Definition
Malignant catarrhal fever (MCF) is a generalized viral disease of
domestic cattle and buffaloes and many species of wild ruminants characterized by high
fever, profuse nasal discharge, corneal opacity, ophthalmia, generalized lymphadenopathy,
leukopenia, and severe inflammation of the conjunctival, oral, and nasal mucosas with
necrosis in the oral and nasal cavities sometimes extending into the esophagus and
trachea. Occasionally central nervous system (CNS) signs, diarrhea, skin lesions, and
nonsuppurative arthritis are observed.
Etiology
The etiologic agent of MCF in Africa is a highly cell-associated
lymphotropic herpesvirus of the subfamily Gamma herpesvirinae. Two viral strains
have recently been designated: alcelaphine herpesvirus-1 (AHV-1) and alcelaphine
herpesvirus-2 (AHV-2), although some continue to designate this agent as bovid
herpesvirus-3. This agent is carried as a latent infection by African antelope of the
family Bovidae, subfamily Alcelaphinae which includes wildebeest (Connochaetes sp.),
hartebeest (Alcelaphus sp.), and topi (Damaliscus sp.). The wildebeest
herpesvirus of MCF (AHV-1) was first isolated by Plowright from a blue wildebeest (Connochaetes
taurinus taurinus) in 1960.
Epidemiologic evidence suggests that domestic and wild sheep and
goats may be additional major reservoirs of a virus causing MCF. Serologic evidence also
suggests this virus may be related but not identical to the alcelaphine herpesvirus-l.
Sheep-associated MCF herpesviruses were isolated from domestic
cattle in Minnesota in 1977 and from domestic cattle in Austria in 1990. On the basis of
morphology and molecular DNA mapping, both isolates appear similar to AHV-1.
Viruses identical or closely related to AHV-1 and AHV-2 have been
isolated from several captive wild ruminant species in two U.S. zoos located in Oklahoma
City and San Diego. Animals infected with AHV-1 were white-tailed gnu, white-bearded gnu,
gaur, greater kudu, Formosan sika deer, axis deer, and nilgai. The AHV-2 was isolated from
a topi and a hartebeest at the San Diego Wild Animal Park.
The agent of MCF on deer farms in Scotland and New Zealand has not
yet been demonstrated by electron microscopy or isolation of cell-free virus in a cell
culture system. However, it has been passaged in lymphocyte cultures, rabbits, and deer.
Host Range
All species of wildebeest, hartebeest, and topi are considered
carriers of alcelaphine MCF virus. There is serologic evidence that several other African
wild ruminants, such as various species of oryx and addax, may also be reservoir hosts,
although MCF virus has not been isolated from these species.
Domestic and wild sheep and goats are also considered reservoir
hosts for MCF virus.
Many exotic ruminant species in zoos have been reported affected
with MCF, including several wild bovines such as bison, water buffalo, gaur and banteng,
and several deer (including white-tailed deer) and antelope species. Interestingly, no
cases of MCF have been reported from antelope species that normally cohabitate wildebeest
grazing areas in Africa.
In cattle and susceptible wild ruminants, MCF affects all ages,
breeds, and sexes.
Geographic Distribution
Sheep-associated MCF occurs worldwide. The alcelaphine
antelope-associated form in cattle occurs chiefly in Africa in the natural habitat of
wildebeest, hartebeest, and topi. This form of MCF has, however, occurred in zoos and wild
animal parks that also kept wildebeest. The increasing popularity in North America and
other areas of the world of wild game animal ranches, often in association with domestic
cattle raising, increases the possibility that MCF will become a more prevalent disease in
cattle and ranched exotic ruminants. There is increasing serologic evidence that cattle
may develop low levels of neutralizing antibodies following exposure to MCF, especially of
sheep or goat origin, without manifesting clinical disease. There is evidence that stress
or some other immunosuppressive effector may be necessary as a precursor of clinical
sheep-associated MCF.
Transmission
The MCF virus in wildebeest, hartebeest, and topi is largely
cell-associated in adult animals and hence rarely transmissible. However, neonatal
wildebeests have been found to shed cell-free MCF virus in nasal and ocular secretions and
in feces. Cell-free MCFV has also been demonstrated in nasal secretions of captive adult
wildebeests after stress or administration of corticosteroids. Transmission to cattle or
other susceptible species may occur by inhalation of cell-free virus in infectious aerosol
droplets, ingestion of feed or water contaminated with infectious secretions or feces, or
possibly mechanically by arthropods. Masai herdsmen believed cattle acquire MCF by contact
with wildebeest placentas or birth hair of neonates. Recent studies have failed to
demonstrate infective MCFV in fetal fluids or placentas of wildebeest probably owing to
the rapid inactivation of virus by sunlight. The mode of transmission of sheep-associated
MCF remains unknown, although relatively close contact between cattle and sheep,
especially lambing ewes, is believed necessary. MCF-affected cattle appear to shed only
cell-associated virus, and thus cattle-to-cattle transmission is thought to be rare or
nonexistent, although there are documented instances where this has occurred.
Incubation Period
The incubation period in natural cases is not known, but
epidemiologic evidence indicates it may be as long as 200 days. Experimentally, the
incubation period has varied from 9 to 77 days.
Clinical Signs
Clinical MCF in cattle has arbitrarily been divided into four
forms as follows:
1. Peracute form: Fever, severe inflammation of the oral and nasal
mucosas and hemorrhagic gastroenteritis with a course of 1 to 3 days.
2. Intestinal form: Fever, diarrhea, hyperemia of oral and nasal
mucosas with accompanying discharges, and lymphadenopathy with a course of 4 to 9 days (Fig. 75).
3. Head and eye form: This is the typical syndrome of MCF with
fever, nasal, and ocular discharges progressing from serous (Fig. 76) to mucopurulent and purulent. Encrustation of the muzzle
and nares occurs in later stages, causing obstruction to the nostrils and dyspnea,
open-mouthed breathing, and drooling (Fig. 77).
There is intense hyperemia and multifocal or diffuse necrosis of the oral mucosa (usually
on the lips, gums, and hard and soft palate) and buccal mucosa. Erosion of the tips of
buccal papillae, leaving them reddened and blunted, is often encountered (Fig. 78).
Ocular signs referable to ophthalmia include lacrimation
progressing to purulent exudation, photophobia, hyperemia, and edema of the palpebral
conjunctiva and injection of scleral vessels. Corneal opacity, starting peripherally and
progressing centripetally, results in partial to complete blindness (Fig. 79). Hypopyon may also be seen. Corneal opacity is usually
bilateral but occasionally is unilateral. Fever is common and usually high (104-107° F
[40-41.6° C ]) until the animal becomes moribund, at which time it is hypothermic.
Clinical features at early onset have included reddening of the skin of the udder, the
coronary bands and interdigital spaces, and marked hyperemia of the oral cavity. Increased
thirst accompanies the fever, and anorexia is seen in late stages. Constipation is common
in this form of MCF, but terminal diarrhea is sometimes observed.
Nervous signs are not frequently seen but may be manifested by
trembling or shivering, uncoordinated gait, and terminal nystagmus.
Necrotic skin lesions occasionally are seen, and horn and hoof
coverings may be loosened or sloughed in some cases. The course of the head and eye form,
which is invariably fatal, is usually 7 to 18 days.
4. Mild forms: These are syndromes caused by experimental
infection of cattle with attenuated viruses and are usually nonfatal.
There is considerable variation and overlap among these artificial
categories, and their use has little value.
Although the manifestations of the "head and eye" form
of MCF are considered the typical syndrome in cattle, clinical signs in exotic ruminants
are often less dramatic and not usually specifically diagnostic, except in members of the
subfamily Bovinae (i.e., wild cattle). In deer and antelope species MCF tends to be
more subtle clinically and usually is manifested by conjunctivitis, photophobia, moderate
corneal clouding (often unilateral), fever, depression, variable lymphadenopathy,
occasionally diarrhea, and usually a mild serous nasal discharge. Death may be sudden
following a brief course of hemorrhagic diarrhea. Inflammation of the oral and nasal
cavity is usually less severe than in cattle and only occasionally progresses to mucosal
erosions.
There is some suggestion from studying cases of MCF among exotic
ruminants of a host-dependent modification with respect to the clinical and pathologic
manifestations of MCF virus infection.
Gross Lesions
Gross lesions vary considerably, depending on the form or severity
and course of the disease. Animals that die of the peracute disease may have few lesions
other than a hemorrhagic enterocolitis.
In the more protracted acute to subacute disease (intestinal and
head and eye forms), the carcass may be normal, dehydrated, or emaciated. The muzzle is
often encrusted and raw. Cutaneous lesions sometimes occur as a generalized exanthema with
exudation of lymph causing crusting and matting of the hair. Where skin is unpigmented,
hyperemia is apparent. These lesions are frequently seen in the ventral thorax and
abdomen, inguinal region, perineum and loins, and sometimes on the head.
Enlarged lymph nodes are characteristic findings in MCF. All nodes
may be involved, but those in the head and neck and periphery are the most consistently
prominent (Fig. 75). Affected nodes
are grossly enlarged and edematous and sometimes have patchy reddened or beige-brown areas
on cut surfaces. Hemolymph nodes are also enlarged and prominent. The spleen is slightly
enlarged, and Malpighian corpuscles are prominent. Pale areas may be seen in the heart
muscle.
Lesions in the respiratory system range from mild to severe. When
the clinical course is short, there is slight serous nasal discharge and hyperemia of the
nasal mucosa. Later the discharge becomes more copious and mucopurulent to purulent and is
accompanied by intense nasal mucosal hyperemia, edema, and small focal erosions.
Occasionally a croupous pseudomembrane formation is seen. Lesions
in the nasal passages and turbinates may extend to the frontal sinuses. The pharyngeal and
laryngeal mucosas are hyperemic and edematous and later develop multiple erosions, often
covered with gray-yellow pseudomembranes (Fig. 80). Inflammation and sometimes petechiation and ulceration
are seen in the tracheobronchial mucosa. The lungs are often edematous and sometimes
emphysematous but in some cases may appear normal. A bronchopneumonia may complicate
chronic cases.
The alimentary tract mucosa may have no gross lesion in peracute
cases. When the course is longer, alimentary lesions are commensurately more severe and
include mild to severe mucosal inflammation (hyperemia and edema), erosions, and
ulcerations— especially on the dental pad and gingival surfaces, the palate (Fig. 81), tongue, and buccal papillae.
Mucosal inflammation, hemorrhage, and erosions may also be found in the rest of the
digestive tract including the esophagus, rumen, omasum, abomasum, small intestines, colon,
and rectum. Petechiation may be seen. Feces are usually scant, dry, pasty, or blood
stained.
Urinary tract lesions include hyperemia and sometimes marked
distention and prominence of bladder mucosal vessels and mucosal edema, perhaps with
petechial to severe hemorrhage and occasionally epithelial erosion and ulceration. Kidneys
may appear normal or mottled with patches of beige, discolored raised areas. Petechiae or
ecchymoses may occur in the renal pelvis and ureters.
The liver is usually slightly enlarged, and, upon close
examination, has a prominent reticular pattern. There may be hemorrhages and erosions in
the gallbladder mucosa.
In most cases, small arterioles are very prominent and tortuous
and have thickened walls. This is usually seen in subcutaneous vessels and those in the
thorax, abdomen, and CNS.
Fibrinous polyarthritis is seen in many cases of MCF.
Morbidity and Mortality
Clinical MCF in cattle in the United States is usually sporadic.
However, in an outbreak in a Colorado feedlot, morbidity was 37 percent. Morbidity in
nonalcelaphine MCF outbreaks in Malaysia ranged from 28 percent to 45 percent. The
prognosis in MCF is poor. Once clinical signs are observed, mortality is usually greater
than 95 percent (90-100 percent). In some parts of New Zealand, MCF is, along with
tuberculosis, the most important cause of mortality in the deer-farming industry.
Diagnosis
Field Diagnosis
A history indicating contact with sheep, goats, or alcelaphine
antelope, especially around the period of parturition, associated with typical clinical
features of MCF, provides grounds for a tentative diagnosis of MCF.
Gross necropsy lesions consisting of corneal opacity; enlarged
lymph nodes; inflammation and erosions in nasal passages, alimentary tract mucosa, and
urinary bladder; and prominent tortuous small arteries in the subcutaneous tissue, thorax,
and abdomen, provide further evidence for a presumptive diagnosis of MCF.
Specimens for Laboratory
1. For animal transmission and inoculation at least 300 to 500 ml
blood in EDTA (1 mg/ml blood), heparin, or ACD solution should be collected and carried or
shipped iced, not frozen. For virus isolation in cell culture, 10 to 20 ml of blood in
EDTA is preferred. This should also be shipped cold but not frozen.
2. Tissues for virus isolation, FA, or immunoperoxidase
examination should also be refrigerated (iced) but NOT FROZEN and should include pieces of
spleen, lung, lymph nodes, adrenals, and thyroids as well as unclotted blood. These should
be collected as soon after death as possible, for the virus becomes inactivated rapidly in
an animal dead more than 1 hour. The most useful specimens for animal inoculation or virus
isolation attempts are those collected from a moribund animal immediately after
euthanasia.
3. Tissues for histopathology, fixed as thin pieces in 10 percent
neutral buffered formalin, should include lung, kidney, liver, adrenals, lymph nodes,
eyes, oral epithelium, esophagus, Peyer's patches, urinary bladder, carotid rete, thyroid,
heart muscle, skin (if lesions are present), and whole brain.
4. Serum for serology should consist of paired samples taken 3 to
4 weeks apart (i.e., the first during the acute phase of disease and the second during
convalescence or at death). Serologic methods currently preferred include virus
neutralization and
competitive inhibition enzyme-linked immuosorbent assay for MCF
antibody.
Laboratory Diagnosis
Microscopic lesions of an extensive fibrinoid necrotizing
vasculitis, perivasculitis, and lymphoreticular proliferation in lymphoid organs with
mononuclear infiltrations in kidney, liver, adrenals, CNS, etc., are pathognomonic for MCF
and are a sound, practical basis for a confirmed diagnosis.
Virologic and serologic examinations provide additional
information that may also ultimately lead to a better understanding of the epizootiology
and differences between viral strains and the clinical manifestations. Methods used
consist of virus isolation, identification of viral isolates, demonstration of the
appearance, or rising titers of MCF antibodies and molecular techniques using viral DNA
probes, or target DNA amplifying methods such as the polymerase chain reaction (PCR).
Because of the presence of MCF antibodies in asymptomatic U.S. cattle, a single antibody
positive serologic sample is of limited value in establishing an etiologic diagnosis. The
PCR method for demonstrating MCF DNA segments is proving to be useful for identifying MCF
carriers as well as diagnosing overtly diseased animals.
Differential Diagnosis
Clinical MCF must be distinguished from other diseases and factors
that produce inflammation and erosions and ulcerations of the nasal and alimentary tract
mucosas such as BVD mucosal disease, bluetongue, rinderpest, vesicular diseases (FMD, VS),
ingested caustics, and some poisonous plants and mycotoxins. The inability to
differentiate the alcelaphine clearly from the sheep-associated MCF by clinical
observations, lesions, or laboratory means presents an enigma in evaluating the
possibility of a foreign animal disease. With our current knowledge, history of
association with sheep, goats, or with alcelaphine antelope remains the only practical
means of differentiating one form from the other.
Vaccination
Cattle and experimentally infected rabbits recovered from MCF have
a solid immunity against all strains of MCF virus.
An effective vaccine is not available for MCF. Some viral strains
have undergone limited attenuation after serial passage in cell cultures and offer hope
for a future modified live virus vaccine. Experimental killed virus vaccines have been
inconsistent in inducing protection against virulent virus challenge, although some have
induced significant titers of serum virus neutralizing antibodies
Control and Eradication
Cattle should be kept separated from potential reservoir hosts
such as sheep, goats, and wildebeest — especially during lambing, kidding, or calving
seasons, respectively.
The stocking of cattle ranches with alcelaphine antelope, wild
sheep, or goats should be discouraged or should require a negative MCF serologic test,
preferably by the serum-virus neutralization method, or a negative PCR test for any wild
ruminants destined for such a facility. Similar testing of such wild ruminants before
being placed in, or transferred between, zoos is also recommended as a means to prevent
the introduction of potential carriers of MCF virus.
Containment of an outbreak usually means the immediate separation
of cattle or the susceptible host from sheep and goats in the case of the domestic disease
and the susceptible host from alcelaphine or wild ruminants in the case of alcelaphine
MCF.
Public Health
There is no evidence that MCF is infectious for humans.
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Werner P. Heuschele, D.V.M., Ph.D., Center for Reproduction of
Endangered Species (CRES) Zoological Society of San Diego (San Diego Zoo), San Diego, CA
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