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MALIGNANT CATARRHAL FEVER
Aetiology Epidemiology Diagnosis Prevention and Control References
AETIOLOGY
Classification of the causative agent
Virus family Herpesviridae, subfamily Gammaherpesvirinae, genus Macavirus. The MCF subgroup of
viruses, called MCFV, contains at least 10 members, five of which are currently known to cause disease.
Wildebeest-associated MCF: alcelaphine herpes virus 1 (AlHV-1). Endemic in wildebeest populations
worldwide.
Sheep-associated MCF: ovine herpesvirus 2 (OvHV-2). Endemic in most sheep populations worldwide.
Caprine-associated MCF: caprine herpesvirus 2 (CpHV-2): Endemic in most domesticated goat
populations worldwide, and causes MCF in cervids.
Unknown origin: causes MCF in white-tailed deer (MCFV-WTD).
Roan antelope origin: Hippotragine herpesvirus-1 was used to experimentally induce MCF in rabbits
Resistance to physical and chemical action
Temperature: No data available, but virus is very labile.
pH: Mostly stable between pH 5.5
–8.5
Disinfectants/chemicals: Inactivated by common disinfectants including sodium hypochlorite (3% solution
if heavy organic debris present)
Survival: Inactivated rapidly by sunlight. Cell-associated virus survives 72 hours outside the host; cell-free
virus is inactivated quickly in dry environments but may survive over 13 days in humid environments
EPIDEMIOLOGY
MCF is a generally fatal disease of cattle and many other species of Artiodactyla, which occurs following
infection with certain herpesviruses of the genus Macavirus. Five herpesviruses have been recognised as
causing MCF, the best characterised being AIHV-1 and OvHV-2. MCF usually appears sporadically and
affects few animals, though both AlHV-1 and OvHV-2 can give rise to epizootics. The disease has been
most often described as affecting species of the subfamily Bovinae and family Cervidae, but is also
recognised in domestic pigs, giraffe and species of antelope belonging to the subfamily Tragelaphinae.
Animals that develop MCF are usually dead end hosts.
AlHV-1:
Transmission in wildebeest occurs perinatally; all calves become infected within the first
few months of life and remain carriers for life
Transmission to susceptible hosts occurs only from wildebeest; there is no definitive
evidence that MCF-affected animals transmit the disease horizontally to others
Most cases of wildebeest-associated MCF occur when susceptible animals are exposed
to parturient wildebeest or young calves, or pasture contaminated by them.
OvHV-2:
A proportion of lambs are infected in utero with most lambs becoming infected
perinatally
Transmission is only from sheep to susceptible hosts, not horizontally between infected
hosts
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Hosts
Carrier species with inapparent infections include wildebeest, sheep, and goats
Clinical infections occur in members of the families Bovidae; Cervidae, and Giraffidae,
such as cattle, water buffalo, bison, deer, and other wild ruminants
Deer species affected: red deer, axis deer, fallow deer, Formosan sika deer, mule deer,
Père
David’s deer, Reeve’s muntjac, swamp deer, white-tailed deer
Other species affected: antelope, banteng, elk, reindeer, gaur, giraffe, greater kudu,
nilgai and wapiti
Domestic pigs in several countries have recently been confirmed as susceptible, and
signs are very similar to those seen in acutely affected cattle
Laboratory rabbits, Syrian hamsters, guinea-pigs and rats have been experimentally
infected
MCFV has been isolated from other exotic ruminants with unknown disease potential:
ibex, musk ox, gemsbok, aoudads, hartebeest and topi.
Transmission
AlHV-1
Transmission of AlHV-1 within free-living wildebeest populations is very efficient: all
wildebeest calves are infected within the first few months of life by in utero, direct contact
or aerosol routes. Contamination of pastures may also contribute to transmission, as
may fomites
Most transmission by wildebeest calves occurs at 1
–2 months of age – transmission
after six months of age is rare
Virus is shed by wildebeest calves in nasal and ocular secretions, mainly in the cell-free
form
Close contact is usually needed but transmission over one hundred metres has been
reported
Congenital transmission of AlHV-1 within infected domestic cows can occur with varying
disease latency periods in newborn calves
OvHV-2
Transmitted mainly by the respiratory route, probably in aerosols
Shed intermittently in nasal secretions, particularly by 6 to 9 month old lambs
A proportion of lambs are infected in utero with most lambs becoming infected
perinatally, though infection may not occur in some situations till after 3 months of age.
Close contact with sheep by susceptible species is usually required, but cases have
been reported when sheep and cattle were separated by 70 metres, and in bison herds
up to 5 km from a lamb feedlot
There is a wide spectrum of susceptibility: Bos taurus and Bos indicus cattle are
relatively resistant to OvHV-2 and cases are usually sporadic; most species of deer,
bison (Bison bison) and water buffalo (Bubalus bubalis) are much more susceptible; and
Bali cattle (Bos javanicus
) and Père David’s deer (Elaphurus davidianus) are extremely
susceptible.
Sources of virus
Nasal and ocular secretions mainly, but also reported in faeces and semen (OvHV-2
DNA detected in semen of domestic rams)
Occurrence
MCF viruses are found worldwide. AlHV-1- associated disease has been reported mainly in sub-Saharan
Africa where cattle and wildebeest comingle, but can cause disease in zoological parks wherever carriers
and susceptible species cohabitate. OvHV-2 - associated disease occurs throughout the world.
For more recent, detailed information on the occurrence of this disease worldwide, see the OIE
World Animal Health Information Database (WAHID) Interface
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[http://www.oie.int/wahis/public.php?page=home] or refer to the latest issues of the World Animal
Health and the OIE Bulletin.
DIAGNOSIS
Incubation period is variable, ranging from 11
–34 days or up to 9 months
Clinical diagnosis
The clinical signs of MCF are highly variable and range from peracute to chronic. In general, the most
obvious signs develop in the more protracted cases.
Peracute: either no clinical signs are detected, or depression followed by diarrhoea and
dysentery may develop 12
–24 hours prior to death
In general: high fever, increased serous lachrymation and nasal exudate progressing to
profuse mucopurulent discharge, inappetance, and decreased milk yields
Progressive bilateral corneal opacity, starting at the periphery, is characteristic.
Skin ulceration and necrosis may be extensive or restricted to the udder and teats
Salivation and oral hyperaemia may be an early sign, progressing to erosions of the
tongue, hard palate, gums and, characteristically, the tips of the buccal papillae
Superficial lymph nodes may be enlarged and limb joints may be swollen
Nervous signs such as hyperaesthesia, incoordination, nystagmus and head pressing
may occur alone or with signs described above
A few infected animals may recover following mild or even quite severe clinical reactions
Lesions
Gross pathological changes reflect the severity of clinical signs, but are generally widespread and may
involve most organ systems.
Erosions and haemorrhages in gastrointestinal tract: contents may be haemorrhagic
Enlarged lymph nodes, but degree varies within an animal
Catarrhal exudate, erosions and diphtheritic membranes often observed in the
respiratory tract
Urinary bladder often has characteristic ecchymotic haemorrhages of the epithelial lining,
especially in bison
Interstitial accumulation of lymphoid cells in nonlymphoid organs, in particular the renal
cortex and periportal areas of the liver, is typical, and in the case of the kidney may be
very extensive with development of multiple raised white foci, each 1-5 mm in diameter
In the absence of molecular diagnosis, histologic changes are often relied on for
diagnosis of MCF and are characteristic: epithelial degeneration, vasculitis, hyperplasia
and necrosis of lymphoid organs, and widespread interstitial accumulations of lymphoid
cells in nonlymphoid organs.
The brain may also show a nonsuppurative meningoencephalitis with lymphocytic
perivascular cuffing and a marked increase in the cellularity of the cerebrospinal fluid
Differential diagnosis
Rinderpest
Bovine viral diarrhoea mucosal disease
Infectious bovine rhinotracheitis
Bluetongue
Epizootic haemorrhagic disease
Foot and mouth disease
Vesicular stomatitis
Ingestion of caustic materials or some toxic plants
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Laboratory diagnosis
AIHV-1 may be recovered from clinically affected animals using peripheral blood leukocytes or lymphoid
cell suspensions. Virus can also be recovered from wildebeest, either from peripheral blood leukocytes or
from cell suspensions of other organs.
OvHV-2 has never been identified formally, although lymphoblastoid cell lines propagated from affected
animals contain OvHV-2-specific DNA and virus particles have been observed in these cells.
Both AlHV-1 and OvHV-2 have been transmitted experimentally to cattle, rabbits and hamsters, which
develop lesions characteristic of MCF.
Viral DNA has been detected in clinical material from cases of MCF caused by both AIHV-1 and OvHV-2
using the polymerase chain reaction. PCR is becoming the method of choice for diagnosing both forms of
the disease.
Samples
Virus isolation and viral detection
Refrigerate but do not freeze tissues.
AlHV-1 is inactivated quickly in dead animals
– the most useful samples are collected
immediately after euthanasia or death.
Tissues for virus isolation: anticoagulated blood- 10
–20 ml in EDTA, spleen, lung, lymph nodes,
and adrenal glands
Tissues for PCR: anticoagulated blood, kidney, lymph nodes, intestinal wall, brain and other
tissues from above. PCR is also possible from fixed tissues with appropriate DNA extraction
protocols
Serological tests
Paired serum samples (5 ml) taken 3
–4 weeks apart
Histopathology
Cattle: lung, liver, lymph nodes, skin (if lesions are present), kidney, adrenal gland, eye, oral
epithelium, oesophagus, Peyer’s patches, urinary bladder, thyroid, heart muscle, carotid rete
and brain
Bison: urogenital and intestinal tract tissue are particularly important
Other species: wide range of tissues
Procedures
Identification of the agent
Virus isolation from peripheral blood leukocytes (AlHV-1) or lymphoid cells.
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Most monolayer cultures of ruminant origin are probably susceptible and develop
cytopathic effect (CPE). Bovine thyroid or turbinate cell cultures have been used
extensively.
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Primary isolates typically produce multinucleated CPE in which viral antigen can be
identified by immunofluorescence or immunocytochemistry.
PCR (AlHV-1 and OvHV-2)
Serological tests
AlHV-1
Infected wildebeest develop antibody to AIHV-1, which can be detected in the four assays below.
However, the antibody response of clinically affected animals is limited, with no neutralising antibody
developing, so that detection relies on the use of immunofluorescence, ELISA or immunoblotting.
Virus neutralisation
Immunoblotting
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Enzyme-linked immunosorbent assay (ELISA)
Immunofluorescence
OvHV-2
Antibody to OvHV-2 can be detected by using AIHV-1 as the source of antigen. Domestic sheep
consistently have antibody that can be detected by immunofluorescence, ELISA or immunoblotting,
although antibody is not always present in more acutely affected animals such as deer.
Immunofluorescence
ELISA
Immunoblotting
For more detailed information regarding laboratory diagnostic methodologies, please refer to
Chapter 2.4.15 Malignant catarrhal fever in the latest edition of the OIE Manual of Diagnostic Tests
and Vaccines for Terrestrial Animals under the heading
“Diagnostic Techniques”.
PREVENTION AND CONTROL
Sanitary prophylaxis
Prevent contact between carriers and clinically susceptible species
Separate susceptible animals from sheep, goats, wildebeest or other suspected
reservoir hosts. Wildebeest appear to transmit AlHV-1 readily, and should always be
separated from cattle.
Cattle should not graze pastures where wildebeest have grazed and given birth
Wildebeest should also be segregated in zoos.
Cattle rarely develop the sheep-associated form of MCF, but separation from sheep
would be advisable, particularly from lambs actively shedding virus. Co-housing of sheep
and cattle should be avoided
Bison, some deer and other highly susceptible species should not be allowed near
sheep. Separation by longer distances is particularly important when the host is highly
susceptible and the concentration of virus is high (e.g. bison and lambs in feedlots).
Access to contaminated fomites must be avoided, especially when the species is highly
susceptible.
OvHV-2 free sheep can be produced by early weaning and isolation
During outbreaks, susceptible animals should be separated immediately from the
suspected source. Cattle and other incidental hosts are thought to be dead end hosts,
and do not need to be culled. Because the incubation period can be very long, cases
can continue to occur for months. Stress reduction can help prevent disease in
subclinically or mildly affected animals
Medical prophylaxis
Commercial vaccines are not available for any MCF virus.
For more detailed information regarding safe international trade in terrestrial animals and their
products, please refer to the latest edition of the OIE Terrestrial Animal Health Code.
REFERENCES AND OTHER INFORMATION
Brown C. & Torres A., Eds. (2008). - USAHA Foreign Animal Diseases, Seventh Edition.
Committee of Foreign and Emerging Diseases of the US Animal Health Association. Boca
Publications Group, Inc.
Coetzer J.A.W. & Tustin R.C. Eds. (2004). - Infectious Diseases of Livestock, 2nd Edition. Oxford
University Press.
Fauquet C., Fauquet, M. & Mayo M.A. (2005). - Virus Taxonomy: VIII Report of the International
Committee on Taxonomy of Viruses. Academic Press.
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Kahn C.M., Ed. (2005). - Merck Veterinary Manual. Merck & Co. Inc. and Merial Ltd.
Spickler A.R. & Roth J.A. Iowa State University, College of Veterinary Medicine -
http://www.cfsph.iastate.edu/DiseaseInfo/factsheets.htm
World Organisation for Animal Health (2012). - Terrestrial Animal Health Code. OIE, Paris.
World Organisation for Animal Health (2012). - Manual of Diagnostic Tests and Vaccines for
Terrestrial Animals. OIE, Paris.
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The OIE will periodically update the OIE Technical Disease Cards. Please send relevant new
references and proposed modifications to the OIE Scientific and Technical Department
(scientific.dept@oie.int). Last updated June 2013.