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Veterinary Forum April 2009 (Vol 26, No 4)

Parvovirus 2c: What's the story?

by Marie Rosenthal

    Opinions differ about the clinical significance of the new variant of canine parvovirus (CPV-2c). Some report that it causes more severe disease, some say less severe. Some say diarrhea is hemorrhagic, some say not. To those outside the research community, there seem to be more questions than answers. Which tests pick up the variant? Is vaccination effective against it? Does it affect older dogs, younger dogs, smaller dogs, larger dogs ≥ cats?

    The lack of consensus might be frustrating, but it is to be expected as researchers find out more about CPV-2c. Veterinary Forum spoke with experts about this new variant and what it means right now to practicing veterinarians. The good news is that every action a veterinarian would normally take to prevent infection or to help an infected animal will work against this variant; the bad news is that you might misread clinical signs in some animals. But the take-home point seems to be if you suspect parvo, trust your instincts: Isolate the animal and manage the condition like parvovirus.

    "Veterinarians need to be more cognizant that any parvo can show a range of signs from severe to moderate, and they need to take into account the background of that animal," says Kate Hurley, DVM, MPVM, program director and assistant clinical professor of shelter medicine and small animal population health at the University of California, Davis, School of Veterinary Medicine. "More than worrying about which variant it is, I think practitioners need to be aware that it does cause a range of signs."

    "Parvovirus is usually described more as a hemorrhagic diarrhea, but we do see a fair number of dogs with the new parvovirus 2c variant in which the diarrhea is yellowish, and we want to emphasize that. We don't want people to think that if the fecal color is yellow, it cannot be parvo," said Sanjay Kapil, DVM, MS, PhD, of the Oklahoma Animal Disease Diagnostic Laboratory in the Center for Veterinary Health Sciences at Oklahoma State University.

    Yet, Nicola Decaro, DVM, PhD, an associate professor of infectious diseases of animals at the University of Bari, Valenzano, Bari, Italy, where CPV-2c was first described in 2000, says it is more virulent. "Variants, especially the new variant 2c, are more virulent than the original type," he says. "The variant is more aggressive and can cause more severe forms of hemorrhagic gastroenteritis."

    CPV-2c is an antigenic variant of the original CPV-2 that emerged as a canine pathogen in the late 1970s. The genetic difference between CPV-2c and CPV-2 is accounted for by seven amino acid residues.

    In contrast, single points in the DNA strand differentiate CPV-2a, 2b and 2c, explains Ronald D. Schultz, PhD, DACVM, of the department of pathobiological sciences, University of Wisconsin School of Veterinary Medicine. The evolution of CPV could be compared with the antigenic drifting of the human influenza virus, which changes slightly every year or so as it circles the globe.

    Soon after its emergence, CPV-2 gave way to two antigenic variants, CPV-2a and 2b, which replaced the original type 2. The original type 2 no longer circulates naturally among the canine population, Decaro explains.

    CPV-2c has been detected in parts of Europe, the United States, Africa and South America.

    Kapil says that the variants probably spread through the importation and movement of dogs. "It is possible that the virus originated in another country, possibly one in Europe. Parvovirus can cross the continent when a dog is imported, and it is possible that it was brought into this country through an infected dog," Kapil says.

    Kapil has reported CPV-2c in 15 states: Alabama, Arizona, Arkansas, California, Delaware, Florida, Georgia, Kansas, Missouri, New Hampshire, New Jersey, Oklahoma, Oregon, South Carolina and Texas. But he cannot say why he is finding it in these areas and not others. "Maybe it is related to animal density and canine parvovirus vaccination in dog populations," Kapil offers. "There may be many reasons for the geographic distribution. We had samples from other states, but they tested negative for CPV-2c."

    It stands to reason that the variant will eventually spread to every state. "The most prevalent variant in the United States is 2b, but 2c is certainly more prevalent now than when it first came here," says Schultz.

    Veterinarians routinely link parvovirus to diarrhea in large-breed dogs, especially black and tan dogs, such as rottweilers and Doberman pinschers. But CPV-2c may be more of an equal opportunity variant. In Kapil's studies, smaller breeds appear to be overrepresented.

    "My first impression was that we were getting a lot of small breeds of dogs with 2c," he says. "But it is possible that the reason we are seeing more 2c in small dogs is because more people are buying those breeds, so that is what is being bred now. In the paper we published, we do say that we detected it more in small breeds."

    "Small breeds tend to be handled in a high-risk way," adds Hurley. "They may come from breeders or puppy mills where the owner has the impression that the vaccines were already given when they were not. Owners also take them to the pet supply store," she says.

    Owners want to socialize their new pups, but Hurley says it might not be a good idea to take younger puppies to the pet supply store. "Pet supply stores are super high-risk areas because puppies can shed virus for 3 days before they show signs. Owners get a puppy from a pet shop or adopt one from a shelter, and then they take it to these stores. I am a big advocate of socializing puppies, but they should not go to pet supply stores until about 5 months of age," she says.

    Another high-risk area is a dog park, says Schultz, and again, many owners take their new puppies to dog parks, but parvovirus is extremely stable in that environment. "We showed that it can remain infectious for up to 1 year in soil," he says.

    Although Kapil saw a disproportionate number of small dogs, Hurley reminds veterinarians that larger-breed dogs are overrepresented in shelters, so she has seen her share of parvovirus in large breeds.

    Unfortunately, shelter and rescue adoption programs may contribute to the spread of virus from one state to another, Hurley adds. "There is an effort to rescue dogs and transfer them from shelters in economically disadvantaged communities into more wealthy communities, where there is a higher potential for adoptive homes. This is a great program because transferring these animals has saved tens of thousands of lives, but it does mean that we are mixing communities with high vaccination rates and communities with lower vaccination rates and a higher parvovirus rate," she explains.

    One controversial area is whether older dogs are affected by parvovirus. "The answer is, 'Yes,'" says Kapil, although the highest occurrence is in dogs younger than 3 months of age.

    "Canine parvovirus, especially types b and c, affects puppies most. The peak of disease is at 2 months, so it is still a puppy disease. But do we believe that it can be detected in older dogs? The answer is, 'Yes' again."

    "We've seen all strains of parvovirus in older dogs," agrees Hurley. "We recently saw two 7-year-olds, last vaccinated as pups, and they both got parvovirus. If dogs are not vaccinated appropriately, they can become infected with any strain of parvovirus, even as adults."

    Seeing parvovirus in older dogs begs the question: Are vaccines protecting against old and new variants of disease? Experts say yes — all of the commercially available vaccines are protective against all variants of parvovirus, but maternal antibodies in a young pup may prevent an immune response to the vaccine virus.

    Therefore, the AVMA and AAHA recommend that a booster dose of parvovirus vaccine be given between 14 and 16 weeks of age, regardless of how many doses preceded that booster, says Schultz, who has conducted several experiments concerning the efficacy of the current CPV vaccines.

    "With the advent of this new variant, we had to answer the question: Do the current CPV-2 and 2b vaccines provide protection?" Schultz says. They tested the vaccines that were available in 2007 from Intervet, Pfizer Animal Health, Fort Dodge Animal Health, Merial and Schering-Plough Animal Health (this study was conducted before the merger of Intervet/Schering-Plough).

    "We had pups with no maternally derived antibodies, so we only needed to use one dose of vaccine. We gave one dose of vaccine, and 5 weeks later, we challenged all of the pups with a combination of virulent strains of CPV-2b and 2c. All of the vaccinated animals were totally protected against disease," Schultz says. "There was no question that all the vaccines provided excellent protection."

    None of the vaccinated pups in any of the five vaccine groups became ill after challenge, but all of the 10 unvaccinated controls broke with parvovirus and many had to be euthanized.

    Because it was a short-term study, Schultz conducted a second long-term study to determine whether the vaccines provided long-term protection. Dogs from 4 to 8 years of age that had been vaccinated as puppies were challenged with CPV-2c and distemper. The puppies had never been revaccinated and were maintained in a parvovirus-free environment. Again, he found no clinical disease.

    Older dogs that break with parvovirus were probably vaccinated when the pups still had robust maternal antibodies that prevented an effective immune response to the vaccine, which is why the current vaccination guidelines recommend a booster at 14 to 16 weeks of age when maternal antibodies wane.

    Decaro believes the jury is still out on this issue, however. "Protection elicited by CPV-2"based vaccines against the field variants still represents a vexata quaestio, as the current opinions are highly divergent," he says.

    Many authors suggest that the old type-2-based vaccines are still protective against the variants; others believe that the immunity induced by CPV-2"based vaccines is effective against the homologous (vaccine) virus but significantly lower against the variants and could allow an aggressive strain to cause infection, according to Decaro.

    "It has been shown that there is one-way cross-reactivity between the antigenic variants and the original CPV-2," Decaro says. "Sera raised against CPV-2 displayed low virus neutralization titers against the heterologous virus, CPV-2b, compared with those obtained when sera raised against CPV-2b were run against the original CPV-2."

    Regardless, the highest risk for death is among the youngest victims of parvovirus, experts say, so it is important to make sure that all dogs are vaccinated against this disease. "The younger the animal [when infected], the more likely that this virus will cause severe disease and death," Schultz says. "We want to get the puppy or young animal immune at the earliest possible age because that is when it is most likely to die of disease if infected — all the heroics are unlikely to save the animal."

    Another reassuring factor about the new variant is that current rapid diagnostics, like the IDEXX SNAP Parvo Test, do detect 2c. "The variant strains are diagnosed using the same methods as the classic CPV-2, including the commercially available rapid tests that are based on ELISA or immunochromatography, albeit these tests are poorly sensitive, especially in the late stages of infection," says Decaro.

    Schultz, who has studied the rapid test methods, also found that they detect the new variant. "Fortunately to date, none of the variants 2a, 2b or 2c has been significant regarding immunity engendered by vaccines and none has been significant regarding the ability of the diagnostic, which contains an antibody for an antigen-capture ELISA, to be in any way affected," Schultz says. "The current vaccines and diagnostics are just as reliable for 2c as for the other variants."

    Isolation and supportive care to restore electrolytes lost through vomiting and diarrhea remain the mainstay for treating puppies with parvovirus, regardless of the variant.

    Because this is a hardy virus that can live for a long time in the environment, disinfection is critical. "I think the biggest take-home message is hygiene. Parvovirus is a density disease," says Kapil. "Wherever you have dogs and susceptible puppies in large numbers, you will find parvo. You will find it in kennels; you will find it in shelters. It is a hardy and stable virus."

    Disinfection with bleach (dilution 1:32) or potassium peroxymonosulfate can help reduce the viral load in the environment. Footbaths are not adequate before entering and leaving an isolation ward, according to Hurley. She says caretakers must wear booties and a jumpsuit that stay in the isolation ward because parvovirus is readily spread and can easily be tracked through the facility. "If outdoor areas or waiting rooms have been contaminated, make sure that those areas are quickly cleaned before potentially vulnerable animals are exposed," Hurley says.

    Whether it is an old or new variant, Hurley says, "My impression is that there is more parvo around. The important thing for people to realize is that the basic tools for control have not changed. In all of the many outbreaks in shelters we have dealt with, attention to disinfection, rapid identification, diagnosis and isolation and vaccination, including that last vaccine at 16 weeks of age, have resolved those outbreaks."

    For more information:

    Cavalli A, Martella V, Desario C, et al. Evaluation of the antigenic relationships among canine parvovirus type 2 variants. Clin Vaccine Immunol 2008;15:534-539.

    Decaro N, Desario C, Parisi A, et al. Genetic analysis of canine parvovirus type 2c. Virology 2009;385:5-10.

    Ikeda Y, Nakamura K, Miyazawa, et al. Feline host range of canine parvovirus: recent emergence of new antigenic types in cats. Emerg Infect Dis 2002;8:341-346.

    Kapil S. Cooper E, Lamm C, et al. Canine parvovirus types 2c and 2b circulating in North American dogs in 2006 and 2007. J Clin Microbiol 2007;45:4044-4047.

    Larson LJ, Quesada M, Mukhtar E, et al. Evaluation of a CPV-2 fecal parvovirus ELISA (SNAP Fecal Parvo Test) from IDEXX Laboratories. Proceedings of the 88th Conference of Research Workers in Animal Diseases; 2007; p. 112.

    Larson LJ, Schultz RD. Do two current canine parvovirus type 2 and 2b vaccines provide protection against the new type 2c variant? Veterinary Therapeutics 2008;9:94-101.

    Schultz RD, Larson LJ. Current canine parvovirus type 2 (CPV-2) vaccines provide excellent immunity to all genotypes of CPV-2 (eg CPV-2a, 2b, and 2c). Proceedings of the 88th Conference of Research Workers in Animal Diseases; 2007; p. 113.

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