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 Prevention of Avian Polyomavirus Infections through Vaccination



Prevention of Avian Polyomavirus Infections

through Vaccination

by

Branson W. Ritchie, DVM, Phd, Kenneth S. Latimer, DVM, PhD,
Joan Leonard*,PhD, Cheryl B. Greenacre, DVM, Denise Pesti, MS,
Raymond Campagnoli, MS, Phil D. Lukert,DVM, PhD


Psittacine Disease Research Group
University of Georgia
College of Veterinary Medicine
Athens, Ga 30602

Reprinted in part with permission from, Avian Viruses: Function and Control and Advances in Exotic Companion Animal Medicine and Surgery, Wingers Publishing, Lake Worth, FL 33466.

For full text and illustrations refer to the source listed above




Introduction
In non-budgeriagar psittacines, avian polyomavirus-induced disease is most common in young birds (up to 150 days of age). However, despite a common misconception, adult birds are readily suseptible to infection and can become ill. Some affected birds die without developing any clinical signs of disease, while others die 12 to 48 hours after developing clinical signs that may include depression, loss of appetite, weight loss, delayed crop emptying, vomiting, diarrhea and bleeding under the skin. In contrast to many young birds that die, most infected adult birds develop transient lethargy, poor appetite and diarrhea with the surviving birds developing antibodies to the virus. Infections classified as "subclinical" (not obvious upon typical examination) are common in adult and young birds. In most aviaries and pet retail establishments, it is these subclinically infected birds that initiate a cycle of infection, and create an opportunity for the virus to be spread from bird to bird. Until recently, preventing birds from being infected with avian polyomavirus was limited to the arduous task of reducing potential exposure to the virus. Fortunately, an inactivated avian polyomavirus vaccine*, which has been shown to help prevent infections is now available.

Strategies for Vaccination
The strategies for using the avian polyomavirus vaccine are similar to those used to control infectious disease of other companion animals, like parvovirus in dogs or panleukopenia virus in cats. Preventing polyomavirus infections within a flock requires the vaccination of two crucial groups of birds: the breeding flock and the young birds, before they leave the nursery.

To reduce polyomavirus infections within the aviary, it is essential to vaccinate the adult birds. There are only two known sources for polyomavirus entering a nursery: either it is transported into the nursery during peiods when infections (which usually go unnoticed) are occurrring in the breeding population, or it is introduced to the nursery by people who bring the virus in from an outside source (
Table 1). Once the breeding flock is vaccinated, the population of birds at risk (those that could be infected) is substantially decreased, and the likelihood of a progressive cycle of transmission among these adult birds is reduced. This in turn lessens the chances that the adult population will serve as a source of virus for the exposure of neonates in the nursery.

If the flock is vaccinated and people do not inadvertently introduce the virus to the nursery it is unlikely that any neonates will be exposed to the virus. This logic is substantiated by observations of polyomavirus outbreaks. In several large aviaries, control of polyomavirus-induced disease occurred when the breeding adults and neonates were vaccinanted. By contrast, aviculturists who attempted to control outbreaks by vaccinating only young birds decreased, but did not eliminate, the incidence of disease. These findings emphasize the importance of vaccinating the adults to prevent polyomavirus infections in the nursery. Once polyomavirus has been controlled within the flock, then it is crucial for young birds that will be leaving the aviary to be protected before they are exposed in the pet trade to birds (particularly budgerigars) which may be shedding the virus.

Recommendations for Vaccination
When using a vaccine, or any therapeutic agent, the manufacturers' recommendations should be followed. The suggestions for vaccination described below have been developed over 5 years of evaluation of an avian polyomavirus vaccine in experimental and field situations, and are provided to supplement the recommendations of the vaccines' manufacturer*.
Adults - Breeding birds should be vaccinated twice, with a two week interval between vaccinations. It is best to vaccinate breeding birds in the non-breeding season. However, in flocks that are experiencing an outbreak of disease, vaccination can be performed during the breeding season. When vaccinating during an outbreak, it is important that the veterinary staff and aviary personnel exercise extreme caution to prevent handling and injection procedures from becoming modes of virus transmission from bird to bird. It should be noted that aviculturists with large breeding facilities rarely handle or evaluate the overall health of their adults. The infrequent attention provided to these adults allows some problems such as liver disease, kidney disease, heart disease, obesity, cancers, bacterial infections, fungal infections and proventricular dilatation disease to slowly progress unnoticed in what appear to be clinically normal birds. Many of these hidden problems may be detected or exacerbated during the handling necessary for vaccination. In the best managed aviaries in which adult birds are rarely handled, during the vaccination process, pre-existing medical problems have been identified in from 2% to 4% of the adults.

Immature Birds - An avian veterinarian may adjust the schedule for vaccinating neonates based on the risk of virus exposure in the nursery. These suggestions are based on the fact that the older a young bird is when it is vaccinated, the more likely it's immune system will respond (Figure 1)
  1. In the ideal aviary, where the aviculturist has vaccinated the breeding birds, does not have a history of polyomavirus-induced disease and sells only weaned birds, vaccination of young birds can be started about 4 weeks prior to weaning. These birds should be vaccinated twice with a 2 to 3 week interval between doses. A bird should receive the last vaccination at least 2 weeks before leaving the aviary. The original certificate of vaccination, provided by the manufacturer*, should be sent with the young bird when it leaves the aviary.

  2. If an aviculturist has vaccinated the breeding birds, does not have a history of polyomavirus-induced disease but sells birds prior to weaning, vaccination of young birds should be started between 40 to 50 days of age. These birds should be vaccinated twice with a 2 to 3 week interval between doses. A bird should receive the last vaccination at least 2 weeks prior to leaving the aviary. The origianal certificate of vaccination, provided by the manufacturer*, should be sent with the young bird when it leaves the aviary.

  3. If necessary, young birds can be safely vaccinated starting at 20 days of age. These birds should receive two additional boosters with a 2 to 3 week interval between doses. A bird should receive the last vaccination at least 2 weeks prior to leaving the aviary. The origianal certificate of vaccination, provided by the manufacturer*, should be sent with the young bird when it leaves the aviary. Companion birds - If a companion bird is maintained in complete isolation, which is not a very realistic scenario, it has minimal risk of being exposed to polyomavirus. However, isolation means that the bird, and its keeper, never leaves the home to go to the veterinarian, groomer, club meetings or anywhere else where direct or indirect exposure to other birds might occur. It also means that all of the food, toys, perches and enclosures for the bird are purchased from mail-order catalogs that ship from warehouses that do not house birds. These items may be contaminated with polyomavirus if they are kept in the same airspace with birds (particularly budgerigars). It seems more logical to vaccinate companion birds than try to maintain such rigorous isolation, although isolation is the best method to reduce a bird's exposure to the infectious agents for which vaccines are not yet available. It is interesting to note that companion dogs and cats that are maintained in relative isolation (those that are confined to indoor living) are routinely vaccinated to protect them from common infectious diseases. Why would one elect to afford a companion bird a lesser level of protection.

    Establishing a Standard
    During the past 25 years, the individuals who breed or enjoy the company of dogs and cats have used vaccines to substantially decrease the incidence of many infectious diseases. By establishing requirements for vaccination, and other health monitoring techniques (for example, testing dogs for heart worms or cats for feline leukemia), quality dog and cat breders and pet retailers have developed a positive reputation that separates them from the "puppy mills" that do not aspire to the same standard. Professional aviculturists and quality pet retailers can use the polyomavirus vaccine as one more tool to help separate themselves from the "birdie millers".

    If you are a pet retailer, you now have a readily available, safe method for reducing the probability that a severe and costly polyomavirus-induced outbreak will occur within you establishment. Additionally, as more consumers become aware of the polyomavirus vaccine, the demand for vaccinated birds will continue to increase. Look for bird breeders who are willing to vaccinate young birds before they leave the nursery, and request that a properly validated certificate of vaccination be sent with each young bird that you buy. (Figure 2).

    If you are a bird breeder, it is critical that you vaccinate your flock to reduce the chances of a polyomavirus outbreak, to protect your reputation and to separate your facility from the "birdie mills", which may choose not to vaccinate. Asolutely no bird should be added to your breeding facility that has not been vaccinated. Every bird that is transferred from your facility should be vaccinated to decrease its chances of being infected by the polyomavirus during transport or upon reaching its destination. The original vaccination certificate provided to you by your veterinarian should be included in the packet of information that you send with a bird. Transferring only vaccinated birds will reduce the chances that one of your birds will succumb to polyomavirus-induced disease and will establish your aviary as a "state of the art" avicultural faciltiy. In several outbreaks of polyomavirus in pet retail establishments, vaccinated birds survived while many unvaccinated birds have died. Retailers who experience these losses eventually seek sources of vaccinated birds. Make sure that once your flock has been vaccinated that your avian veterinarian registers your flock with the vaccine's manufacturer*.

    If you are obtaining a bird from any source, insist that the bird be vaccinated. You should request that the origianl vaccination certificate accompany the bird. If a breeder is not willing to vaccinate your bird, you should consider finding a different source.

    Evaluating a Vaccine
    Prior to USDA registration of the avian polyomavirus vaccine, it was evaluated for:
      (a) safety - the lack of unaceptable local or systemic reactions.
      (b) immunogenicity - the capacity of the vaccine to stimulate a measurable immune response.
      (c) efficacy - the capacity of the vaccine to induce an immune response that protects a vaccinate from experimental challenge with live virus.
    The safety of the inactivated avian polyomavirus vaccine has been evaluated in more than 80 species of psittacine birds including lovebirds, cockatiels, macaws, cockatoos, African grey parrots, Amazon parrots and eclectus parrots (Figure 3). In an experimental trial designed to challenge the safety of an inactivated polyomavirus vaccine, no adverse clinical changes occurred when previously infected birds were vaccinated 5 times during a 49 day period. This finding suggest that vaccination is as safe for previously infected birds as it is for their previously uninfected conspecifics. In addition, an experimental group of 18 birds have been vaccinated 6 to 12 times over a 5 year period to exacerbate the potential for an adverse reaction, and a group of approximately 300 birds have been vaccinated 3 times over a 2 year period, with no adverse side effects. In fact, with over 15,000 doses of the vaccine in use, in species as varied as lovebirds to hyacinth macaws, there have been no post-vaccination systemic reactions reported. The polyomavirus vaccine has been shown to be effective in protecting birds from infection. In multiple trials the vaccine protected more than 90% of vaccinates from infection. This is in stark contrast to unvaccinated birds, where 97% were susceptible to infection.

    Reactions at the site of a properly administered subcutaneous vaccine are minimal (slight yellow discoloration of the skin in some birds). If the vaccine is administered intradermally, it may cause thickening of the skin or formation of a self-limiting knot. If you are an aviculturist who is obtaining vaccine from your veterinarian, make sure that you are clearly advised on how to use the vaccine. Many avian veterianarians who have extensively used the vaccine are confident enough in its safety that they will treat any local reaction that might occur free-of-charge. If an adverse reaction occurs, it should be reported immediately to the vaccine's manufacturer*.

    What is a "Carrier"?
    It is occasionally suggested, albeit incorrectly, that the avian polyomavirus vaccine is of limited value in adults because it does not eliminate the "carrier" state. The term "carrier" is frequently and loosely discussed in association with polyomavirus infections in companion birds. By definition, a carrier is "an idividual who harbors a specific organism and is capableof transmitting the infectious organism that can cause a disease but shows no clinical signs". This is a simple definition for a rather complex interaction between infectious organisms and their host. It is a particularly simple definition with respect to avian polyomavirus. In scientific literature which discusses viral infections, the term "carrier" is rarely used. In its place, the term "persistent infection" is used to describe animals that are infected with a virus, shed the virus for an extended period of time and exhibit no easily observed clinical signs. There are then two types of persistent infections: latent infections and chronic infections, and the characteristics of each must be understood when evaluating how to prevent avian polyomavirus infections. The characteristics of these infections are listed in
    Table 2.

    A common example of a latent infection is the herpes simplex virus that causes "cold sores" in humans. Once an individual is infected with this virus, he remains infected for life and intermittently sheds the virus. More than 10 years ago, it was demonstrated the budgerigars infected with avian polyomavirus develop a latent infection (infected for "life" with intermittent shedding of the virus). Fortunately, an increasing body of information suggests that larger psittacine birds (as well as mice and chickens) infected with polyomavirus are more likely to develop transient, rather than latent infections. These transiently infected non-budgerigar psittacine birds may shed the virus for a certain period, but they appear able to mount an appropriate immune response which controls the infection and eventually stops the bird from shedding the virus. The most important consideration for preventing polyomavirus within a flock is to reduce the opportunity for these temporary shedders to infect other birds.. Toward this end, vaccinating a flock helps to protect uninfected birds from the virus and inhibits the amplification of virus activity through the susceptible birds within a flock. Additionally, the polyomavirus vaccine has not been shown to have any adverse affect on a bird that has already been infected with the virus, making flock vaccination both practical and safe.

    The propensity of non-budgerigar psittacine birds to develop transient polyomavirus infections is critical to control of the virus within an aviary. By vaccinating the breeding birds, the cycle of transmission can be reduced, and over time, it should be possible to functionally "eradicate" the virus from a particular aviary. Even if non-budgerigar psittacine birds were to develop latent infections, vaccination may still be a valuable method of preventing disease. Vaccination programs in other species (humans, cats, dogs, cattle, etc.) have been very effective in controlling many viruses that are known to cause latent infections.

    Because budgerigars respond differently to polyomavirus infections than do non-budgerigar psittacine birds, the recommendations for controlling infections in non-budgerigar psittacines may not apply to budgerigars. Research is currently under way to determine how to effectively vaccinate budgerigars for polyomavirus. It is important that unvaccinated psittacine birds not come in direct or indirect contact with budgerigars.

    Controlling a Polyomavirus Outbreak
    As is the case with many viral-induced disease in companion animals, vaccination will play a pivotal role in reducing the incidence of avian polyomavirus infections. However, because no vaccine is 100% effective, vaccination should not be expected to compensate for the deleterious effects of poor management or hygiene. The techniques recommended for decreasing the occurrence of any infectious disease are listed in
    Table 3.

    Controlling polyomavirus in an outbreak requires vaccinating the adults and neonates to stimulate flock immunity, as well as cleaning and disinfecting of the contaminated faciltiy. While vaccinating during a polyomavirus outbreak has been shown to be advantageous, it should be stressed that deaths may continue in neonates until flock immunity has been increased, generally 2 to 3 weeks after the last booster vaccination. Once an outbreak has occurred, it is important the the nursery be thoroughly cleaned and disinfected to prevent virus contaminating this environment from infecting neonates before the time that their immune systems will respond to vaccination. It is crucial during an outbreak that the adults be vaccinated to reduce the amplification of the virus.

    A DNA probe-based assay** is extremely valuable for identifying birds that are shedding virus in their excrement during an outbreak. Birds that are shedding the virus can be separated from others in a nursery to reduce further virus transmission, while vaccinated birds are developing antibodies to the virus. Birds that are clinically ill, are found to be shedding polyomavirus, or are in direct contact with birds that are clinically ill or shedding polyomavirus, should be isolated (placed in a separate geographic location and serviced by separate aviary personnel) from birds that are clinically normal and not shedding virus.

    Acknowledments
    Major sustained contributions that have made this work possible have been provided by the Cowan Avian Health Foundation, the International Avian Research Foundation, Veterinary Medical Experiment Station , Joe and Sue Still, Terry Clyne, Richard and Luanne Porter, Knick Enterprises, Kathleen Szabo, Allen Berk, Bobbi Brinker, International Aviculturist's Society, Avian Research Associates, Midwest Avian Research Exposition, National Aviary, Puerto Rican DNR, Ann Arbor Cage Bird Club, Aviary and Cage Bird Club of South Florida, Avicultural Socity of Puget Sound, Central Indiana Cage Bird Club, Charlotte Metrolina Cage Bird Society, Cream City Feathered Friends, Dallas Cage Bird Society, Feathered Friends Society, Gateway Parrot Club, Greater Brandon Avian Society, Hookbill Hobbyists of Southern California, Kentuckian Bird Society, Louisiana Aviculture Socity, Northwest Ohio Exotic Bird Club, South Jrsey Bird Club, Wasatch Avian Education Soiety, West Valley Bird Society, Lafeber Inc. and Zeigler Brothers Inc. Hundreds of aviculturists, bird clubs and veterinarians have also made significant contributions.

    Footnotes

    * - Biomune, Lenexa Kansas, 913-0230
    ** - Avian Research Associates, Milford, OH. 513-248-4700
    *** - Horizon Microenvironments, Watkinsville, GA 706-769-0127


    Table 1: Methods by which aviary personnel may introduce polyomavirus to the nursery.
      Adding unvaccinated birds to the flock
      Failing to quarantine
      Allowing a contaminated visitor into the aviary
      Returning a neonate to the nursery that has been exposed to other birds or a contaminated environment.
      Mixing neonates from multiple sources in the same airspace.
      Exposing ones self to other birds (bird fair, pet retailer, veterinarians office) and returning to the nursery or aviary without proper disinfection.
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    Table 2: Some characteristics of two types of persistent infections
    Latent infections are characterized by:
      A long-term infection, frequently for the life of the animal.
      Intermittent shedding of the causative organism.
      An immune response the is unable to clear the causative organism from the body.
    Some chronic infections can be characterized by:
      A long-term infection, can be weeks to months.
      Shedding of the causative organism for a defined period with eventual cessation of shedding.
      An immune response that is eventually able to clear the infectious agent.
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    Table 3: Techniques for preventing or controlling infectious disease in the psittacine nursery and aviary.
    Prevention
      Vaccinate susceptible adults and neonates
      Never ship or accept an unvaccinated bird.
      Do not maintain budgerigars in the same airspace with other unvaccinated psittacines.
      Clean and disinfect the nursery environment regularly.
      Ship only weaned birds
      Use biosecure shipping container*** to reduce exposure to infectious agents during transport
      Maintain a closed aviary, and stricly limit visits by non-aviary personnel.
      Never return a neonate to the nursery if it has been directly or indirectly exposed to other birds.
      If new birds must be added to the flock, vaccinate and quarantine them for a minimum of 60-90 days.
      Never mix neonates from multiple sources in the same airspace.
      Use separate feeding instruments for each bird.
      Never use a feeding utensil and place it back in a common food container.

    Control
      Isolate clinically affected birds.
      Carefully vaccinate exposed birds making sure that virus transmission is not facilitated by handling.
      Never place a clinically ill bird in the same airspace with birds in the nursery.
      Isolate birds in direct contact with clinically ill birds or those that are shedding.
      Completely clean and disinfect the nursery environment.
      Replace contaminated nest boxes
      Use the DNA probe to test the nursery environment and aviary for viral-contamination.

    An overview of some of the most important features of the avian polyomavirus vaccine:
      The vaccine has been shown to be safe in more than 80 species of psittacine birds.
      The vaccine is safe for use in previously infected as well as previously uninfected birds.
      To date, no post-vaccination systemic reactions have been reported.
      Reactions at the site of a properly administered vaccine are minimal
      This inactivated vaccine does not itself induce shedding of the virus
      The vaccine decreases polyomavirus-induced disease in experiemntal and field settings.
      Aviculturists can receive information about the vaccine by calling the vaccine's manufacturer*
      It is better to vaccinate and prevent polyomavirus infections, than attempt to control an outbreak.
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