Malignant catarrhal fever: experimental transmission of the 'sheep-associated' form of the disease from cattle and deer to cattle, deer, rabbits and hamsters

Attempts to transmit malignant catarrhal fever (MCF) from 16 bovine cases of the 'sheep-associated' form of the disease are described. On two occasions disease was transmitted to bovine calves but transmission to red deer (Cervus elaphus) was not achieved. In addition, MCF was transmitted from one experimentally affected calf to a rabbit and on another occasion directly to rabbits with material from a field case which failed to transmit to a bovine calf or red deer. Subsequently each of these isolates was readily passaged through rabbits and one was also passaged to Syrian hamsters. Tissue from MCF-affected red deer consistently produced disease on inoculation into rabbits and deer but failed to cause disease in bovine calves. Contact infection between red deer occurred once and roe deer (Capreolus capreolus) were also shown to be susceptible to infection by inoculation. Passage of MCF in rabbits with an isolate from red deer failed to produce evidence of further adaptation even after 125 serial passages. Despite the failure to transmit disease from cattle to deer or from deer to cattle it is considered probable that there is only one sheep-associated agent which causes MCF in both species. The reasons for the anomalies in transmission of this form of the disease are discussed.     

Transmission and virological studies of a malignant catarrhal fever syndrome in the Indonesian swamp buffalo (Bubalus bubalis)

A malignant catarrhal fever-like syndrome in indonesian swamp buffalo was experimentally transmitted to one of 2 Bos indicus and 3 of 3 Bos javanicus cattle by intravenous inoculation of 250 ml of citrated, whole blood from affected buffaloes. The 4 cattle developed clinical signs of disease on average 32.5 days after receiving the inoculation of blood. The 4 cattle died after a variable period of illness. None of a further 3 B. javanicus cattle inoculated intravenously with a spleen homogenate prepared from another affected buffalo developed the disease. The experimental disease was clinically and pathologically similar to the natural disease in buffaloes although differences were noted. Attempts to adapt the agent to mice, guinea pigs and rabbits failed. A cytopathic agent (Japanese encephalitis virus) was isolated from the spleen of one buffalo with clinical signs but was not considered significant. Sixty-three B. indicus, 7 B. javanicus (and 6 of their crosses), 3 B. taurus and 4 Bubalus bubalis (Murrah buffalo) were kept in the same quarters where 50 of 177 swamp buffaloes died between September 1979 and May 1982. Four of the 7 B. javanicus cattle developed the clinical signs of disease and died. All the other cattle in contact remained healthy.     

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.     

Foot-and-mouth disease virus in the llama (Lama glama): diagnosis, transmission, and susceptibility

Foot-and-mouth disease virus (FMDV) was shown to be transmitted from either cattle to llamas, llamas to swine (interspecies), or llamas to llamas (intraspecies). Response to FMDV varied greatly in the 6 llamas studied; 3 llamas developed generalized clinical disease with mild pyrexia, 2 after intradermolingual inoculation, and 1 after exposure to a calf infected with FMDV serotype A24. Another contact llama developed vesicular lesions on all 4 extremities but no oral lesions. Two contact llamas, in separate study groups, did not seroconvert or develop clinical signs of FMDV infection. All 4 llamas showing clinical disease developed virus-neutralizing antibodies against FMDV A24 and antibodies against the virus-infection-associated antigen. Virus-neutralizing antibody titers remained elevated for over 200 days postinoculation or exposure. Antibodies to virus-infection-associated antigen were detected several days after virus-neutralizing antibody appeared and became weaker 100-125 days post-FMDV exposure in 3 of the 4 clinically affected llamas. One inoculated llama was still positive for virus-infection-associated antigen at 360 days after inoculation. Foot-and-mouth disease virus A24 was not detected from esophageal-pharyngeal fluid specimens beyond 8 days postexposure using in vitro techniques.     

Experimental infection of calves with epizootic hemorrhagic disease virus.

OBJECTIVE: To determine whether experimental inoculation with a field strain of epizootic hemorrhagic disease virus serotype-2 (EHDV-2) suspected of causing clinical disease in naturally infected cattle would cause clinical disease in calves. ANIMALS: 8 calves. PROCEDURE: A strain of EHDV-2 isolated from a white-tailed deer that died of hemorrhagic disease was passaged twice in deer and used to inoculate 6 calves SC and ID; the other 2 calves were used as controls. Physical examinations, CBC, lymphocyte blastogenesis assays, and coagulation assays were performed; rectal temperature, interferon production, and serum neutralizing antibody responses were measured; and virus isolation was attempted every other day for 21 days after inoculation and then every fourth day for another 30 days. Calves were euthanatized on postinoculation day 51, and necropsy was performed. RESULTS: Calves inoculated with EHDV-2 became infected, as evidenced by development of viremia and seroconversion. However, the virus did not cause detectable clinical disease, clinicopathologic abnormalities, or gross lesions. Viremia was prolonged despite development of a serum neutralizing antibody response. A white-tailed deer inoculated with the same EHDV-2 strain developed clinical signs of epizootic hemorrhagic disease, demonstrating that the inoculum was virulent. CONCLUSION: Calves experimentally infected with EHDV-2 developed viremia and seroconverted but did not develop detectable clinical disease.     

Congenital contraction of the gastrocnemius and superficial digital flexor muscles in a friesian calf

The red deer (Cervus elaphus) is a host for two louse species, Damalinia longicornis and Solenopotes burmeisteri. Little is known of their prevalence or population dynamics; numbers are likely to peak in winter. Numbers may increase secondarily to malnutrition or disease. Lice are unlikely to seriously affect deer health under most conditions. “Pour-on” insecticides have been used for treatment but their efficacy has not been critically assessed. Animals can be sprayed using garden spray equipment, providing that such equipment has not been used for other toxic chemicals such as weed killers. Little is known of the toxicity of insecticides for deer, so they should be used with care and not used on stressed animals. No lice have been recorded from the fallow deer (Dama dama) in New Zealand.

Dictyocaulus viviparus infects red and fallow deer and can cause high mortalities of young farmed red deer in their first autumn and winter. In clinical cases respiratory signs are seldom obvious but loss of condition and dullness of coat may be evident. Clinical evidence and lung lesions suggest that the pathogenesis of disease may differ from that in cattle. Anthelmintics effective against D. viviparus in cattle are not necessarily effective in deer. Little is known of the significance of lungworm to farmed fallow deer. Research on lungworm in deer is urgently needed.     

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.     

Lesion development in white-tailed deer (Odocoileus virginianus) experimentally infected with Mycobacterium bovis

The recent discovery of tuberculosis in free-living white-tailed deer in northeastern Michigan underscores the need for increased understanding of the pathogenesis of tuberculosis in wildlife species. To investigate lesion development in white-tailed deer, 32 deer were experimentally infected by intratonsilar instillation of 300 colony-forming units of Mycobacterium bovis. Three deer each were euthanatized and examined at days 15, 28, 42, and 56 after inoculation, and five deer each were euthanatized and examined at days 89, 180, 262, and 328 after inoculation. Microscopic lesions first were seen in the medial retropharyngeal lymph node and lung 28 and 42 days after inoculation, respectively. Lung lesions were present in 12 (38%) of 32 deer, involving 23 lung lobes. Left caudal and right middle and caudal lobes were involved in 17 (74%) of the 23 affected lung lobes. Lesions in the medial retropharyngeal lymph node first appeared as granulomas composed of aggregates of macrophages and Langhans-type giant cells. Some early granulomas contained centrally located neutrophils. As granulomas developed, neutrophils were replaced with a central zone of caseous necrosis that first showed signs of mineralization 42 days after inoculation. Granulomas increased in size as the zone of caseous necrosis expanded. Peripheral fibrosis, first seen at 56 days after inoculation, progressed to only a thin fibrous capsule by 328 days after inoculation. By the termination of the study, the central necrotic core of the granuloma contained abundant liquefied necrotic material and grossly resembled an abscess. Although tuberculous lesions in white-tailed deer follow a developmental pattern similar to that in cattle, fibrosis is less pronounced and the advanced lesions may liquefy, a change seldom reported in cattle. An understanding of lesion development will aid in the identification of the spectrum of disease that may be seen in this important wildlife reservoir of tuberculosis.     

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.     

Studies on the Pathogenesis of Experimental Epizootic Hemorrhagic Disease of White-tailed Deer

Observations were made of clinical signs, gross and microscopic lesions in white-tailed deer infected with epizootic hemorrhagic disease (EHD) virus. Typically, animals became weak and lethargic and developed hyperemia of the oral and nasal mucosa, tongue, ears and sclera of the eyes six to seven days following intramuscular inoculation with virus. Body temperature increased initially and then fell to subnormal levels just prior to death.

A decrease in levels of circulating blood platelets was correlated with the occurrence of fever and the appearance of platelet and fibrin thrombi in small vessels of many organs of the body. Thrombosis resulted in tissue degeneration, necrosis and hemorrhages in the terminal stages of the disease. Tissues most seriously affected were oral, nasal and tongue mucosa, mandibular salivary glands, myocardium and epithelium of the forestomachs. The lesions resembled those of blue-tongue in deer.

Inoculation of domestic sheep with EHD virus-infected deer spleen tissues was without clinical effect. Blood collected from the sheep, representing the third blind passage of EHD virus in sheep, was not infective for deer.

     

Experimental transmission of chronic wasting disease (CWD) of elk (Cervus elaphus nelsoni), white-tailed deer (Odocoileus virginianus), and mule deer (Odocoileus hemionus hemionus) to white-tailed deer by intracerebral route

To compare clinical and pathologic findings of chronic wasting disease (CWD) in a natural host, 3 groups (n = 5) of white-tailed deer (WTD) fawns were intracerebrally inoculated with a CWD prion of WTD, mule deer, or elk origin. Three other uninoculated fawns served as controls. Approximately 10 months postinoculation (MPI), 1 deer from each of the 3 inoculated groups was necropsied and their tissues were examined for lesions of spongiform encephalopathy (SE) and for the presence of abnormal prion protein (PrP(d)) by immunohistochemistry (IHC) and Western blot (WB). The remaining deer were allowed to live until they developed clinical signs of the disease which began approximately 18 MPI. By 26 MPI, all deer were euthanatized on humane grounds. Obvious differences in clinical signs or the incubation periods were not observed between the 3 groups of deer given CWD. In 1 of 3 nonclinical deer euthanatized at 10 MPI, minimal microscopic lesions of SE were seen in the central nervous system (CNS) tissues, and PrP(d) was observed by IHC in tissues of all 3 deer. In the clinical deer, CNS lesions of SE and PrP(d) accumulations were more severe and extensive. It is concluded that the 3 sources of CWD prion did not induce significant differences in time to clinical disease or qualitative differences in signs or lesions in WTD. However, this observation does not imply that these CWD agents would necessarily behave similarly in other recipient species.     

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.     

Experimental transmission of malignant catarrhal fever to red deer (Cervus elaphus)

Abstract

Malignant catarrhal fever was transmitted from affected to recipient red deer (Cervus eluphus) using bloodor lymphoid suspension as inoculum. Incubation periods ranged from 11 to 26 days. The disease was also transmitted using lymphoid suspension stored overnight at 4°C or at ?70°C for 8 months.

The experimental disease was characterised by fever, depression, anorexia, diarrhoea and dysentry. The course of the disease was approximately 96 hours.

Major lesions consisted of acute mesenteric lymphadenitis and acute haemorrhagic typhlitis and colitis. Lesions in the caecum and colon started as multifocal mucosal haemorrhages and progressed rapidly to massive mucosal haemorrhage.     

Congenital Cerebellar Cortical Degeneration in Holstein Cattle in Southern Brazil

A congenital progressive cerebellar disorder is described in Holstein calves. The clinical signs were progressive and were characterized by ataxia, hypermetria, a wide stance and fine head tremors. When the affected cattle were forced to run, the signs were exacerbated, leading to epileptiform attacks. Histological lesions consisted of a very selective cerebellar cortical degeneration, almost exclusively affecting the Purkinje cells. The disease affected 6 out of 200 Holstein calves from the same bull. However, results of mating tests of the bull with his daughters and granddaughters suggested that it was not hereditary (p = 0.0062) although an environmental–genetic interaction could not be ruled out.     

MALIGNANT CATARRHAL FEVER IN FARMED RUSA DEER (CERVUS TIMORENSIS): 1. Clinico-Pathological Observations

SUMMARY A sporadic fatal disease is described in 7 Rusa deer (Cervus timorensis) from 5 deer farms in Victoria. Bilateral ophthalmia and wasting were the most significant signs in a clinical course varying from 4 to 34 days. Bilateral hypopyon, peripheral corneal opacities and interstitial mononuclear cell infiltration of the renal cortex with pronounced mural thickening and dilatation of vessels at the cortico-medullary junction were the only consistent lesions. Haemorrhagic ileitis, colitis and typhlitis were the major lesions in two deer that died 4 and 6 days after onset of clinical disease. Ecchymotic haemorrhages and sub-serosal haematomas on the intestines and mesentery were the main finding in cases with a longer clinical course. Other gross lesions varied between cases. The most significant histological lesion was fibrinoid necrotising vasculitis with adventitial lymphoid cell infiltration characteristic of bovine malignant catarrhal fever. Mucosal erosions seen in protracted cases of this disease were associated with lymphoid cell infiltration into foci of degenerating epithelial cells. In many lymph nodes there was severe follicular necroses. In chromic cases extensive proliferation of lymphoblastoid cells was seen in the parafollicular cortex and medullary sinuses of nodes which also showed discrete follicular necrosis.     

Foot-and-mouth disease in British deer: transmission of virus to cattle, sheep and deer.

After exposure for two hours to cattle with foot-and-mouth disease, each of the five species of deer found in the British countryside became infected. Clinical disease was typical and severe in the roe and muntjac deer, with some animals dying, less severe in the sika deer and usually subclinical in the fallow and red deer. Each species transmitted disease to its own species and to cattle and sheep. The amounts of virus present in the blood, and in oesophageal/pharyngeal samples and excreted as an aerosol during the course of the infection in the deer were similar to those recorded for the sheep and cattle in the same experiment. The fallow and sika deer commonly carried virus in the pharynx beyond 28 days after exposure; some red deer also became carriers. In epidemics of foot-and-mouth disease in the UK, it is likely that deer would have such intimate contact with farm animals as occurred in this study. The natural behavior of free-living deer in the UK suggests that, although the five species are susceptible to foot-and-mouth disease, they are unlikely to be an important factor in the maintenance and transmission of the virus during an epidemic of foot-and-mouth disease in domestic livestock.     

Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer

Fourteen, 3-month-old calves were intracerebrally inoculated with the agent of chronic wasting disease (CWD) from white-tailed deer (CWDwtd) to compare the clinical signs and neuropathologic findings with those of certain other transmissible spongiform encephalopathies (TSE, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, CWD of mule deer [CWDmd], bovine spongiform encephalopathy [BSE], and transmissible mink encephalopathy). Two uninoculated calves served as controls. Within 26 months postinoculation (MPI), 12 inoculated calves had lost considerable weight and eventually became recumbent. Of the 12 inoculated calves, 11 (92%) developed clinical signs. Although spongiform encephalopathy (SE) was not observed, abnormal prion protein (PrPd) was detected by immunohistochemistry (IHC) and Western blot (WB) in central nervous system tissues. The absence of SE with presence of PrPd has also been observed when other TSE agents (scrapie and CWDmd) were similarly inoculated into cattle. The IHC and WB findings suggest that the diagnostic techniques currently used to confirm BSE would detect CWDwtd in cattle, should it occur naturally. Also, the absence of SE and a distinctive IHC pattern of CWDwtd and CWDmd in cattle suggests that it should be possible to distinguish these conditions from other TSEs that have been experimentally transmitted to cattle.     

Field observations during the bluetongue serotype 8 epidemic in 2006. I. Detection of first outbreaks and clinical signs in sheep and cattle in Belgium, France and the Netherlands

Starting August 2006, a major epidemic of bluetongue (BT) was identified in North-West Europe, affecting The Netherlands, Belgium, Germany, Luxemburg and the North of France. It was caused by BT virus serotype 8 (BTV-8), a serotype previously unknown to the European Union (EU). In this outbreak, the virus caused clinical disease in a few individual animals within cattle herds, whereas overt clinical disease was usually restricted to sheep. Investigations in Belgium suggested that the first clinical signs of BTV-8 appeared mid July 2006 in a cattle herd, while the first suspicion of a BT-outbreak in Belgium was reported on 17 August 2006. In the first 10 BTV-8 outbreaks in the Netherlands, the owners indicated that the first clinical signs started approximately 12-17 days before a suspicion was reported to the veterinary authorities via a veterinary practitioner. In BTV-8 affected sheep flocks, erosions of the oral mucosa, fever, salivation, facial and mandibular oedema, apathy and tiredness, mortality, oedema of the lips, lameness, and dysphagia were among the most frequent clinical signs recorded. The most prominent clinical signs in BTV-8 affected cattle herds were: crusts/lesions of the nasal mucosa, erosions of lips/crusts in or around the nostrils, erosions of the oral mucosa, salivation, fever, conjunctivitis, coronitis, muscle necrosis, and stiffness of the limbs. Crusts/lesions of nasal mucosa, conjunctivitis, hyperaemic/purple coloration and lesions of the teats, and redness/hypersensitivity of the skin were relatively more seen on outbreak farms with cattle compared to sheep. Mortality, oedema of the head and ears, coronitis, redness of the oral mucosa, erosions/ulceration of tongue mucosa, purple coloration of the tongue and tongue protrusion and dyspneu were relatively more seen on outbreak farms with sheep compared to cattle.     

Experimental infections in young red deer (Cervus elaphus) with a bovine and an ovine strain of Mycobacterium avium subsp paratuberculosis

AIMS: To compare the virulence of a 'bovine' and an 'ovine' strain of Mycobacterium avium subsp paratuberculosis (M. ptb) in red deer (Cervus elaphus) after experimental inoculation orally, and to examine the relationship between the dose of the bovine strain given and immunological, clinical and histopathological outcomes in young red deer. METHODS: Newly-weaned 4-month-old male red deer (n=81) were randomly assigned to one of five groups. Three groups (n=16) received high (10(9) colony forming units (cfu); HB), medium (10(7) cfu; MB) or low (10(3) cfu; LB) oral doses of a bovine strain of M. ptb, one group (n=16) received medium (10(7) cfu; MO) doses of an ovine strain of M. ptb, and a Control group (n=17) was not dosed. The HB and Control groups were grazed together, the MB and LB groups were grazed together, and the MO group was grazed alone, in separate small paddocks on a quarantined area of the farm for 45 weeks. Liveweight, clinical signs and immunoglobulin G1 (IgG1) antibody levels were monitored for up to 45 weeks. Deer affected with Johne's disease were euthanised when they showed obvious clinical signs. Unaffected deer were slaughtered at the end of the trial (Week 45), and all deer were necropsied. Faeces and tissue samples were cultured for M. ptb, and fixed tissues were examined for histopathology. RESULTS: Between 21 and 38 weeks post-challenge (pc), 5/16 animals in the HB group developed early signs of Johne's disease and were euthanised. The remaining deer in the five groups were all apparently healthy and reached good liveweights (approximately 100 kg average), and were euthanised and examined 45 weeks pc. Three deer (two HB and one MB) had small caseous lesions in their jejunal lymph nodes (JJLNs) and one HB animal had a small caseous lesion in a retropharyngeal lymph node. The remaining animals had no grossly-visible lesions. Mycobacterium avium subsp paratuberculosis was cultured from samples from 100% of the HB and MB animals, 50% of the LB group, 69% of the MO group and all Control animals. Thus all Control deer were infected by natural transmission from the HB group but none developed signs of clinical disease. Examination of histological sections of jejunum, ileocaecal valve (ICV) and associated lymph nodes showed a gradation of severity of lesions that was positively correlated (p<0.001) with dose of the bovine strain administered; mean lesion severity scores were 4.8, 2.9 and 0.9 for HB, MB and LB groups, and 2.2 and 0.9 for the Control and MO groups, respectively. IgG1 antibody levels at the time of euthanasia were also correlated with lesion severity scores at slaughter (p<0.001). CONCLUSIONS: The ovine strain of M. ptb used in this study was less virulent for red deer than the bovine strain. The correlation between dose of the bovine strain and the severity of lesions suggests that clinical Johne's disease in yearling red deer likely results from high oral challenge with a bovine strain whilst they are young. The minimum oral infective dose may be close to 10(3) cfu for this bovine strain.