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 (banteng), 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 is seen sporadically and affects single animals. MCF is typically fatal; however, there are outbreaks in which several animals are affected, with evidence of recovery and mild or inapparent infections in some cases. It 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 has emerged as a severe threat to the commercial bison industry.
MCF results from infection by one of several members of a group of closely related ruminant gammaherpesviruses of the Rhadinovirus genus. While the MCF group of ruminant rhadinoviruses currently comprises about 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 has caused 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 at 1–2 mo of age by aerosol transmission from other individuals within the flock and begin to actively shed virus at ∼6 mo of age. Shedding decreases at ∼10 mo, with adults shedding at a much lower rate than adolescents. Wildebeest calves, in contrast, are infected in the perinatal period by horizontal and occasional intrauterine transmission, and actively shed virus until 3–4 mo of age. Transmission is by transfer of virus-laden nasal secretions by direct contact or poorly defined airborne routes. In Africa, most wildebeest-associated MCF is seen around the time of calving; however, sheep-associated MCF (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 the 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 numbers, population density, and species of susceptible hosts involved; the closeness of contact; and the amount of shed virus available for transmission. Cases usually are seen sporadically in European breeds of cattle (Bos taurus), as they are a relatively resistant species. By contrast, Bali cattle, bison, and some but not all cervid species (eg, white-tailed deer, Pere David's deer) are highly susceptible. 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. About 800 head died in one outbreak in the USA in 2003.
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.
Acute MCF cases caused by ovine herpesvirus-2 and alcelaphine herpesvirus-1 are similar clinically and pathologically. Disease course may range from peracute to chronic. Cases in deer 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 (106°–107°F [41–41.5°C]) and depression are common. Other signs that may be present 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, convulsions). 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. Variation in organ system involvement sometimes can be seen 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, swollen lymph nodes and severe eye lesions (panophthalmitis, hypopyon, corneal erosions) are more frequent, and hemorrhagic enteritis and cystitis less frequent, than in deer and bison. Skin lesions (erythema, exudation, cracking, crust formation) are common in animals that do not succumb quickly. Hematologic changes are variable. Up to 25% of cattle experience chronic disease, and sometimes the disease waxes and wanes. Mortality rates in clinically affected animals generally approach 95%. However, in limited circumstances, survival in cattle can be higher.
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 signs. Whether this strain of virus causes disease in species other than deer is not known.
The disease is systemic, and lesions may be found in any organ, although severity and frequency varies 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 classic but not pathognomonic histologic lesion is fibrinoid necrosis of small muscular arteries, but 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 kidney.
Diagnosis of MCF is based on clinical signs, gross and histologic lesions, and laboratory confirmation. Primary differential diagnoses include bovine viral diarrhea/mucosal disease, rinderpest, infectious bovine rhinotracheitis, and East Coast fever (theileriosis). When CNS involvement is prominent, MCF can resemble rabies and the tickborne encephalitides. A history of contact with a carrier species (sheep, goats, or wildebeest) can be helpful, although recrudescent cases can be seen 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 to detect viral DNA. Preferred tissues for testing are anticoagulated blood, kidney, intestinal wall, lymph node, and brain.
Serology is used for surveying normal 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, immunofluorescence, and ELISA. The polyclonal assays are hampered by cross-reactivity. The monoclonal-based competitive ELISA is currently the most specific and detects antibody against all of the known MCF group viruses. Only PCR can discriminate between the different viruses.
Treatment and Control
The prognosis is grave. No treatment has been found to provide any consistent benefit. Stress reduction of subclinical or mildly affected animals is indicated. No vaccine 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.
Last full review/revision March 2012 by Robert J. Callan, DVM, MS, PhD, DACVIM