Canine Distemper Update from Research to Clinical Practice
World Small Animal Veterinary Association Congress Proceedings, 2018
Somporn Techangamsuwan, DVM, MS, PhD, DTBVP
Associate Professor, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok, Thailand

Canine distemper is a fatal infectious disease which distributed worldwide not only in domestic mammals but also spread through wildlife animals leading to depopulation in endangered species1. The causative pathogen is canine distemper virus (CDV); belonging to the genus Morbillivirus, family Paramyxoviridae; and affects the broad host ranges of the order Carnivora, including Canidae (dogs, foxes), Felidae (cats, lions), Mustelidae (ferret, mink, badger), Procyonidae (raccoons, kinkajous, lesser panda), Ursidae (bear), and Viverridae (civet)2. Recently, CDV expanded its susceptible hosts into the order Rodentia (rodent), and nonhuman primate (monkey)3,4. Additionally, there were some studies reported the detectable antibody titer against CDV in Artiodactyla (pig, dear) and Proboscidea (Elephant)5,6. Viral antigen was also accidentally detected in fleas (Ceratophyllus sciurorum) collected from the carcass of dead mink (Neovison vison). Nevertheless, domestic dogs have been suspected as a probable reservoir for free-ranging wildlife infections due to the potential for asymptomatic carrier animals. CDV has been known causing multisystemic disease and severe immunosuppression in infected hosts.

The main route of infection is via aerosol droplet secretions from the oral or nasal cavities of infected animals and by direct contact from infected to non-infected dogs. However, the role of the horizontal transmission vector, for example flea, remains elusive and need further investigations7. The infection is associated with all lymphatic tissues, epithelium of respiratory, gastrointestinal, and urogenital tracts, as well as the central nervous system (CNS); and optic nerves are also susceptible.

Clinical signs of affected dogs are often listless and have a decreased appetite. In milder cases, signs may be similar to other pathogens causing canine infectious respiratory disease complex (CIRDC)8. In subclinical infection, the viral shedding may also occur depending upon the level of specific humoral immunity in the host during the viremic period. Systemic signs are most common in unvaccinated dogs, particularly puppies aged less than 6 months, as maternal immunity wanes. Conjunctivitis, nasal discharge, cough, and fever are classic signs. Respiratory infection may involve the lower respiratory tract with possible primary viral pneumonia. Secondary bacterial infection is frequently associated and leads to fatal pneumonia. Vomiting and diarrhea may be present. Neurologic signs may be concurrent with epithelial signs, such as respiratory disease, conjunctivitis, vomiting, diarrhea) with encephalitis due to direct viral replication. Seizures and myoclonus are two of the more common signs, in which the latter may affect limbs or may manifest as chewing gum motion. Ocular disease may also present; lesions include anterior uveitis, optic neuritis, and retinal detachment. Infection during pregnancy may lead to abortion or stillbirth. Puppies infected prior to permanent dentition may have enamel hypoplasia. Digital hyperkeratosis may occur in some dogs.

Genome of CDV contains 15,690 nucleotides and possesses a non-segmented, negative sense, single-stranded RNA encoding six core-structural proteins. The proteins are phospho (P)-, nucleocapsid (N)-, large polymerase (L)-, matrix (M)-, fusion (F)- and hemagglutinin (H) proteins. Despite the L, N and P proteins serving together as a viral RNA constitute the ribonucleic protein (RNP), the H and F glycoproteins are well-recognized as a part associated with viral entry process by facilitating the binding and fusion to the host cells, respectively. Moreover, the H glycoprotein, which has a highly genetic variation, also acts as a protective antigen playing an important role of humeral antibody induction. The H gene is now contributed to be a part for strain classification based on genetic and related geographic diversities. To date, the CDV strains have been established at least 14 genetic lineages composing of America-1 and its vaccine strains, America-2, Europe Wildlife, Arctic, South Africa, America-1/Europe, South America-1, -2 and -3, Rockborn, Asia-1, -2, -3, and -4. The CDV Asia-4 strain, which was classified as a new lineage based on the H gene, was initially discovered in domestic dogs in Thailand and recently also detected in China 9,10.

Antemortem diagnosis can be done via virus identification in a clinical sample through use of convention or real-time reverse transcription polymerase chain reaction (RT-PCR) of whole blood, a swab of conjunctiva or nasal, cerebrospinal fluid (CSF), urine. Urine is a good choice for PCR testing in dogs with CDV encephalitis after resolution of epithelial signs. CDV may be detected in urine for a longer period than other sample types. Postmortem diagnosis based on microscopic findings is used to confirm the infection. The pathognomonic lesion is eosinophilic intranuclear/intracytoplasmic inclusion bodies in such infected as glial cells, neurons, epithelial respiratory cells, and cells of the gastrointestinal and urogenital tracts. Virus isolation is the gold standard for diagnosis and is useful in low levels of virus infection through observation of typical syncytial cell formation.

Attenuated live vaccines have been used for controlling the disease for many decades, yet a number of CDV infections in vaccinated dog were still observed. In Thailand, we identified circulating CDV strains into 2 clusters; Asia-1 and Asia-4. By using the restriction fragment length polymorphism (RFLP) techniques, we could effectively differentiate among individual wild-type and vaccine lineages presenting in Thailand.

References

1.  McCarthy AJ, Shaw MA, Goodman SJ. Pathogen evolution and disease emergence in carnivores. Proc Biol Sci. 2007;274(1629):3165–3174.

2.  Techangamsuwan S, Banlunara W, Radtanakatikanon A, Sommanustweechai A, Siriaroonrat B, Lombardini ED, Rungsipipat A. Pathologic and molecular virologic characterization of a canine distemper outbreak in farmed civets. Vet Pathol. 2015;52:724–731.

3.  Qiu W, Zheng Y, Zhang S, Fan Q, Liu H, Zhang F, Wang W, Liao G, Hu R. Canine distemper outbreak in rhesus monkey, China. Emerg Infect Dis. 2011;17:1541–1543.

4.  Sakai K, Nagato N, Ami K, Seki F, Suzaki Y, Iwata-Yoshikawa N, Suzuki T, Fukushi S, Mizutani T, Yoshikawa T, Otsuki N, Kurane I, Komase K, Yamaguchi R, Hasegawa H, Saijo M, Takeda M, Morikawa S. Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008. J Virol. 2013;87:1105–1114.

5.  Heffelfinger JR, Olding RJ, Wesche SL, Reggiardo C. Serologic survey for antibodies to canine distemper virus in collared peccary (Tayassu tajacu) populations in Arizona. J Wildl Dis. 2003;39(1):221–223.

6.  Oni O, Wajjwalku W, Boodde O, Chumsing W. Canine distemper virus antibodies in the Asian elephant (Elaphas maximus). Vet Rec. 2006;;159(13):420–421.

7.  Neovison vison. PLoS ONE. 2014;9: e85598.

8.  Piewbang C, Rungsipipat A, Poovorawan Y, Techangamsuwan S. Development and application of multiplex PCR assays for detection of virus-induced respiratory disease complex in dogs. J Vet Med Sci. 2016;78(12):1847–1854.

9.  Radtanakatikanon A, Keawcharoen J, Charoenvisal N, Poovorawan Y, Prom-petchara E, Yamaguchi R, Techangamsuwan S. Genotypic lineages and restriction fragment length polymorphism of canine distemper virus isolates in Thailand. Vet Microbiol. 2013;166:76–83.

10. Woma TY, van Vuuren M, Bosman AM, Quan M, Oosthuizen M. Phylogenetic analysis of the haemagglutinin gene of current wild-type canine distemper viruses from South Africa: lineage Africa. Vet Microbiol. 2010;143;126–132.

 

Speaker Information
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Somporn Techangamsuwan, DVM, MS, PhD, DTBVP
Department of Pathology
Faculty of Veterinary Science
Chulalongkorn University
Bangkok, Thailand


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