Infectious Disease Update
World Small Animal Veterinary Association World Congress Proceedings, 2015
Richard B. Ford1, DACVIM, DACVPM (hon)
North Carolina State University, Raleigh, NC, USA

A. Antibody Titers vs. Vaccination

Today, the in-clinic titer test kits for canine distemper (CDV), canine parvovirus (CPV), canine adenovirus (CAV), and feline parvovirus (panleukopenia, FPV) do, in fact, correlate well with appropriate "gold standard" tests. A "positive" test result, when performed properly using an in-clinic test kit, reliably indicates the patient has protective levels of antibody against the test virus. A patient with a "negative" test result does not have protective levels of circulating antibody.

Indications for Antibody Testing

The following indications apply to antibody test results for canine distemper, parvovirus, and adenovirus-1 and for feline panleukopenia (feline parvovirus):

Evaluating immune response following initial administration of core vaccines

For clients wishing to determine whether or not a young dog/cat responded to the initial vaccination series (usually 3 doses), in-clinic test kits provide an excellent means of identifying those that did not respond and, therefore, remain susceptible, versus those that did respond. Current vaccination guidelines recommend administration of core vaccines to 14–16 weeks of age in puppies and 16 weeks of age in cats.

Antibody titers may be determined as early as 2 to 4 weeks following completion of the initial vaccination series. A puppy or kitten that is seronegative at 18 weeks of age should be revaccinated and tested again 2 to 4 weeks later.

Management of infection among vaccinates

For veterinarians faced with treating confirmed parvovirus infection in a well-vaccinated dog or cat, antibody testing can be used to rapidly determine whether or not the affected animal developed a protective immune response following the initial vaccination series. A "positive" antibody test suggests the vaccinated patient was infected during a period of susceptibility (e.g., in the presence of maternally derived antibody [MDA]). The antibody test does not distinguish vaccine-induced seroconversion from that caused by the infection. Patients with a negative test result may be susceptible (genetic) non-responders (or low-responders).

Determining the antibody level in lieu of revaccination

Among patients with a history of a known, or suspected, serious vaccine adverse event (reaction), determining the level of antibody will determine whether or not the patient has previously developed a protective immune response to vaccination. Patients with a "positive" test result can avoid the need for revaccination and the potential risk for a recurring adverse event.

Assessing adult dogs and cats with an unknown vaccination history

Clientele who have adopted an adult (stray) dog/cat and are without knowledge of previously administered vaccines, may elect to avoid vaccination if a protective level of immunity can be determined serologically.

Antibody testing in lieu of annual revaccination

International guidelines for the administration of core vaccines to adult dogs and cats consistently recommend triennial revaccination schedules. The promotion of annual wellness exams in veterinary medicine offers an opportunity to assess the immune status of patients during annual wellness visits until such time that revaccination is scheduled.

Management of infection risk among animals entering a shelter

The immunization status of young animals presented to animal shelters is often unknown. Because the infection risk among shelter-housed dogs and cats is high, determining the antibody status of an animal at the time of entry allows the opportunity to vaccinate and separate (foster) those animals deemed susceptible until such time that a "positive" test result can be obtained.

Management of outbreaks within an animal shelter

Access to antibody test kits offers shelters a unique management advantage when faced with an infectious disease outbreak involving canine distemper, parvovirus, or panleukopenia. The ability to identify and separate animals that have a "positive" (protected) antibody test from those that are "negative" (susceptible) serves to avoid unnecessary euthanasia. When feasible, "negative" animals could be isolated from the general population, thereby limiting propagation of the outbreak. Isolated seronegative survivors can be placed or adopted once the incubation period for the infectious agent has passed (2 weeks for canine and feline parvovirus; 6 weeks for canine distemper virus).

B. Feline Herpesvirus and Calicivirus...Why Do Well-Vaccinated Cats Still Become Infected?

First, both FHV-1 and FCV are readily transmitted when infected cats are housed with susceptible cats. Second, FHV-1 and FCV vaccines currently sold in the US and Canada do not provide "sterile" immunity. The immunity a cat derives from vaccination does reduce the severity of clinical signs subsequent to exposure and infection. It does not, however, prevent infection nor does it prevent development of a carrier state and viral shedding. (REF: 1) The immune response to both FHV-1 and FCV vaccination is therefore deemed "non-sterile" (regardless of the product used and the route of administration). Note: In contrast, the immune response subsequent to feline parvovirus (panleukopenia virus) vaccination is considered "sterile." Vaccinates enjoy protection from both infection and clinical disease if exposed.

In effect, vaccination of cats against FHV-1 and FCV offers limited protection. As long as the number of co-housed cats is low, exposure risk is low, and vaccination offers satisfactory protection. However, as the number of cats within a household increases, the risk that chronic virus-carrier (viral shedding) cats will be introduced also increases. Vaccinated cats, if exposed, become infected and are still likely to become chronic virus carriers. Susceptible, non-vaccinated cats, on the other hand, will become infected and develop the full spectrum of clinical signs of acute-onset upper respiratory infection. And the cycle repeats.

It should not be surprising that chronic virus-carrier cats are highly prevalent in the population and disease is endemic in high-density populations. It also explains why shelter-housed cats and cats residing in rescue facilities have high infection rates despite routine vaccination. As the proportion of young, susceptible kittens within the population increases, the risk for serious clinical disease can be expected to increase as well.

Management Options

Vaccination

Despite the limitations outlined above, all cats should receive the initial series of vaccine against FHV-1 and FCV. The revaccination interval varies depending on the exposure risk of the individual cat. Cats living inside and in households with low population density can be protected if revaccinated every 3 years. Cats residing in high-density populations are likely to have a high exposure risk and should be revaccinated annually.

In some locations, feline vaccines for B. bronchiseptica, as well as Chlamydophila (Chlamydia) felis, are available. The recommendation to vaccinate against either C. felis or B. bronchiseptica should be limited to households where infection, and associated clinical signs, has been established. Veterinarians should use discretion when recommending vaccination against chlamydiosis and bordetellosis. Vaccination of individual household cats living in low-density environments is unlikely to be necessary. Cats, especially kittens, residing in high-density populations (shelter-housed cats breeding colonies) may benefit from vaccination.

High-density Populations

Physical separation of vaccinated cats from non-vaccinated cats and, when feasible, separating cats with a known history of respiratory disease is important in reducing the risk of exposing healthy cats to chronic carrier cats. Also, separating susceptible kittens from the adult (chronic virus carrier) population is fundamental in reducing the incidence of acute infections, particularly with FHV-1 and FCV.

Feeding

Within high-density populations, feeding should be ordered in such a way that healthy cats are fed first and cats with signs of upper respiratory disease are fed last. Ideally, disposable gloves should be used between cats or between cages of co-housed cats. Disposable feeding bowls should be used. If using washable food bowls, soak bowls in fresh solution of 1 part household bleach to 30 parts water (1:30). Allow bowls to thoroughly dry before using.

Ventilation

Adequate ventilation, defined as 16 air exchanges per hour, is important in reducing the concentration of virus within the environment and maintaining a healthy population.

C. Why Parvovirus Vaccination "Fails"

Over the past few years, veterinarians have reported observing clinical signs (including a positive fecal antigen test result) of parvovirus infection among vaccinated (young) dogs. Such observations cause considerable concern for owners and veterinarians alike. Veterinarians are often quick to blame the vaccine for the failure which culminates in complaints to the manufacturer, product returns, and the purchase of vaccine from another manufacturer.

There are some known reasons for parvovirus vaccination failure:

1.  Interference from maternally derived antibody is still the most common reason for 'vaccination failure.' The parvovirus vaccination protocol poses some special considerations. Current AAHA Canine Vaccination Guidelines (2011) stress the importance of administering an initial series (typically 3 doses) of core vaccines (distemper-parvovirus-adenovirus2) such that the last dose is given between 14 and 16 weeks of age.
This is important. Interfering levels of maternal antibody to parvovirus are likely to persist longer than maternal antibody to distemper and adenovirus-2. Therefore, vaccine interference among dogs receiving the last dose of a core vaccine (as per most manufacturer's recommendations) vaccinated at 12 weeks of age may leave them susceptible to infection and disease if exposed. In my reviews of practices experiencing outbreaks of parvovirus among vaccinated dogs, this appears to be the most common reason for perceived 'vaccine failure.'
Note: All puppies should receive a dose of core vaccines at 14 to 16 weeks of age, regardless of the product being used.

2.  Genetics...failure among individual dogs to respond to the parvovirus antigen in vaccine was well recognized in the early 1980s following the introduction of the first parvovirus vaccines. Many (although not all) well-vaccinated Dobermans and Rottweilers develop fulminant parvovirus disease... many died. Although that same breed predisposition to not respond to parvovirus antigen does not appear to be prevalent today, serological studies on vaccinates that developed clinical parvovirus provides strong evidence that "non-responders" to parvovirus vaccination still exist in the population. Some have suggested that some lines of Pit Bull Terriers may be at particular risk.
Note: simply administering more vaccine to a non-responder is not likely to stimulate a protective immune response. These dogs may be genetically "programmed" not to respond to parvovirus...which leaves them susceptible to infection if exposed. No simple solution here...other than avoid exposure risk.

3.  Administering killed vaccine and modified-live virus (MLV) vaccine at the same time and at the same location in the dog. Some immunologists and, recently, a published research study (Taguchi 2010) suggest that subcutaneous administration of a killed vaccine (such as leptospirosis) in combination with a MLV vaccine (such as distemper-adenovirus-parvovirus) may result in a less than protective antibody response to parvovirus, and in some dogs, distemper virus. The popularity of combination products (i.e., leptospirosis bacterin as the diluent used to reconstitute the MLV virus vaccine 'cake') may, in some dogs, leave them susceptible to parvovirus and/or distemper virus if exposed.
Suggestion: When, and if, feasible, it is reasonable to administer killed (Leptospira) vaccines at a separate site from MLV vaccines (e.g., left leg vs. right leg) to promote antigen processing by separate lymph nodes.

4.  Vaccine handling. Core vaccines for dogs are attenuated (modified-live) products and are shipped and stored in a lyophilized (freeze-dried) 'cake.' Once reconstituted, deterioration of the immunizing antigens begins. Although canine parvovirus vaccine antigen retains its viability for several hours following reconstitution, canine distemper antigen loses viability and immunogenicity quickly. Therefore, it is strongly recommended that following reconstitution of any lyophilized vaccine, the product should be administered within one hour. Beyond that time, the dose should be discarded.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Richard B. Ford, DVM, MS, DACVIM, D(Hon)ACVPM
North Carolina State University
Raleigh, NC, USA


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