by Jeffrey E Barlough,D.V.M.,
PhD., Margaret Barr,D.V.M., PhD., Fred W Scott,D.V.M., PhD., and James R Richards,D.V.M.
Cornell Feline Health Center, College of Veterinary Medicine, Cornell University
A virus, in the words of one eminent scientist, can be thought of as "a piece of bad news wrapped in protein." Unlike bacteria and fungi, viruses are not living organisms; rather, they consist in essence of a length of nucleic acid-their genetic material-that is surrounded and protected by a protein coat. (Some viruses have, in addition to this coat, a soft outer envelope, which confers some special properties.) The genetic material of viruses is composed of one type of nucleic acid, which may be either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA).
Viruses carry out no independent metabolism: they do not respirate, they do not process nutrients, they do not generate waste products, and they rely on living cells of the host for their reproduction. A virus outside a cell is an inert bit of particulate matter; once inside, however, the virus seizes command of the cell's biosynthetic machinery, converting the cell into a "high-tech" factory for the production of new virus particles.
Many viruses eventually kill their host cells, resulting in disease and provoking an assault by the immune response of the host. Sometimes, this response goes away, so that the harmful effects of the immune response are actually more serious than those of the viral disease itself Other viruses provoke little, if any, reaction, and some can remain dormant, or latent, in the host for years. The vast majority of all virus infections appear to be asymptomatic in nature that is, the infections are so mild and the host response so effective that clinical signs of disease never develop.
Very few viral diseases are responsive to specific antiviral therapy. Instead, the secondary effects of a viral infection are addressed in an effort to protect the host against secondary bacterial or fungal infection while the immune response to the virus is developing. Most successful attacks against viral invasion are carried out by the body itself The most effective therapy for viral diseases is prevention, that is, vaccination. Most antibiotics and antifungals have no effect on viruses; clinically useful drugs with specific antiviral activity are still relatively few in number and restricted almost exclusively to some very specific virus infections.
Feline Panleukopenia Virus (FPV)
Feline panleukopenia (also called feline infectious enteritis, feline "distemper," and feline ataxia or incoordination) is a highly contagious viral disease of cats characterized by its sudden onset, fever, inappetence (loss of appetite), dehydration, depression, vomiting, decreased numbers of circulating white blood cells (leukopenia), and often a high mortality rate. Intrauterine (within the uterus) infection may result in abortions, stillbirths, early neonatal deaths, and cerebellar hypoplasia (underdevelopment of the cerebellum) manifested by incoordination (ataxia) in kittens beginning at two to three weeks of age. All members of the cat family (Felidae) are susceptible to infection with feline panleukopenia virus (FPV), as are raccoons, coatimundis, and ringtails, in the family Procyoniclae. Many excellent vaccines are available to protect cats against panleukopenia. In unvaccinated populations, however, panleukopenia remains the most severe and destructive disease of cats.
THE CAUSE. Feline panleukopenia virus is a very small and very stable virus classified in the parvovina group. The genetic material of the virus is composed of a single"strand of DNA. The virus is highly resistant to most disinfectants ether, chloroform, acid, alcohol, and heat (56'C, or 132.8'F, for thirty minutes)but is susceptible to Clorox bleach. Replication (reproduction) of the virus in the host occurs in cells that are themselves actively reproducing.
OCCURRENCE AND TRANSMISSION. Although it can affect cats of all ages, feline panleukopenia is primarily a disease of kittens. The characteristics of the disease may vary considerably from population to population and from outbreak to outbreak. In susceptible populations, the disease may affect nearly 100 percent of individuals; in other populations, only a few animals may be affected. Panleukopenia rarely occurs in populations in which vaccination is routinely practiced.
There is a seasonality to the occurrence of panleukopenia that usually coincides with the production of new populations of susceptible kittens. This seasonal effect may vary according to geographic location. In the northeastern United States, most cases of panleukopenia are seen during the summer and early fall. However, outbreaks of panleukopenia may occur at any time of the year.
Transmission of FPV occurs most commonly by direct contact with infected cats or their excretions. During the early stages of the infection, virus is shed in feces, urine, saliva, and vomitus. In addition, fleas may transmit FPV from infected to susceptible cats during the acute stage of the disease. The virus may also be spread by contact with contaminated objects, such as food bowls, litter pans, bedding, and cages, or by persons (on hands or clothing, for example).
The remarkable resistance of FPV to environmental conditions requires thorough cleansing and disinfection of the premises before the introduction of new cats. Once infection with FPV has occurred on the premises, however, the infectious virus may persist for months to years. New cats should be vaccinated against panleukopenia at least two weeks before their introduction to infected premises.
PATHOGENESIS. The virus usually enters orally, with infection occurring primarily in the lymphoid tissues of the oropharynx (tonsillar area) and intestine. Within twenty-four hours of infection, virus is present in the blood, which distributes it throughout the body. Within two days of infection, nearly every body tissue contains significant amounts of virus. As circulating antibodies appear, the amount of virus present gradually decreases. Small quantities of virus may persist for up to one year in certain tissues, but the strong immune response of the host usually neutralizes the virus as it is shed, so that most persistently infected kittens are not infectious.
The most severely damaged tissues in the
infected newborn cat are those undergoing rapid cell division -the thymus (lymph organ in
the chest) and the cerebellum (rear of the brain). Cells of the small intestine, which
have a slow turnover rate in neonates (newborns), are not damaged, although the virus is
present within them. In older kittens, the development of the disease also depends on the
reproductive activity of the various tissues within the body. Lymphoid tissues, bone
marrow, and the surface cells of the intestine are the most severely affected.
CLINICAL SIGNS. The severity of the clinical signs exhibited can vary tremendously from case to case. Many cats undergo a subclinical infection and do not show signs at all; the only method of diagnosis would be viral isolation or serology (detection of antibody in the blood). Others may experience a very mild clinical infection, in which a mildly elevated temperature, slight inappetence, and a borderline drop in the white blood cell count are observed. in the "typical" case of panleukopenia, clinical signs develop suddenly. The animal may have a rectal temperature of 104oF or greater and may be severely depressed and not eating. Vomiting usually occurs, and severe diarrhea may develop in twenty-four to forty-eight hours. If vomiting and diarrhea continue, severe dehydration and electrolyte imbalances occur.
Affected cats often assume a typical "hunched" posture with the head between the forepaws. Sometimes the head will hang over a water bowl or food dish. They often act as though they would like to drink and may even take a lap or two of milk or water, but they are unable or reluctant to swallow. The hair coat becomes rough and dull and there is a loss of elasticity of the skin due to the dehydration. The third eyelid (the haw in the corner of the eye toward the nose) often appears. The abdomen is painful, and touching it will elicit a pain response. The lymph nodes in the abdomen are enlarged, and the digestive tract contains excessive amounts of gas and liquid. Cats that are not going to survive develop a subnormal temperature, with coma and death following in a few hours.
The mortality rate in an outbreak of panleukopenia may vary from 25 to 75 percent. Acute deaths may occur, with kittens showing no warning signs, often causing the owner to suspect poisoning. More commonly, deaths occur within the first five days of illness in uncomplicated cases, or later in cases subsequently complicated by other problems. if a cat survives the first five days of illness, and secondary complications such as bacterial infections or dehydration do not develop, then recovery should follow fairly rapidly. it usually requires several weeks, however, for the animal to regain its lost weight and condition.
Signs in kittens infected in utero or just after birth go unnoticed before sudden death, or until the development of ataxia at about two weeks of age when the kittens begin ambulating. The incoordination is exemplified by rolling or tumbling as the cat attempts to walk, by an involuntary twitching of the head, or by swaying of the body. If they are coordinated enough to obtain food, the kittens will survive; however, the ataxia will persist throughout life with little, if any, improvement or compensation as they grow older.
DIAGNOSIS. A presumptive diagnosis of feline panleukopenia can be made by the veterinarian on the basis of the history, the clinical signs, and the presence of leukopenia. The diagnosis can be confirmed by necropsy (autopsy) examination, virus isolation (growth of the virus in cells in the laboratory), identification of the virus in infected tissues, or by demonstration of an increase in circulating antibodies by testing paired (acute and convalescent) serum samples taken several weeks apart (the increase in antibodies indicates recent infection).
TREATMENT. Panleukopenia. normally has a high mortality rate, but with diligent effort and good nursing care this can often be reduced. The main objective is to keep the affected animal alive and in reasonably good health until the natural defenses take over (i.e., the appearance of antibodies and an increase in number of circulating white blood cells). Antibodies usually appear about three to four days after the first signs of illness; two to three days later, the sharp "rebound" in white blood cell number can be expected to occur. Thus, if the patient can be supported for five to seven days after onset of the disease, the chances of recovery usually are good. Veterinary supportive care is aimed at the vomiting, diarrhea, and dehydration, which may dangerously upset fluid and electrolyte balance, and at preventing secondary bacterial infections. Secondary viral respiratory infections are common complications of panleukopenia. The FPV infection may act to trigger a latent respiratory virus, such as feline viral rhinotracbeitis virus or feline calicivirus. Simultaneous FPV and respiratory virus infections usually produce a more severe illness than if either virus alone had infected the animal.
PREVENTION. There are several excellent vaccines available to immunize cats against panleukopenia. These vaccines are highly effective and produce long-lasting immunity. Because panleukopenia is an entirely preventable disease, one cannot overemphasize the importance of proper immunization.
Immunization should be initiated by the veterinarian when kittens are eight to ten weeks of age. A second vaccination should be given four weeks later. In areas where the prevalence of infection is high, and for maximal protection, a third vaccination may be indicated at sixteen weeks of age. if a kitten is twelve weeks of age or older at the time of initial vaccination with a modified live virus vaccine, a booster vaccination need not be given until it is at least one year of age. Annual booster vaccinations are recommended for all cats.
Immunity acquired from the queen via colostrum (initial breast milk) must be considered when establishing a routine vaccination program. interference by maternally acquired (passive) immunity is the most common cause of vaccine failure. There exists a direct correlation between the FPV antibody level of the queen at the time of birth and the duration of passive immunity in the kitten. This passive immunity, if of sufficient strength, will not only protect the kitten against virulent FPV but will also react with the vaccine virus and interfere with immunization. Vaccination must be performed after kittens have lost most or all of their maternally derived immunity.
The use of FPV antiserum (clear blood liquid
containing antibody) to immunize cats passively is indicated if an unvaccinated animal has
been exposed to the virus or is likely to be exposed before vaccine induced immune
responses can develop. Antiserum is also indicated for colostrum-cleprived or orphaned
kittens. The routine use of antiserum in unexposed kittens is not recommended, however;
instead, kittens should be vaccinated during their first visit to the veterinarian's
office, and revaccinated as indicated.
Feline Leukemia Virus (FeLV)
The feline leukemia virus (FeLV) is the causative agent of the most important fatal infectious disease complex of American domestic cats today. it is an RNA (ribonucleic acid) virus belonging to the family Retroviridae. Oncogenic (tumor-causing) retroviruses similar to FeLV have been identified in a number of animal species: cattle, domestic fowl, certain nonhuman primates, and rodents. The oncogenic retroviruses are commonly referred to as RIVA tumor viruses, or oncornaviruses (oncogenic RNA viruses).
Other retroviruses, known as lentiviruses, can produce noncancerous diseases in cats, sheep, goats, and horses. The feline lentivirus, known as feline immunodeficiency virus (FIV) (see in later section), is the cause of an immunodeficiency syndrome similar to that produced in humans by the human immunodeficiency virus HIV, which causes AIDS.
Retroviruses carry with them an enzyme, reverse transcriptase. This enzyme is used to produce a DNA copy of the retroviral RNA, which is then inserted into the genetic material of the infected cell. This alien invader, known as a provirus, then is reproduced whenever the host cell reproduces and can serve as the blueprint for the production of new retrovirus particles. A cell infected with a retrovirus thus is infected for the length of its lifetime, as are all of its daughter cells. Because a version of their genetic material becomes a part of the total genetic information of the cells they infect, retroviruses are among the most intimate parasites known in nature.
THE CAUSE. Individual particles of FeLV consist of two distinct morphologic (structural) components: a dense inner core, or nucleoid, and an outer envelope containing an immunologically important protein known as ~V70. This protein is the principal antigen (substance against which an immune response can be mounted) present on the virus surface. Virus-neutrahzing antibody (VNA) directed against gp70 is an essential component of a successful immunologic response to FeLV, and its presence in the blood is an indication of past FeLV exposure. Most cats with high levels of VNA are resistant to subsequent FeLV infection. Most persistently viremic cats (cats, many of which are otherwise healthy, in which FeLV circulates in blood cells for a prolonged period of time, as the result of an ineffective immune response) produce little or no VNA. It should be noted, however, that some cats with high VNA titers (levels) are not protected against FeLV infection, whereas some cats with little or no VNA are immune to infection.
A second major antigen of the FeLV particle is the protein p27, which is a structural component of the inner viral core. This protein can be found in great abundance in infected blood cells and in soluble form in plasma and serum of viremic cats. The primary importance of p27 lies in its role as the major FeLV antigen detected by the two FeLV tests-the IFA (immunofluorescence assay) test and the ELISA (enzyme-linked immunosorbent assay) test-commonly used in veterinary clinical practice today.
Suppression of normal protective immunologic responses is one of the most important consequences of persistent infection with FeLV. The significance of FeLV-induced immunosuppression is especially apparent when considering the array of secondary diseases associated with FeLV. A specific FeLV structural protein, p15(E), which is associated with the viral envelope, has been implicated in the production of some of this immunosuppression. The importance of p I 5(E) as an immunosuppressive agent is highly questionable, however, and incorporation of this protein in "inactivated" virus vaccines has not resulted in any apparent suppression of immune function in vaccinated cats.
In nature, FeLV infections appear to be restricted to members of the cat family, including domestic breeds and certain small exotic cats-sand cats, European wildcats, jungle cats, and possibly leopards. The prevalence of FeLV infection in domestic cats of the United States is estimated to be 2 to 3 percent, with most of the cases occurring in young adult cats (about 3 years of age).
PATHOGENESIS. After infection of lymphatic tissues surrounding the site of initial virus penetration, a low-grade transient viremia (brief presence of virus in the blood stream) involving small numbers of infected white blood cells occurs within two weeks of exposure. In this way, the virus is transported to other regions of the body, especially systemic lymphatic tissue, intestinal tissue, and bone marrow. These areas contain populations of rapidly dividing cells wherein FeLV replication can be enhanced. Infection of white blood cell and platelet (cells involved in blood clotting) precursors in the bone marrow, plus the subsequent release of infected cells into the circulation, results in a second, more profound viremia (persistent viremia). In those cats that resist widespread infection with FeLV, virus containment takes place in the early lymphatic stage of infection, after a transient viremia has occurred. in those animals destined to become persistently viremic, infection proceeds to extensive involvement of the bone marrow, pharynx, esophagus, stomach, bladder, respiratory tract, and salivary glands.
All persistently viremic FeLV cats excrete infectious FeLV and probably do so for the rest of their lives. Consequently, they serve as a source of infection for healthy, uninfected, susceptible cats with which they come into contact. Cats that develop immunity experience an initial transient viremia lasting from one to two days and for as long as eight weeks, during which time they too may shed infectious FeLV.
Excretion of FeLV occurs primarily in the salivary secretions, although the virus may also be present in respiratory secretions, feces, and urine. The social grooming habits of cats, licking and biting, sneezing, and the urban practice of sharing litter boxes and feeding bowls, probably represent the major modes of spread of FeLV among pet cats. In utero transfer of FeLV across the placenta and excretion of FeLV in colostrum and milk are also known to occur, so that kittens may become infected either through an infected queen or by close contact with other persistently viremic cats. Prolonged close contact (days to weeks) between cats is probably required for effective transmission of FeLV. Virus can also be spread in blood transfusions from viremic cats.
Very young kittens are the most susceptible to FeLV infection following exposure to the virus. Susceptibility to persistent infection decreases rapidly for older kittens and adult cats. Ultimately, about 60 to 70 percent of adult cats that are exposed to FeLV develop immunity and do not become persistently viremic. In some of these cats, however, the virus may remain sequestered for a variable period of time somewhere in the body as a latent infection. The primary hazard associated with latent infection is the possibility that some latently infected queens may transmit FeLV to their kittens through the milk. Latently infected cats do not transmit FeLV by any other route and are much less likely to develop any of the FeLV-associated diseases, although recent studies indicate that some of these cats may develop immunosuppression. The duration of these latent infections is variable, but most cats appear to become truly FeLV free within two or three years after their infection first occurred. Unfortunately, there is no readily available test to identify latently infected cats. Like a number of other similar viruses, FeLV is extremely labile (chemically unstable) once outside the cat and is rapidly inactivated by alcohol and most common household detergents and disinfectants. The infectivity of the virus in saliva left to dry at room temperature has been shown to decline to inconsequential levels within three or four hours.
CLINICAL SIGNS. Persistently viremic FeLV cats are subject to development of a number of diseases that are either directly or indirectly caused by FeLV. Those directly caused by FeLV include lymphosarcoma, a number of myeloproliferative disorders, several types of anemia, the panleukopenialike and thymic atrophy syndromes (shrinking or wasting away of the thymus), at least one form of kidney disease, and certain reproductive disorders. Diseases indirectly caused by FeLV include a myriad of conditions that develop secondary to FeLV-induced immunosuppression. The prognosis for survival of persistently viremic cats is poor; approximately 50 percent die within six months of infection, while over 80 percent die within three years of infection.
Lymphosarcoma (LSA). Lymphosarcomas are among the most common malignancies of American domestic cats. These tumors consist primarily of solid masses of proliferating lymphocytes (a type of white blood cell) and comprise the majority of the malignancies caused by FeLV. Several forms of LSA have been identified; their classification is based most commonly on their anatomic distribution.
The alimentary form of LSA is characterized by tumor-cell infiltration of the digestive tract and other organs (e.g., lymph nodes, liver, kidneys, and spleen). Common presenting signs include inappetence, weight loss, vomiting, diarrhea, bloody stool, and jaundice. Occlusion (blockage) of the bowel by the proliferating tumor results in constipation or obstipation (difficult, painful bowel movements or complete blockage). The alimentary form of LSA is associated with persistent FeLV infection in only about 50 percent of affected cats.
The thymic (of thymus gland in the chest) or mediastinal (of area between the lungs) form is characterized by the presence of a large tumor mass infiltrating within the chest, with spread to regional lymphatic tissue and sometimes to other structures. Clinical signs are a reflection of pressure effects of the mass and the severe fluid accumulation within the chest that frequently accompanies the tumor. Physical examination may reveal difficult respiration, muffled heart sounds, coughing, difficult swallowing, and incompressibility of the chest wall. Thymic LSA is usually seen in young cats (less than three years of age).
The multicentric form of LSA is characterized by primary involvement of many lymphatic tissues of the body, with additional involvement of other structures, such as the liver, bone marrow, kidneys, spleen, and lungs. Presenting signs are variable, depending on the precise anatomic distribution of the tumor, but they often include painless swelling of peripheral lymph nodes and enlargement of the spleen, liver, and, often, of the intestinal lymph nodes.
Atypical forms of LSA also occur and consist usually of solitary tumor masses involving primary sites of origin in nonintestinal, nonlymphatic structures. These include the kidneys, central nervous system, eyes, and, rarely, the skin or bones. Presenting signs vary according to the location of the tumor.
Lymphocytic leukemia is characterized by the presence of circulating cancerous lymphocytes in the blood and bone marrow. Lymphocytic leukemia may precede the development of LSA, or it may be associated secondarily with LSA. Presenting signs usually consist of nonspecific inappetence, depression, and weight loss. More specific signs that may be seen include anemia, fever, jaundice, and enlargement of the liver, spleen, and lymph nodes.
Myeloproliferative disorders. These primary bone marrow disorders are characterized by abnormal proliferation of one or more hematopoietic (blood cell-forming) cell lines. Presenting signs often include inappetence, depression, weight loss, relentlessly progressive anemia, fever, jaundice, peripheral lymph node enlargement, and enlargement of the liver and spleen secondary to massive infiltration by abnormally proliferating cells.
Nonregenerative anemia. NRA is probably one of the most common manifestations of FeLV infection. This type of anemia, also known as hypoplastic, aplastic, or depression anemia, is characterized by a severe reduction in the number of red cell precursors in the bone marrow, resulting in failure to produce an adequate number of circulating red cells. Sometimes there may be a pancytopenia, in which red cell, white cell, and platelet cell precursors are all affected. NRA may occur alone, or it may be associated with LSA or myeloproliferative disease, or it may precede the development of an FeLV-induced malignancy. Because many severely ill cats with NRA are euthanatized, the true incidence of subsequent malignancy cannot be accurately determined. Unfortunately, clinical signs are usually not detected until the anemia is well advanced. Common signs include inappetence, depression, weight loss, respiratory difficulty, pallor of the mucous membranes, and increased heart rate. Coinfection with Haemobartonella felis, the parasite causing feline infectious anemia, may contribute to the severity of the anemia.
Panleukopenia-like syndrome. As the name implies, this is a syndrome resembling panleukopenia (feline "distemper") that has been observed in some FeLV-infected cats known to be properly immunized against panleukopenia. Presenting signs often include inappetence, depression, dehydration, weight loss, fever, vomiting, diarrhea (which may be bloody), and a profound reduction in the number of circulating white blood cells. Anemia may also be present. Although affected cats may respond transiently to supportive therapy, the disease is progressive and always fatal.
Kittens born to persistently viremic queens often develop a syndrome of lethargy, inappetence, wasting, stunted growth, atrophy of the thymus gland and other lymphoid structures, and enhanced susceptibility to infection with other disease-causing agents ("fading kittens"). The degree of thymic atrophy can be severe, amounting to virtual disappearance of the organ in some cases. These kittens do not gain weight and often do not nurse vigorously. Many die from secondary bacterial or viral infections within the first few weeks of life. Those that survive are carriers of FeLV and thus are capable of transmitting the virus to other susceptible cats. The syndrome may also precede the development of an FeLV-induced malignancy.
Glomerulonepbnas. This type of kidney disease has been described in cats in association with LSA, lymphocytic leukemia, and granulocytic leukemia (cancer of granulocytes, a type of white blood cell). in addition, glomerular disease in the absence of malignancy has been reported in FeLV-infected cats. In one study, the leading cause of death in an FeLV-infected household of 134 cats over a five-and-a-halfyear period was glomerulonephritis.
Queens infected with FeLV may experience one or more reproductive disorders, including fetal resorption (biochemical disintegration of the fetus), abortion, infertility, endometritis (inflammation of the uterine lining), and the birth of fading kittens. Abortions characteristically occur late in gestation and are more frequent in high-density, multiple-cat households. it has been reported that nearly 75 percent of FeLV-infected queens will experience abortions or fetal resorptions.
The array of secondary disease entities associated with FeLV-induced immunosuppression represents one of the most important manifestations of FeLV infection. it has been estimated that nearly 50 percent of all cats with severe bacterial infections and infectious anemia and 75 percent of cats with toxoplasmosis (a protozoan disease) have an underlying FeLV infection. In addition, FeLV-induced immunosuppression has also been associated with chronic mouth and gum infections, poorly healing or recurrent abscesses, deep skin infections, chronic respiratory infections, acute colitis (inflammation of the large bowel), severe ear infections, and feline infectious peritonitis. (it should be kept in mind that all of these problems may also be seen in cats not infected with FeLV.) FeLV induced immunosuppression probably contributes also to the development of FeLV-induced malignancies.
DIAGNOSIS OF FeLV INFECTION. Two types of FeLV blood tests are in common use: the enzyme-linked immunosorbent assay (ELISA, or kit test, which can be performed in the veterinarian's office) and the immunotluorescence assay (IFA, Hardy test, or slide test, which must be sent out to a diagnostic laboratory). Both tests detect the p27 protein of FeLV as it circulates in the bloodstream, either free in the blood (ELISA test) or within infected white blood cells (IFA test).
FeLV is present in the blood during two different stages of the infection. The ELISA test can detect the primary (or transient) viremia stage, before the bone marrow has become infected, when the cat's immune system has an opportunity to ward off the virus. Transiently viremic cats characteristically test ELISA-positive and then revert to negative status within about eight weeks. it is important that a positive FeLV test be repeated in eight to twelve weeks to determine whether the viremia is transient or persistent. The ELISA test can also detect the virus in the persistent viremia stage-after the virus, in a certain percentage of cats, invades the bone marrow and establishes a firm and lifelong foothold. ELISA tests are also available to detect FeLV in secretions-saliva and tears. There is some degree of variability in these latter tests, and some positive animals may be missed. At this time, saliva/tear tests are probably best reserved for screening purposes and for testing cats that are difficult to bleed.
The IFA test detects the circulating virus primarily during the second stage. if the infection progresses to this stage, a "point of no return" is reached. Thus the majority of cats testing positive by the IFA test remain positive for life. These cats, as well as most (70 to 100 percent) of those that are ELISA positive, are shedding FeLV in the saliva and are infectious to other cats. Occasional discrepancies between the two FeLV tests have been noted. When such a discrepancy arises, it is important to remember that the two tests detect FeLV in two different "compartments" of the blood (blood fluid versus white blood cells).
If a cat is positive by ELISA and negative by IFA at the same time, it may mean that the virus is at the primary viremia stage. However, some healthy cats may remain ELISA positive and IFA negative for a prolonged period of time. These cats are still carrying FeLV but are apparently not shedding it in saliva (and thus will not transmit it to companion cats), and most appear to be resistant to the disease-producing effects of FeLV.
TREATMENT. The therapeutic goals of the veterinarian in treating many of the FeLV-associated diseases are to provide palliative relief from clinical signs and to prolong life. However, therapy should be advocated only if there is the possibility of maintaining a good quality of life for the prospective patient. In addition, ethical questions regarding prolonged treatment of persistently viremic cats shedding an oncogenic (tumor-causing) virus into their environment must also be addressed by both the veterinarian and cat owner.
A variety of chemotherapeutic regimens have been developed for FeLV-induced tumors, and in certain cases these can produce a temporary remission. Cats in remission may continue in a reasonably healthy state for a period of weeks to several months (some longer). However, it must be understood that these are only remissions and, in most cases, not lifelong cures. The drugs that are used are very potent and their effects must be monitored carefully so as not to overdose the patient.
PREVENTION. Elimination of FeLV from an infected household can be achieved by implementation of an FeLV-test-and-removal program using the IFA test. This program has been highly effective in removing FeLV from infected multiple-cat households. In a survey of forty-five households from which 159 FeLV-positive cats were removed, 561 of 564 (99.5 percent) FeLV-negative cats remained negative on subsequent retesting. Multiple-cat households in which the FeLV test-and-removal program has not been implemented have experienced infection rates over forty times greater than those experienced by households in which the program has been successfully introduced.
FeLV-test-and-removal. All cats in the household should be tested by IFA, regardless of age or condition. All cats found positive should be removed and the household premises cleaned with a commercial detergent or disinfectant (a solution containing four ounces of household bleach per gallon of water is often recommended, but soap and water will work as well). All litter boxes and food and water bowls should be replaced. Cats that initially tested negative should be retested several times over a period of eight to twelve months, in the event that they were infected just before the first test, prior to the onset of detectable virernia, or are cycling in their level of detectable viremia. The time period between exposure and viremia is extremely variable, and an infected cat that tested negative initially may be positive when tested again later. During the testing period, no new cats should be allowed to enter the household. if any FeLV-positive cats are found on subsequent testing, then they should be removed and another period of quarantine and testing imposed. All cats in the household should test negative for FeLV on two tests taken at least three months apart for the household to be considered free of infectious FeLV.
All new cats entering an FeLV-negative household should be tested prior to entry. Any positive cats should be excluded from entering the household. ideally, cats testing negative should be quarantined in separate quarters for three months and retested negative one to two times before being allowed to intermix with the established FeLV-negative household population. New cats should ideally be obtained only from other FeLV-negative households or catteries. Routine yearly or twice-yearly testing for FeLV is suggested for cats in catteries because of the variable incubation period of infection. Persistently viremic cats should never be used for breeding purposes, in part because infected queens will transmit the virus to their viable offspring.
If an FeLV-positive cat is removed from a single-cat household, a waiting period (up to thirty days) should be observed before repopulation with one or more FeLV-negative cats. The litter box and feeding dishes should be replaced and the premises thoroughly cleansed.
Certain modifications of the test-and-removal program may be made for households in which both FeLV-negative and FeLV-positive cats are kept. The positive cats in these households should be isolated from contact with all other cats. This will not only prevent the spread of infectious FeLV to susceptible cats, but it will also decrease exposure of potentially immunosuppressed, viremic cats to other infectious agents, to which they may have a heightened susceptibility. No new cats should be introduced at any time, and the FeLV-positive cats should not be allowed to breed. Separate litter boxes and feeding dishes should be maintained for positive and negative cats. Cleanliness and personal hygiene should be observed at all times, and it has been suggested that separate clothing be kept for contact with FeLV-positive cats to minimize mechanical transmission of the virus. As we have seen, however, FeLV is relatively labile in the environment, and although the degree of virus transmission possible under these circumstances is uncertain, it is probably minimal.
Several vaccines are currently available commercially for prevention of FeLV infection; however, vaccination does not confer immunity against persistent FeLV infection in all cats. Vaccination should be considered an additional safeguard rather than a primary means of protection against FeLV infection. The decision to vaccinate is made on an individual basis and should be an important point of discussion with the veterinarian. There are complex pros and cons to vaccinating against FeLV; the advice and experience of the veterinarian are essential in helping owners reach a correct decision.
PUBLIC HEALTH SIGNIFICANCE.
The public health significance of FeLV, most importantly the question of oncogenic
potential for human beings, is still largely unsettled. Surveys designed to determine the
prevalence of circulating FeLV and/or antibody to FeLV in human serum have produced
conflicting results over the years. However, most recent surveys have failed to find
evidence of FeLV infection of human beings, including many with LSA or other malignancies.
Until a more complete understanding of the public health implications of FeLV can be
obtained, it is prudent to restrict as much as possible human exposure to persistently
viremic cats. Neonates (human infants) and immunosuppressed individuals (those on
immunosuppressive drug therapy, or AIDS patients, for example) are of special concern in
this regard. It must be emphasized, however, that as of this writing there is no
conclusive evidence that any human illness (including cancer) has ever been caused by
Feline Immunodeficiency Virus (FIV)
Feline immunodeficiency virus (FIV), previously called feline T-lymphotropic lentivirus (FTLV), is a feline virus belonging to the family Retroviridae. Although it is related to feline leukemia virus (FeLV), FIV does not cause cancer and is not classified with FeLV in the oncornavirus subfamily of retroviruses. instead, FIV has been placed in the lentivirus subfamily, along with the viruses causing progressive pneumonia in sheep, infectious anemia in horses, arthritisencephalitis in goats, and acquired immunodeficiency syndrome (AIDS) in human beings.
THE CAUSE. The genetic material of FIV, like that of other retroviruses, consists of single-stranded RNA. The production of a double-stranded DNA copy of this RNA is an essential step in the replication (reproduction) of FIV within the host. This step requires a special viral enzyme, reverse transcriptase, which the virus carries with it when it infects a cell. The doublestranded copy of the viral genetic material then is inserted into the DNA of the host cell, where it may remain in an inactive state for some time before production of new virus particles is initiated.
Antibodies to FIV do not bind to FeLV, nor do antibodies to FeLV bind to FIV, so that the two viruses are antigenically unrelated. in addition, FIV is not antigenically related to human immunodeficiency virus (HIV), the lentivirus responsible for AIDS.
OCCURRENCE AND TRANSMISSION. The immunodeficiency syndrome associated with FIV, with its array of secondary infections, anemia, and low white blood cell counts, is indistinguishable from the noncancerous syndromes associated with FeLV infection. Prior to the first identification of FIV in California, cats that presented with what seemed to be an FeLV-associated disease, but that repeatedly tested negative for FeLV, were nevertheless assumed to be infected with FeLV. Now that a test for FIV is available, it is apparent that at least 15 percent of such FeLV-negative sick cats are in reality infected with FIV. The prevalence of FIV infection in the general, healthy, United States cat population, however, is estimated to be about I to 3 percent.
In addition to infecting domestic cats, FIV infects several species of nondomestic cats, including lions, tigers, snow leopards, pumas, bobcats, Pallas' cats, and cheetahs. Each species apparently is infected with its own unique type of FIV. The potential for disease production associated with FIV infection in the nondomestic cats is not clear at this time.
The primary mode of FIV transmission is through bite wounds. Casual, nonaggressive contact among cats rarely results in the spread of FIV. Transmission from an infected queen to her kittens occurs infrequently, as an in utero event, during the birth process, or through ingestion of infected colostrum or milk. This type of maternal transmission occurs primarily when the queen is exposed to FIV and becomes infected during gestation or lactation. Spread of FIV through sexual contact is theoretically possible but does not occur frequently during either experimental or natural infections.
PATHOGENESIS. Following initial infection, FIV is carried to regional lymph nodes, where it replicates in a subpopulation of white blood cells known as T lymphocytes or T cells. These cells are primary target cells of FIV (culture techniques often require the use of feline T lymphocytes to grow the virus in the laboratory). The virus then spreads to lymph nodes throughout the body, resulting in a generalized lymphadenopathy (enlargement of the lymph nodes). At this point, much of FIV replication occurs in another white blood cell, the macropbage. This stage of the disease usually passes unnoticed by an owner unless the nodes are greatly enlarged. Some time later-perhaps days but possibly weeks to months-the cat may develop a fever and a drop in the white blood cell count (leukopenia). A low red blood cell count (i.e., anemia) also may develop. The cause of these sometimes precipitous declines in blood cell types is not clear, but it may result from suppression or loss of precursor cells in the bone marrow. There then follows a largely enigmatic period (sometimes measured in years), during which the cat appears normal, despite being persistently infected with FIV. However, during this clinically quiescent period, there is a progressive decline in the number of a type of T lymphocyte known as a CD4 + T helper cell. The CD4 + T cell is extremely important in maintaining proper immune system function. Eventually, signs of immunodeficiency begin to develop, compromising the cat's ability to protect itself against infection. Bacteria, viruses, protozoa, and fungi, which can be found in the cat's everyday environment and generally are innocuous to a healthy animal, can cause severe illness in an immunocompromised individual. These secondary infections are responsible for most of the clinical signs associated with FIV infection.
CLINICAL SIGNS. The clinical progression of FIV infection can be divided into five stages, using the system described for HIV infection in humans: (1) acute infection (the first four to sixteen weeks of infection); (2) asymptomatic carrier (this stage may last months to years); (3) persistent generalized lymphadenopathy (PGL-this stage is usually very short and difficult to observe in FIV-infected cats); (4) AIDS-related complex (ARC-signs of gastrointestinal and respiratory disease are usually apparent); and (5) acquired immunodeficiency syndrome (AIDS cats develop opportunistic infections accompanied by fever and wasting). Cats in the ARC or AIDS stage of infection generally live for less than one year.
The clinical signs of the immunodeficiency syndrome are diverse in nature because they involve an array of secondary infections. General unthriftiness (failure to thrive) may be the first outward sign that a problem exists. Fever of 103'F or greater is often present in the ARC and AIDS stages of disease. A very common presenting complaint is a loss of appetite or evidence of pain while eating, caused by infection of the gums (gingivitis) and mouth (stomatitis). These conditions can lead to inflammation of the tissue around the teeth (periodontitis), with eventual loss of the teeth.
Chronic, nonresponsive, or recurrent infections of the skin, urinary bladder, and upper respiratory tract are often seen. Persistent diarrhea and ocular disease are also frequent problems. Abortion of kittens or other reproductive failures have been seen in infected queens. Some infected cats have experienced seizures, dementia (mental deterioration), sleep disorders, and other neurologic manifestations. Slow but progressive weight loss also is common, with severe wasting occurring late in the disease process.
DIAGNOSIS. Diagnosis is based on the history, the clinical signs, and the result of an FIV antibody test. Detection of FIV antibody is the diagnostic test of choice, because the levels of virus in the blood of an infected cat are frequently so low as to be undetectable by conventional means. An ELISA test is available in kit form for use in private veterinary clinics. All positive results should be confirmed by a second test, preferably using a different procedure. Confirmatory tests, which are performed at certain commercial diagnostic laboratories, include IFA assays and a test called the Western blot or immunoblot procedure. A positive FIV antibody test indicates that a cat is infected with FIV (probably for its lifetime-established infections are rarely cleared) and is capable of transmitting the virus to other susceptible cats. it should be noted that eight to twelve weeks (and occasionally more) may elapse after infection before detectable antibody levels appear.
Because FIV tests depend on the detection of antibodies to the virus rather than the virus itself, kittens of FIV infected (antibody-positive) queens will almost always test positive for FIV antibodies during the first three to four months of life. in this case, a positive FIV test does not mean that the kitten is actually infected with FIV. Such kittens should be tested for FIV at six to eight months of age, after the loss of maternally derived antibodies, to determine their true infection status.
TREATMENT. Therapy of the secondary infections associated with FIV is based on the clinical signs and the nature of the infectious agent. Use of antiniicrobial (antibacterial or antifungal) drugs to control bacterial and fungal infections has been moderately successful, but must be continued for long periods or reinstituted as new infections occur. Supportive care, including intravenous fluids, blood transfusions, and feeding of high-caloric dietary supplements, is frequently required. The use of corticosteroids or other anti-inflammatory drugs may be indicated in some cases to control gingivitis and stomatitis. Anabolic steroids (those that promote growth and tissue repair) may help to combat weight loss and wasting. it must be kept in mind that these measures are not directed at combating FIV itself. The drug AZT, useful in therapy for AIDS patients, may also be of use against FIV, but the drug is expensive and difficult to obtain, and its side effects are apparently greater in cats than in humans. Drugs designed to enhance or modify the immune system, such as interferons and acemannan, appear to be useful in treating some FIV-associated diseases; however, such drugs do not eliminate the infection.
PREVENTION. No vaccine is available to prevent FIV infections. Owners can protect their cats only by preventing them from contacting infected cats. Pets kept indoors and away from free-roaming cats are
highly unlikely to contract FIV infection. Catteries and multiple-cat households should test all their cats and isolate or remove any positives. Once FIV-negative status has been achieved, all prospective additions should be quarantined for eight to twelve weeks, then tested prior to introduction to the household.
PUBLIC HEALTH SIGNIFICANCE. Although FIV is similar structurally to HIV and causes a disease in cats similar to AIDS in humans, it is a highly species-specific agent. Only cells of feline origin have been found to support replication of most primary FIV isolates. There is no significant cross-reactivity between FIV and any of the other lentiviruses. Initial studies indicate that veterinarians, owners, and researchers who have had close contact with FIV infected cats show absolutely no evidence of FIV infection. It appears at this time that FIV infections are restricted solely to cats.
Even though the risk of transmission of FIV from cats to humans is minimal, immunocompromised persons (such as those undergoing chemotherapy, HIV-infected persons, and some pregnant women and newborn infants) should not be exposed to cats with FIV or FeLV infections. Cats with retrovirus-induced immunosuppression are especially susceptible to infection with several parasitic organisms that can cause severe disease in immunosuppressed individuals.
Feline Infectious Peritonitis (FIP)
Feline infectious peritonitis (FIP) is an important and complex disease of cats caused by a virus belonging to the family Coronaviridae. Coronaviruses are a large and widely distributed group of RNA viruses and are important causes of disease in birds and mammals. Feline coronavirus (FCoV) infections appear to be restricted to members of the cat family, including domestic breeds as well as certain exotic species: sand cats, caracals, lynx, cougars, cheetahs, jaguars, leopards, and lions. in addition to FCoV, cats are susceptible to infection with several other viruses in this group, including canine coronavirus (CCV) and the swine agent, transmissible gastroenteritis virus (TGEV).
THE CAUSE. Different strains of FCoV possess
different virulences (disease-causing ability). Some strains that have been isolated and
grown in a laboratory are avirulent or of low virulence (strains commonly known as feline
enteric coronavirus or FECV), whereas other strains produce FIP (strains commonly known as
feline infectious peritonitis virus or FIPV). FECV strains typically produce disturbances
of the digestive tract that affect only a minority of infected cats-usually very young
Feline coronavirus infections are extremely common in multicat environments. in densely housed groups of cats, it is not unusual to find that most cats -up to 80 to 90 percent in some situations-have been exposed to FCoV. in households with only one or two cats, the risk of FCoV exposure is much lower. As a result, FIP is rare in households with few cats, with estimates as low as I cat in 5000. However, in households with high population densities, FIP deaths may reach 5 percent or higher. As one way of explaining the sporadic nature of the disease, some researchers speculate that FIPV may be an in vivo (within the living body) mutation of the more common FECV. The ability of the individual cat to mount an effective immune response is also believed to be a major factor determining FIP development.
The routes by which FCoV is spread from cat to cat have not been identified with absolute certainty, but it is most likely that initial infection results from ingestion or inhalation of the virus. Close contact with infected cats or their excreta is usually required for efficient virus transmission. Transmission across the placenta to the developing fetus is suggested by occasional observations of FIP in stillborn kittens, but the frequency with which this occurs is unknown.
In common with many other viruses of this type, FCoV is relatively unstable outside the host and is rapidly inactivated by many common soaps, detergents, and disinfecting agents. Household bleach diluted 1:32 in water has been recommended for decontamination purposes.
PATHOGENESIS. Studies performed over the past several years have succeeded in identifying some of the major host-virus interactions of FIPV infection. After infection of white blood cells (leukocytes) within lymphoid tissue at or near the site of initial virus penetration, a primary viremia. involving virus and/or virus-infected cells occurs within one week after exposure. In this way, virus is transported to other areas of the body, especially to organs such as liver, spleen, and lymph nodes. These structures contain large populations of certain leukocytes, such as macrophages, which appear to be primary target cells for FIPV infection. Blood-borne spread of virus also results in infection of circulating white blood cells (monocytes) and, importantly, in localization of virus and virus-infected cells within the walls of small blood vessels. A secondary viremia may occur after initial infection of target tissues and result in further spread of virus throughout the body. Deposition of virus, virus-infected white blood cells, and virus-antibody complexes within blood vessel walls produces an intense, destructive inflammatory response (vasculitis), which damages vessels and allows the escape of fluid components of blood into intercellular spaces, eventually accumulating as characteristic "FIP fluid" within body cavities.
CLINICAL SIGNS. Though it is possible that mild cases of FIP that spontaneously resolve may occasionally occur, this is considered a rarity. Virtually all cats with FIP will die.
Most cases of FIP occur in cats less than three or four years of age. The onset of clinical signs may be sudden (especially in kittens) or it may be slow and insidious, with the severity of signs gradually increasing over a period of weeks. Some of these signs may be quite nonspecific: intermittent inappetence, depression, weight loss, fever. In many cases, affected cats may continue to eat and remain alert and responsive for a considerable period of time; however, fever (which may fluctuate at different times of the day) is a constant finding and usually persists until the last few hours of life.
The two major forms of FIP can be distinguished on the basis of fluid accumulation-the presence of fluid in one or more body cavities in effusive ("wet") FIP, and its absence in noneffusive' ("dry") FIP. Effusive FIP is the more fulminant (sudden and severe) form of the disease, with a more rapid onset and shorter clinical course than the noneffusive form.
An accumulation of fluid within the abdorninal cavity, with progressive, painless enlargement of the abdomen, is probably the most common clinical manifestation of effusive FIP. Respiratory distress may develop when abdominal fluid accumulation is excessive or, more commonly, when accumulation of fluid occurs within the chest cavity, resulting in compression of the lungs. Other signs that may be seen include jaundice (yellowing of the mucous membranes and skin)
and a mild anemia (low red blood cell count). This anemia be exacerbated by coinfection with feline leukemia virus or Haemobartonella felis (the organism causing feline infectious anemia).
Gastrointestinal, ocular, and neurologic signs may also occur in cases of effusive FIP. The course of effusive FIP is quite variable, but the usual survival time after onset of clinical signs is about two or three months. Some young kittens may survive for no longer than a few days, whereas some adults may live for six to eight months with active clinical disease.
The onset of noneffusive FIP is often insidious, with clinical signs reflective of involvement of specific organ systems in the FIP inflammatory process. Weight loss, depression, anemia, and fever are almost always present, but fluid accumulation is usually minimal. Clinical signs of kidney failure (such as increased water consumption and urination), liver failure (jaundice, neurologic signs), pancreatic disease (vomiting, diarrhea, voracious appetite, diabetes mellitus), neurologic disease (hind limb incoordination, loss of balance, tremors, behavioral changes, paralysis, seizures), or ocular disease (inflammation of the eye, retinal disease, blindness) may be seen in various combinations in cats with severe organ impairment. The disease course is usually more chronic than in effusive FIP. Some cats, especially those with primary ocular involvement, may survive for as long as a year or more.
FIPV was once incriminated as a possible cause of reproductive problems in breeding queens-infertility, fetal resorptions. (biochemical disintegration of the fetus), abortions, stillbirths, birth of weak "fading" kittens, congenital malformations, and neonatal heart disease (acute congestive cardiomyopathy). There is no conclusive published evidence that the virus plays a role in any of these disease processes. To date, the only disease of neonates known to be caused by FIPV is FIP itself.
DIAGNOSIS. The clinical diagnosis of FIP is made by evaluation of the history and presenting signs and the results of supporting laboratory tests. it must be kept in mind that a definitive diagnosis of FIP can be made only by microscopic examination of tissues either by biopsy or at necropsy. Any diagnosis made in the absence of such examination must be considered presumptive; hence, the vast majority of clinical diagnoses of FIP are presumptive in nature. However, when the clinical signs and laboratory data support a presumptive diagnosis of FIP, then such a diagnosis may be made with a very high degree of confidence, especially when the typical effusion fluid is present. Evaluation of effusion fluid remains one of the most useful diagnostic aids for FIP.
Most cats with FIP have moderate to high titers (levels) of coronavirus antibody, but this finding must not be over-interpreted. The presence of coronavirus antibody in any cat, healthy or diseased, is indicative of only one thing; previous exposure to FCoV or one of the closely related viruses (CCV, TGEV). The antibody test does not prove that a cat has FIP. it therefore follows that the diagnosis of FIP must never be made simply on the basis of a coronavirus antibody test.
The natural reservoir of FCoV appears to be
infected cats. The most important source may be clinically healthy carrier cats-those that
carry and excrete FCoV but show no ill effects. The problem that arises is that, as of
this writing, there are no diagnostic tests for identifying these carriers (i.e., there is
no test that is equivalent to the Hardy test, or ELISA test for feline leukemia virus).
Thus a cat with a positive antibody test is not necessarily carrying or shedding FCoV. The
polymerase chain reaction (PCR) is a powerful tool capable of detecting minute quantities
of coronavirus RNA in blood, serum, tissue, or feces. It promises to further the
understanding of FIP and the FCoV carrier state. Although as yet not diagnostic for FIP,
PCR technology may ultimately lead to an accurate test that can identify contagious
cats. PCR is
is presently only capable of detecting coronaviruses in general, not necessarily those that cause
FIP. The immunoperoxidase test can diagnose FIP more accurately than traditional histopathologic examination because it detects virus-infected cells in the tissue. A biopsy of affected tissue is necessary for evaluation.
TREATMENT. No curative therapy for FIP currently exists; the disease is virtually always fatal once clinical signs have become apparent. Palliative therapy combines high levels of corticosteroids, other immunosuppressive medications, and broad-spectrum antibiotics, in an attempt to slow down the FIP inflammatory disease process and minimize secondary bacterial infections. This therapy serves only to modify the disease course and, in most cases, does not provide a cure. if successful treatment of FIP is to be developed in the future, it will likely involve a combination of medications, including anti-inflammatory or immunosuppressive drugs, immune-modulating medications, and antiviral drugs.
A number of supposed treatments for FIP have been touted in recent years, including experimental medications and megavitamin supplementation. To date, there is no published scientific evidence that any of these potions is of benefit to affected cats.
PREVENTION. Research shows that any cat exposed to FCoV has the potential to develop FIR If FlPV is indeed an in vivo mutation of a less virulent feline coronavirus, the most successful control strategies will hinge on reducing FCoV infections in general and promoting healthy immunity in cats at risk. Breeders should be advised to remove cats persistently infected with feline leukemia virus or feline immunodeficiency virus, reduce cattery crowding, and develop management strategies that minimize fecal contamination. Because some studies suggest a genetic predisposition for the development of FIP, breeding pairs of cats that tend to produce kittens with FIP should be discouraged.
At this time, there is no practical way to eliminate FCoV infections or prevent FIP from occurring within a group of cats. Although extremely successful in eliminating FeLV infections, a test-and-removal program for healthy coronavirus antibody-positive cats cannot be recommended on the basis of current knowledge. There is no available diagnostic test that can specifically identify carriers of FCoV, so there is no medical reason for destroying healthy antibody-positive cats (i.e., a positive antibody test indicates only past exposure; it does not mean necessarily that a cat is still carrying the virus).
It is believed that the major source of feline coronavirus is the feces of an infected cat, and that other cats become infected by ingesting (or inhaling) the virus. Therefore, minimizing fecal contamination decreases the transmission of the virus from one cat to another in multiple-cat households. Fecal contamination can be reduced by locating litter boxes in easy-to-clean areas distant from food and water dishes. There should be at least one litter box for every two cats, and the litter should be scooped clean of feces once daily. The entire litter box should be cleaned and disinfected at least weekly.
If possible, breeders should consider keeping cats in stable groups of four cats or less. Devoting a special area for pregnant queens, and providing individual queening boxes separate from other cats during parturition and nursing, can reduce transmission of infectious agents to kittens. Maintaining an area where weaned kittens are strictly isolated from all the other cats helps prevent infection during this most susceptible age. Early weaning of kittens-as early as five to six weeks of age-followed by strict isolation from other cats has been shown to markedly reduce FCoV infection of kittens; however, this procedure can succeed only if strict isolation is maintained.
A commercially available vaccine has shown questionable efficacy in preventing FIP in both experimentally and naturally infected cats. The vaccine is a temperature-sensitive mutant (it grows only at temperatures slightly lower than core body temperature) of FIPV that is given intranasally. in laboratory trials, the efficacy of the vaccine varies from zero to approximately 85 percent, depending on the amount and type of virus used in challenging (infecting) the cats. In a natural setting, if given to cats prior to exposure to FCoV, the vaccine has shown efficacy of 0 to 75 percent. The usefulness of this vaccine for the control of FIP in cattery situations appears to be limited at this time. It is difficult to determine whether the cell-mediated immune response of the cat or the vaccine is responsible for immunity. The vaccine may yet prove beneficial; as of this writing, further studies evaluating the safety and efficacy of the vaccine not been completed.
The specter of rabies has been known throughout Asia and Europe since the days of antiquity. Today, rabies can be found on all continents of the world except Australia and Antarctica. it is ordinarily a disease of bats and carnivores, including the domestic dog and cat and many wild species. Despite the availability of excellent human and animal rabies vaccines, rabies remains a spe7cial cause of concern among human populations, especially in the developing world.
In the developed nations, canine rabies vaccination programs have all but eliminated cases of rabies among human beings. Animal rabies, however, still occurs with varying frequency. Among domestic species in the United States, cats now surpass dogs in the number of rabies cases reported each year. Although those numbers remain small, they serve as a reminder of the continual presence of this ancient scourge.
THE CAUSE. Rabies is caused by a bullet-shaped, virus belonging to the family Rhabdoviriclae. Rhabdo viruses are enveloped viruses and hence are relatively easily destroyed by common household soaps and detergents.
OCCURRENCE AND TRANSMISSION. Rabiesis maintained in nature by wild and domestic carnivores and by certain other wildlife species. in the United States, skunks play a major role in spreading the disease, especially in the Midwestern portion of the country, where they are now the primary reservoirs of infection. Raccoons are important in transmission in the southeastern states and have recently begun to spread the disease to northern areas of the Atlantic seaboard. Wild foxes are important reservoir hosts in Europe and to a certain extent in North America as well. In the Caribbean and much of the Americas, bats are important reservoirs. In Latin America, vampire bats are particularly notorious for spreading rabies. The only rodent species of any importance in rabies transmission appears to be the woodchuck, in the mid-Atlantic and Midwestern United States. Among domestic species, only dogs and cats are important carriers of the infection. in most developing nations today, dogs remain the primary reservoir of the disease and the principal source of human exposure. Rabid animals excrete vast numbers of rabies virus particles in their saliva-a fact that accounts for the primary means of rabies virus transmission, the bite of an infected animal.
PATHOGENESIS. The incubation period-the time between exposure to the rabies virus and the development of signs quite variable, ranging from one week to one year. Most of this variability appears to reflect the length of time the rabies virus spends within muscle cells at the site of the bite, prior to gaining access to the nervous system. Once the virus has entered nerve endings, however, it advances relentlessly up the nerve bodies until it reaches the spinal cord and eventually the brain. From there, it can spread to other tissues important in transmission of the virus-the salivary glands, respiratory system, and digestive tract. To date, the actual mechanism by which the virus produces locomotion and cerebral derangement, with eventual death of the host, remains unclear.
CLINICAL SIGNS. In general, signs of rabies in cats are similar to those observed in other domestic species, but the signs seen in each individual case may vary widely. Two principal forms of rabies are recognized: an excitatory or "furious" form, and a paralytic or "dumb" form. In actuality, most rabid animals exhibit some manifestations of both forms. The paralytic form of rabies always represents the terminal or end stage; however, some animals may die during the convulsive seizures of the furious stage without exhibiting the final stage. Some will show few or no signs of excitement, the clinical picture reflecting instead the effects of paralysis.
During the furious stage, which lasts variably for one to seven days, affected animals become wild and aggressive. Rabid cats are extremely dangerous animals because of their viciousness and quickness of action. Rabid animals frequently snap at imaginary objects and may attempt to bite any animals or humans that approach them. If restrained, an animal may chew viciously on metal chains or the bars of its cage. It may break its teeth, lacerate its mouth and gums, and drool a ropy saliva tinged with blood.
Within a short time, these signs give way to those of the final or paralytic stage, which lasts only for a day or two. The paralysis usually appears first in the muscles of the head and neck, the most characteristic sign being difficulty in swallowing. Signs of localized paralysis are quickly succeeded by more generalized paralysis, with death following usually within two to four days of onset.
For both animals and humans, rabies is an inevitably fatal disease once clinical signs have appeared (only three human survivors are documented in the medical literature). Therefore, utmost care must be taken if one suspects that a pet has been exposed to the rabies virus.
DIAGNOSIS. A definitive diagnosis of rabies can be made only by laboratory examination of brain material from an affected animal. Considering the grave prognosis for recovery from rabies once clinical signs have appeared, it is imperative that an accurate diagnosis be obtained. Any wild or domestic mammal that has bitten a human being and is showing signs suggestive of rabies should be humanely destroyed, and the head submitted to a qualified rabies laboratory for diagnostic testing. In addition, any bat or wild carnivore, regardless of signs manifested, that has bitten a human being should be destroyed immediately and the brain examined for the presence of the rabies virus (this latter action is necessary because of the variable period of salivary virus-shedding that can occur before clinical signs appear). Any healthy domestic animal that has bitten a human being should be confined for at least ten days and observed for the development of clinical signs of rabies.
An unvaccinated domestic animal that has been bitten by or exposed to a known rabid animal should either be destroyed or placed in quarantine for six months and vaccinated for rabies one month prior to release. A rabies vaccinated domestic animal that has been bitten by or exposed to a known rabid animal should be given a rabies booster immunization immediately and observed by the owner for ninety days. if signs of rabies appear during the time of observation, the animal should be humanely destroyed and the brain examined to confirm the diagnosis of rabies.
Currently, three methods are available for the laboratory diagnosis of rabies: immunofluorescence microscopy, the most rapid and accurate method, in which slides of brain tissue are examined for the presence of the rabies virus using special antibodies and a fluorescent microscope; histopathology, in which sections or smears of brain tissue are examined for the presence of Negri bodies, intracellular inclusion bodies seen in many (but not all) cases of rabies; and mouse inoculation, which is frequently used to confirm positive results or to investigate further suspected cases that have proven negative by other methods.
TREATMENT. Because of the potential risk of exposing susceptible humans to the rabies virus, treatment of animals suspected of having rabies is strongly discouraged. Treatment of humans exposed to a rabid animal, however, must be aggressively applied. Treatment of humans consists of thorough flushing and cleansing of the bite wound with soap and water (the importance of this simple step cannot be overemphasized); administration of rabies immune globulin (rabies virus antiserum) to exposed individuals who have never been vaccinated against rabies; and administration of the human diploid-cell rabies vaccine in five doses, given on days 0, 3, 7, 14, and 28 postexposure.
PREVENTION. In the United States and most other countries of the world, effective rabies vaccines are available for use in domestic animals. Mass immunization of dogs has been employed for many years to control the spread of rabies by creating an "immunological barrier" between wildlife reservoirs of rabies and human populations. Several countries, including England, Iceland, Japan, and the Scandinavian nations, have succeeded in eradicating rabies by implementing control programs and very strict quarantine regulations. It is recommended that all dogs and cats be vaccinated for rabies at three months of age and revaccinated as required by vaccine specifications. At present, there are no rabies vaccines licensed for use in wild animals; however, genetically engineered rabies vaccines are being tested in selected wildlife populations.
PUBLIC HEALTH SIGNIFICANCE. The signs and course of rabies in humans are similar to those seen in animals. Both excitatory and paralytic symptoms may be manifested. The incubation period, as in animals, is quite variable from about two weeks to as long as one year-but on the whole it averages between three and six weeks. The course of the disease is short-only a few days-and the mortality rate is essentially 100 percent. For the safety of humans and their pets, cat and dog owners should see to it that their animals are routinely vaccinated against this most deadly and uncompromising of viral diseases.