
    An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

     from sheep and from cattle with BMCF is cross reactive with AlHV-1.
  • AHV-1/OHV-2 can also cause problems in zoological collections, where inapparently infected hosts (wildebeest and sheep) and susceptible hosts are often kept in close proximity.
  • Feedlot
    Feedlot
    A feedlot or feedyard is a type of animal feeding operation which is used in factory farming for finishing livestock, notably beef cattle, but also swine, horses, sheep, turkeys, chickens or ducks, prior to slaughter. Large beef feedlots are called Concentrated Animal Feeding Operations . They...

     bison in North America not in contact with sheep have also been diagnosed with a form of BMCF. OHV-2 has been recently documented to infect herds of up to 5 km away from the nearest lambs, with the levels of infected animals proportional to the distance away from the closest herds of sheep.

The incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

 of BMCF is not known, however intranasal challenge with AHV-1 induced MCF in one hundred percent of challenged cattle between 2.5 and 6 weeks.

Symptoms

The most common form of the disease is the head and eye form. Typical symptoms of this form include fever, depression, discharge from the eyes and nose, lesions of the buccal cavity and muzzle, swelling of the lymph nodes
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...

, opacity
Opacity (optics)
Opacity is the measure of impenetrability to electromagnetic or other kinds of radiation, especially visible light. In radiative transfer, it describes the absorption and scattering of radiation in a medium, such as a plasma, dielectric, shielding material, glass, etc...

 of the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...

s leading to blindness, inappetance and diarrhea. Some animals have neurologic signs, such as ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

, nystagmus, and head pressing. Peracute, alimentary and cutaneous clinical disease patterns have also been described. Death usually occurs within ten days. The mortality rate in symptomatic animals is 90 to 100 percent. Treatment is supportive only.

Diagnosis

Diagnosis of BMCF depends on a combination of history and symptoms, histopathology and detection in the blood or tissues of viral antibodies by ELISA or of viral DNA by PCR. The similarity of MCF clinical signs to other enteric diseases, for example blue tongue, mucosal disease and foot and mouth make laboratory diagnosis of MCF important. The world organisation for animal health recognises histopathology as the definitive diagnostic test, but laboratories have adopted other approaches with recent developments in molecular virology. No vaccine has as yet been developed.

Vaccine

Unfortunately a vaccine for malignant catarrhal fever (MCF) has not yet been developed. Developing a vaccine has been difficult because the virus will not grow in cell culture and until recently it was not known why. Researchers at the Agricultural Research Service
Agricultural Research Service
The Agricultural Research Service is the principal in-house research agency of the United States Department of Agriculture . ARS is one of four agencies in USDA's Research, Education and Economics mission area...

 (ARS) found that the virus undergoes changes within the animal’s body, a process known as “cell tropism switching.” In cell tropism switching, the virus targets different cells at different points in its life cycle. This phenomenon explains why it has been impossible to grow the virus on any one particular cell culture.

Because the virus is transmitted from sheep to bison and cattle, researchers are first focusing on the viral life cycle in sheep. The viral life cycle is outlined in three stages: entry, maintenance, and shedding. Entry occurs through the sheep’s nasal cavity and enters into the lungs where it replicates. The virus undergoes a tropic change and infects lymphocytes, also known as white blood cells, which play a role in the sheep’s immune system. In the maintenance stage the virus remains on the sheep’s lymphocytes and circulates the body. Finally, during the shedding stage, the virus undergoes another change and shifts its target cells from lymphocytes to nasal cavity cells, where it is then shed through nasal secretions. http://www.ars.usda.gov/is/AR/archive/apr10/animal0410.htm This discovery undoubtedly puts scientists on the right track for developing a vaccine- starting with the correct cell culture for each stage of the virus lifecycle- but ARS researchers are also looking into alternative methods to develop a vaccine. Researchers are experimenting with the MCF virus that infects tofi (an African antelope) because it will grow in cell culture and does not infect cattle. Researchers hope that inserting genes from the sheep MCF virus into the tofi MCF virus will ultimately be an effective MCF vaccine for cattle and bison. While there is much ground left to cover, scientists are getting closer and closer to developing a vaccine.
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