Recommendations on vaccination for Asian small animal practitioners: a report of the WSAVA Vaccination Guidelines Group.

In 2012 and 2013, the World Small Animal Veterinary Association (WSAVA) Vaccination Guidelines Group (VGG) undertook fact-finding visits to several Asian countries, with a view to developing advice for small companion animal practitioners in Asia related to the administration of vaccines to dogs and cats. The VGG met with numerous first opinion practitioners, small animal association leaders, academic veterinarians, government regulators and industry representatives and gathered further information from a survey of almost 700 veterinarians in India, China, Japan and Thailand. Although there were substantial differences in the nature and magnitude of the challenges faced by veterinarians in each country, and also differences in the resources available to meet those challenges, overall, the VGG identified insufficient undergraduate and postgraduate training in small companion animal microbiology, immunology and vaccinology. In most of the countries, there has been little academic research into small animal infectious diseases. This, coupled with insufficient laboratory diagnostic support, has limited the growth of knowledge concerning the prevalence and circulating strains of key infectious agents in most of the countries visited. Asian practitioners continue to recognise clinical infections that are now considered uncommon or rare in western countries. In particular, canine rabies virus infection poses a continuing threat to animal and human health in this region. Both nationally manufactured and international dog and cat vaccines are variably available in the Asian countries, but the product ranges are small and dominated by multi-component vaccines with a licensed duration of immunity (DOI) of only 1 year, or no description of DOI. Asian practitioners are largely unaware of current global trends in small animal vaccinology or of the WSAVA vaccination guidelines. Consequently, most practitioners continue to deliver annual revaccination with both core and non-core vaccines to adult animals, with little understanding that "herd immunity" is more important than frequent revaccination of individual animals within the population. In this paper, the VGG presents the findings of this project and makes key recommendations for the Asian countries. The VGG recommends that (1) Asian veterinary schools review and increase as needed the amount of instruction in small animal vaccinology within their undergraduate curriculum and increase the availability of pertinent postgraduate education for practitioners; (2) national small animal veterinary associations, industry veterinarians and academic experts work together to improve the scientific evidence base concerning small animal infectious diseases and vaccination in their countries; (3) national small animal veterinary associations take leadership in providing advice to practitioners based on improved local knowledge and global vaccination guidelines; (4) licensing authorities use this enhanced evidence base to inform and support the registration of improved vaccine product ranges for use in their countries, ideally with DOI for core vaccines similar or equal to those of equivalent products available in western countries (i.e. 3 or 4 years). The VGG also endorses the efforts made by Asian governments, non-governmental organisations and veterinary practitioners in working towards the goal of global elimination of canine rabies virus infection. In this paper, the VGG offers both a current pragmatic and future aspirational approach to small animal vaccination in Asia. As part of this project, the VGG delivered continuing education to over 800 Asian practitioners at seven events in four countries. Accompanying this document is a list of 80 frequently asked questions (with answers) that arose during these discussions. The VGG believes that this information will be of particular value to Asian veterinarians as they move towards implementing global trends in small companion animal vaccinology.

Age and long-term protective immunity in dogs and cats.

Vaccination can provide an immune response that is similar in duration to that following a natural infection. In general, adaptive immunity to viruses develops earliest and is highly effective. Such anti-viral immune responses often result in the development of sterile immunity and the duration of immunity (DOI) is often lifelong. In contrast, adaptive immunity to bacteria, fungi or parasites develops more slowly and the DOI is generally short compared with most systemic viral infections. Sterile immunity to these infectious agents is less commonly engendered. Old dogs and cats rarely die from vaccine-preventable infectious disease, especially when they have been vaccinated and immunized as young adults (i.e. between 16 weeks and 1 year of age). However, young animals do die, often because vaccines were either not given or not given at an appropriate age (e.g. too early in life in the presence of maternally derived antibody [MDA]). More animals need to be vaccinated to increase herd (population) immunity. The present study examines the DOI for core viral vaccines in dogs that had not been revaccinated for as long as 9 years. These animals had serum antibody to canine distemper virus (CDV), canine parvovirus type 2 (CPV-2) and canine adenovirus type-1 (CAV-1) at levels considered protective and when challenged with these viruses, the dogs resisted infection and/or disease. Thus, even a single dose of modified live virus (MLV) canine core vaccines (against CDV, cav-2 and cpv-2) or MLV feline core vaccines (against feline parvovirus [FPV], feline calicivirus [FCV] and feline herpesvirus [FHV]), when administered at 16 weeks or older, could provide long-term immunity in a very high percentage of animals, while also increasing herd immunity.

Extensive remyelination of the CNS leads to functional recovery.

Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occurring simultaneously. Cats that were returned to a normal diet recovered slowly so that by 3-4 months they were neurologically normal. Histological examination of the CNS at this point showed extensive remyelination that was especially notable in the optic nerve where almost the entire nerve was remyelinated. Biochemical analysis of the diet and tissues from affected cats showed no dietary deficiencies or toxic accumulations. Thus, although the etiology of this remarkable disease remains unknown, it shows unequivocally that where axons are preserved remyelination is the default pathway in the CNS in nonimmune-mediated demyelinating disease. Most importantly, it confirms the clinical relevance of remyelination and its ability to restore function.

Do two current canine parvovirus type 2 and 2b vaccines provide protection against the new type 2c variant?

Three groups (n=9 or 10) of 12-week-old canine parvovirus type 2 (CPV-2) antibody-negative puppies were vaccinated: one group with a product containing modified-live CPV-2b (Galaxy DA2PPv; Schering-Plough Animal Health), one group with a product containing modified-live CPV-2 (Continuum DAP, Intervet), and one group (controls) with sterile saline. All puppies receiving CPV-2 and CPV-2b vaccines developed antibody as determined by the hemagglutination inhibition assay. All groups of puppies were challenged with a combination of virulent CPV-2b and CPV-2c 5 weeks after vaccination. All puppies in the CPV-2 and CPV-2b vaccinated groups were protected from disease, whereas all control group puppies developed disease and 50% died or were euthanized. This study demonstrated that the CPV-2 and CPV-2b vaccine components of the Continuum DAP and Galaxy DA2PPv products, respectively, provided protection against the CPV-2b virus and also provided complete protection against the new CPV-2c variant.

Enhanced bactericidal activity against Escherichia coli in calves fed Morinda citrifolia (Noni) puree.

BACKGROUND: Although adequate colostrum intake and properly used antibiotics can provide much protection for the bovine neonate, increased antibiotic scrutiny and consumer demand for organic products have prompted investigations of natural immunomodulators for enhancing calf health. One plant-based immunomodulator, Morinda citrifolia (noni) fruit, is a well-recognized natural product that has a broad range of immunomodulatory effects. HYPOTHESIS: Neonatal calves fed noni puree would demonstrate whole blood phagocytic capacity in Gram-negative and Gram-positive in vitro assays. ANIMALS: Blood samples from 18 neonatal Holstein bull calves. METHODS: Calves were divided into 2 groups: Group 1 comprised control calves, whereas Group 2 received 30 mL of noni puree twice a day in milk replacer. Day 0 blood samples were obtained between 36 and 48 hours of age before the first feeding of puree. Ethylenediaminetetraacetic acid anticoagulated blood was collected from each calf on days 0, 3, 7, and 14. Bactericidal assays were performed to estimate the percentage killing of Escherichia coli and Staphylococcus epidermidis. RESULTS: Blood samples from noni puree-fed calves displayed significantly more E. coli bacterial killing than did controls on day 14, and although differences were not significant on days 0, 3, and 7, bacterial killing progressively increased over time. There was no significant difference between the groups for S. epidermidis killing. CONCLUSIONS AND CLINICAL IMPORTANCE: The immunomodulatory effect of noni puree may prove valuable in the future as production animal antibiotic use becomes more restricted. Additional clinical trials are warranted to investigate the clinical application of noni puree in promoting calf health.

Three-year duration of immunity in dogs vaccinated with a canarypox-vectored recombinant canine distemper virus vaccine.

Two studies evaluated the duration of serologic response to the recombinant, canarypox-vectored canine distemper virus vaccine (Recombitek, Merial). Serologic duration of immunity was shown to be at least 36 months. Thus, Recombitek provides protection when administered less frequently than the manufacturer's label. After the initial vaccination protocol of two or more doses administered approximately 4 weeks apart, with the last dose given at 12 to 16 weeks of age or older, and re-vaccination at 1 year of age, Recombitek can confidently be readministered every 3 years with assurance of protection in immunocompetent dogs. This allows the vaccine to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force and others.

Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine.

A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.

Effect of recombinant canine distemper vaccine on antibody titers in previously vaccinated dogs.

Two canine distemper virus (CDV) vaccine types are currently commercially available: modified-live virus (MLV) vaccines and a canarypox recombinant CDV (rCDV) vaccine (Recombitek, Merial). This study compared the ability of the rCDV vaccine and MLV vaccines to significantly enhance (boost) the antibody response of previously immunized adult and juvenile dogs. A significant (fourfold or greater) increase in titer occurred in significantly more dogs revaccinated with Recombitek C-4 or Recombitek C-6 than with the MLV-CDV vaccines. This study demonstrates that Recombitek, the only vaccine for dogs containing rCDV, is more likely to significantly boost the CDV antibody response in previously vaccinated dogs than are the MLV-CDV vaccines. Because rCDV vaccine can boost the antibody titer of dogs previously vaccinated with an MLV vaccine, it can and should be used when core vaccines are readministered.

Effect of vaccination with recombinant canine distemper virus vaccine immediately before exposure under shelter-like conditions.

Vaccination with modified-live virus (MLV) canine distemper virus (CDV) vaccine has historically been recommended for animals in high-risk environments because of the rapid onset of immunity following vaccination. Recombinant CDV (rCDV) vaccine was deemed a suitable alternative to MLV-CDV vaccination in pet dogs, but insufficient data precluded its use where CDV was a serious threat to puppies, such as in shelters, kennels, and pet stores. In this study, dogs experimentally challenged hours after a single dose of rCDV or MLV vaccine became sick but recovered, whereas unvaccinated dogs became sick and died. Dogs vaccinated with a single dose of rCDV or MLV vaccine 1 week before being experimentally challenged remained healthy and showed no clinical signs. Dogs given one dose of rCDV vaccine hours before being placed in a CDV-contaminated environment did not become sick. These findings support the hypothesis that rCDV vaccine has a similar time-to-immunity as MLV-CDV vaccines and can likewise protect dogs in high-risk environments after one dose.

Cats differ from mink and ferrets in their response to commercial vaccines: a histologic comparison of early vaccine reactions.

Early histologic changes in lesions at vaccine sites were compared in cats, mink, and ferrets. Twenty-four 4-month-old cats, 20 4-month-old mink, and 20 12-month-old ferrets were vaccinated with three rabies virus vaccines, two feline leukemia virus vaccines, alum adjuvant, and saline. Injection sites were excised at selected time points up to 21 days postvaccination. Histologic examination of the tissue revealed significant differences among the cats, mink, and ferrets in the local response to the commercial vaccines. When compared with ferrets and mink, cats had more lymphocytes in response to all three rabies vaccines. Production of fibroblasts, collagen, and macrophages differed among the three killed aluminum-adjuvanted vaccines in cats but did not differ significantly in mink or ferrets. Cats produced fewer binucleate cells than did mink or ferrets in response to the two adjuvanted leukemia virus vaccines. Differences seen in early tissue response of cats to commercial vaccines may be related to the increased predisposition of cats to vaccine-associated sarcomas.

Canine vaccination.

New technologies for vaccine development and infectious disease diagnosis are likely to be introduced in the near future. With this new technology comes the opportunity to vaccinate companion animals against even more infectious agents than is currently practiced in the United States. As we look forward, it becomes particularly important to review current vaccination standards applied to dogs with respect to current knowledge of duration of immunity, awareness of incidence, and likelihood of injurious or even fatal adverse events associated with vaccination, and individual risk factors that dictate which vaccines are most appropriate at which stage of life.

Serologic survey for selected infectious disease agents in swift and kit foxes from the western United States.

A serologic survey of swift fox (Vulpes velox) and kit fox (V. macrotis) from the western USA was conducted for 12 infectious diseases. Samples from swift fox were collected between 1987 and 1992 from Colorado (n = 44), Kansas (n = 10), and Wyoming (n = 9). Samples from kit fox were collected in California (n = 86), New Mexico (n = 18), Utah (n = 9), and Arizona (n = 6). Overall antibody prevalence rates were 33 of 110 (30%) for canine parvovirus (CPV), 9 of 72 (13%) for canine distemper virus (CDV), 23 of 117 (20%) for vesicular stomatitis New Jersey, 16 of 117 (14%) for vesicular stomatitis Indiana, six of 117 (5%) for Cache Valley virus, five of 117 (4%) for Jamestown Canyon virus, one of 97 (1%) for rabies virus, one of 117 (1%) for Colorado tick fever virus, and one of 117 (1%) for western equine encephalitis virus. In addition, antibodies were not found to Yersinia pestis, Francisella tularensis, and Borrelia burgdorferi in serum from 25 Colorado swift fox. Adult swift fox from Colorado had serologic evidence of exposure to CPV more often than juveniles. No juvenile swift fox from Colorado had serum antibodies to CDV. There were season-specific differences in serum antibody prevalence for CPV for swift fox from Colorado. No viruses were isolated from ectoparasites or fox from Colorado.

Growth hormone receptor and regulation of gene expression in fetal lymphoid cells.

The role of growth hormone (GH) in modulating the adult immune response is receiving increased attention; however, its role in the development of immune competence in the fetus has not been defined. In order to begin to address the role of GH in the ontogeny of the immune response. cells from bovine fetal spleen and thymus were examined for GH receptor and responsiveness to GH. Northern analysis and ligand binding studies showed that growth hormone receptor (GHR) was readily detected in early- and mid-gestational fetal thymocytes, but it was less readily detected in thymocytes from older fetuses. In contrast, GHR was easily detected in splenocytes at all fetal ages. Thymocytes and splenocytes from mid-gestational fetuses expressed low levels of cell surface GHR by flow cytofluorometric analysis, and CD4+ and CD8 (single positive) thymocyte subsets were positive. Northern analyses were employed to determine the effects of in vitro GH treatment on expression of several proto-oncogenes, cytokines, and GHR in thymocytes from fetuses at approximately mid-gestation. GH treatment for 30 min down-regulated c-jun and c-fos mRNA approximately 2- and 2.8-fold, respectively. After 6 h treatment, GH increased transcript levels for interleukin (IL)-1alpha, IL-1beta, IL-6, and GM-CSF about 2.5-, 2.2-, 3-, and 2-fold, respectively. GH also down-regulated the expression of its own receptor about 3.2-fold after 8 h of incubation. The presence of GHR in fetal lymphoid cells and its temporal and spatial regulation suggest a potential role for GH in the development and or function of the fetal bovine immune system. Although the mechanism(s) is unclear, our results suggest that GH is intimately involved in lymphocyte function and expression of certain cytokines during a critical period of fetal immune development.

Comparison of selected canine vaccines for their ability to induce protective immunity against canine parvovirus infection.

OBJECTIVE: To compare the ability of 6 commercially available multicomponent canine vaccines to stimulate antibody production in pups with variable amounts of maternally derived canine parvovirus (CPV) antibody and to induce protective immunity against challenge exposure. ANIMALS: Sixty-three 5- to 6-week-old Beagle pups with passively acquired CPV antibody titer between 1: 20 and 1:320. PROCEDURE: 9 pups were assigned to each of 6 vaccine groups and 1 control group. Eight pups in each group were inoculated with vaccine or saline solution twice, with 3 weeks between administrations. The ninth pup served as an uninoculated contact control. Serum samples were obtained weekly and tested for CPV antibody by hemagglutination-inhibition assay. All pups were challenge exposed with virulent CPV-2a and CPV-2b at 14 to 15 weeks of age. RESULTS: 3 of the vaccines failed to provide protective immunity against challenge exposure because all pups in these groups became infected and most died. A fourth vaccine protected against death, but not infection and disease. Two of the 6 vaccines induced an immune response that was protective against infection and disease. CONCLUSION AND CLINICAL RELEVANCE: Substantial differences existed among commercial vaccines available in 1994 in their ability to immunize pups with maternally derived CPV antibody. These differences caused many vaccinated pups to be susceptible to CPV disease for variable periods because some vaccines failed to immunize. Importantly, all 4 of the vaccines that performed poorly have recently been replaced by more effective products so that the 6 vaccines now perform similarly.

Serological survey for diseases in free-ranging coyotes (Canis latrans) in Yellowstone National Park, Wyoming.

From October 1989 to June 1993, we captured and sampled 110 coyotes (Canis latrans) for various diseases in Yellowstone National Park, Wyoming (USA). Prevalence of antibodies against canine parvovirus (CPV) was 100% for adults (> 24 months old), 100% for yearlings (12 to 24 months old), and 100% for old pups (4 to 12 months old); 0% of the young pups (< 3 months old) had antibodies against CPV. Presence of antibodies against canine distemper virus (CDV) was associated with the age of the coyote, with 88%, 54%, 23%, and 0% prevalence among adults, yearlings, old pups, and young pups, respectively. Prevalence of CDV antibodies declined over time from 100% in 1989 to 33% in 1992. The prevalence of canine infectious hepatitis (ICH) virus antibodies was 97%, 82%, 54%, and 33%, for adults, yearlings, old pups, and young pups, respectively. The percentage of coyotes with ICH virus antibodies also declined over time from a high of 100% in 1989 to 31% in 1992, and 42% in 1993. Prevalence of antibodies against Yersinia pestis was 86%, 33%, 80%, and 7%, for adults, yearlings, old pups, and young pups, respectively, and changed over time from 57% in 1991 to 0% in 1993. The prevalence of antibodies against Francisella tularensis was 21%, 17%, 10%, and 20%, for adults, yearlings, old pups, and young pups, respectively. No coyotes had serologic evidence of exposure to brucellosis, either Brucella abortus or Brucella canis. No coyotes were seropositive to Leptospira interrogans (serovars canicola, hardjo, and icterohemorrhagiae). Prevalence of antibodies against L. interrogans serovar pomona was 7%, 0%, 0%, and 9%, for adults, yearlings, old pups, and young pups, respectively. Antibodies against L. interrogans serovar grippotyphosa were present in 17% of adults and 0% of yearlings, old pups, and young pups. Many infectious canine pathogens (CPV, CDV, ICH virus) are prevalent in coyotes in Yellowstone National Park, with CPV influencing coyote pup survival during the first 3 months of life; eight of 21 transmitted pups died of CPV infection in 1992. The potential impact of these canine pathogens on wolves (C. lupus) reintroduced to Yellowstone National Park remains to be documented.