Canine distemper virus infection of vaccinal origin in a 14-week-old puppy
Emily Rätsep1 and Davor Ojkic2
Animal Health Laboratory, University of Guelph, Kemptville, ON1 and Guelph, ON2
AHL Newsletter 2023;27(3):24.
Canine distemper virus (CDV) is a morbillivirus in the Paramyxoviridae family, causing subacute to acute systemic and/or neurological disease in dogs and other carnivorous species. With the increased use of a modified live-virus vaccine against CDV, infections in domestic animals have decreased. Although uncommon, CDV infections can still occur in vaccinated animals. Emergence of new wild type strains resulting in vaccine failure, complications by lingering maternal immunity, and reversion to virulence of a modified life vaccine have all been reported.
A 14-week-old puppy presented for postmortem following a history of intermittent issues with anorexia and lethargy since 10 weeks of age. Various potential causes including intussusception, intestinal foreign body, hypothyroidism, hepatic shunt and cardiac disease were ruled out with no change in presentation. Initial vaccines (canine morbillivirus, adenovirus, parainfluenza and parvovirus) were administered at 7 and 12 weeks. The 12-week vaccine was later than desirable as the puppy was too sick for vaccination at an earlier date. The puppy had not yet been vaccinated for rabies. The puppy’s clinical signs progressed to pyrexia and lethargy with pruritic skin rash, green mucoid nasal discharge, decreased mentation, dysphagia, muscle twitches and ventral strabismus of the right eye within 48 hours of euthanasia. Focal seizures (4 in one day) were the ultimate reason for electing euthanasia.
On gross postmortem examination, a mucopurulent rhinitis and pulmonary edema were noted. Histologically, changes in the lungs were far more florid and consisted of marked necrosis with fibrin deposition and abundant neutrophilic inflammation (Fig. 1). A neutrophilic and lymphohistiocytic rhinitis was confirmed. The cortical grey and white matter of the brain contained rare small glial nodules (Fig. 2). Rare individual neutrophils were occasionally seen in the choroid. Other histological findings included tracheitis (presumed secondary to the pulmonary changes), and a portal bridging fibrosis with mild biliary hyperplasia (significance undetermined). The combination of the initial gross and histological findings suggested acute septicemia and aspiration pneumonia were possible causes of the decline in this puppy. While bronchopneumonia was present, no distinct syncytial cells or viral inclusions were observed in any tissue, nor were any histological changes supportive of demyelinating leukoencephalitis observed. Other findings typically associated with canine distemper such as enamel hypoplasia, hyperkeratosis of the footpads and conjunctivitis were also not observed.
Considering the clinical history and change in mentation, testing for canine distemper virus (CDV) by PCR was carried out on lung and brain tissue, and both were PCR-positive for CDV with cycle threshold numbers of 22.09 and 25.26, respectively. Immunohistochemistry was performed on brain for further confirmation, and CDV was detected (Fig. 3). Moderate growths (2+) of Staphylococcus pseudintermedius were cultured in both tissues also, suggesting that a concurrent bacterial infection was present, possibly secondary to aspiration and systemic spread, explaining some of the lesions observed in the lung and brain.
The PCR-positive sample from the brain was genotyped, and was a 99.9% match to the Rockborn strain of CDV (Fig 4), providing evidence to support the hypothesis that the disease in this case was vaccinal in origin. The Rockborn CDV strain was originally isolated in Sweden and attenuated in canine kidney cells, and has been used since the 1960s in several live-attenuated CDV vaccines.
Vaccine-associated canine distemper infections have been reported in multiple breeds, usually following vaccination with attenuated or modified-live canine distemper virus vaccines. Clinical signs typically develop within 3 weeks of vaccination, and can include seizures and circling, or changes in behaviour. Reversion to virulence most commonly occurs in immunosuppressed animals (immunocompromised or animals with concurrent infections, including parvovirus), or is demonstrated in isolated cases as a post-vaccinal encephalitis. In these and in peracute cases, characteristic inclusion bodies or prominent demyelination may be absent; therefore, demonstration of the CDV antigen in neurons is required to confirm the diagnosis.
In this case, CDV antigen was expressed in neural tissue (IHC) and confirmed by PCR testing of the lung and the brain. Additionally, CDV hemagglutinin gene sequencing allowed for confirmation that the virus was identical to a vaccine strain. This case serves as a reminder of the possibility of reversion to virulence when using modified-live vaccines, and the importance of assessing general health and wellness of an individual prior to vaccination. AHL
Figure 1. Lung from a 14-week-old puppy. There is necrosis of alveolar walls with fibrin deposition and numerous macrophages and degenerate neutrophils (H&E stain, 10x)
Figure 2. Brain from a 14-week-old puppy. There are rare clusters of increased glial cells (*) in the cortical grey mater (H&E stain, 20x)
Figure 3. Brain (hippocampus) from a 14-week-old puppy. Clusters of neuronal cell bodies and nerve processes are intensely positive for expression of the canine distemper virus antigen (IHC stain canine distemper virus, 20x)
Figure 4. Sequence distances comparing the clinical sample with CDV hemagglutinin gene sequences from GenBank. Percent identity in upper triangle; percent divergence in lower triangle.
References
1. Martella V, et al. Canine distemper virus. Vet Clin Small Anim 2008;38:787-797.
2. Cornwell HJ, et al. Encephalitis in dogs associated with a batch of canine distemper (Rockborn) vaccine. Vet Rec 1988;122(3):54-9.
3. Durchfeld B, et al. Vaccine-associated canine distemper infection in a litter of African hunting dogs (Lycaon pictus). J Vet Med B 1990;37:203-212.
4. Appel MJG. Reversion to virulence of attenuated canine distemper virus in vivo and in vitro. J Gen Virol 1978;48:385-393.
5. Feijoo G, et al. Central nervous system lesions caused by canine distemper virus in 4 vaccinated dogs. J Vet Diagn Invest 2023;33(4):640-647.
6. Martella V, et al. Lights and shades on an historical vaccine canine distemper virus, the Rockborn strain. Vaccine 2011;29(6):1222-7.