Avian Newcastle Virus Infection

Avian Newcastle disease virus (Paramyxovirus) has been experimentally inoculated into the CNS of domestic adult cats and kittens, producing disseminated encephalomyelitis.22,33 Neonatal kittens can also be infected by intraocular or intranasal exposure to large quantities of virus. The incubation period of oculonasally administered virus was relatively long (11 to 17 days) compared with that after direct CNS inoculation (3 to 4 days). Clinical signs of encephalomyelitis were seizures, head tilt, and myoclonus. Progressive lower motor neuron paralysis developed in limbs and cranial nerve musculature. In some affected animals, behavioral alterations were present. A disseminated nonsuppurative meningoencephalitis was found histologically; virus appeared to spread throughout the nervous system along descending and ascending neuronal pathways.

Untyped Paramyxovirus Infection

A paramyxovirus-like agent has also been isolated from the CNS of naturally infected cats that had focal demyelinating encephalitis and inclusion body formation.¹¹ The virus was isolated from affected cats by cocultivating CNS tissue with fetal feline kidney cell lines. The isolated virus, serologically unrelated to known paramyxoviruses, was inoculated into the CNS of neonatal mice that developed a similar encephalitis 5 months later.

Paramyxovirus-like nucleocapsids have also been observed by electron microscopy in explant cultures of CNS tissue from clinically healthy cats or those with demyelinating optic nerve lesions that were cocultured with feline kidney or Vero cell lines.⁶⁴ The significance of these ultrastructural findings is uncertain.

Nonsuppurative encephalitis has been reported in a captive adult Siberian tiger (Panthera tigris), in which intranuclear inclusion bodies detected on light microscopy and nucleocapsid material detected on electron microscopy were found to be similar to those of viruses of the family Paramyxoviridae.²¹ These observations could represent infections with canine distemper virus (CDV) or a variant, but definitive information is unavailable. A morbillivirus, suspected to be CDV, was detected by immunohistochemical methods reported in the CNS of a free-ranging Siberian tiger (Panthera tigris altaica) with neurologic dysfunction.^50a

Canine Distemper Virus Infection

CDV, a Morbillivirus, has been shown to infect a wide variety of terrestrial carnivores. Domestic cats were experimentally inoculated, but clinical signs were absent (see Epidemiology, Chapter 3). Domestic cats housed in close proximity to dogs have had virus-neutralizing antibodies to CDV; however, clinical illness has not been documented.^30,32 In contrast to domestic cats, large exotic Felidae appear to be more susceptible to infection with CDV. Isolates appear to be immunologically similar to virulent isolates from other carnivores, but this finding does not exclude differences in viral biotypes.⁵ Mutant viral strains, originating from wildlife and domestic dogs in close proximity to the exotic cats, are the most likely explanation for common prevalence of seropositive results to CDV, and outbreaks of CDV infection, in non-CDV vaccinated exotic cats.* Noncanid carnivores, such as raccoons, may also act as vectors of CDV for exotic cats in zoological gardens.³¹

A number of investigations have been reported concerning the possible role of CDV in causing clinical illness in exotic cats. CDV and other viruses were not identified as a cause of chronic progressive myelopathy in cheetahs (Acinonyx jubatus).⁵⁶ However, a chronic, progressive, nonsuppurative meningoencephalitis, clinically and pathologically similar to that caused by CDV in dogs, has been described in a Bengal tiger (P. tigris).² Marked increases in serum and cerebral spinal fluid antibodies against CDV were found. Myoclonus was similar to that seen in other paramyxovirus-type infections in dogs and cats. CDV was suspected as the cause of respiratory and neurologic disease in two snow leopards (Uncia uncia) that had simultaneous feline panleukopenia.¹⁹ CDV was not isolated; however, histologic lesions, intranuclear inclusions, virus ultrastructure, immunofluorescence, and serologic testing were all positive for CDV infection. Feline panleukopenia virus–induced immunosuppression was presumed to have allowed development of CDV infection.

Sequential serosurveys of captive lions (Panthera leo) from a zoologic exhibit in Japan indicated seroconversion in greater than 50% of the animals substantiating an outbreak.¹⁴ Canine distemper outbreaks have occurred in captive leopards (Panthera pardus), tigers, lions (P. leo), and a jaguar (Panthera onca) in North America.^5,66 Initial illness was manifest systemically by anorexia, gastrointestinal or respiratory signs (or both), followed by CNS signs of ataxia, myoclonus, seizures, and coma. The source of infection for one of these latter epizootics was CDV-infected raccoons and skunks having a concurrent outbreak. Viruses isolated from the affected cats were identified as CDV by monoclonal antibody testing and genetic analysis. The isolates were linked to strains from the feral nonfelid hosts and not vaccine virus.²⁶ CNS lesions were focal and mild, consisting of nonsuppurative polioencephalitis, lymphocytic meningitis, and mild microgliosis in white matter. These lesions were less extensive and severe and did not have the demyelination and perivascular cuffing as typically observed in infected dogs. These features are more typical of acute CDV infection in susceptible carnivores (see Chapter 3).⁶¹

In 1994, an outbreak of CDV infection occurred in lions in the Serengeti in Tanzania.24,38,54,58 Clinical signs included seizures, myoclonus, and other neurologic symptoms. Pathologic findings were encephalitis and pneumonia. Histopathologic changes typical for CDV infection was seen in 18 of 19 lions examined. Inclusion bodies immunologically cross-reacting with CDV proteins were identified in 14 of 19 lion samples that were available for examination. Of 83 serum samples tested for anti-CDV antibodies, 71 were found to be positive for CDV.⁵⁴ To determine the genetic relationship of the virus involved in the disease outbreak with other morbilliviruses, buffy-coat cells collected from two lions with neurologic signs were subjected to reverse transcriptase–polymerase chain reaction, and the nucleotide sequence of the conserved P gene was determined.⁵⁴ These tests suggested that the lion CDV isolate was closely related to the Onderstepoort strain of CDV. The belief holds that the lion distemper outbreak originated from distemper infections in domestic dogs living around the Serengeti parks. However, for transmission between dogs and lions, hyenas were probably responsible. Based on neurologic signs, several hyenas were found to be affected and were also proved to be infected with CDV. In addition, hyenas, in contrast to lions, are known to roam into the villages of the local inhabitants, where they may have come into contact with domestic dogs. Natural exposure or infections with CDV have been shown in wild canids in Africa.^1,57 To determine whether the presence of other lion viruses may have favored the susceptibility to CDV, serum samples were tested for presence of antibodies to feline immunodeficiency virus feline herpesvirus-1, feline calicivirus, feline panleukopenia virus, and feline coronaviruses. No relationship between the occurrence of CDV and antibodies to these other pathogens was found. Despite the apparent recent appearance of outbreaks of CDV infection in exotic Felidae, retrospective analysis of cases indicated infections as far back as 1972.⁴⁵ CDV mortality in free-roaming lions has been correlated with simultaneous surges in hemoparasitism with Babesia in conjunction with droughts and extreme climatic conditions.⁴²

To reduce the probability of future outbreaks of CDV in lions, a program to vaccinate the domestic dogs living around the parks has been initiated, and vaccination is recommended for all captive large Felidae. Inactivated distemper virus vaccine has been recommended to protect large exotic Felidae against infection with this virus.⁵ However, the efficacy of inactivated vaccines in dogs and other exotic carnivores, not to mention cats, has not been documented. Because chick embryo–adapted (Onderstepoort strain) or recombinant vector-based vaccines are generally safer than tissue culture–adapted (Rockborn strain) ones, they should be considered for evaluation in large Felidae.^4,5

Hendra Virus (Equine Morbillivirus) Infection

In September 1994, an outbreak of acute respiratory disease in horses occurred in Hendra, a suburb of Brisbane, Queensland, Australia.16,43 The horses developed pneumonia that was clinically characterized by anorexia, depression, pyrexia, tachypnea, and ataxia. Terminally, head pressing and a frothy nasal discharge occurred. A stable hand and horse trainer became ill with an influenza-like illness. The stable hand was ill for 6 weeks, and the trainer died of respiratory distress. A novel virus closely related to but distinct from Morbillivirus was isolated from both the horses and the people. Another episode was retrospectively identified in Mackay, a town in North Coastal Queensland in a farmer who developed an acute progressive encephalitis.⁵⁵ The farmer had assisted with treatment and subsequent necropsy of the affected horses. Most interestingly, the horses developed myoclonic twitches similar to those observed in dogs with canine distemper. Meningoencephalitis has subsequently been documented in experimentally infected horses.⁶⁵

The predominant pathologic lesions in horses from the Hendra outbreak were in the lungs, which were congested and edematous. Histologically, interstitial pneumonia with pneumocyte and capillary degeneration was apparent.²⁹ Virus was immunologically detected in the endothelial cells by direct fluorescent antibodies. In the Mackay episode, virus was detected by positive polymerase chain reaction in cerebrospinal fluid and in the Hendra episode, in brain tissue and serum.⁴⁸

The Hendra virus was unusual in its ability to grow in cell cultures originating from a significant number of animal species, including submammalian vertebrates.⁸ A large number of laboratory animal species, including dogs and cats, were experimentally inoculated subcutaneously with the virus.^29,63 The dogs and cats were vaccinated for common viral diseases but notably the dogs for CDV. The dogs did not become ill, but the cats developed inappetence and tachypnea by the fifth day postinoculation and died on the sixth and seventh days postinoculation. The cats had gross lesions of pulmonary edema, hilar lymphadenomegaly, pneumonia, and pleural effusion. Histologic lesions of vasculitis matched those in affected horses. The virus was isolated from the lungs, spleen, kidney, and brain. Surviving cats did not develop specific serum viral neutralizing antibody. Cats have also been experimentally infected via intranasal and oral exposure to virus and by direct contact with previously infected cats.²⁸ Because Hendra virus is so genetically distinct from other morbilliviruses, it is suspected to have existed for a long time and to have been acquired from a mammalian reservoir host. Of all laboratory species inoculated, cats were most susceptible and developed an illness that matched that in horses and in people. Virus does enter the nervous system of cats; however, they develop no signs of neurologic dysfunction.

A limited serosurvey of cats in the metropolitan Brisbane area did not reveal detectable antibody to the virus.⁶³ Subsequent studies in cats have shown that they can be infected by nonparenteral routes and that the virus can spread naturally among cats.⁶² Of many wildlife species tested, Pteropus bats have serum antibodies to the virus and may be the reservoir species.⁶⁷ Transmission from bats to another species, such as the horse, may be required for human exposure.

In-contact transmission studies have shown that the virus is not highly contagious. Horses in direct contact with experimentally infected cats and infected horses in contact with other horses or cats did not transmit infection.⁶⁵ Similarly experimentally infected cats did not transmit the infection to horses. In experimentally infected animals, regardless of species, organisms were most prevalent in the kidney and urine, which suggests urinary transmission as the means of spread.⁶⁵ The organism was isolated for up to 3 weeks after infection of a horse and 14 months in a human developing infection, suggesting viral persistence and a carrier state.