Transmission of a malignant catarrhal fever-like syndrome to sheep: preliminary experiments

The transmission of a malignant catarrhal fever-like syndrome to sheep is reported. Fetal sheep between 40 and 66 days gestation were inoculated intravenously with viable cells either from a red deer with clinical malignant catarrhal fever or from rabbits with the disease. Of the 21 fetuses in the experiment only five were born live and of these four developed clinical signs similar to malignant catarrhal fever in other species and died or were killed 10, 16, 47 and 175 days after birth. The fifth lamb remained unaffected. Histology of the four affected lambs revealed a generalised lymphoproliferation, with T-dependent areas of lymphoid tissues being affected, and an overall paucity of immunoglobulin containing cells. In addition arteritis and interstitial infiltration of many organs by lymphoid cells was present. The infectious agent was not reisolated in rabbits from lambs or passed to red deer housed in the same pen and it is thus considered possible that gene expression of the putative virus was incomplete.     

An outbreak of malignant catarrhal fever in Père David's deer (Elaphurus davidianus)

Thirteen (54%) of 24 Père David's deer (Eluphurus duvidianus) imported from England died of malignant catarrhal fever (MCF) within a year of arrival at Invermay Agricultural Centre. The duration of clinical illness was from one to approximately 33 days, and the most common clinical signs were depression, a hunched stance and diarrhoea. On post-mortem examination, most deer showed recent localised haemorrhages, often into the large intestine. In all deer there was histological vasculitis especially in the brain.     

Experimental transmission of sheep-associated malignant catarrhal fever from sheep to Japanese deer (Cervus nippon) and cattle

The assumption that sheep carry ovine herpesvirus-2 (OvHV-2), the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), is widely accepted, albeit OvHV-2 has not been isolated. We attempted experimental contact transmission of MCF from Japanese sheep persistently infected with OvHV-2 to Japanese deer (Cervus nippon) and cattle. In Experiment 1, a deer was kept in close quarters with an infected ewe. In Experiment 2, a second deer was kept with the same ewe. In Experiment 3, two cows were each kept with two infected wethers. In Experiment 1, the deer developed clinical signs at 138 days after first contact and then died. OvHV-2 genes by polymerase chain reaction (PCR) and fluorescent antibodies to Alcelaphine herpesvirus-1 were detected in the affected deer. Moreover, sequences of PCR products (423bp), obtained by amplification of materials from the sheep and from the affected deer, coincided. These results clearly confirmed that the sheep was a carrier of OvHV-2, and that this virus had induced SA-MCF in a deer. In other experiments, no OvHV-2 infection occurred in deer and cattle during the 6-18 months periods of contact, though viral genes were detected in the nasal swabs and white blood cells of the sheep. To our knowledge, this is the first report on successful experimental transmission of MCF from OvHV-2-infected sheep to deer.     

MALIGNANT CATARRHAL FEVER IN FARMED RUSA DEER (CERVUS TIMORENSIS): 2. Animal Transmission and Virological Studies

SUMMARY A disease with clinical signs and histological lesions similar to malignant catarrhal fever in cattle was transmitted from Rusa deer (Cervus timorensis) to rabbits. This was accomplished on 3 separate occasions, and the disease was serially passaged in rabbits up to 11 times. The clinical signs in affected rabbits were pyrexia, depression, anorexia, mucopurulent conjuctivitis, nasal discharge and diarrhoea. These signs were seen in 27 of 38 inoculated rabbits with the mean incubation period being 12 days (range 8 to 20 days). Histologically, affected rabbits exhibited mononuclear perivascular cuffing and vasculitis in the brain, heart, liver and kidney. Lymph nodes and spleen showed destruction and loss of mature lymphocytes and lymphoid follicles and an increased number of large lymphoblastoid cells. These clinical signs and lesions were not detected in control rabbits. The disease was not transmitted to cattle, sheep, guinea pigs or mice, nor was an agent isolated in cattle, deer or rabbit tissue cultures, or in chicken embryos.     

Detection of OvHV-2 from an outbreak of sheep associated malignant catarrhal fever from crossbred cattle of Southern India

An outbreak of sheep associated malignant catarrhal fever in crossbred cattle in a village of Andhra Pradesh, southern India, affected thirteen adult cows and two calves from a population of forty animals. All the affected animals were died between December and January 2013–14. The clinical and gross postmortem findings were typical of MCF in Indian crossbred cattle. Migrating sheep flocks were suspected source of infection for the cattle. The diagnosis was confirmed by heminested PCR in all the affected cattle and the suspected sheep flock. The PCR provided evidence of ovine herpes virus type 2.     

Concurrent malignant catarrhal fever and bovine virus diarrhoea virus infection in a dairy herd

An account is given of an outbreak of malignant catarrhal fever which occurred in a 98-cow dairy herd. Ten animals died or were slaughtered and the disease was confirmed by clinical and histological examination. Serological tests for malignant catarrhal fever virus were positive in three of four animals. The diagnosis of malignant catarrhal fever was complicated by the presence of bovine virus diarrhoea virus infection in three of the early cases. The initial cases of malignant catarrhal fever occurred in a group of nine-month-old calves which were housed in an old milking parlour with 19 pedigree Suffolk ewes at lambing time. Later cases occurred in two adult cows and in two heifers. Investigations of the remainder of the herd for evidence of bovine virus diarrhoea virus did not reveal the presence of any persistently infected cattle. Serological examinations for antibody to malignant catarrhal fever and bovine virus diarrhoea virus were carried out on the 19 Suffolk ewes. Six of them had neutralising antibody titres to malignant catarrhal fever virus and three were positive in the indirect immunofluorescence test. The possible roles of bovine virus     

An outbreak of malignant catarrhal fever in red deer (Cervus elephus)

Nine of 15 housed red deer developed an acute disease. Six died and three were killed when severely affected. The clinical and post mortem changes suggested a diagnosis of malignant catarrhal fever (MCF) which was consistent with the pantropic lymphoproliferative histopathological lesions observed. Attempts to isolate an agent or transmit the condition to cattle failed. The relation of the vasculitis to the pathogenesis of the disease and the susceptibility of red deer are discussed.     

Mural folliculitis and alopecia caused by infection with goat-associated malignant catarrhal fever virus in two sika deer

Two sika deer from a zoo in Florida were examined because of chronic hair loss and skin lesions. No common causes of alopecia were identified in either deer. One deer was treated with prednisone, but the condition worsened when the dosage was decreased. Both deer were euthanatized after several months because of continued disease. The predominant histologic lesion in skin specimens was granulomatous mural folliculitis. Serologic testing and sequencing of fragments produced with a consensus polymerase chain reaction assay indicated that both deer were infected with caprine herpesvirus-2, a newly recognized member of the malignant catarrhal fever group of viruses. Disease in these deer was substantially different from that typically seen following infection with ovine herpesvirus-2, the sheep-associated malignant catarrhal fever virus. Findings in these deer establish the pathogenicity of caprine herpesvirus-2 in sika deer and illustrate the ability of this group of complex herpesviruses to cause a wide variety of clinical abnormalities in diverse species.     

Caprine herpesvirus-2-associated malignant catarrhal fever in white-tailed deer (Odocoileus virginianus).

A subacute disease presenting primarily as alopecia and weight loss occurred in 2 white-tailed deer (Odocoileus virginianus) on farms in Minnesota and in Texas. A presumptive diagnosis of malignant catarrhal fever (MCF) was made on the basis of histological lesions. Antibody against an epitope conserved among the MCF group viruses was detected in the serum of both deer. DNA samples from the deer were subjected to a variety of PCR amplifications. Alignment of the amplified sequences from the diseased animals revealed that they were 100% identical to each other and to the same DNA fragment from the newly recognized member of the MCF virus group endemic in domestic goats (Capra hircus), provisionally named caprine herpesvirus 2 (CpHV-2). A seroprevalence survey from one of the deer farms showed a high rate of subclincal infection in the deer population. This study provides further confirmation that CpHV-2 is a pathogen, at least for deer, and emphasizes the risk of loss from MCF when mixing cervids with goats.     

Bilateral perirenal hemorrhage in two Stone's sheep (Ovis dalli stonei): a possible manifestation of malignant catarrhal fever

Malignant catarrhal fever (MCF)-like disease was diagnosed at postmortem in 2 Stone's sheep (Ovis dalli stonei). On gross examination, the predominant abnormality in both sheep was severe perirenal hemorrhage and multiple renal infarcts. Microscopically, there was severe, multisystemic lymphocytic arteritis. Both sheep were positive for Ovine herpesvirus 2 (OvHV-2) on polymerase chain reaction, and partial sequencing of the viral DNA polymerase genes from the 2 sheep revealed >99% homology, with 96% similarity to the reference GenBank OvHV-2 viral sequence. Based on the histological lesions, polymerase chain reaction results, and viral DNA polymerase gene sequencing, a diagnosis of OvHV-2-mediated MCF was made. Massive perirenal hemorrhage has not been described previously as a manifestation of MCF.     

Isolation and characterisation of lymphoblastoid cells from cattle and deer affected with 'sheep-associated' malignant catarrhal fever

Cells with the histological and ultrastructural characteristics of large granular lymphocytes (LGL) have been obtained in culture from both cattle and red deer (Cervus elaphus) reacting with 'sheep-associated' malignant catarrhal fever (MCF). Such cells have been derived from thymus, lymph node and spleen suspensions as well as from cerebrospinal fluid cells and cultured cornea. On most occasions their presence was observed only transitorily but by providing the cells with feeder monolayers and, or, interleukin-2, several lines were maintained indefinitely, and some became independent of these factors after prolonged culture. A similar cell line was also derived from a Père David's deer affected with MCF at Whipsnade zoological park. Functionally, cultured LGL were cytotoxic to both primary cell cultures and cell lines and their cytotoxicity was not restricted to histocompatible target cells. These findings suggest that the cultured cells have natural killer cell-like activity and that they are important targets for the agent of MCF in cattle and deer. One cell line derived from a red deer transmitted the disease but none of the cells generated from cattle did.     

Failure of sheep to respond to repeated inoculations with an alcelaphine herpesvirus-1-like virus, isolated from a case of malignant catarrhal fever in American cattle.

The replication of an alcelaphine herpesvirus-1-like virus (707K), isolated from a clinical case of malignant catarrhal fever in American cattle, was studied in sheep. Viraemia was not observed in any of the six sheep repeatedly inoculated with the 707K virus or in four steers susceptible to malignant catarrhal fever which were housed together with these sheep for one year. None of the four steers seroconverted and only two of the six inoculated sheep showed a negligible and short-lived seroconversion. The inability of the sheep to seroconvert adequately after repeated inoculations with the 707K virus, and the failure to recover the agent from them suggests that this agent does not replicate in sheep.     

Dexamethasone-induced recrudescence of malignant catarrhal fever and associated lymphosarcoma and granulomatous disease in a Formosan sika deer (Cervus nippon taiouanus)

Malignant catarrhal fever (MCF) was diagnosed in a 2-week-old Formosan sika deer. The fawn had been previously exposed to a clinically normal neonatal wildebeest calf from which alcelaphine herpesvirus-1 was isolated. Alcelaphine herpesvirus-1 was isolated from buffy coat leukocytes and nasal and ocular secretions of the fawn during the acute illness. The fawn clinically recovered after 3 weeks. Virus was not recovered from blood at this time. Dexamethasone, given 4 months after clinical recovery, resulted in reisolation of MCF virus from blood and recrudescence of clinical MCF. The deer was euthanatized. At necropsy, pathognomonic lesions of MCF, granulomatous disease, and malignant lymphoma were observed. Antibodies to bovine leukosis viral antigens were not detected in the serum. The epidemiologic and pathogenetic importance of the findings are discussed.     

Derivation of a DNA clone corresponding to the viral agent of sheep-associated malignant catarrhal fever

Malignant catarrhal fever is a fatal lymphoproliferative and degenerative disease of ruminants. One causative agent is the gammaherpesvirus alcelaphine herpesvirus 1 (AHV-1), which produces no disease in its natural host, the wildebeest (Connochaetes species). Epidemiological evidence implicates sheep as the carrier of a similar virus. However, attempts to culture this virus from sheep or from animals affected with sheep-associated malignant catarrhal fever (SA-MCF) have failed. Lymphoblastoid cells have been propagated from cattle, deer and rabbits with SA-MCF. Although these cells show no evidence of viral particles or antigens, hybridisation experiments now show that they contain DNA sequences homologous to those of AHV-1. A genomic library was constructed from one of these lymphoblastoid cell lines and a clone identified which hybridised to cloned AHV-1 DNA. The authors believe that this clone contains part of the SA-MCF viral genome, and that the SA-MCF virus and AHV-1 are closely related gammaherpesviruses.     

Lymphoproliferation in captive wild ruminants affected with malignant catarrhal fever: 25 cases (1977-1985)

The severity of lymphoproliferative disease associated with malignant catarrhal fever was extremely variable among 25 animals at the San Diego Wild Animal Park. Severe lymphoproliferative disease was seen in 3 of 10 Formosan Sika deer (Cervus nippon taiouanus), 3 of 6 Indian Axis deer (Cervus a axis), 3 of 6 Barasingha deer (Cervus d duvauceli), and 1 of 3 Nilgai (Boselaphus tragocamelus). Two Sika deer and 2 Barasingha deer had lesions morphologically indistinguishable from lymphosarcoma. Our findings were consistent with the hypothesis that alcelaphine herpesvirus-1 has oncogenic potential.     

Detection and molecular characterization of naturally transmitted sheep associated malignant catarrhal fever in cattle in India

Malignant catarrhal fever (MCF) is a fatal herpesvirus infection of domestic and wild ruminants, with a short and dramatic clinical course characterized primarily by high fever, severe depression, swollen lymph nodes, salivation, diarrhea, dermatitis, neurological disorders, and ocular lesions often leading to blindness. In the present study, fatal clinical cases of sheep associated malignant catarrhal fever (SA-MCF) were identified in cattle in the state of Karnataka. These cases were initially presented with symptoms of diarrhea, respiratory distress, conjunctivitis, and nasal discharges. Laboratory diagnosis confirmed the detection of ovine herpesvirus-2 (OvHV-2) genome in the peripheral blood samples of two ailing animals. The blood samples collected subsequently from sheep of the neighboring areas also showed presence of OvHV-2 genome indicating a nidus of infection in the region. The positive test results were further confirmed by nucleotide sequencing of the OIE approved portion of tegument gene as well as complete ORF8 region of the OvHV-2 genome. Phylogenetic analysis based on the sequence of the latter region indicated close genetic relationship with other OvHV-2 reported elsewhere in the world.     

Outbreak of wildebeest-associated malignant catarrhal fever in Ankole cattle

During an outbreak of malignant catarrhal fever in a herd of Ankole cattle in a zoological collection, two adult cows and one adult bull from a herd of 15 died or were euthanased between July and November 2004. The clinical, gross postmortem and histological findings were typical of the disease in uk native domestic cattle. The diagnosis was confirmed by serology in two animals, and by pcr in all three; the pcr provided evidence of alcelaphine herpesvirus type 1 infection in all three animals and also of ovine herpesvirus type 2 infection in one.     

Antibody to alcelaphine herpesvirus-1 (AHV-1) in hamsters experimentally infected with AHV-1 and the 'sheep-associated' agent of malignant catarrhal fever

Malignant catarrhal fever was induced in four groups of hamsters by the inoculation of cells infected with either the C/500 isolate of alcelaphine herpes-virus-1 (AHV-1) or the sheep-associated agent derived from cattle, red deer or Père David's deer. Using an indirect immunofluorescence assay, antibody to AHV-1 was detected in sera of clinically affected animals of all four groups. The reaction of sera from hamsters affected with malignant catarrhal fever induced by AHV-1 caused diffuse cytoplasmic staining while that from sera of hamsters with the sheep-associated form of the disease stained particulate nuclear antigens. Tests employing three other bovid herpesviruses were negative and no reaction was found with sera from normal hamsters. These studies provide convincing evidence that a virus antigenically related to AHV-1 is the cause of sheep-associated malignant catarrhal fever and that the same virus probably causes this form of the disease in both cattle and deer.     

Development of a management program for a mixed species wildlife park following an occurrence of malignant catarrhal fever

During late 2001 and early 2002, a mixed species wildlife park in North Carolina experienced an acute outbreak of morbidity and mortality in Pere David's deer (Elaphurus davidianus), axis deer (Axis axis), blackbuck antelope (Antelope cervicapra), white-tailed deer (Odocoileus virginianus), and Rocky Mountain elk (Cervus elaphus). Clinical signs varied from fulminant disease, progressing from depression to bloody scours to death in fewer than 4 days in Pere David's deer, to a more protracted form of disease, ranging from 2 wk to 3 mo, in axis deer. In moribund axis deer, high levels of anti-malignant catarrhal fever (MCF) virus antibody by competitive-inhibition enzyme-linked immunosorbent assay were detected. Ovine herpesvirus 2 (OvHV-2) DNA was detected in peripheral blood leukocytes of the affected axis deer. No other MCF viruses were detected. Retrospective examination of frozen tissue samples from the affected Pere David's deer and blackbuck antelope also confirmed the presence of OvHV-2 DNA. Initial control efforts were directed at preventing further deaths of clinically susceptible animals by removing MCF virus reservoir species, particularly ovine species. The most prevalent ovine species in the wildlife park was mouflon sheep (Ovis musimon). All sheep were removed from the park by June 2002, and the last MCF death occurred in October 2002. Since mouflon sheep had been a prominent attraction in the wildlife park, the owner wanted a means to reintroduce this species to the park. Derivation of OvHV-2-uninfected mouflon lambs was undertaken using the previously described program for production of OvHV-2-free sheep (Ovis ovis). The rederived MCF virus-negative mouflon sheep were introduced into the park in approximately January 2004. As of December 2007, no further cases of MCF have occurred since the removal of OvHV-2-positive mouflon sheep and reintroduction of the virus-free lambs. This paper describes the successful management and control of MCF in a densely populated mixed species animal park.     

The clinico-pathology of a malignant catarrhal fever syndrome in the Indonesian swamp buffalo (Bubalus bubalis)

Between September 1979 and May 1982, 50 of 177 swamp buffaloes became sick and died S3 to 719 days (mean 271) after being transferred to a research facility and housed in quarters adjacent to where sheep and goats were kept. The major clinical signs were anorexia, fever, conjunctivitis, scleral hyperaemia, ocular discharge, hyperaemia of skin, enlargement of lymph nodes and depression. Postmortem and histopathological lesions were observed in most of the tissues and organs of the body. A vasculitis with adventitial mononuclear cell infiltration and lymphoreticular reactions suggested a relationship to malignant catarrhal fever. The occurrence of serofibrinous epicarditis and myocarditis, which was seen in buffaloes in all cases, has not been a common finding in ruminants with malignant catarrhal fever.