pet connection

Melissa Kennedy, DVM, PhD., DACVM, a clinicial virologist at the University of Tennessee Veterinary Teaching College and infectious disease and immunology consultant for the Veterinary Information Network, spoke with Pet Connection contributing editor Christie Keith about rumors of a new, deadly strain of canine parvovirus that some dog owners worry is not protected against by current vaccines.

CK: Although the press release from Oklahoma State University does not say that current canine parvovirus vaccines will fail to protect against the CPV-2c virus, many dog owners interpreted it that way. Is there any reason to think that dogs in the United States who are vaccinated for canine parvovirus are not being protected against this strain, too?

Dr. Kennedy: All of the CPV variants have about 99 percent DNA homology in their genomes, so they are all very closely related. The vaccine virus is undoubtedly cross-reactive and thus cross-protective.

The problem may be that one or more of the mutations occurring (about 1-4 amino acid changes have been noted in these various CPV 2c strains – minor differences in Asia vs Europe vs US isolates) are in neutralizing epitopes; that is, regions of the virus recognized and bound by protective antibodies. This is an important defense against parvo; thus changes in these sites could make pre-existing antibody somewhat less effective.

This would be of most concern in puppies who depend almost completely on antibodies they received from their mom for protection (vaccinal immunity has not “kicked in”). Antibodies the mother dog made in response to vaccination with CPV-2 or CPV-2b transferred to the pups may not completely protect against CPV-2c in the pups receiving this antibody in colostrum.

However, in well-immunized adult dogs, where immunity depends not only on antibodies, but cell-mediated immunity as well, this shouldn’t be as big of a concern.

One thing to bear in mind when hearing anecdotal evidence about “vaccine failures” in adult dogs – if a dog is well-vaccinated, then contracts the disease against which he is vaccinated, it cannot necessarily be laid at the feet of the vaccine. There are a lot of factors that impact protection, including the individual animal’s immune response, challenging dose of the “real virus” that the dog was exposed to, concurrent immunosuppressive conditions in the dog, etc. IF, and it’s a big IF, we start to see many adults, well-vaccinated, contracting parvo, then the alarm bells should go off.

But right now, with CPV-2c, the main concern should be with pups, which are always the most vulnerable, and should be protected from exposure until at least 16-20 weeks of age, regardless of whether 2c is circulating or not.

CK: Is there anything in this information that dog owners should be aware of, or
ask their own vets about?

Dr. Kennedy: The biggest concern I have currently with CPV-2c is that the point-of-care ELISAs done to detect and diagnose CPV infection may be missing some of these cases. Most of these kits use a monoclonal antibody (specific for a single epitope) to detect the parvovirus in the fecal sample. If a mutant has an amino acid change at this epitope (and I don’t know that that is the case, as I don’t know what epitope these ELISAs are specific for), there could be false negative results. That is something we are looking at currently – testing fecal samples from suspect CPV cases that are negative by ELISA with electronmicroscopy (visualize the virus) and PCR (sequence the virus) to see if this is indeed occurring.

Otherwise, normal management/precautions should minimize the risk for most owners.

CK: Is parvovirus disease caused by CPV-2c more dangerous than the other strains
to dogs? To puppies?

Dr. Kennedy: Perhaps to puppies for the reason I described above. As for dogs in general, the current indications are no, that it is a similar disease progression to existing strains (not to minimize how bad it can be – it is a terrible disease). The case of a breeder losing 600 puppies in one night described on the OSU website, could create a lot of fear; it is stated in that news release that it is not known precisely what these pups died from, so it is way too soon to say this strain is more virulent. One must be careful in discussing anecdotal information, as it can create false impressions as to the risk.

CK: Is there anything else you’d like to say to dog owners about CPV-2c or the
press release from OSU?

Dr. Kennedy: CPV is a nasty pathogen, and precautions and protective measures should be taken to protect one’s dog, especially puppies, whether one is talking about CPV-2b (the most common strain now) or CPV-2c. The same measures should be taken for any strain of CPV : vaccinate puppies through 16-20 weeks of age (may vary with the specific vaccine – follow your vet’s recommendations for vaccine protocol); Avoid mingling pups with other dogs, or even taking them to environments where other dogs have been like parks (the virus can last for months in the environment – very hardy) until 16-20 weeks of age to minimize chances of exposure. Boost puppy vaccines at 1 year, then approximately every 3 years to maintain immunity. Special precautions may be needed for breeding kennels, etc where puppy populations can be high, such as stringent disinfection and biosecurity control to prevent introduction and spread of this hardy virus (all parvoviruses).

Vaccines will undoubtedly be modified in the future to include the newer variants. But again, these variants are all closely related. That doesn’t mean we shouldn’t have concern, and diligence in monitoring the situation.

But this is completely different from the emergence of CPV-2 in 1978. Then, we were seeing a truly “new” virus in dogs, and the population had no immunity. Thus, we saw tremendous amounts of disease and high mortality in both adults and pups. This new strain of CPV does bear monitoring, and eventual inclusion in vaccines will likely occur, but a repeat of the scenes from the late 70’s and early 80’s is not what we are facing. Concern, and monitoring, but not fear and hysteria!

CK: Why is this different from the influenza viruses, for which there is a new flu vaccine every year? Why are we telling them they don’t need a new parvovirus for this strain?

Dr. Kennedy: One big difference is parvoviruses have DNA as their genome, whereas influenze viruses have RNA as their genome. RNA viruses as a group tend to have a much higher mutation rate than DNA viruses.

Having said that, I will say that parvoviruses, among the DNA viruses, do seem to have a higher rate themselves, probably because they don’t have double-stranded DNA, they have single-stranded DNA. That seems to pre-dispose them to a little bit more mutation.

The other thing that’s different with influenza is that each of their genes is on a separate piece of genetic material; you could think of it as a cup of marbles. If an animal is infected with more than one influenza at a time, those marbles could get mixed up. So you get new viruses. That’s the concern with influenza HN51 that’s out there (note: the so-called “Avian flu”). It’s called “re-assortment,” where two viruses will exchange complete genes.

So you have with influenza not only these small changes, like from season to season that we see with the regular, run-of-the-mill flu, because of their high mutation rate, but also we have the opportunity for big changes because they can exchange complete genes between viruses.

Some animals are actually mixing pots for influenza, like pigs for example, they can get infected with both bird flu viruses and mammalian flu viruses at the same time. So they can mix them all up and come out with a new virus that would be spread to humans, and we would not have any pre-existing immunity. It would truly be a new virus.

CK: Whereas parvo is… ?

Dr. Kennedy: We don’t see mixing, because their genome is just one big piece, they can’t exchange genes, at least, not anywhere near as easily as influenza virus can.

CK: So the takeaway message here is more about diagnostics than treatment or prevention, particularly in adult dogs?

Dr. Kennedy: My biggest concern is with diagnostics, because most of these kits pick up the virus in the fecal sample by using antibody to capture it, to pull it out of the poo. If that antibody that they’re using only recognizes a single epitope – viruses have lots of epitopes but they’ve made these antibodies to just one of them, and if that one epitope on that virus changes, then that test won’t work very well.

We have seen in a couple of cases, these anecdotal reports from veterinarians saying look, the ELISA’s negative but this looks like parvo. And I tell them, send me a sample, and we test it by these other methods, like electron microscopy, where we take the feces and actually look at it under an electron microscope, and look for parvo, it doesn’t matter if it’s 2b, 2c, or you know, elephant parvo (?), we could see it. So that test works. And then we also have the PCR test. The advantage of PCR is a genetic test that in most cases tends to be so exquisitely sensitive, much more so than the ELISAs, we can find parvo. The other thing is, we generally target a region of the genetic material that is unlikely to change from virus to virus, because if the virus did change in that region, it probably wouldn’t replicate and would perish. So we design these PCRs to go after vital genes that are unlikely to change. So we have a chance of finding those viruses that the ELISA might miss. And at least two veterinarians have sent samples to us that were PCR-positive, but negative in-house.

Now, that’s anecdotal. It certainly wasn’t a scientific study.

CK: So for the average dog owner, other than the fact that your dog might have parvo and the test says they don’t, there’s really nothing dog owners need to be worried about right now?

Dr. Kennedy: No, and no additional precautions, just the same precautions as always. In terms of lack of protection, my biggest concern is puppies who are totally dependent on the antibodies that they got from their mom to protect them, and in that case they don’t have any backup. So if the antibodies don’t work, they’re going to be in trouble. Whereas adult dogs have not only antibodies, but cell-mediated immunity which can help protect them.