FIP: Research can explain correlation between high titers, poor prognosis

Q It seems like I have been diagnosing an increasing number of casesof feline infectious peritonitis (FIP). Is the incidence of feline infectiousperitonitis on the increase? Are laboratory tests useful?

 A Two excellent reviews on the subject of feline infectiousperitonitis (FIP) have recently appeared:

• The journal publication of Pollard RE, et al: Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals. JAVMA 218:1111-1115, 2001.
• The Web site www.vetscite.org review entitled "An Update on Feline Infectious Peritonitis" authored by Drs. Marian C. Horzinek, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands and Hans Lutz, Department of Internal Veterinary Medicine, University of Zurich, Zurich, Switzerland.

This column will abstract some of the pertinent information about FIPfrom these two reviews to answer these questions.

Epidemiology of FIP

Evidence suggests FIP virus is the result of a mutation of feline entericcoronavirus (FECV). FIP and FECV are grouped together as feline coronavirus(FCoV) for our current discussion.

According to the results from the mentioned epidemiological study, approximatelyone of every 200 new feline and one of every 300 total feline accessionsat veterinary medical teaching hospitals in North America and approximatelyone of every 100 accessions at the diagnostic laboratories represented catswith FIP during a 10-year period from January 1986 to December 1995.

The proportion of new accessions for which a diagnosis of FIP was recordeddid not vary significantly among years, months or regions of the country.In today's world, cats with FIP are significantly more likely to be young(59 percent from 2 months to 2 years), from pedigree breeding, and be sexuallyintact males and significantly less likely to be spayed females.

Exposure to FCoV is required for subsequent development of FIP, and thehigh potential for exposure of cats to FCoV is, in part, responsible forthe high proportion of cats with FIP.

The seroprevalence of antibodies to FCoV is estimated to be 25 percentfor single-cat households and 75 percent to 90 percent for multiple-cathouseholds.

About diagnosis

A diagnosis of FIP can be made in cats with the effusive form of diseasebased solely on the results of physical examination and fluid evaluation.

Because of the poor prognosis and limited options for long-term therapeuticsuccess, cats with the effusive form of FIP are probably less likely tobe referred to a veterinary medical teaching hospital for further evaluation.

On the other hand, diagnosis is more difficult in cats with the dry formof FIP, which represent approximately one of four cats with FIP, and suchcats are likely to be referred for further diagnostic testing.

Therefore, the prevalence of FIP among sick cats examined at privateveterinary practices may be similar to or greater than that among cats examinedat veterinary medical teaching hospitals.

According to international feline researchers,. Horzinek and Lutz, FIPis an important disease to the clinician for several reasons:

• It is fatal in most clinical cases
• Its biology is poorly understood
• Prevention is difficult.

Serology

The serologic diagnosis of FIP has been covered in many textbooks andarticles. A negative serologic result would not invalidate the diagnosisbased on clinical and CBC/serum chemistry profile information.

In the absence of clinical signs, serology is of no use for the prognosisin individual cats. A statistical correlation indeed exists between antibodytiters and post-mortem confirmation of FIP three months after testing. However,about 40 percent of the cats with titers of <300 do develop FIP, andof those with titers exceeding 1,000 only about one-half succumb. In otherwords, about half of the tested cats that remained healthy showed the samehigh titer values as the cats at risk. Tossing a coin would have given asimilar result.

How does the other face of that coin look?

About 12 percent of the cats with titers <100 still developed FIPin the observation period. Based on these data, one in eight owners wouldhave been sent home with the erroneous information that nothing will happento their cat.

Serology does not distinguish between harmless and FIP-inducing FCoVmutants, it only shows past - and in many cases still ongoing - infection.Any seropositive cat may succumb to FIP, irrespective of the titer.

Prognostic, diagnostic testing

We now can explain this statistical correlation between high titers andpoor prognosis.

Expansion of the coronavirus quasispecies cloud obviously not only providesmuch genomic material with the increased probability for FIP-inducing mutantsto occur, it also provides the large antigenic mass to induce high levelsof antibody. However, FIP-inducing mutants can always occur, also at lowreplication levels (with low antibody production), though with a lesserlikelihood.

On the other hand, an uninfected cat - which is not synonymous with aseronegative cat - will not develop into a case of FIP. This may sound asa truism, nevertheless some consideration is justified. In a cattery studyin Hanover, Germany, a few seronegative kittens shed FCoV in both fecesand plasma, some in feces only, and others in plasma only. Eighty-six percentpositive animals were detected using polymerase chain reaction (PCR) testing,while serology showed only 71 percent positives. However, not a single seropositiveanimal tested PCR-negative.

The question must be asked whether there is a place for diagnostic andprognostic laboratory testing for FIP at all.

There are presently no diagnostic assays available - neither in-practicetests nor assays performed in the research laboratory - that would distinguishbetween virulent FIP virus and avirulent FCoV variants. Also the "novel"PCR formats touted by some companies do not keep this promise, irrespectiveof their claims. We have reasons to believe that discriminatory assays basedon the molecular properties of the variants will not be feasible, perhapsnot even possible. However, there is a future for tests based on the evidenceof immunological changes in a cat developing FIP.

Both serology and PCR are able to detect infected cats, with differentsensitivity, and are invaluable for the management of catteries. They canbe used for monitoring the success of the quarantine and early weaning programs,for controlling the specified pathogen-free and the coronavirus-free statusof catteries. Especially PCR could be useful for monitoring individual catsto be introduced into FCoV-free catteries.

A promising approach to controlling FIP based on isolation of littersafter early weaning has been developed by the research group in Glasgow,Scotland, but it is laborious, requires the dedicated cooperation of catowners and has no veterinary appeal.

Incidentally, other studies performed under similar conditions showedonly marginal effects. Another possibility is the removal of strong sheddersfrom a multiple-cat society. This can now be done by using the TaqMan technique.For a reliable characterization of the shedding pattern it is sufficientto test four feces samples taken at weekly intervals.

Strong shedders

Strong shedders can be identified under field conditions and separatedfrom the cat group, thereby decreasing infection pressure for the remainingcats. It remains to be shown whether this approach will work. However, commonsense suggests that in conjunction with other measures (keeping cats insmall groups, without contact between groups, frequent cleaning of litterboxes, introduction of new cats only after quarantine and PCR testing, etc.)the elimination of strong shedders might be useful.

The seronegative catteries established through any control program mustof course be protected against re-introduction of virus, and the live temperature-sensitiveFIP vaccine could prove useful for this purpose.