A144 Case Study Vaccinations For Dogs

Perspectives
Vaccinating Dogs Against Lyme Disease:
Two Points of View

January/February 2014   •   (Volume 4, Number 1)


Meryl P. Littman, VMD, Diplomate ACVIM, University of Pennsylvania, & Richard E. Goldstein, DVM, Diplomate ACVIM & ECVIM (Companion Animal), The Animal Medical Center, New York City

The decision on whether to vaccinate dogs against Lyme disease remains an ongoing debate. Drs. Littman and Goldstein present two different viewpoints.


Despite availability of a consensus statement and up-to-date canine vaccination guidelines (see Lyme Disease Vaccination Guidelines), the decision whether or not to vaccinate dogs against Lyme disease remains an ongoing debate among many veterinary professionals.

Today’s Veterinary Practice has gathered 3 experts to discuss this topic—Dr. Meryl Littman and Dr. Richard Goldstein evaluate the benefits and risks of vaccination, while Dr. Richard Ford outlines the current vaccination recommendations.

FIRST DO NO HARM:LYME DIAEASE VACCINATION MAY PRESENT MORE RISKS THAN BENEFITS

Meryl P. Littman, VMD, Diplomate ACVIM

When veterinary clinicians decide whether to recommend a particular vaccine for a particular patient, risks and benefits are weighed. The “vaccinometer” tool, developed by Larry Glickman, was designed to help practitioners determine whether or not to recommend a vaccine.1

As we investigate Lyme disease vaccination, the questions posed by the vaccinometer help highlight many unanswered questions and potential risks related to this vaccine. With these concerns in mind, I choose “first do no harm.” In other words, if we use proper tick control, vaccination is unnecessary.

Question:What is the prevalence and risk of exposure/infection in your area (eg, infectiousness)?

Answer: Risk of Lyme disease exposure/infection is high in my area, but proper tick control lowers the risk greatly.

The CDC website2 shows that 95% of human Lyme disease is found in 12 endemic states in the Northeast, Mid-Atlantic, and Upper Midwest U.S. In some endemic areas, seroprevalence in healthy dogs is as high as 70% to 90%.3 In high-risk areas, risk of exposure can be lowered dramatically with adequate tick control, which also decreases the risk for other tick-borne diseases, such as anaplasmosis, babesiosis, bartonellosis, ehrlichiosis, and Rocky Mountain spotted fever.

Question:How great is the risk of severe disease once the dog is infected (eg, pathogenicity and virulence)?

Answer:Risk of Lyme disease becoming severe is low, but possibly somewhat higher in retriever dogs.

Less than 5% of seropositive (and seronegative) dogs had signs attributed to Lyme arthritis,3 which generally responds rapidly to antimicrobial therapy. Perhaps 10% to 15% of treated dogs remain non-clinical carriers.3 One study showed that 40% of dogs diagnosed with Lyme disease were misdiagnosed and had another condition instead.4 Adult beagles experimentally infected with Lyme disease via tick exposure became seropositive but remained nonclinical, and exposed puppies showed only self-limiting signs of arthritis, anorexia, and fever, which did not require treatment.3

Perhaps less than 2% of exposed dogs develop the more serious Lyme nephritis,5 an immune-mediated glomerulonephritis, with high Lyme disease-specific antigen–antibody circulating immune complexes (CICs) and deposition in glomeruli, causing protein-losing nephropathy (PLN).6 This entity has not been duplicated in any experimental model, and is seen mostly in Labrador and golden retrievers.

However, even in seropositive retrievers, Lyme nephritis is uncommon,7 and we do not understand why some dogs develop it while many do not, despite their high titers and high CICs. It appears that a genetic predisposition exists, and that inflammation from Lyme antigens, and possibly inflammation from other infectious and inflammatory conditions, may be an environmental trigger. A genetic podocytopathy identified in soft-coated wheaten terriers8 may predispose them to further glomerular damage; a similar condition may exist in affected retrievers.

In general, coinfections appear to result in more serious illness (eg, anaplasmosis/Lyme disease), which emphasizes the importance of tick control.9

Question:How effective is the vaccine?

Answer: Not as effective as other vaccines we use.

Lyme vaccines appear to prevent seroconversion or illness in most (60%–86%)3 vaccinates, but not consistently in all dogs, and not for a very long duration of immunity, thus annual (or even every 6 months10) boostering has been recommended.

Question:How safe is the vaccine?

Answer: These vaccines are not as safe as other vaccines we use.

In the Banfield study of 1.2 million vaccinated dogs, the Lyme disease vaccine (monovalent bacterin), when used alone, produced more postvaccinal adverse events within 3 days than any other canine vaccine.11 Adverse events associated with Lyme disease vaccine were described as “moderate” by an AVMA council in 2002.12

All canine Lyme disease vaccines contain outer surface protein A (OspA), which attaches the spirochete to the tick’s midgut and is expressed on Borrelia burgdorferi while in the tick, and induces anti-OspA antibodies.

  • OspA without adjuvant is a polyclonal B cell mitogen that induces pro-inflammatory cytokines,5 causes arthritis in rats,13 and causes a strong TH1 response in people with HLA-DR4 haplotype, immune-mediated arthritis, and high anti-OspA antibodies after natural infection.14
  • Lyme bacterin as well as OspA alone causes arthritis in hamsters15 and sensitization16 so that more severe arthritis is produced with boosters.17
  • Lyme bacterins were not developed for humans since various Lyme disease antigens appear to have a role in post Lyme disease immune-mediated diseases.18
  • In dogs with suspected Lyme nephritis, immunohistochemistry and elution studies have shown positive staining of glomerular immune complexes for a variety of Lyme antigens, including OspA and others, which are also found in Lyme disease vaccines.5

Remember, inflammation or deposition may be delayed for months after vaccination and not seem temporally related nor recognized as a problem associated with vaccination.

Original reports of Lyme nephritis suspect cases19 demonstrated that 30% had received Lyme disease vaccine, from 2 weeks to 15 months prior to illness. There is no experimental model for Lyme nephritis, which makes it impossible to study whether Lyme disease vaccine prevents, sensitizes, or aggravates it. However, since the most serious forms of Lyme disease are immune-mediated, I choose not to administer Lyme vaccine antigens that may elevate Lyme disease specific CICs (that increase after vaccination, as they should), which would circulate and need to be cleared (or deposited) for weeks to months after vaccination.

In addition, should we vaccinate retrievers (some of which are genetically predisposed dogs) that may develop Lyme nephritis or PLN? These patients are most likely the very ones we should NOT vaccinate lest we add more complexes or sensitize them for a more intense immune-mediated reaction when they are boostered or exposed naturally.

Question: What is the potential for zoonotic spread to human contacts, and zoonotic spread to other dogs?

Answer: Potential for zoonotic transmission of Lyme disease is minimal.

B burgdorferi is transmitted via tick bites, and is not contagious from dogs to humans or dogs to dogs via excretions or blood transfusion. The reservoir hosts are wildlife, such as mice, small mammals, and birds. Seropositive dogs are sentinels that their human companions are at risk for exposure—not from dogs, but from ticks in the environment.

IN SUMMARY

The conclusions we can draw from the questions posed are:

  • Tick control is important: it prevents pets from acquiring the numerous tick-borne infectious agents, and prevents ticks from feeding on sentinel dogs, thereby acquiring the agent and transmitting it to their next host.
  • Most dogs exposed to B burgdorferi seroconvert, but are nonclinical and do not need antibiotics.20 While most dogs do not exhibit illness after vaccination against Lyme disease, neither do dogs that are naturally exposed.
  • Dogs that have Lyme arthritis respond quickly to inexpensive/safe antibiotics.
  • Lyme disease vaccines have lower efficacy, shorter duration of immunity, and cause more post vaccinal adverse events than other vaccines we use.
  • Without an animal model for Lyme nephritis, we do not know if the Lyme disease vaccine prevents, sensitizes, or causes more immune complex deposition in kidneys, especially in genetically predisposed dogs.
  • Accordingly, the subset of dogs that possibly need the most protection (eg, retrievers) from the serious (immune-mediated) forms of Lyme disease may be the very ones predisposed to complications.

WITH TICK CONTROL & VACCINATION IN ENDEMIC AREAS, LYME DISEASE IS PREVENTABLE

Richard E. Goldstein, DVM, Diplomate ACVIM & ECVIM

Lyme disease, its causative tick-borne agent—Borrelia burgdorferi, and Ixodes ticks are all on the rise. In August 2013, the Centers for Disease Control and Prevention (CDC) increased their estimate of the number of new human cases of Lyme disease from 30,000 to 300,000 annually.1

Tick removal and control is an important part of prevention of Lyme disease, but so is Lyme disease vaccination. No vaccine is completely without risk, but when weighing the risks versus the benefits, I believe the evidence strongly supports the following:

  1. In endemic regions, Lyme disease negative dogs should be vaccinated. As part of a Lyme disease prevention protocol, dogs must be vaccinated in addition to tick removal and control. One infected tick that escapes those first 2 barriers can easily cause infection. There is no evidence of any deleterious effects due to vaccinating Lyme disease negative dogs.
  2. In endemic regions, Lyme disease positive dogs with no clinical signs of disease should be vaccinated when risk of reinfection is high. There is no natural immunity due to previous infection, which likely results due to bacteria “hiding” themselves from the immune system, mainly in tissue, such as synovial membranes, and down-regulating immunogenic surface proteins.2 In a recent paper on infections in humans with recurrent signs, it appeared that humans can be re-infected over and over again, almost annually, causing severe clinical disease.3
  3. In endemic regions, Lyme disease positive dogs with clinical signs should be vaccinated when risk of reinfection is high, and should receive antibiotic therapy, prior to or immediately following vaccination.
  4. Lyme disease vaccination should be performed annually, with the currently available vaccines. In addition, tick control, even in vaccinated dogs, must be stressed to owners since very heavy exposure to Lyme disease may override vaccinal protection.

FACTS ON HUMAN VACCINATION

There is a race to bring a “new” human Lyme disease vaccine to market, with some vaccines already in advanced stages of development.4, 5 A previous Lyme disease vaccine for humans had been approved for use in the U.S., but was removed from the market. The observation that this vaccine was unsuccessful due to lack of sales is often misused as an argument against canine Lyme disease vaccination.

The University of Pennsylvania’s world renowned vaccinologist, Stanley Plotkin, described the human vaccine situation in 2011: A vaccine against Lyme disease was licensed in the United States in 1998 but was subsequently removed from the market because of lack of sales. I believe that the poor acceptance of the vaccine was based on tepid recommendations by the CDC, undocumented and probably nonexistent safety issues, and insufficient education of physicians…The fact that there is no vaccine for an infection causing 20,000 annual cases is an egregious failure of public health.6

FOUR SAFE & EFFECTIVE VACCINES

Compared to humans, dogs are lucky. There are currently 4 extremely safe, effective, and reliable vaccines7-9 (Table) on the market that have all been through the United States Drug Administration licensing requirements for safety, efficacy, purity, and potency.

All available canine Lyme disease vaccines produce borreliacidal antibodies in the dog in response to vaccinal outer surface protein A (OspA). These antibodies work in the tick’s gut to bind the bacteria during the blood meal, sterilizing the gut of the tick and preventing transmission of bacteria into the dog.

OspC is the main immunogenic protein exhibited by Borrelia in the tick’s salivary glands and in the dog’s body during natural infection. Three of the current Lyme disease vaccines contain 2 strains of inactivated Borrelia isolates—1 OspA producing strain and 1 unique OspC producing strain, which perhaps adds an additional layer of protection.

EFFICACY OF THE VACCINE

These vaccines are extremely safe and, in conjunction with tick removal and control, prevent B burgdorferi infection and clinical Lyme disease, including Lyme nephritis.

The anecdotal evidence for this fact is overwhelming, but it has also been shown prospectively in multiple controlled studies in experimental infection and in the field. Following are just a few of many examples of such evidence in the field.

  • Levy showed excellent field efficacy of canine Lyme disease vaccination in 2003.10
  • In 2010, Hebert and Eschner proved the efficacy of the Lyme disease prevention protocol, including vaccination in a large Rhode Island practice.11
  • In a population of guide dogs in New York, implementation of strict tick control and mandatory Lyme disease vaccination regimen reduced the number of Lyme nephritis cases from approximately 10/year to less than 1/year over 7 years.12

COMBATING CONCERNS ABOUT VACCINATION

There are still some who believe that Lyme disease is not a disease “worth” vaccinating against or the vaccine causes more harm than good. This is despite the:

  • Extremely large number of clinical Lyme disease cases and nonclinical Lyme infections seen in small animal practice in endemic areas in the U.S., including the often fatal syndrome of Lyme nephritis
  • Millions of dogs that receive Lyme disease vaccines annually with no data to suggest any resulting harm from the vaccine.

Lyme Nephritis

Concerns have also been raised that vaccination can contribute to clinical signs of Lyme disease or the syndrome known as Lyme nephritis.13 However, there is no evidence that Lyme nephritis is a vaccine-induced phenomenon or even commonly aggravated by vaccination.

In addition to the evidence from the case study in guide dogs,12 I have evaluated or been a consultant on over 300 cases of dogs with Lyme nephritis; of these dogs, less than 10% were vaccinated. Moreover, I am not aware of a documented case in which a dog vaccinated against Lyme disease, but not infected with it, contracted Lyme nephritis. Ultimately, if we prevent Lyme disease, we prevent Lyme nephritis.

Adverse Events

It has been demonstrated experimentally that, upon vaccination of Lyme disease negative dogs, only a transient, relatively clinically insignificant rise in Lyme disease specific circulating immune complexes (CICs) occurs, and this rise lasts 8 weeks of less.14 When Lyme disease positive dogs were vaccinated, CICs rose, but this rise was most likely much lower than that seen with new infection, and could likely be mitigated with antibiotic therapy, prior to or immediately following vaccination of Lyme positive dogs.15

The alternative—not vaccinating Lyme disease positive dogs and risking additional Lyme disease infections—is very likely more detrimental than the possible rare negative effects of vaccination.

In the next issue of Today’s Veterinary Practice, Dr. Richard Ford will provide an in-depth discussion on Lyme disease vaccination guidelines in the Vital Vaccination column.

CDC = Centers for Disease Control and Prevention; CIC = circulating immune complexes; OspA = outer surface protein A; PLN = protein-losing nephritis

Littman References

  1. Fiala J. Researcher creates tool to gauge vaccine needs. DVM360 Magazine 2003; available at http://veterinarynews.dvm360.com/dvm/article/articleDetail.jsp?id=70130.
  2. CDC website; available at http://www.cdc.gov/lyme/.
  3. Littman MP, Goldstein RE, Labato MA, et al. ACVIM small animal consensus statement on lyme disease in dogs: diagnosis, treatment, and prevention. J Vet Intern Med 2006; 20(2):422-434.
  4. Speck S, Reiner B, Streich WJ, et al. Canine borreliosis: A laboratory diagnostic trial. Vet Microbiol 2007; 120:132-141.
  5. Littman MP. State-of-the-art-review: Lyme nephritis. J Vet Emerg Crit Care 2013; 23:163-173.
  6. Littman MP. Protein-losing nephropathy in small animals. In Acierno MJ, Labato MA (eds): Kidney disease and renal replacement therapies. Vet Clin N Am Small Animal Pract 2011; 41(1):31-62.
  7. Goldstein RE, Cordner AP, Sandler JL, et al. Microalbuminuria and comparison of serologic testing for exposure to Borrelia burgdorferi in nonclinical Labrador and golden retrievers. J Vet Diagn Invest 2007; 19:294-297.
  8. Littman MP, Wiley CA, Raducha MG, Henthorn PS. Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft coated wheaten terrier dogs. Mamm Genome 2013; 24:119-126.
  9. Beall MJ, Chandrashekar R, Eberts MD, et al. Serological and molecular prevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, and Ehrlichia species in dogs from Minnesota. Vector Borne Zoonotic Dis 2008; 8:455-464.
  10. Topfer KH, Straubinger RK. Characterization of the humoral immune response in dogs after vaccination against the Lyme borreliosis agent: a study with five commercial vaccines using two different vaccination schedules. Vaccine 2007; 25:314–326.
  11. Moore GE, Guptill LF, Ward MP, et al. Adverse events diagnosed within three days of vaccine administration in dogs. JAVMA 2005; 227(7):1102-1108.
  12. Klingborg DJ, Hustead DR, Curry-Galvin EA, et al. AVMA council on biologic and therapeutic agents’ report on cat and dog vaccines. JAVMA 2002; 221:1401-1407.
  13. Gondolf KB, Mihatsch M, Curschellas E, et al. Induction of experimental allergic arthritis with outer surface proteins of Borrelia burgdorferi. Arthritis Rheum 1994; 37:1070-1077.
  14. Steere AC, Drouin EE, Glickstein LJ. Relationship between immunity to Borrelia burgdorferi outer-surface protein A (OspA) and Lyme arthritis. Clin Inf Dis 2011;52 (Suppl 3):S259-S265.
  15. Lim LC, England DM, DuChateau BK, et al. Development of destructive arthritis in vaccinated hamsters challenged with Borrelia burgdorferi. Infect Immun 1994; 62:2825–2833.
  16. Croke CL, Munson EL, Lovrich SD, et al. Occurrence of severe destructive Lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi. Infect Immun 2000; 68:658-663.
  17. Littman MP. Perspectives in veterinary medicine: Why I don’t use Lyme disease vaccines. Comp Cont Ed Pract Vet 1997; 19(11):1269, 1272, 1274-1275.
  18. Littman MP. Immune-mediated reactions against Lyme vaccines. ACVIM Proc 2000; pp 629-630.
  19. Dambach DM, Smith CA, Lewis RM, Van Winkle TJ. Morphologic, immunohistochemical, and ultrastructural characterization of a distinctive renal lesion in dogs putatively associated with Borrelia burgdorferi infection: 49 cases (1987–1992). Vet Pathol 1997; 34:85-96.
  20. Littman MP. A matter of opinion: Should we treat asymptomatic, nonproteinuric Lyme-seropositive dogs with antibiotics? Clin Brief 2011; 9:13-16.
  21. Dai J, Wang P, Adusumilli S, et al. Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent. Cell Host Microbe 2009; 6(5):482-492.
  22. Schuijt TJ, Hovius JW, van der Poll T, et al. Lyme borreliosis vaccination: The facts, the challenge, the future. Trends Parasitol 2011; 27:40-47.
  23. Embers ME, Narasimhan S. Vaccination against Lyme disease: Past, present, and future. Front Cell Inf Microbio 2013; 3(6):1-15.

Goldstein References

  1. Kuehn BM. CDC estimates 300,000 US cases of Lyme disease annually. JAMA 2013; 310(11):1110.
  2. Grimm D, Tilly K, Byram R, et al. Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals. Proc Natl Acad Sci USA 2004; 101(9):3142-3147.
  3. Nadelman RB, Hanincová K, Priyanka Mukherjee P, et al. Differentiation of reinfection from relapse in recurrent lyme disease. N Engl J Med 2012; 367:1883-1888.
  4. Embers ME, Narasimhan S. Vaccination against Lyme disease: Past, present, and future. Front Cell Infect Microbiol 2013; 3:6.
  5. Barrett PN, Portsmouth D. A novel multivalent OspA vaccine against Lyme borreliosis shows promise in Phase I/II studies. Expert Rev Vaccines 2013; 12(9):973-975.
  6. Plotkin SA. Correcting a public health fiasco: The need for a new vaccine against Lyme disease. Clin Infect Dis 2011; 52(3):S271-S275.
  7. LaFleur RL, Callister SM, Dant JC, et al. One-year duration of immunity induced by vaccination with a canine Lyme disease bacterin. Clin Vaccine Immunol 2010; 17(5):870-874.
  8. LaFleur RL, Dant JC, Wasmoen TL, et al. Bacterin that induces anti-OspA and anti-OspC borreliacidal antibodies provides a high level of protection against canine Lyme disease. Clin Vaccine Immunol 2009; 16(2):253-259.
  9. Conlon JA, Mather TN, Tanner P, et al. Efficacy of a nonadjuvanted, outer surface protein A, recombinant vaccine in dogs after challenge by ticks naturally infected with Borrelia burgdorferi. Vet Ther 2000; 1(2):96-107.
  10. Levy SA, Lissman BA, Ficke CM. Performance of a Borrelia burgdorferi bacterin in borreliosis-endemic areas. JAVMA 1993; 202(11):1834-1838.
  11. Hebert D, Eschner A. Seroprevalence of Borrelia burgdorferi-specific C6 antibody in dogs before and after implementation of a nonadjuvanted recombinant outer surface protein A vaccine in a Rhode Island small animal clinic. Vet Ther 2010; 11(3).
  12. Personal communication with Jody Sandler, DVM, Director of Veterinary Services, Guiding Eyes for the Blind, Yorktown, New York.
  13. Littman MP, Goldstein RE, Labato MA, et al. ACVIM small animal consensus statement on Lyme disease in dogs: Diagnosis, treatment, and prevention. J Vet Intern Med 2006; 20(2):422-434.
  14. Goldstein RE, Atwater DZ. Serologic and circulating immune complex analysis in dogs naturally infected with Borrelia burgdorferi (abstract). ACVIM Forum Proc 2006.
  15. Goldstein RE, Atwater DZ. Serology and circulating immune complexes in dogs naturally infected with Borrelia burgdorferi before and after doxycycline therapy (abstract). ACVIM Forum Proc 2006.

Meryl P. Littman, VMD, Diplomate ACVIM, is a professor of medicine at the University of Pennsylvania School of Veterinary Medicine. Her research includes canine tickborne diseases. She received her VMD from University of Pennsylvania.

 

Richard E. Goldstein, DVM, Diplomate ACVIM & ECVIM (Companion Animal), is chief medical officer at The Animal Medical Center in NYC. His research includes canine Lyme disease and leptospirosis. He received his DVM from Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Israel.

(Revised 1/18)

Introduction

The UC Davis VMTH vaccination guidelines below have been based on published studies and recommendations made by task forces (including the AAFP/AFM Advisory Panel on Feline Vaccines, AAHA Canine Vaccine Task Force, and World Small Animal Veterinary Association), which include representatives from academia, private practices, governmental regulatory bodies, and industry. These groups have evaluated the benefits versus risks of the vaccines currently available on the market. Interested readers are referred to documents published by these groups for further information (see References and Resources listed at the end of this document). The document below has been generated by a group of faculty and staff at UC Davis School of Veterinary Medicine for the purposes of VMTH veterinary student education and as a reference for referring veterinarians. These are only general guidelines, as the vaccine types recommended and the frequency of vaccination vary depending on the lifestyle of the pet being vaccinated, i.e. indoor vs outdoor pets, travel plans, kennel/boarding plans, and underlying disease conditions such as immune-mediated diseases or pre-existing infections such as FIV infection. Because these factors may change over time, we recommend the vaccination plan for each individual pet be decided by the owner at routine annual examinations, following a discussion between the veterinarian and the client regarding the animal’s lifestyle in the year ahead. Guidelines for vaccination in shelter situations can be accessed at the Center for Companion Animal Health's shelter medicine website. A previous history of vaccination reactions in an individual pet will also affect recommendations for vaccination. For all vaccines given, the product, expiration date, lot number, route and location of injection must be documented in the record.

It should also be noted that much research in the area of companion animal vaccinology is required to generate optimal recommendations for vaccination of dogs and cats. As further research is performed, and as new vaccines become available on the market, this document will be continuously updated and modified.

I. Canine Vaccination Guidelines

Canine Core Vaccines

Core vaccines are recommended for all puppies and dogs with an unknown vaccination history. The diseases involved have significant morbidity and mortality and are widely distributed, and in general, vaccination results in relatively good protection from disease. These include vaccines for canine parvovirus (CPV), canine distemper virus (CDV), canine adenovirus (CAV), and rabies. In addition, the leptospirosis vaccine is now recommended as a core vaccine for dogs in California because the disease has the potential to occur in any dog (even in urban environments), can be life-threatening, and the vaccines are considered safe and efficacious, with recent improvements in safety over the last decade.

Canine Parvovirus, Distemper Virus, and Adenovirus-2 Vaccines

For initial puppy vaccination (< 16 weeks), one dose of vaccine containing modified live virus (MLV) CPV, CDV, and CAV-2 is recommended every 3-4 weeks from 6-8 weeks of age, with the final booster being given no sooner than 16 weeks of age. For dogs older than 16 weeks of age, two doses of vaccine containing modified live virus (MLV) CPV, CDV, and CAV-2 given 3-4 weeks apart are recommended. After a booster at 6 months to one year, revaccination is recommended every 3 years thereafter, ideally using a product approved for 3-year administration, unless there are special circumstances that warrant more or less frequent revaccination. Note that recommendations for killed parvovirus vaccines and recombinant CDV vaccines are different from the above. These vaccines are not currently stocked by our drug room or routinely used at the VMTH. We do not recommend vaccination with CAV-1 vaccines, since vaccination with CAV-2 results in immunity to CAV-1, and the use of CAV-2 vaccines results in less frequent adverse events.

Canine Rabies Virus Vaccines

In accordance with California state law, we recommend that puppies receive a single dose of killed rabies vaccine at 12 weeks or 3 months of age. Adult dogs with unknown vaccination history should also receive a single dose of killed rabies vaccine. A booster is required one year later, and thereafter, rabies vaccination should be performed every 3 years using a vaccine approved for 3-year administration.

Canine Leptospira Vaccines

Multiple leptospiral serovars are capable of causing disease in dogs, and minimal cross-protection is induced by each serovar. Currently available vaccines do not contain all serovars, and duration of immunity is probably about 1 year. However, leptospirosis is not uncommon in northern Californian dogs both from urban backyards and also with exposure histories involving livestock and areas frequented by wild mammals. In addition, the disease can be fatal or have high morbidity, and also has zoonotic potential. Therefore, we suggest annual vaccination of all dogs with vaccines containing all four Leptospira serovars (Grippotyphosa, Pomona, Canicola and Icterohaemorrhagiae). The initial vaccination should be followed by a booster 2-4 weeks later, and the first vaccine be given no earlier than 12 weeks of age. In general, Leptospira vaccines have been associated with more severe postvaccinal reactions (acute anaphylaxis) than other vaccines. The recent introduction of vaccines with reduced amounts of foreign protein has reduced this problem. Reaction rates for vaccines containing Leptospira, while higher than those for vaccines that do not contain Leptospira, are still low in incidence (in one study, < 0.6%). Vaccination of dogs that have had previous reactions to Leptospira vaccines should be avoided if possible. The VMTH does not recommend administering different vaccine antigens at separate time points because it reduces the chance that vaccines will be administered and there is poor evidence that it decreases the risk of reactions occurring.

Canine Non-Core Vaccines

Non-core vaccines are optional vaccines that should be considered in light of the exposure risk of the animal, ie. based on geographic distribution and the lifestyle of the pet. Several of the diseases involved are often self-limiting or respond readily to treatment. Vaccines considered as non-core vaccines are canine parainfluenza virus (CPiV), canine influenza virus H3N8, canine influenza virus H3N2 distemper-measles combination vaccine, Bordetella bronchiseptica, and Borrelia burgdorferi. Vaccination with these vaccines is generally less effective in protecting against disease than vaccination with the core vaccines.

Canine Parainfluenza Virus and Bordetella bronchiseptica

These are both agents associated with 'kennel cough' or canine infectious respiratory disease complex (CIRDC) in dogs. For Bordetella bronchiseptica, mucosal vaccination with live avirulent bacteria is recommended for dogs expected to board, be shown, or to enter a kennel situation within 6 months of the time of vaccination. We currently stock the intranasal vaccine containing both B. bronchiseptica and CPiV. For puppies and previously unvaccinated dogs, only one dose of this vaccine is required (recommendations differ for the parenteral, killed form of this vaccine). Most boarding kennels require that this vaccine be given within 6 months of boarding; the vaccine should be administered at least one week prior to the anticipated boarding date for maximum effect. Although some kennels require immunization every 6 months, annual booster vaccination with B. bronchiseptica vaccines is considered adequate for protection.

Canine Influenza Virus (CIV)

Canine influenza virus H3N8 emerged in the United States in greyhounds in Florida in 2003. The virus is now enzootic in many dog populations in Colorado, Florida, Pennsylvania, New Jersey and New York. The virus causes upper respiratory signs including a cough, nasal discharge, and a low-grade fever followed by recovery. A small percentage of dogs develop more severe signs in association with hemorrhagic pneumonia. Canine influenza virus H3N2 emerged in 2015 in Illinois and has spread to several other states, including California. Several affected dogs have recently (December 2017/January 2018) been identified in the south bay area in Northern California. Disease caused by CIV H3N2 may be slightly more severe than that caused by CIV H3N8, and the virus has affected more dogs in veterinary hospitals and the community (H3N8 has largely remained confined to shelters). Vaccines for both infections are commercially available, including a combination H3N8/H3N2 vaccine. In Northern California, use of the H3N2 vaccine may be warranted for dogs that contact other dogs, such as those that board. Vaccines may reduce clinical signs and virus shedding in dogs infected by CIV. Vaccination may have the potential to interfere with the results of serological testing, which in non-endemic areas are useful to assist diagnosis.

Canine Distemper-Measles Combination Vaccine

This vaccine has been used between 4 and 12 weeks of age to protect dogs against distemper in the face of maternal antibodies directed at CDV. Protection occurs within 72 hours of vaccination. It is indicated only for use in households/kennels/shelters where CDV is a recognized problem. Only one dose of the vaccine should be given, after which pups are boostered with the CDV vaccine to minimize the transfer of anti-measles virus maternal antibodies to pups of the next generation. The UC Davis VMTH does not stock this vaccine as situations requiring their use do not arise commonly in our hospital population.

Canine Borrelia burgdorferi (Lyme) Vaccine

The incidence of Lyme disease in California is currently considered extremely low. Furthermore, use of the vaccine even in endemic areas (such as the east coast of the US) has been controversial because of anecdotal reports of vaccine-associated adverse events. Most infected dogs show no clinical signs, and the majority of dogs contracting Lyme disease respond to treatment with antimicrobials. Furthermore, prophylaxis may be effectively achieved by preventing exposure to the tick vector. If travel to endemic areas (ie the east coast) is anticipated, vaccination could be considered, followed by boosters at intervals in line with risk of exposure. The UC Davis VMTH does not stock the Lyme vaccine or recommend it for use in dogs residing solely in northern California.

Other Canine Vaccines

Several other canine vaccines are currently available on the market. These are vaccines for canine coronavirus, canine adenovirus-1, and rattlesnake envenomation. The reports of the AVMA and the AAHA canine vaccine task force have listed these three vaccines as not generally recommended, because ‘the diseases are either of little clinical significance or respond readily to treatment’, evidence for efficacy of these vaccines is minimal, and they may ‘produce adverse events with limited benefit’. Currently, information regarding the efficacy of the canine rattlesnake vaccine is insufficient. The UC Davis VMTH does not stock or routinely recommend use of these vaccines.

Canine Enteric Coronavirus Vaccine

Infection with canine enteric coronavirus (CCV) alone has been associated with mild disease only, and only in dogs < 6 weeks of age. It has not been possible to reproduce the infection experimentally, unless immunosuppressive doses of glucocorticoids are administered. Serum antibodies do not correlate with resistance to infection, and duration of immunity is unknown. In mixed infections with CCV and canine parvovirus (CPV), CPV is the major pathogen. Vaccination against CPV therefore protects puppies from disease following challenge with both canine enteric coronavirus and CPV. Thus, the UC Davis VMTH does not routinely recommend vaccination against canine enteric coronavirus and the vaccine is not stocked by our drug room.

Canine Rattlesnake Vaccine

The canine rattlesnake vaccine comprises venom components from Crotalus atrox (western diamondback). Although a rattlesnake vaccine may be potentially useful for dogs that frequently encounter rattlesnakes, currently we are unable to recommend this vaccine because of insufficient information regarding the efficacy of the vaccine in dogs. Dogs develop neutralizing antibody titers to C. atrox venom, and may also develop antibody titers to components of other rattlesnake venoms, but research in this area is ongoing. Owners of vaccinated dogs must still seek veterinary care immediately in the event of a bite, because 1) the type of snake is often unknown; 2) antibody titers may be overwhelmed in the face of severe envenomation, and 3) an individual dog may lack sufficient protection depending on its response to the vaccine and the time elapsed since vaccination. According to the manufacturer, to date, rare vaccinated dogs have died following a bite when there were substantial delays (12-24 hours) in seeking treatment. Boosters are recommended at least annually while dogs remain at risk. Adverse reactions appear to be low and consistent with those resulting from vaccination with other products available on the market. Based on existing evidence, the UC Davis VMTH does not currently recommend routine vaccination of dogs for rattlesnake envenomation, and the vaccine is not stocked by our drug room.

II.Feline Vaccination Guidelines

In general, guidelines for vaccination of cats have been strongly influenced by the appearance of vaccine-associated sarcomas in cats, and in particular their epidemiologic association with feline leukemia virus vaccines and killed rabies virus vaccines. Thus, there is clear evidence for minimizing frequency of vaccination in cats. The recommendations below have been made in light of the AVMA/AAHA/AAFP/VCS task force recommendations on vaccine-associated sarcomas in cats. Risk factors for sarcomas should be discussed with cat owners at the time of examination. If a cat develops a palpable granuloma at the site of previous vaccination, the benefits vs risks of future vaccinations should be carefully considered. All vaccine-associated sarcomas should be reported to the vaccine manufacturer.

Feline Core Vaccines

The definitions of core and non-core vaccines described in the canine vaccination guidelines above also apply to the feline vaccines. The core feline vaccines are those for feline herpesvirus 1 (FHV1), feline calicivirus (FCV), feline panleukopenia virus (FPV), feline leukemia virus (FeLV - kittens) and rabies.

Feline Herpesvirus 1, Feline Calicivirus and Feline Panleukopenia Virus Vaccines

For initial kitten vaccination (< 16 weeks), one dose of parenteral vaccine containing modified live virus (MLV) FHV1, FCV, and FPV is recommended every 3-4 weeks from 6-8 weeks of age, with the final booster being given no sooner than 16 weeks of age. For cats older than 16 weeks of age, two doses of vaccine containing modified live virus (MLV) FHV1, FCV, and FPV given 3-4 weeks apart are recommended. After a booster at 6 months to one year, revaccination is suggested every 3 years thereafter for cats at low risk of exposure. It is recommended that these vaccines be administered on the right thoracic limb as distally as possible. Note that recommendations for killed and intranasal FHV1 and FCV vaccines are different from the above. Killed and intranasal varieties of these vaccines are not routinely used at the VMTH, but there may be some advantages to the use of non-adjuvanted vaccines that that include two inactivated FCV strains over those that contain one strain. The use of FPV MLV vaccines should be avoided in pregnant queens and kittens less than one month of age.

Feline Rabies Virus Vaccines

Cats are important in the epidemiology of rabies in the US. In general we recommend that kittens receive a single dose of killed or recombinant rabies vaccine at 12-16 weeks of age. Adult cats with unknown vaccination history should also receive a single dose of killed or recombinant rabies vaccine. For the recombinant vaccines, boosters are recommended at yearly intervals. We currently stock and suggest the use of the recombinant rabies vaccine, because there is some evidence that it is associated with a decreased risk of sarcoma formation (Srivastav et al, 2012). For the killed rabies vaccines, a booster is required at one year, and thereafter, rabies vaccination should be performed every 3 years using a vaccine approved for 3-year administration. According to recommendations of the vaccine-associated sarcoma task force, rabies vaccines are administered subcutaneously as distally as possible in the right rear limb.

Feline Leukemia Virus Vaccine

A number of FeLV vaccines are available on the market. The whole inactivated viral vaccines have recently been shown to be highly efficacious based on the results of molecular detection methods for FeLV, even producing sterilizing immunity, although this was not found to be the case for an inactivated mixed subunit vaccine (Torres et al, 2009). We recommend vaccination of all FeLV-negative kittens and any FeLV-negative adult cats allowed to go outdoors or cats having direct contact with other cats of unknown FeLV status. Vaccination is most likely to be useful in kittens and young adult cats, because acquired resistance to infection develops beyond 16 weeks of age. Vaccination is not recommended for FeLV-positive cats and indoor cats with no likelihood of exposure to FeLV.

Use of the recombinant FeLV vaccine offers the potential advantage of a decreased risk of sarcoma formation (Srivastav et al, 2012). However, there is some evidence that the inactivated vaccines may be more efficacious (Patel et al, 2015). Until further supporting evidence is available from independent investigators that supports improved efficacy of the inactivated over the recombinant vaccine, the VMTH does not have a preference over whether inactivated or recombinant vaccines are used, but we currently stock the recombinant vaccine.

Initially, two doses of FeLV vaccine are given at 2-4 week intervals, after which annual boosters (recombinant vaccine) or 3-yearly boosters (inactivated vaccine) are recommended depending on risk. According to recommendations of the vaccine-associated sarcoma task force, parenteral FeLV vaccines are administered subcutaneously as distally as possible in the left rear limb.

Feline Non-Core Vaccines

Optional or non-core vaccines for cats consist of the vaccines for feline immunodeficiency virus, Chlamydia felis, and Bordetella bronchiseptica.

Feline Immunodeficiency Virus Vaccine

The FIV vaccine was an inactivated, adjuvented dual subtype vaccine that was released in July 2002. It is no longer being made or distributed in North America. Unfortunately, vaccination of FIV-negative cats rendered currently available serologic tests (ELISA and Western blot) positive for at least a year following vaccination, and polymerase chain reaction (PCR)-based tests do not reliably identify cats with natural infection. Previous vaccination does not prevent infection, and the significance of a positive test result in a vaccinated cat cannot be assessed. Questions remained regarding the vaccine’s ability to protect against all of the FIV subtypes and strains to which cats might be exposed. The UC Davis VMTH drug room did not stock this vaccine, and its routine use in indoor cats is not recommended.

Feline Chlamydia felis Vaccine

Chlamydia felis causes conjunctivitis in cats that generally responds readily to antimicrobial treatment. Immunity induced by vaccination is probably of short duration and the vaccine provides only incomplete protection. The use of this vaccine could be considered for cats entering a population of cats where infection is known to be endemic. However, the vaccine has been associated with adverse reactions in 3% of vaccinated cats, and we do not recommend routine vaccination of low-risk cats with this vaccine. The C. felis vaccine is therefore not stocked by the VMTH drug room.

Feline Bordetella bronchiseptica Vaccine

This is a modified live intranasal vaccine. Bordetella bronchiseptica is primarily a problem of very young kittens, where it can cause severe lower respiratory tract disease. It appears to be uncommon in adult cats and pet cats in general. For these reasons, the UC Davis VMTH does not recommend routine vaccination of pet cats for Bordetella bronchiseptica. The vaccine could be considered for young cats at high risk of exposure in large, multiple cat environments. The UC Davis VMTH drug room does not stock this vaccine.

Other Feline Vaccines

The feline infectious peritonitis (FIP) vaccine has been listed as ‘Not Generally Recommended’ by the AAFP.

Feline Infectious Peritonitis Vaccine

The FIP vaccine is an intranasal modified live virus product. The efficacy of this vaccine is controversial, and duration of immunity may be short, although the vaccine appears to be safe. Although exposure to feline coronaviruses in cat populations is high, the incidence of FIP is very low, especially in single-cat households (where it is 1 in 5000). Most cats in cattery situations where FIP is a problem become infected with coronaviruses prior to 16 weeks of age, which is the age at which vaccination is first recommended. Vaccination could be considered for seronegative cats entering a cattery where FIP is common. We do not routinely recommend vaccinating household cats with the FIP vaccine, and the vaccine is not stocked by our drug room.

REFERENCES AND RESOURCES/SUGGESTED FURTHER READING

Day MJ, Horzinek MC, Schultz RD, et al. 2016. Guidelines for the Vaccination of Dogs and Cats. Compiled by the Vaccination Guidelines Group of the World Small Animal Veterinary Association. J Small Anim Pract. 57(1): E1-E45

Elston T and Rodan I. 1998. Feline Vaccination Guidelines. Compend Contin Educ Small Anim Practit. 20(8):936-941

Klingborg DJ, Hustead DR, Curry-Galvin EA et al 2002. AVMA Council on Biologic and Therapeutic Agents' report on cat and dog vaccines.  J Am Vet Med Assoc.  221(10):1401-1407

Klingborg DJ, Hustead DR, Curry-Galvin EA et al 2001. AVMA's Principles of Vaccination.  J Am Vet Med Assoc.  219:  575-576 (also http://www.avma.org/policies/vaccination.htm )

Paul MA, Appel M, Barrett R et al. 2003. Report of the American Animal Hospital Association (AAHA) Canine Vaccine Task Force: Executive Summary and 2003 Canine Vaccine Guidelines and Recommendations. J Am Anim Hosp Assoc. 39(2):119-131 (also http://www.aahanet.org  via the AVMA Login  (green))

Srivastav A, Kass PH, McGill LD, et al. Comparative vaccine-specific and other injectable-specific risks of injection-site sarcomas in cats. J Am Vet Med Assoc 2012;241:595-602.

Torres AN, O’Halloran KP, Larson LJ, et al. 2009. Feline leukemia virus immunity induced by whole inactivated vaccination. Vet Immunol Immunopathol. Epub ahead of print. Doi:10.1016/j.vetimm.2009.10.017

The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel Report. J Am Vet Med Assoc. 229: 1405-1441 (also http://www.aafponline.org/resources/practice_guidelines.htm)

American Association of Feline Practitioners: 2000 Feline Vaccination Guidelines. http://www.aafponline.org/about/guidelines_vaccine.pdf

1998 Report of the American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on Feline Vaccines. 1998. J Am Vet Med Assoc. 212:227-241

What You Should Know About Vaccination: a client brochure that emphasizes the importance of vaccines while explaining the factors veterinarians consider when making customized vaccine recommendations.  http://www.avma.org/communications/brochures/vaccination/vaccination_brochure_outside.pdf
http://www.avma.org/communications/brochures/vaccination/vaccination_brochure_inside.pdf

Additional vaccine brochure titles are available at http://www.avma.org/communications/brochures/default.asp

Wilson S, Greenslade J, Saunders G, et al. Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection. BMC Vet Res 2012;8:125.

Wallis DM and Wallis JL. 2005. Rattlesnake Vaccine to Prevent Envenomation Toxicity in Dogs. Proceedings of the 77th Annual Western Veterinary Conference, Las Vegas, NV.

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