Malignant catarrhal fever (MCF) is an infectious systemic disease that presents as a variable complex of lesions affecting mainly ruminants and, rarely, swine. It is principally a disease of domestic cattle, water buffalo, Bali cattle (bantengs), American bison, and deer. In addition to these farmed animals, MCF has been described in a variety of captive ruminants in mixed zoologic collections. In some species, such as bison and some deer, MCF is acute and highly lethal, capable of affecting large numbers of animals. With occasional exceptions, the disease in cattle normally occurs sporadically and affects single animals.
MCF is typically fatal; in some outbreaks, however, several animals can be affected, with evidence of recovery and mild or inapparent infections in some cases. MCF also occasionally presents as chronic alopecia and weight loss. Its distribution is essentially worldwide, mirroring that of the principal carriers domestic sheep and wildebeest. MCF has long been a major problem in farmed deer operations, and in recent years it has emerged as a severe threat to the commercial bison industry.
Etiology of Malignant Catarrhal Fever in Animals
Malignant catarrhal fever results from infection by one of several members of a group of closely related ruminant gammaherpesviruses of the Macavirus genus. Although the MCF group of ruminant rhadinoviruses currently comprises ~10 known members, only a few are known to be pathogenic under natural conditions. The principal carriers and their viruses are sheep (ovine herpesvirus-2), wildebeest (alcelaphine herpesvirus-1), and goats (caprine herpesvirus-2). Another strain, of unidentified origin, causes MCF in white-tailed deer. Virtually all clinical cases are caused by the sheep or wildebeest viruses.
The viruses are maintained within the sheep and wildebeest populations in similar but not identical patterns. Lambs are infected usually when 3–6 months old by aerosol transmission from other individuals within the flock and begin to actively shed virus when ~6–9 months old. Shedding decreases at an age of ~10 months, with adults shedding at a much lower rate than adolescents. Wildebeest calves, in contrast, are infected in the perinatal period by horizontal and, occasionally, intrauterine transmission, and they actively shed virus until the age of 4–6 months.
Transmission is by transfer of virus-laden nasal secretions by direct contact or poorly defined airborne routes. Transmission from sheep to cattle has been demonstrated at distances of at least 70 m in cattle and up to 5.1 km in bison. In Africa, most wildebeest-associated MCF occurs around the time of wildebeest calving; however, sheep-associated malignant catarrhal fever (SA-MCF) does not follow the same pattern. Ewes do not shed virus in placental tissues or secretions and do not experience more frequent shedding episodes around lambing time. The only rational and established factors contributing to seasonality of SA-MCF are climatic influences on virus survival and age-related shedding patterns in lambs. The epidemiology of the caprine MCF virus appears similar to that of sheep.
The severity of SA-MCF outbreaks depends on factors such as the total number, population density, and species of susceptible hosts involved; the closeness of contact; and the amount of shed virus available for transmission. Cases usually occur sporadically in European breeds of cattle (Bos taurus), because they are a relatively resistant species. By contrast, Bali cattle, bison, and some cervid species (eg, white-tailed deer, Père David’s deer) are highly susceptible. An infectious dose of virus is a primary determinant of infection and clinical disease, with bison being >1,000 times more susceptible to infection than cattle are. As agricultural systems involving bison and deer production have developed, MCF has become more troublesome. It is a leading cause of infectious disease losses on New Zealand deer farms. In bison exposed to large numbers of adolescent sheep, losses can be devastating. Approximately 800 head died in one outbreak in the US in 2003. The incubation period is variable, ranging from 14 to >200 days after initial exposure.
Among animals that survive, infection is lifelong. Some susceptible species, including cattle and bison, may be latently infected. Recrudescence of latent infections is possible and must be considered for cases with no known history of contact with carriers.
MCF is transmitted only between carriers and clinically susceptible animals. Affected animals do not transmit MCF to their cohorts.
Clinical Findings of Malignant Catarrhal Fever in Animals
Acute cases of malignant catarrhal fever caused by ovine herpesvirus-2 and alcelaphine herpesvirus-1 are similar clinically and pathologically. Disease course may range from peracute to chronic, and severe vasculitis results in most observed clinical cases. Cases in deer and bison are often peracute, with sudden death. Deer that survive for a few days and bison usually develop hemorrhagic diarrhea, bloody urine, and corneal opacity before expiring. High fever (41°C–41.5°C [106°F–107°F]) and depression are common. Other possible clinical signs include catarrhal inflammation; erosions and mucopurulent exudation affecting the upper respiratory, ocular, and oral mucosa; swollen lymph nodes; lameness; and CNS signs (depression, trembling, hyporesponsiveness, stupor, aggressiveness, seizures).
Historically, MCF has been described as having several “forms”—mild, peracute, head and eye, intestinal, etc. There is little basis for this division and it is of little utility. Organ system involvement sometimes varies in the same outbreak and is at least partially related to survival time after disease onset. On average, the time to death in European cattle breeds is somewhat longer than in deer, bison, water buffalo, and Bali cattle. In cattle, lymphadenopathy and severe eye lesions (panophthalmitis, hypopyon, corneal opacity) are more frequent, and hemorrhagic enteritis and cystitis less frequent, than in deer and bison. Peripheral (centripetal) corneal opacity is an important clinical sign suggestive of MCF in cattle. Skin lesions (erythema, exudation, cracking, crust formation) are common in animals that do not succumb quickly. Hematologic changes vary, and an inflammatory leukogram may not be present, even in febrile animals with severe lesions.
Although the mortality rate in clinically affected animals is very high, some cattle experience chronic disease, and sometimes the disease waxes and wanes. Survivors only rarely are able to return to previous levels of production.
In a few outbreaks, the goat MCF virus (caprine herpesvirus-2) induced disease in white-tailed and sika deer. These cases were subacute to chronic, with weight loss, dermal inflammation, and alopecia as the primary clinical signs. Whether this strain of virus causes disease in species other than deer is not known.
MCF is systemic, and lesions may be found in any organ, although the severity and frequency vary greatly. The principal lesions are inflammation and necrosis of respiratory, alimentary, or urinary mucosal epithelium; subepithelial lymphoid infiltration; generalized lymphoid proliferation and necrosis; and widespread vasculitis. Mucosal ulcerations and hemorrhage are common. Hemorrhages may be present in many parenchymatous organs, particularly lymph nodes. A typical but not pathognomonic histologic lesion is fibrinoid necrosis of small muscular arteries; however, vessels of all types may be inflamed, including those in the brain. Prominent white nodules representing intramural and perivascular proliferation may be apparent, particularly in the kidneys.
Diagnosis of Malignant Catarrhal Fever in Animals
Diagnosis of malignant catarrhal fever is based on clinical signs, gross and histologic lesions, and laboratory confirmation. Primary differential diagnoses include:
bovine herpesvirus Bovine Ulcerative Mammillitis (Bovine Herpesvirus II and IV) Bovine herpesvirus (BHV) II and IV can cause an acute, ulcerative condition of teat and udder skin of dairy cows that is often referred to as bovine ulcerative mammillitis or simply herpes mammillitis... read more (infectious bovine rhinotracheitis)
When CNS involvement is prominent, MCF can resemble rabies Rabies Rabies is an acute, progressive encephalomyelitis caused by lyssaviruses. It occurs worldwide in mammals, with dogs, bats, and wild carnivores the principle reservoirs. Typical signs include... read more and the tickborne encephalitides Meningitis, Encephalitis, and Encephalomyelitis in Animals Meningitis, encephalitis, and encephalomyelitis are terms used to describe inflammatory conditions of the meninges, brain, or brain and spinal cord, respectively. These inflammatory processes... read more . A history of contact with a carrier species (sheep, goats, or wildebeest) can be helpful, although recrudescent cases can occur without such a history.
Reliable and specific laboratory assays for antibody and for viral DNA are available. The test of choice for clinical diagnosis is PCR assay to detect viral DNA. Preferred tissues for testing are anticoagulated blood, kidney, intestinal wall, lymph node, and brain. Intralesional ovine herpesvirus-2 antigens can be identified using immunohistochemistry.
Serology is used to survey healthy animals and is indicative only of infection; latent infection among susceptible animals may render serology alone inconclusive evidence of current disease. Several seroassays are available, including viral neutralization, immunoperoxidase technique, immunofluorescence, and ELISA. The polyclonal assays are hampered by cross-reactivity. The monoclonal-based competitive ELISA is currently the most specific technique and detects antibody against all of the known MCF group viruses. Only PCR assay can discriminate the different viruses.
Treatment and Control of Malignant Catarrhal Fever in Animals
Early weaning and isolation
Separation of carriers from susceptible species
The prognosis of malignant catarrhal fever is grave. No treatment has been found to provide any consistent benefit. Stress reduction of subclinical or mildly affected animals is indicated.
No commercial vaccine against MCF is currently available. Sheep can be produced that are free of virus by early weaning and isolation. The only other effective control strategy is separation of carriers from susceptible species. When large numbers of potent shedders are present, such as in lamb feedlots, distances >1 km may be necessary to protect highly susceptible species such as bison.
Malignant catarrhal fever is a severe disease, common in ruminants, that is caused by gammaherpesviruses.
Case fatality is high, and treatment is usually unrewarding.
Separation of carrier animals from susceptible ruminants is the mainstay of prevention.