Dr Lynda Bonning
Canterbury Veterinary Clinic & Hospital
721 Canterbury Rd, Surrey Hills, Victoria 3127
This paper explores the diagnosis, treatment, containment, quarantine and preventative management of a Canine Distemper Virus (CDV) outbreak in a large group of ferrets in a rescue facility.
Education and implementation of quarantine, disinfection and vaccination protocols stopped the spread of CDV. Vitamin ADE injections attenuated the course of the disease and reduced the potential mortality rate from 100% to 4%. As a result, it is recommended that the treatment of any ferret displaying symptoms of CDV should include Vitamin ADE injections. (i.e. Vitamin A 50,000 IU intramuscularly once daily for 2 days). To prevent infection vaccination of ferrets over the age of 10 weeks should be carried out. Vaccination protocol is 1/5th of a dose of trivalent canine vaccine given twice, 4 weeks apart (1,2,3) and then annually.
Canine Distemper Virus (CDV) is an acute contagious disease affecting mainly the respiratory system, nervous system and skin (1,2,3), it produces severe symptoms and can have a 100% mortality rate in ferrets (1,2,3). CDV has a world-wide distribution and a large host range (8). Although dogs are the main reservoir of CDV, it is a multihost pathogen. Dogs, dingoes, foxes, coyotes, wolves, ferrets, badgers, mink, weasels, racoons and hyenas are amongst the carnivores that are susceptible to CDV. Some of these species, in particular the feral fox, could act as a source of infection for domestic dogs and ferrets in Australia (5,6,7,8).
Vaccination of dogs with attenuated live or recombinant vaccines since the 1960’s has provided immunity and dramatically reduced the incidence of canine distemper. However, recent studies have suggested a world-wide increase in the incidence of CDV, in both vaccinated and unvaccinated populations and outbreaks in ferrets have also been reported (8). It is not thought that this increase in incidence is due to lack of vaccine efficacy, but rather is due to lack of vaccination in susceptible populations, improper vaccine timing, incorrect administration, storage or handling or patient immunosuppression (8).
The Incidence of CDV disease in dogs and ferrets in Australia is low. In a retrospective study Wyllie et al (8) found 48 individually affected dog and ferrets in 27 case groups from 2006 – 2014. Of this 48, 20 were confirmed ferret CDV cases.
CDV is a Morbillivirus in the paramyxoviridae family, closely related to the measles virus in humans and Rinderpest virus in cattle (1,2,3). The virus is relatively fragile in the environment but can remain viable for up to 20 minutes on fomites (1). Transmission is primarily aerosol (1,2,3) and macrophages carry the virus from nasal cavity, pharynx and lungs to the local lymph nodes where it replicates (2). Viraemia occurs within 2 days of exposure (2). Incubation period is 7 – 10 days and shedding can start 7 days after exposure (1,2). Replication occurs rapidly in multiple organs and viraemia persists until the virus is neutralised by antibodies or the ferret dies (3). Ferrets shed virus in all body excretions: conjunctival and nasal exudates, urine, faeces and skin (1,2,3); and unvaccinated ferrets usually die within 12 – 35 days after exposure depending on the severity of the strain (3).
Symptoms of CVD in ferrets include (1,2,3):
The disease is characterised by a diphasic fever, first occurring at day 7 – 8 post infection at which time signs are inapparent or mild. The second fever occurs at day 11- 12 post infection when symptoms become more obvious. Virus shedding occurs during the entire time. Anti-CDV antibodies develop 10 -14 days post infection. Within 1 – 3 weeks depression and neurological signs become apparent and the mortality rate is almost 100%. (1,2,3,4).
Three, of a litter of five, 20-week-old female entire ferrets from a ferret rescue facility presented with purulent conjunctivitis, blepharospasm, dermatitis of the lips, chin and ear margins, swelling of the pinnae and pyrexia (40.2 C). All three ferrets were anorexic and dehydrated. This litter of 5 had been at the ferret rescue centre for 5 days and the symptoms had started 2 days before presentation. They were housed with 2 other unrelated ferrets that were asymptomatic (Cage A).
The differential diagnosis was a dermatological disease (bacterial infection, fungal infection, parasitic disease, autoimmune) or CDV (1,2,3,). As the ramifications for the ferrets and the implications for the facility if it were CDV was critical, immediate action was taken assuming a CDV outbreak.
At this time there were 54 ferrets housed at the facility, including a jill with a litter of 4 one-week old kits. The client was advised of the possibility of 100% mortality and strict disinfection and containment protocols were put in place to try to manage the possible outbreak.
All 3 symptomatic ferrets were euthanised and sent to Australian Specialised Animal Pathology (ASAP) for full post mortem, histopathology and Polymerase Chain Reaction (PCR) for CDV. Gross Post mortem changes were identified in the skin, periocular tissues and lungs that could be consistent with CDV however other causes of dermatitis needed to be excluded. Skin samples and periocular tissue from all ferrets were placed in formalin, as well as a range of other tissues including brain for histopathology. Ocular swabs were taken from all animals and lung samples were frozen.
Forty-eight hours later the other two litter mates from Cage A presented with blepharospasm and eyelid dermatitis. In addition, two unrelated adult ferrets (2 and 3 years old) with ocular signs and chin dermatitis were identified from a Cage B. Cage B was in an area geographically isolated from Cage A and housed 8 ferrets. This confirmed an infectious agent and cross contamination between cages through fomites (1,2,3).
The two ferrets with mild ocular signs in Cage A were treated symptomatically with Betamox (Norbrook Amoxycillin 50mg/ml ) – 12.5 mg orally twice daily; Conoptyl eye gel (Dechra Fusidic acid 10mg/g) – 1 drop in each eye twice daily; and Pyohex lotion (chlorhexidine) for topical treatment of the skin. They were also given an intramuscular injection of Vitamin ADE – see Management and Outcome section below for more detail. The two symptomatic adult ferrets from Cage B were euthanised.
Histopathology results from the first three ferrets revealed chronic hyperkeratotic and hyperplastic dermatitis with follicular keratosis and folliculitis. Numerous yeast and a moderate bacterial load was found. Occasional intranuclear and intracytoplasmic inclusion bodies consistent with Canine Distemper Virus infection were also identified. However, confirmation of the diagnosis of CDV with PCR (on ocular swabs) was required.
On day 9 of the outbreak a ferret was found with periorbital and lip dermatitis as well as pasty loose stools and a mild rectal prolapse This ferret was in Cage C which was underneath Cage B. This ferret was treated symptomatically with Betamox (Norbrook Amoxycillin 50mg/ml ) – 12.5 mg orally twice daily; Conoptyl eye gel (Dechra Fusidic acid 10mg/g) 1 drop in each eye twice daily and Pyohex lotion (chlorhexidine) for topical treatment of the skin and . This ferret was also given an intramuscular injection of Vitamin ADE – see Management and Outcome section below for more detail.
On day 10 of the outbreak the two ferrets from Cage A deteriorated significantly. Symptoms included anorexia, dehydration, reduced mentation, hind limb ataxia and collapse. No seizures were observed, both were euthanised.
Management and Outcome
Instructions were issued for the facility to be in lock down – no animals in or out until further notice and strict disinfection and containment protocols were implemented. (Appendix 1). All ferrets in the facility were observed twice daily for signs of illness. Any symptomatic ferrets were quarantined for further veterinary assessment.
As the vaccination status of rescued and surrendered ferrets was unknown, immediate vaccination of all ferrets over the age of 10 weeks was undertaken. The vaccination protocol is two vaccinations 4 weeks apart (1,2,3). As no vaccine for CDV alone is available in Australia a one fifth dose of Nobivac DHP (contains attenuated Canine Distemper Virus, Canine Adenovirus type 2 and Canine Parvovirus) was given. This was achieved by reconstituting the vaccine with 1.5 ml of diluent and administering 0.3mls subcutaneously to each ferret. Forty-eight of the fifty-three ferrets were vaccinated (four nursing kits were not vaccinated) and the two ferrets identified with chin and periocular dermatitis were euthanised – Cage B.
Vaccinations were given the day after the first three ferrets presented (day 1).
As The vaccine takes 14 days to stimulate effective antibody protection (1,2,3,4) all in-contact non-vaccinated ferrets are susceptible to infection during this time. Symptoms usually occur within 10 days of exposure to the virus, which would imply 15 days + 10 days is required to determine if a ferret had been exposed and infected with CDV. Although 25 days should have been a sufficient time frame, 50 days of facility lock down was implemented. After the quarantine period, it was recommended thatonly vaccinated ferrets be accepted into the facility for boarding and rescued ferrets of unknown immune status were to be vaccinated and quarantined within the facility or fostered out for 14 days while they develop protective antibodies.
Rodeheffer et al (4) demonstrated that Vitamin A (Retinol palmitate (Aquasol A Mayne Pharma) supplementation at the time of CDV infection can significantly reduce morbidity in ferrets. Specifically they found that ferrets on a balanced diet (Vitamin A replete) infected intranasally with CDV(Control Group) developed the following symptoms: epidermal rash of the mouth, chin, ears and torso, pyrexia, conjunctivitis, coryza, cough, diarrhoea and dehydration. Ferrets on a balanced diet (Vitamin A replete) that received an intramuscular Vitamin A injection (50,000 IU) at the time of intranasal infection with CDV (day 0) and a second dose of 50,000 IU on day 1 (Experimental Group) developed epidermal rash of the mouth, chin, ears and torso. The symptoms in this group were so mild that they did not meet the clinical definition of CDV as defined for this study.
The study proved that Vitamin A supplementation reduced morbidity associated with CDV in experimentally infected ferrets. Rodeheffer et al hypothesised that Vitamin A directly inhibits CDV replication in vivo and delays secretion from infected cells or blocks replication or clearance from secondary target tissues. This still remains a hypothesis and is yet to be confirmed experimentally.
Based on the results of this study all the adult ferrets in the facility were treated with Vitamin A. As Vitamin A injection alone was not available, a combination product Vitamin ADE (Troy Vitamin A 500,000 IU /ml, Vitamin D3 50,000 IU/ml and Vitamin E 50mg/ml) was used. Forty-one Ferrets were administered Vitamin A 50,000 IU, Vitamin D3 5,000 IU/ml and Vitamin E 5mg/ml) (0.1ml) intramuscularly.
The Vitamin ADE injections were given on day 2 of the outbreak.
On day 10 a second round of Vitamin ADE injections were given to three symptomatic ferrets and ten high risk ferrets housed in Cage A, B and C.
As CDV has been isolated from fleas found on minks in European mink farms where previous outbreaks have occurred (5,7), 6 mg Selamectin was applied to all ferrets (5,7) at this visit.
A positive PCR result for CDV on a pooled sample (three ferrets) was received on day 18. (ASAP Lab Number 16-99756911 – Appendix B)
On day 30 the second round of booster DHP vaccination was given to 39 ferrets. The 4 kits were given their first vaccination at 8 weeks of age on day 43. They required two more vaccinations 3 -4 weeks apart to guarantee immunity.
The quarantine period ended on day 50, there had been no new cases of CDV since Day 9.
Of the population of 57 ferrets, aged from 1 week to 6 years, both entire and desexed, in varying states of general health:
CDV is an uncommon highly contagious virus. Even though there is a high level of compliance of vaccinations in dogs within Australia this is not the case with ferrets. This case study confirms the continued presence of the virus. Possible sources include unvaccinated dogs and feral fox populations in suburban areas. The virus is fragile and sensitive to appropriate disinfection.
In this case study the rescue facility did not have appropriate disinfection and quarantine procedures in place. Foot traffic, hands and clothing of staff and visitors likely contributed to the spread of the virus, as did the sharing of food bowls and bedding. This is evident from the appearance of CDV in cage B which was geographically isolated from Cage A. Cage C contamination was more likely from direct contact with infected secretions from the ferret in cage B as the floor of Cage B was pervious. Once appropriate containment and disinfection protocols were instigated the spread of virus was dramatically altered and confined to ferrets that were housed with infected ferrets. The use of Vitamin ADE injections attenuated the disease in 5 of the 7 symptomatic ferrets producing a 70% survival rate instead of 100% mortality.
Vaccination was also a vital key in preventing further deaths.
Although uncommon, CDV is an infectious disease of ferrets with an estimated 100% mortality rate (8). With low vaccination rates in Australian ferrets this population is vulnerable to a CDV epidemic (8).
Recommendation: all ferrets over the age of 10 weeks should be vaccinated with a DHP vaccination, and another given 3-4 weeks later and then annually. As occasional deaths have been reported following the administration of the trivalent canine vaccination in ferrets (1,2), administering a Vitamin ADE injection at the time of vaccination may be pertinent.
Vitamin ADE injections attenuated the progression of CDV disease in ferrets reducing the potential mortality rate of 100% to 30%.
Recommendation: any ferret with symptoms that could be attributed to CDV should be given intramuscular Vitamin ADE as part of their treatment regime.
Shedding of virus for several months in recovered ferrets is possible (3).
Recommendation: Any ferret that has recovered from CDV should not be housed with unvaccinated ferrets.
Preventing outbreaks in ferret populations
Recommendation: Any facility which houses surrendered or stray ferrets of unknown vaccination status should quarantine these animals on arrivalfor 14 days, vaccinate them with trivalent DHP (1/5th of the canine dose) and treat them with Selamectin. If symptoms of CDV develop within the quarantine period treatment, two intramuscular injections of Vitamin ADE (15mg) 1 day apart should be given (3). Quarantine should be extended a further 3 weeks from the time the symptoms arefirst noted. DHP vaccination is repeated 3 – 4 weeks later.
Any facility that boards ferrets must have written proof that their vaccination status is current before they enter the facility.
Delany’s book was not published at the time of the outbreak but it does however include as a treatment for CDV Vitamin A: 50,000 IU, intramuscularly, once daily for 2 days (3).
This document is written specifically for Distemper virus control but is applicable to other infectious diseases.