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PubMed1989

A serious outbreak of canine distemper among sled-dogs in northern Greenland.

A canine distemper outbreak in a highly susceptible sled dog population of Northern Greenland was recognized in the beginning of January 1988. A high morbidity and mortality in all age groups was a characteristic of the epizootic. The actual canine distemper virus infection was identified by isolation of the virus and demonstration of viral antigens by immunofluorescence and also by demonstration of conventional inclusion bodies. Virus specific IgM antibodies were demonstrated in affected dogs. In places where vaccination was carried out too late to be effective, the losses were up to 80 per cent. In a settlement, which was under rabies quarantine four weeks before the distemper outbreak started in other settlements, no cases occurred before or after vaccination. The spread of canine distemper seems connected with a Canadian outbreak and communicated by foxes. Once established the further spread apparently was by travelling dog teams. Suitable future prophylactic measures are discussed.

Animals↗
PubMed1987

[Canine distemper: then and now].

Canine distemper was known as a severe systemic infection of dogs and other carnivores for some centuries now. Symptoms of the gastrointestinal and respiratory tracts are particularly prominent. Nervous symptoms are also regularly observed. A paper on canine distemper by J.C. van der Slooten appeared in Tijdschrift voor Veeartsenijkunde en Veeteelt in 1894, in which a number of features of this disease was discussed. This paper was also published in the present issue of Tijdschrift voor Diergeneeskunde (see page 309). On the basis of this paper, several developments are described, which contributed to our current knowledge of canine distemper. Particular attention is paid to the aetiology, pathogenesis and epizootiology as well as the prevention of distemper by vaccination.

Animals↗
PubMed1968

International standard for anti-canine-distemper serum.

The Central Veterinary Laboratory, Weybridge, England, was requested by the WHO Expert Committee on Biological Standardization to obtain suitable material for an international standard for anti-canine-distemper serum and to arrange a collaborative assay. Seven laboratories in 6 countries assayed a batch of anti-canine-distemper serum against 3 test preparations. On the basis of the results obtained, the material has been established as the International Standard for Anti-Canine-Distemper Serum and the International Unit of Anti-Canine-Distemper Serum has been defined as the activity contained in 0.0897 mg of the International Standard.

Animals↗
PubMed1983

Immunoperoxidase study of canine distemper virus pneumonia.

Forty-two cases of canine pneumonia were examined for the presence of canine distemper virus. For that purpose canine distemper virus inclusion bodies were located. The histopathological lesions were related to the presence of canine distemper antigen, as demonstrated with an immunoperoxidase technique. This technique was more sensitive for detecting canine distemper infection in lung tissue than was the study of inclusion bodies. Attention was also paid to combined infection with canine adenovirus and Bordetella bronchiseptica.

Adenoviridae Infections↗
PubMed1965

SIMULTANEOUS GROWTH OF RABIES AND CANINE DISTEMPER VIRUSES IN CHICK EMBRYOS.

Rabies virus and canine distemper virus were grown simultaneously, and possibly symbiotically, in the same chick embryos. There seemed to be no adverse effect on either virus when cultured in such manner.Bivalent vaccines for rabies and canine distemper were produced. The potencies and the virus titers of such vaccines were comparable to those of rabies vaccine and canine distemper vaccine produced separately.

Animals↗
PubMed1993

Phocine distemper in a harp seal (Phoca groenlandica) from the Gulf of St. Lawrence, Canada.

The first case of phocine distemper in a seal from Canadian waters and the first case of clinical phocine distemper in a harp seal, Phoca groenlandica, is reported. A two-month-old female harp seal stranded on Prince Edward Island in May 1991. Significant clinical findings were lethargy and severe conjunctivitis. Pulmonary congestion was the main necropsy finding, and histological lesions included diffuse demyelinating nonsuppurative encephalitis and mild multifocal interstitial pneumonia. Acidophilic intracytoplasmic and intranuclear inclusions were present in cerebral neurons and astrocytes. Immunoperoxidase staining confirmed phocine distemper virus (PDV) antigen in the cytoplasm and nuclei of neurons, bronchiolar gland epithelium and transitional epithelium of the bladder. Infectivity titers of canine distemper virus (CDV) (Onderstpoort strain) and a morbillivirus isolated from a grey seal were significantly reduced by serum from the harp seal.

Animals↗
PubMed1985

Spread and distribution of viral antigen in nervous canine distemper.

Canine distemper virus (CDV) antigen was demonstrated immunocytochemically in the central nervous system (CNS) of 19 dogs killed from 16 to 170 days after infection. In the earliest lesions, infection of glial cells preceded demyelination, and the degree of myelin destruction correlated with the amount of viral antigen in the tissue. It was concluded that initial demyelination in distemper is directly viral-induced, but the nature of the infected glial cells remains uncertain. Ependymal infection and spread of virus in the subependymal white matter was often seen, suggesting invasion of CDV into the CNS along the CSF pathways. Inflammation during the latter stages of the infection appeared to be associated with viral clearance from the CNS in most dogs. In two dogs with chronic progressive neurologic distemper, viral antigen was still present in the brain suggesting that viral persistence and associated immunologic reactions may contribute to further myelin damage. With the exception of one dog that survived for 6 months after infection, viral antigen was no longer detected in the dogs that had recovered.

Animals↗
PubMed1986

Canine distemper virus clearance in chronic inflammatory demyelination.

The distribution of canine distemper virus (CDV) antigen was examined in the brains of 14 dogs with chronic nervous distemper using a monoclonal antibody against a major viral protein. In ten of these dogs, neutralizing anti-CDV antibody titers were determined in serum and unconcentrated cerebrospinal fluid (CSF). In 19% of the inflammatory demyelinating lesions, large amounts of CDV antigen were found; in 34% of these lesions only residual traces of virus were seen and in almost half of the lesions (47%) no CDV could be demonstrated. In four dogs neutralizing antibodies were found in the serum only; in one dog in the CSF only and in 5 dogs both in serum and CSF. Because of the correlation between the presence of inflammation, intrathecal antiviral antibodies and disappearance of CDV from the lesions, it was concluded that the inflammatory response in distemper is associated with viral clearance from the lesions. Associated immune-mediated cytotoxic reactions could explain exacerbation of the initial virus-induced demyelinating lesions. Despite the presence of an apparently effective intrathecal antiviral immune response, fresh non-inflammatory lesions as a result of viral replication and spread in the white matter coexisted with inflammatory ones in which viral clearance had taken place. The role and mechanism of such virus persistence are discussed.

Animals↗
PubMed2005

Up-regulation of mRNA for matrix metalloproteinases-9 and -14 in advanced lesions of demyelinating canine distemper leukoencephalitis.

Matrix metalloproteinases (MMPs) comprise a family of proteolytic zinc- and calcium-dependent enzymes that are capable of disrupting the blood-brain barrier and mediating the destruction of extracellular matrix and myelin components. MMPs are also involved in facilitating leukocyte migration into inflammatory sites of the central nervous system. To determine the cellular localization and the amount of mRNA for MMP-9, MMP-14 and a tissue inhibitor of metalloproteinases (TIMP-1) in dogs with spontaneous demyelinating distemper encephalitis, formalin-fixed paraffin-embedded cerebella were investigated by in situ hybridization using specific digoxigenin-labeled RNA probes. Additionally, immunohistochemistry was performed to characterize the different types of plaques of demyelinating leukoencephalitis. Furthermore, virus antigen and mRNA were detected by immunohistochemistry and in situ hybridization. Healthy control dogs revealed a weak signal for mRNA for MMP-9, MMP-14, and TIMP-1 in various numbers of neurons, astrocytes, microglial cells and oligodendrocytes. In the cerebella of dogs with distemper, a strong increase of both number and staining intensity of MMP-9, MMP-14, and TIMP-1 mRNA-expressing cells, mainly in subacute inflammatory lesions and chronic plaques, was observed. The number of cells expressing mRNA for MMP-9 and MMP-14 increased about two- to threefold compared to TIMP-1 mRNA-expressing cells, whereas staining intensity of individual cells was similar. In early lesions, especially astrocytes and activated macrophages/microglial cells displayed a positive signal for MMPs and TIMP-1, whereas in older lesions activated microglia/macrophages and infiltrating lymphocytes represented the main source for MMP-9, MMP-14, and TIMP-1 mRNA synthesis as revealed by double-labeling techniques. In summary, the proportionally higher increase of MMP mRNA-expressing cells might indicate an MMP/TIMP imbalance as a cause for lesion initiation and progression in demyelinating canine distemper leukoencephalitis.

Animals↗
PubMed1992

Phocine distemper virus, the agent responsible for the 1988 mass mortality of seals.

The biochemical characterisation of phocine distemper virus (PDV) has shown that PDV is related to but clearly distinct from canine distemper virus (CDV) and relative to its relationship with CDV is only remotely related to the other morbilliviruses, namely measles virus (MV) or rinderpest virus (RPV) and peste-des-petits-ruminants virus (PPRV). Comparative studies with monoclonal antibodies indicate that the virus is serologically closely related to CDV with many conserved epitopes, particularly on the internal proteins of the virus, while the external attachment (H) protein shows the greatest level of variability among the distemper virus isolates. The analysis of the viral proteins by electrophoresis indicates molecular weight differences between CDV and PDV in the fusion (F), phosphoprotein (P), H, nucleocapsid (N) and matrix (M) proteins. The RNA profiles of CDV and PDV are indistinguishable and different from those for RPV and MV. Nucleotide sequence analysis of cDNA clones of the virus show approximately 70% homology between CDV and PDV and approximately 48% with MV. These data prove that PDV is a different virus from CDV and co-circulates with it probably primarily in sea mammals.

Animals↗
PubMed1987

Demyelinating canine distemper encephalomyelitis: measurement of myelin basic protein in cerebrospinal fluid.

Beagle dogs were experimentally infected with the Cornell A75-17 strain of canine distemper virus. At three time points post-infection (PI), immunoreactive myelin basic protein (MBP) was measured in cerebrospinal fluid (CSF). Levels were correlated with neuropathological findings, interferon in CSF and virus isolation from the brain. CSF from animals inoculated with Cornell A75-17 strain often showed detectable immunoreactive MBP late in the disease course. As anticipated from earlier morphological studies, CSF drawn around day 20 PI lacked MBP while subsequent samples were positive. Dogs with severe demyelination had elevated values of immunoreactive MBP while dogs with only mild inflammation had little or none. Release of MBP or MBP peptides into CSF of dogs with canine distemper may be a valuable laboratory test in studies of the natural history of this disease and in assessing the response to treatment. Whether an immune response to MBP plays an immunopathogenic role in the chronic, demyelinating phase of canine distemper encephalitis remains to be determined.

Animals↗
PubMed2005

Canine distemper virus-induced depletion of uninfected lymphocytes is associated with apoptosis.

Canine distemper virus (CDV), a negative stranded RNA morbillivirus, causes a multisystemic disease in dogs, which is associated with a severe immune suppression. The aim of the study was to examine the influence of early CDV infection on leukocyte depletion, lymphopenia and virus-induced cell death in dogs infected with a virulent CDV strain. From 10 infected dogs, peripheral blood leukocytes were harvested periodically, phenotyped and analyzed for CDV antigen content and apoptosis using Annexin V-FITC and propidium iodide labeling. CDV infection induced a severe CD3+ T cell and CD21+ B cell depletion in all animals at 3 days post-infection (d.p.i.). For dogs with severe distemper, developing virus persistence in the lymphoid tissue and central nervous system, this lymphopenia lasted until the end of the experiment. Increased levels of lymphocyte apoptosis were found at 3 d.p.i., and monocyte apoptosis at 6 d.p.i. This was more prominent in the group of animals with severe distemper. At 3 d.p.i. no leukocyte infection was detectable indicating that the early lymphocyte depletion and apoptosis was not a direct consequence of virus infection. Taken together, our results demonstrate that CDV-induced lymphopenia is an early event and that the degree of lymphocyte depletion correlates with the severity of disease and virus persistence in the lymphoid tissue and central nervous system.

Animals↗
PubMed2005

Canine distemper virus associated proliferation of canine footpad keratinocytes in vitro.

Infection of canine footpads with canine distemper virus (CDV) can result in so-called hard pad disease characterized by footpad epidermal proliferation and hyperkeratosis. Cultured canine footpad keratinocytes (CFK) were inoculated with a virulent canine distemper virus strain (A75/17-CDV) to study the effects of CDV-infection on keratinocyte proliferation. Infection was analyzed by immunohistochemistry and in situ hybridization for CDV nucleoprotein (N-protein) antigen and mRNA. CDV caused a persistent, non-cytocidal infection with spread from single cells to infection of the confluent cell layer 7 days post infection (p.i.). Absolute cell numbers were significantly higher in infected cultures compared to control cultures from day 4 until day 6 p.i. Infected cultures contained significantly more total DNA on day 5 p.i. compared to controls. Immunohistochemical investigation of proliferation markers Ki67 and BrdU demonstrated a nearly two-fold increase in numbers of positive cells on day 5 p.i. compared to controls. These findings demonstrate that canine distemper virus infection of canine footpad keratinocytes in vitro was associated with proliferation.

Animals↗
PubMed2001

Distemper vaccination of farmed fur animals in Finland.

The most important farmed fur animal species in Finland are the American mink (Mustela vison), blue fox (Alopex lagopus), silver fox (Vulpes vulpes) and raccoon dog (Nyctereutes procyonoides); all are susceptible to canine distemper. The only distemper vaccines currently available are for mink, although they also have been used for fox and raccoon dogs in emergency situations. The efficacy in eliciting neutralizing antibodies and the safety of three mink-distemper vaccines were studied under field conditions with mink and silver fox. Two of the vaccines were also studied with raccoon dogs and blue fox. All three vaccines elicited a satisfactory antibody response in mink, whereas the response varied in the other species. No side effects were observed in any species tested. One of the vaccines was safe and immunogenic in all four species.

Animals↗
PubMed2001

Partial protection and intrathecal invasion of CD8(+) T cells in acute canine distemper virus infection.

Initial non-inflammatory demyelination in canine distemper virus infection (CDV) develops against a background of severe immunosuppression and is therefore, thought to be virus-induced. However, recently we found a marked invasion of T cells throughout the central nervous system (CNS) in dogs with acute distemper despite drastic damage to the immune system. In the present study, this apparent paradox was further investigated by immunophenotyping of lymphocytes, following experimental CDV challenge in vaccinated and non-vaccinated dogs. In contrast to CDV infected, unprotected dogs, vaccinated dogs did not become immunosuppressed and exhibited a strong antiviral immune response following challenge with virulent CDV. In unprotected dogs rapid and drastic lymphopenia was initially due to depletion of T cells. In peripheral blood, CD4(+) T cells were more sensitive and depleted earlier and for a longer time than CD8(+) cells which recovered soon. In the cerebrospinal fluid (CSF) we could observe an increase in the T cell to B cell and CD8(+) to CD4(+) ratios. Thus, partial protection of the CD8(+) cell population could explain why part of the immune function in acute distemper is preserved. As found earlier, T cells invaded the CNS parenchyma in these dogs but also in the protected challenged dogs, which did not develop any CNS disease at all. Since markers of T cell activation were upregulated in both groups of animals, this phenomenon could in part be related to non-specific penetration of activated T cells through the blood brain barrier. However, in diseased animals much larger numbers of T cells were found in the CNS than in the protected dogs, suggesting that massive invasion of T cells in the brain requires CDV expression in the CNS.

Acute Disease↗
PubMed2002

Application of N-PCR for diagnosis of distemper in dogs and fur animals.

The immunofluorescence test, routinely used for laboratory diagnosis of canine distemper virus (CDV) in Poland, is not sufficiently sensitive and specific. Therefore, the application of reverse transcriptase polymerase chain reaction (RT-PCR), nested PCR (N-PCR) and Southern blot hybridization for detection of phosphoprotein (P) gene of CDV in peripheral blood mononuclear cells (PBMCs) or internal organs of dogs and fur animals was the aim of these studies. The optimal parameters for two-step PCR were elaborated for reference strains of distemper virus and used for testing biological samples collected from dogs, foxes, ferret and mink with spontaneous distemper. PCR product of 1069bp was obtained in one out of 10 dog blood samples, three out of 14 homogenates of internal organs of dogs and one out of five homogenates of internal organs of fox. Reamplification with the use of CDVa and CDVb primers demonstrated the 429bp fragment in six samples, negative by PCR: two samples collected from dogs, two from foxes, one from mink and one from ferret. The specificity of N-PCR was confirmed by Southern blot hybridization. We conclude that two-step PCR is sensitive and specific method for diagnosis of CDV infection.

Animals↗
PubMed2005

Comparison of the immunofluorescence assay with RT-PCR and nested PCR in the diagnosis of canine distemper.

Two pairs of primers were prepared, both localized within the sequences of the nucleoprotein gene (NP) of canine distemper virus (CDV). A number of experiments were done to optimize the conditions of RT-PCR and nested PCR methods. The nucleic acids of the Onderstepoort, Rockborn, Snyder Hill and Lederle strains of CDV could be detected with these primers. However, they did not react with the sequences of the Edmonston strain of the measles virus. The detection limit for RT-PCR was 10 TCID50 and for nested PCR 0.1 TCID50 of CDV. The RT-PCR was able to demonstrate the nucleic acid of CDV in the blood of all seven puppies vaccinated with a modified live virus. Blood samples of 23 dogs clinically suspected of distemper were examined by RT-PCR combined with nested PCR, and the results were compared with the detection of the CDV antigen in the smears from the mucous membranes by the direct immunofluorescence (IF) test. Of the 23 dogs, 12 were positive in nested PCR, six in the IF assay, and only two in single RT-PCR. It is concluded that nested PCR seems to be the most sensitive method for ante-mortem diagnosis of canine distemper, especially in its subacute or chronic forms.

Animals↗
PubMed1999

A case of narcolepsy-cataplexy associated with distemper encephalitis.

Narcolepsy associated with localized brain lesions is described in a 10-month-old Argentine Dogo. Neurological examination and MRI study suggested an inflammatory lesion of the left frontal lobe. Postmortem examination revealed diffuse encephalitis in the forebrain and marked necrotic lesions in the ventral pontine area. Immunohistochemistry for distemper virus antigen showed positive staining of the cytoplasm of many neurones of the pons and cerebral cortex. The pathological pattern was suggestive of post-vaccinal distemper encephalitis and the localization of the lesions was consistent with the neurological syndrome shown by the animal. At any event, the possibility of coincidental findings of distemper encephalitis and idiopathic narcolepsy must be accounted for.

Animals↗