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A Winn Feline Foundation Report On ...

Feline Infectious Peritonitis - Virus Shedding and Infection - The British Experience


Virus Excretion of Feline Coronavirus
Diane D. Addie, BVMS, PhD and Oswald Jarrett, BVMS, PhD University of Glasgow, Scotland

Aim of the project

The aim of the project is to determine precisely how FCoV (feline coronavirus) spreads among domestic cats so that control measures can be established to prevent infection and development of FIP (feline infecious peritonitis).

Animals recruited

One hundred and six cats from a total of 25 households have been enrolled in the survey. Six cats are from single cat households and a seventh is from a home which became a two-cat household this year. The other cats are from multicat households of up to 13 cats. Some are outdoor cats, but most are kept indoors. There is a variety of purebred and domestic cats. Although we have reached our target number of cats, we would like to enroll more for three reasons: first, some of the most interesting findings so far have occurred in only a tiny number of cats; second, almost 20% of the cats have stopped shedding FCoV; third, nine cats have died or left the survey. Greater numbers of cats will be essential in order to make statistically viable comparisons.

The fate of survey cats

Nine cats have been lost to the survey: two have moved to new homes; two developed FIP; one was euthanized because of chronic diarrhea; two developed alimentary lymphosarcomas; one was euthanized because of acute urethral blockage; one developed a cholangiocarcinoma.

Both cats which died of FIP had chronic, intractable diarrhea before developing FIP. One cat had been seronegative for 20 months before seroconverting, and she died of FIP within three months of seroconverting. She had been in a household where seropositive and seronegative cats had been kept apart. The second cat was in isolation (he was a stud cat) within a multicat household, and died within four months of his FCoV infection being discovered.

Conclusions:

  • The deaths to FIP, though few, occurred within six months of infection, as previously reported (Addie et al, 1995). Cats are at greatest risk of developing FIP following their first infection.
  • It follows that keeping FCoV-naive seronegative cats away from FCoV excreters is absolutely essential in the prevention of FIP.
  • Three cats have had chronic, intractable diarrhea and two developed FIP. The roll of FCoV in diarrhea in the adult cat warrants further investigation (Kipar et al, 1997) and may be an early indictor of a cat being in danger of developing FIP.

Nineteen cats stopped shedding FCoV and became seronegative

All of the cats in five households have eliminated FCoV infection: three were in single-cat households, three more cats formed one household. Seven seronegative cats are part of a 14-cat group which has been divided between two premises: the seronegative cats were removed to a new house with the owner, the seropositive cats remained at the mother's house. As cats become seronegative, they are removed to the owner's house.

The remaining six cats which have become seronegative are from multicat households of up to seven cats. Three cats are from one household where segregation of shedding cats from non-shedding cats is being attempted. Of the remaining three cats: one cat was kept in total isolation until she became seronegative and the other two cats have become seronegative despite being in contact with others which are still shedding virus. It remains to be seen whether these latter two seroconvert again.

Conclusions:

  • So far, FCoV infection has been temporary in 20% of the survey households.
  • Segregating seropositive cats from seronegative cats is effective in the elimination of FCoV infection from a household.
  • Seronegative cats need to be monitored every six to 12 months to confirm that spontaneous recrudescence of infection does not occur in the seronegative animal.
  • More cats need to be enrolled in the survey to take their places.

Some cats' antibody titers fall despite being in contact with FCoV-shedding cats

Four cats' antibody titers are in decline despite being in households of FCoV-shedding cats, and a further two cats remain seronegative despite being in contact with FCoV-shedding cats. If we can identify sufficient cats which are eliminating FCoV infection despite being in an environment where the virus is endemic, we might be able to define which immune response is protective: Is it a particular class or type of antibody; is it a response to a particular epitope of the virus; or does the cat's management determine its ability to fight off infection? One of the seronegative cats is from a household of seven cats who are free-ranging. Since their feces, which constitute the greatest source of virus to other cats, is buried outside, are free-ranging cats therefore more likely to eliminate this infection?

In our previous survey we followed 50 cats whose antibody titers declined and then increased again (Addie et al, 1995). In the present survey there are cats following the same pattern, but this time we have the advantage of being able to monitor their virus excretion. Our findings so far seem to confirm those of Foley et al (1997) that in most cats the pattern of FCoV infection is exposure, virus shedding, seroconversion, temporary immunity, and then re-exposure which starts the cycle all over again.

Conclusions:

  • The key to elimination of FCoV from an infected cattery is to interrupt the cycle of reinfection.
  • Our previous assumption that cats' antibody titers can remain elevated due to exposure to the virus from in-contact cats (as well as to the virus in their own bodies) appears to be erroneous: cats in contact with virus-shedders often still become seronegative. One cannot conclude, therefore, that if some cats have reducing antibody titers, then in-contacts with stable antibody titers must not be shedding virus.
  • Some cats appear not to seroconvert or, at least, not to make immunofluorescent antibodies, despite being exposed to FCoV.
  • We are building up a valuable bank of sera (from blood samples of study cats) which will be used for further investigation into the immune response to FCoV.

Does declining antibody titer mean that a cat has eliminated FCoV infection?

Two cats continued to shed virus while their antibody titers were reducing, even when their immunofluorescent antibody titres (IFAT) were as low as 40.

Conclusions:

  • Only cats with IFATs of under 40 are definitely not shedding virus.

Chronic FCoV shedding in feces

In another survey (Foley et al, 1997), 10 cats of 121 which were serially tested shed virus at more than 75% of tests. In this survey, five cats have been identified as chronic virus shedders. Two cats from single cat households were, in fact, part of a previous survey and have been known to be seropositive to FCoV for nine years. This year another cat was introduced into one of these households and seroconverted, confirming the infectivity of the resident cat. The other cat is kept indoors and in isolation. One of the other chronic shedders belongs to a household of seven cats where separation of shedding and non-shedding cats is being attempted. The remaining two cats are kept in isolation as part of a large multicat breeding household. It is crucial that we establish the role of the chronic FCoV excretor in maintaining infection in a multicat household. Clearly, most cat owners will not be able to RT-PCR test their cats monthly for two years to establish which cats are chronic shedders; it is hoped that we will be able to find another marker for detecting these cats.

We are now able to answer some of the questions posed in our 1996 report: chronic carriers do not appear to be at greater risk of developing FIP; they seem not to stop shedding virus; their antibody titers are indistinguishable from those of cats which shed virus only transiently.

Conclusions:

  • In most cats, FCoV infection is temporary.
  • Chronic FCoV excretors exist, however, and such cats may be the mechanism by which FCoV persists in a household.
  • A technique for identifying chronic FCoV shedders needs to be found, as at present there is no way to differentiate them from cats undergoing a transient infection other than by repeated testing over many months.

When can you say that a seropositive cat is not a FCoV shedder?

In multicat households, when a cat which had stopped shedding FCoV begins to shed virus again, it is impossible to know whether this is because it has been reinfected by one of the other cats, or because of reactivation of virus latent in its gut or elsewhere. In four cats in single cat households there have been occasions when virus was not detected at one sampling, but was detected at the next sampling. The possible explanations for this finding are: the cat is truly shedding virus intermittently; RNA-ases (contaminant enzymes which destroy RNA) were inadvertently introduced, causing a false-negative test; or the positive test after the negative one was a false positive, due to contamination. At present, we do not consider a cat to have ceased shedding FCoV until it has been negative on three consecutive monthly samples (this figure is arbitrary). Further work is required to clarify this question.

Conclusions:

  • Some seropositive cats appear to shed virus intermittently. More cats from single cat households need to be followed to establish criteria for knowing when a cat has truly ceased to be infectious.

Salivary FCoV shedding

The vast majority of saliva tests on survey cats were negative. Twelve cats have had RT-PCR positive saliva swabs on a solitary occasion. There were two curious positive results on two cats which did not seroconvert. These may have been false positive results, since contamination is a risk in PCR. Alternatively, they may indicate that in some cats infection may be contained at the level of the oropharynx.

Conclusions:

  • RT-PCR of saliva swabs is not useful in detecting which cats are potentially infectious.
  • Since most cats do not shed FCoV in their saliva, mutual grooming and food bowls are presumably not a major source of transmissible virus.
  • It is possible that the immune response in the oropharynx is important in determining the outcome of infection.
  • More cats need to be saliva tested to establish whether this hypothesis is true. If so, the immune response that contains the infection needs to be determined.

Conclusion

Two-thirds of the way into the survey we have answered many of the questions that we asked at the outset pertinent to the practicing veterinarian, cat breeder and ordinary cat owner. It remains to build up statistically significant numbers in the last year, so that the conclusions outlined above may either be proven or disproven with certainty and the results published to benefit cats everywhere.

References

  1. Addie D.D., Toth S., Murray G.D., Jarrett O. (1995), "The risk of feline infectious peritonitis in cats naturally infected with feline coronavirus," Am. J. Vet. Res. 56 4, 429-434
  2. Foley J.E., Poland A., Carlson J., Pedersen N.C. (1997), "Patterns of feline coronavirus infection and fecal shedding from cats in multiple-cat environments," JAVMA 210 9 1307-1312
  3. Kipar A., Kremendahl J., Addie D.D., Leukert W., Grant C.K., Reinacher M. (1998), "Fatal enteritis with coronavirus infection in cats," J. Comp. Path. 119:1-14.

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