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    Management of a Canine Distemper Virus outbreak in a ferret rescue facility

    Dr Lynda Bonning
    Canterbury Veterinary Clinic & Hospital
    721 Canterbury Rd, Surrey Hills, Victoria 3127

     

    Abstract

    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.

     

    Introduction

    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):

    • Inflamed, pruritic rash on the chin
    • Oedema of the chin and lips
    • Blepharospasm, photophobia and periorbital crusts
    • Dermatitis of the anus and inguinal areas which may spread over the whole body
    • Generalised pruritis, with hyperkeratosis
    • Foot pad hyperkeratosis
    • Pasty faeces and soiled inguinal area
    • Slight distention of the rectum resembling a prolapse
    • Coughing, tachypnoea, laboured respiration
    • Neurological signs such as ataxia, paresis, muscular tremors, convulsions, collapse and coma.

    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).

     

    Case Presentation

    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.

     

    (ASAP Lab Number 16-99756911 – Appendix B)

    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.

     

    (ASAP Lab Number 16-99756911 – Appendix B)

    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.

     

    Summary

    Of the population of 57 ferrets, aged from 1 week to 6 years, both entire and desexed, in varying states of general health:

    • 50 were vaccinated
    • 46 were given a single intramuscular Vitamin ADE injection
    • 13 high risk or symptomatic ferrets were given a second intramuscular Vitamin ADE injection
    • There were 12 cases of CDV
    • 7 were euthanised (5 of these were prior to any preventative procedures)
    • 5 recovered

     

    Discussion

    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.

     

    Conclusion

    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.

    Post Script
    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).

     

    References

    1. Ferrets, Rabbits and Rodents Clinical Medicine and Surgery. 2ND Edition, includes Sugar Gliders and Hedgehogs. 2004 Quesenberry K E, Carpenter J W. Saunders An Imprint of Elsevier, St Louis, Missouri, USA, p72 – 74
    2. The Five-Minute Veterinary Consult – Ferret and Rabbit. Oglesbee B L. 2006 Blackwell Publishing Professional, Ames, Iowa, USA, p15 – 16
    3. Ferret Medicine and Surgery. Johnson Delaney C A. 2017. CRC Press, An Imprint of the Taylor and Francis Group, Boca Raton, Florida USA, p 312 – 315 and 284
    4. Disease Manifestations of Canine Distemper Virus Infection in Ferrets are Modulated by Vitamin A Status. Rodeheffer C, von Messling V. et al. The Journal of Nutrition May 2007, p1916 – 1922
    5. Canine distemper: re-emergence of an old enemy. Norris J, Krockenberger MB, et al Australian Veterinary Journal, Vol 84. No 10, October 2006 p362 – 363
    6. Canine Distemper Spill over in Domestic Dogs from Urban Wildlife. Kapil S, Yeary TJ. Vet Clinics Small Animal Vol 41 (2011) p1069 – 1086
    7. Wildlife Reservoirs of Distemper Virus Resulted in a Major Outbreak in Danish Mink (Neovison vison), Trebien R, Chriel M et al. PLOS ONE, January 2014, Vol 9, Issue 1, p1 – 11.
    8. Epidemiology and clinical presentation of canine distemper disease on dogs and ferrets in Australia, 2006-2014. Wyllie, SE; Kelman, M; Ward, MP. Australian Veterinary Journal, Vol 94, No 7 July 201, p215 – 222.

     

    Appendix 1

    Control measures and sanitation instructions for infectious disease control.

    This document is written specifically for Distemper virus control but is applicable to other infectious diseases.

    1. Distemper virus information
      Distemper virus is extremely contagious and has a high fatality rate in unvaccinated ferrets. It is an enveloped virus that in general is fairly fragile in the environment. The main route of infection is via aerosol droplet secretions from infected animals. This means secretions from the eyes, nose, mouth and potentially urine/faeces can be sources that allow infection to spread.We have vaccinated all your remaining ferrets and given them each an injection of high dose Vit A (50,000units) as this is meant to help them fight the Distemper infection.
    2. Quarantine period
      Infected ferrets usually succumb to the disease and die within 35 days. As such, we recommend that your entire facility be treated as a quarantine zone for at least 35 days from the date of last known infection. This means that there should be NO movement of ferrets in or out of your property. No new ferrets should be accepted, no ferrets should be sent to new homes and no desexing will be conducted at our clinic until further notice.When you are able to accept incoming ferrets again, a dedicated quarantine area should be set up using cages that are easily disinfected (metal or plastic – not wooden). Each new ferret stays in this quarantine cage/area for a period of 14 days for observation. If the ferret is not already vaccinated (written proof is required to confirm vaccination) then it should be vaccinated on arrival (with DHP vaccine 0.3ml) subcutaneously. The vaccine is to be repeated in 4 weeks time to ensure lasting immunity. If the ferret(s) show any signs of being unwell, then the cause of the illness should be investigated and treatment implemented where appropriate. The 14 day quarantine period starts again once the ferret is well.IMPORTANT NOTE – If ferrets are from different sources and are placed in the same quarantine cage on different dates, the quarantine time starts on the date the last ferret was placed in the cage.
    3. Reducing contamination in the environment
      Virisan (8% quaternary ammonium compound).We have supplied you with Virisan and it should be the standard disinfectant used in the future. It must be diluted to the appropriate concentration of 1:5 (ie. 1 litre Virisan to 4 litres water). It is important that you measure the volumes out each time or the solution will not work properly. Contact time should be at least 20 minutes before the solution is rinsed off. This means that bedding/bowls/litter trays etc need to be soaked for 20 minutes in the solution before rinsing off.General guidelines for the environment:

      • All bedding that can be thrown out should be disposed of
      • Each cage should be treated as if it is infectious. Each cage should have dedicated food/water bowls, utensils, toys and bedding. Having a separate small container to store these items associated with each cage might be helpful so they don’t get mixed up. If that’s not possible and these items are to be transferred to another cage for use by a different group of ferrets, they MUST be disinfected by soaking in Virisan (1 in 5 dilution) for at least 20 minutes.
      • Soak all bedding in Virisan for 20 minutes before washing in washing machine (warm/hot cycle). Add in 1 capful of Virisan into washing load. This needs to be done at least weekly.
      • Soak all food bowls, water bowls, utensils and toys in Virisan for 20 minutes before rinsing off thoroughly. This MUST be performed daily and especially if food/water bowls are shared as infected drops from saliva/eye or nasal discharge are the main route of infection.
      • Each cage should have a dedicated litter tray and these should not be shared. Trays should be cleaned daily, which means soaking in Virisan for 20 minutes before rinsing.
      • Each cage and all bench tops should be cleaned with Virisan. They can be wiped down with 1 in 5 diluted solution that should be left on for 20 minutes before rinsing off.
      • Cages that are stacked on top of each other can be treated as if they are one cage from a cleaning/disinfection point of view as contamination from the top to the bottom cage is unavoidable.
      • Consider putting up solid barriers (e.g. metal or plastic solid dividers in between cages) to reduce infectious droplets spreading via aerosol between one cage to next as your cages are spaced fairly close together. These dividing panels can then be wiped down with Virisan daily.
    4. Keeping yourself and other helpers clean
      You and anyone helping you can be an important route of disease spread. You can harbour infected droplets from the ferret’s nasal, oral and eye secretions or urine/faeces stuck on your clothes, shoes and body. This can then be transmitted to other ferrets on your property if you handle them without following proper cleaning procedures.General guidelines for yourself and other helpers:

      • Use disposable plastic coveralls and latex gloves for all cleaning and ferret handling activities. It is especially important to change coveralls and gloves in between cages, in between handling ferrets, and in between cleaning cages and cleaning other surfaces.
      • If disposable coveralls are not available an alternative is to have dedicated full cover plastic aprons for each cage. These can be hung next to the cages and soaked and cleaned in Virisan once weekly in the same way bedding is to handled.
      • For this specific episode, purchase a new set of boots or if using an old pair of shoes, soak in Virisan for 20 minutes before using again.
      • Prepare a footbath of Virisan (diluted 1:5) in a tray outside the door of each ferret room/enclosure. Anyone entering the room and exiting the room should step in the footbath. On exit, leave boots soaking in Virisan tray for 20min before rinsing off and wearing them into another part of your facility. In between cages, spray the outside and soles of your boots with Virisan.
      • Antiseptic hand rub should be used before and after entering any room. We have provided you with a suitable hand rub. Apply onto hands, and rub well in between fingers and hands, extending up to elbows. Make sure there is adequate solution to wet these areas and leave on for 90 seconds before entering room and after exiting room. If you are entering room, gloves should be worn on top of cleaned hands.

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