Max J. G. Appel

Canine Distemper Virus

Distemper is not a very precise description of a disease entity, and the Oxford Dictionary lists a vast number of different meanings for the word “distemper”: “It argues sickness and distemper in the mind as well as in the body.” In connection with dogs it has been applied for centuries for “that fatal disorder proper to the canine race called par excellence, the distemper”. Besides rabies, canine distemper (CD) is the only virus disease in dogs with a high mortality rate. It has a worldwide distribution and only few dogs in isolated areas remain without contact with the virus. According to some reports (Kirk, 1922; Geiger, 1939) CD made its first appearance in Europe in Spain in 1761, introduced from either Asia or Peru. From Spain it spread to all European countries within the same century. Jenner, well known for his development of a successful smallpox vaccine, made its first accurate description in 1809.

Canine Distemper Epizootic in Lions, Tigers, and Leopards in North America:

Canine distemper virus (CDV) infection occurred in captive leopards (Panthera pardus), tigers (Panthera tigris), lions (Panthera leo), and a jaguar (Panthera onca) in 1991 and 1992. An epizootic affected all 4 types of cats at the Wildlife Waystation, San Fernando, California, with 17 mortalities. CDV-infected raccoons were thought to be the source of infection in these cats. Two black leopards died at the Naibi Zoo, Coal Valley, Illinois, and 2 tigers died at the Shambala Preserve, Acton, California. Initial clinical signs were anorexia with gastrointestinal and/or respiratory disease followed by seizures. Canine distemper virus was isolated from 3 leopards, 3 tigers, and 3 lions that died or were euthanized when moribund. Monoclonal antibody testing identified the virus isolates as CDV. Gross and histopathologic findings were similar to those found in canids with distemper with a few exceptions. There were fewer lesions in the brain, and there was a pronounced type 2 cell proliferation in the lung, with inclusion bodies and CDV antigen demonstrated by immunohistology. Neutralizing antibody to CDV was found in high titers in serum from most animals but was absent or was found only in low titers in some cats that succumbed after CDV infection. There was a marked difference in neutralizing antibody titers when tests were done with different strains of CDV.

Pathogenicity of morbilliviruses for terrestrial carnivores

Many different species of the order Carnivora are susceptible to canine distemper and the mortality rate varies greatly between species. Ailuridae, Canidae, Hyaenidae, Mustelidae, Procyonidae, Ursidae, Viverridae and now Felidae have been reported to be susceptible to canine distemper virus infection. Although distemper outbreaks in dogs, fur farms and in zoo carnivores have been greatly reduced in recent years due to vaccination, there are still regular outbreaks in free-living carnivores. Unexpected outbreaks of canine distemper have occurred in exotic felids in a California wildlife park and in the Serengeti in Tanzania as well as in javelinas (collared peccaries, Tayassu tajacu) in Arizona. Although safe and efficacious in dogs, modified live canine distemper virus vaccines may be dangerous for a variety of zoo and wildlife carnivores, especially red pandas (Ailurus fulgens) and black footed ferrets (Mustela nigripes).

Viruses of the Serengeti: Patterns of Infection and Mortality in African Lions

Summary 1. We present data on the temporal dynamics of six viruses that infect lions (Panthera leo) in the Serengeti National Park and Ngorongoro Crater, Tanzania. These populations have been studied continuously for the past 30 years, and previous research has documented their seroprevalence for feline herpesvirus, feline immunodeficiency virus (FIV), feline calicivirus, feline parvovirus, feline coronavirus and canine distemper virus (CDV). A seventh virus, feline leukaemia virus (FeLV), was absent from these animals. 2. Comprehensive analysis reveals that feline herpesvirus and FIV were consistently prevalent at high levels, indicating that they were endemic in the host populations. Feline calici‐, parvo‐ and coronavirus, and CDV repeatedly showed a pattern of seroprevalence that was indicative of discrete disease epidemics: a brief period of high exposure for each virus was followed by declining seroprevalence. 3. The timing of viral invasion suggests that different epidemic viruses are associated with different minimum threshold densities of susceptible hosts. Furthermore, the proportion of susceptibles that became infected during disease outbreaks was positively correlated with the number of susceptible hosts at the beginning of each outbreak. 4. Examination of the relationship between disease outbreaks and host fitness suggest that these viruses do not affect birth and death rates in lions, with the exception of the 1994 outbreak of canine distemper virus. Although the endemic viruses (FHV and FIV) were too prevalent to measure precise health effects, there was no evidence that FIV infection reduced host longevity.

Nonreplicating viral vectors as potential vaccines: recombinant canarypox virus expressing measles virus fusion (F) and hemagglutinin (HA) glycoproteins.

The development of canarypox virus (CPV) recombinants expressing the hemagglutinin (HA) and fusion (F) glycoproteins of measles virus (MV) is described. Inoculation of the CPV-MV recombinants into avian or nonavian tissue culture substrates led to the expression of authentic MVF and MVHA as determined by radioimmunoprecipitation and surface immunofluorescence. In contrast to avian-derived tissue culture, no productive replication of the CPV recombinant was evident in tissue culture cells derived from nonavian origin. On inoculation of dogs, a species restricted for avipoxvirus replication, the recombinants elicited a protective immune response against a lethal canine distemper virus (CDV) challenge. The level of MV neutralizing antibodies and the level of protection induced against CDV challenge achieved by the host-restricted CPV vector were equivalent to that obtained by vaccinia virus vectors expressing the same MV antigens.

AFRICAN WILD DOGS (LYCAON PICTUS) ENDANGERED BY A CANINE DISTEMPER EPIZOOTIC AMONG DOMESTIC DOGS NEAR THE MASAI MARA NATIONAL RESERVE, KENYA

A longitudinal study of canine distemper (CD) among domestic dogs on Maasai communal land to the north of the Masai Mara National Reserve in Kenya was conducted from 1989 to 1991. Prevalence of antibodies to CD was very low among domestic dogs in 1989 and 1990 (4%, n = 49; and 1%, n = 119, respectively) and no African wild dogs (Lycaon pictus; n = 16) collected simultaneously from the same area had detectable antibodies. Among 51 domestic dogs sampled in 1991, however, prevalence of CD antibodies rose significantly (P < 0.01) to 76%. Disease-related mortality rates among domestic dogs were estimated from 1990 to 1992; they rose significantly (P < 0.01) from 21% in 1990 to 50% in 1991 and then decreased significantly (P < 0.01) to 38% in 1992. The 1992 mortality rate remained significantly (P < 0.01) higher than that of 1990. Signs observed in clinically ill domestic dogs were consistent with CD and included listlessness, decreased appetite, bilateral serous to mucopurulent oculonasal discharge, and diarrhea. No carcasses could be retrieved for virus isolation and postmortem examination. Concurrent with this CD epizootic in domestic dogs, the known African wild dog packs in this region disappeared.

Studies on manifestations of canine distemper virus infection in an urban dog population.

An upsurge of canine distemper was recognized at the beginning of 1991 in the urban dog population of the Copenhagen area. The outbreak had the characteristics of a virulent morbillivirus introduction in a partly immune population, where the disease primarily was manifested in young individuals. Testing of single serum samples for the presence of canine distemper virus (CDV) IgM antibodies using an IgM ELISA confirmed current and recent CDV infections in an urban dog population, where the use of attenuated CDV vaccines was widespread. In 49 out of 66 sera from clinical cases suspected of canine distemper we detected CDV IgM antibodies, as compared to the detection of viral antigen by indirect immunofluorescence in 27 of 65 specimens of conjunctival cells. The antigenic make-up of isolates from acute and subacute clinical cases was investigated with a panel of 51 monoclonal antibodies directed against CDV and the related phocine distemper virus. The isolates exhibited an homogeneous reaction pattern and shared overall antigenic characteristics of the CDV prototype. The majority of cases were diagnosed among unvaccinated dogs and individuals with unknown or obscure vaccination record. However, severe clinical cases were also diagnosed in vaccinated individuals.

Canine distemper encephalomyelitis: Variation with virus strain

Disease induced by 3 virulent strains of Canine Distemper Virus (CDV) was compared in specific pathogen-free Beagle dogs. All strains produced an encephalomyelitis but variation was observed in the severity, clinical course and resulting neuropathology. Infection with Snyder Hill strain of CDV was consistently acute; dogs either succumbed 14 to 19 days post-inoculation (PI) or recovered. Lesions in the neuraxis were those of a polioencephalomyelitis. In contrast, CDV strain A75-17 produced subacute to chronic disease in which demyelination was the predominant finding. Some dogs succumbed, generally around 28 to 42 days PI. Total recovery was again recorded for some members of the group. Others developed persistent central nervous system (CNS) infection but remained clinically stable until electively killed with barbiturate, up to 62 days PI. CDV strain R252 also induced delayed, predominantly white matter disease with a mixed pattern of mortalities, persistent infections and recoveries, similar to A75-17. Neutralizing antibody responses correlated with the disease course. Dogs which died had low serum titres or lacked serum antibody. Recovering dogs had the earliest and highest titres. A few dogs with persistent CNS infection had antibody in the cerebrospinal fluid also. Current concepts of the pathogenesis of canine distemper encephalomyelitis (CDE) are discussed and a basis for the strain-dependent clinical and pathological expression of CDE is proposed. Viral strain appears to be an important factor in this common disease of the canine CNS.

Genetic diversity of the attachment (H) protein gene of current field isolates of canine distemper virus

To characterize the variability of recent field isolates of canine distemper virus (CDV) from different hosts and geographical areas, we conducted nucleotide sequence analysis of the gene encoding the haemagglutinin (H), the attachment protein of this virus. Pronounced differences between field isolates were revealed in comparison to the Convac and Onderstepoort vaccine strains. The diversity of CDV appeared to exceed that determined for measles virus. Phylogenetic analysis also separated the field isolates of CDV from the vaccine strains and provided evidence for the existence of different contemporary genotypes of CDV. Isolates from a Greenlandic sledge dog and a Siberian seal formed a distinct lineage. The remaining isolates formed a group. This group contained two European isolates from mink and ferret, a single lineage comprising three European dog isolates, and another separate lineage of North American isolates from dog, javelina, raccoon and captive leopards.

Early events in canine distemper demyelinating encephalomyelitis

SummaryThe early neuropathological development of demyelinating Canine Distemper Encephalomyelitis (CDE) was studied in SPF dogs. Neural tissues were examined up to 30 days post infection (PI). Three phases of activity were observed. The primary event (first observed 8 days PI) was a nonsuppurative encephalomyelitis associated with the initiation of central nervous system (CNS) infection by virus-laden lymphocytes. At 24 days PI noninflammatory demyelination occurred in well defined, subependymal foci. Cell fusion and syncytia formation accompanied this early demyelination. The third phase, found at day 30 PI in one dog showing signs of recovery, was a second wave of nonsuppurative inflammation. The initial encephalomyelitis was widely disseminated throughout the CNS but subsequent demyelination appeared to be initiated from within the ventricular system. Myelin was phagocytosed by endogeneous CNS macrophages often infected with Canine Distemper Virus (CDV). The possible importance of viral induced cell fusion as well as immune factors in the mechanism of demyelination are discussed.