Managing and preventing feline febrile diseases (Proceedings)

Pathophysiology

The 2 major differentials for elevated body temperature (> 102.5 F) are fever (pyrexia) and hyperthermia. Hyperthermia results from increased muscle activity, increased environmental temperature, or increased metabolic rate (i.e. hyperthyroidism). Fever develops when the thermoregulatory set point in the hypothalamus is increased, resulting in increased body temperature from physiologic mechanisms inducing endogenous heat production or heat conservation. If the cause of fever is not apparent for > 2 weeks, the case is classified as having fever of unknown origin.

Fever results when leukocytes, particularly mononuclear cells and neutrophils, are activated. Leukocytes are generally stimulated by contact with bacterial, viral, fungal, and parasitic agents, neoplasia, tissue necrosis (extensive trauma and pancreatitis included), and primary immune-mediated diseases like immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, and systemic lupus erythematosus. Activated leukocytes release a variety of soluble factors like interleukin 1 and tumor necrosis factor, which enter the central nervous system and change the thermoregulatory set point. The thermoregulatory set point may also be altered by intracranial disease including trauma and neoplasia, or drugs like tetracyclines. Shivering and vasoconstriction are 2 of the most important physiologic responses to a thermoregulatory set point change that result in generation and conservation of heat, respectively.

Fever < 105°F may be beneficial for the management of infectious diseases due to potentiation of phagocytosis, interferon release, and lymphocyte transformation. During chronic inflammatory conditions resulting in fever, activated mononuclear cells also sequester serum iron, decreasing bacterial replication. Body temperatures > 106 F can be detrimental due to effects on cellular metabolism. Disseminated intravascular coagulation can result from extreme increase in body temperature. Compared to dogs, cats are less likely to develop the detrimental effects of fever.

Clinical findings

The differential list for fever in cats is long. In cats, infectious causes of fever are much more common than primary immune diseases or neoplasia. Initially, the clinician should use the signalment, history and physical examination to identify the initial differential list. Diagnostic tests or therapeutic trials are then used to confirm the primary differential.

Signalment

The age, breed, and sex of the cat can help rank the differential list for fever. For example, young cats often have infectious diseases; old cats often develop neoplasia. Inbreeding can result in predisposition for infectious diseases. For example, feline infectious peritonitis is most common in pure-breed cats. Male cats are more likely to fight, partially explaining the increased incidence of feline immunodeficiency virus in this sex.

History

History can help determine the likely source of elevated body temperature. It should be determined whether the cat is being administered a drug of any type; some can induce fever, in particular, tetracyclines. It should be determined whether vaccines were administered within the previous 1 to 2 months. Vaccine reactions can induce elevated body temperatures via immune-mediated reactions (any vaccine) or if a live, attenuated vaccine is used, via replication of the attenuated agent in the host. This seems to be most common with attenuated Chlamydophila felis vaccination of kittens which results in fever and stiffness in some, several days after inoculation. It is also important to determine which vaccines the cats have been administered and the interval between vaccines. Immune responses can wane with time, predisposing the cat to infection. This is unlikely to be a problem with panleukopenia virus; administration of a killed vaccine, twice to cats resulted in 100% immunity at 7.5 years.

Since many causes of fever in cats are transmissible, it should be ascertained whether the cat has had recent exposure to other cats, excrement, or ectoparasites. Cats with history of fever and bite wounds in the past may be infected with FIV or the hemoplasmas. Cats with fever and fleas might be infected with Mycoplasma haemofelis, 'Candidatus M. haemominutum,' 'Candidatus M. turicensis,'or Bartonella spp.. Cats in housed with other cats are more likely to come in contact with cats carrying infectious agents. It should be determined whether other animals or family members have similar clinical signs of disease. Some infectious agents are regional and so it should be determined whether the cat has traveled recently. For example, in the United States, Cryptococcus neoformans infection is most common in southern California and around Vancouver. Determining the prey species for outdoor cats can help rank the infectious disease differential list; ingestion of songbirds (salmonellosis), rabbits (tularemia), or rodents (Yersinia pestis or toxoplasmosis) can transmit infectious diseases associated with fever.

The owner should be questioned concerning clinical signs involving organ systems commonly associated with fever including the oral cavity, central nervous system, cardiopulmonary system, urogenital system, subcutaneous tissues, peritoneal cavity, and gastrointestinal tract.

Physical examination

Anorexia, depression, hyperpnea, reluctance to move, and stiffness from muscle, joint, or meningeal discomfort are common non-specific manifestations of fever in cats. Clinical signs or physical examination findings associated with the primary organ systems involved with the primary infection, tissue necrosis, neoplasia, or immune-mediated disease may be evident. In some cases, the only physical examination finding is fever. Hyperthermia should be differentiated from fever by determining whether the cat has been exposed recently to increased environmental temperature or has increased muscle activity due to excitement, physical exertion, or seizures. All apparently normal cats with elevated body temperature should be encouraged to lay quietly in the examination room with the client for 15-20 minutes followed by repeat measurement of the body temperature. Some normal cats will have persistently elevated body temperature in the clinic due to hyperthermia; these cats should have the body temperature measured at home during periods of rest to determine whether fever is occurring.

The oral cavity should be examined carefully for dental diseases, infiltrative diseases, increased mucus, red or pale mucous membranes, petechia, or tonsillar enlargement. The nares should be examined for evidence of discharges; mucopurulent discharge generally indicated primary bacterial infection, secondary bacterial infection, or fungal infection. The chest should be ausculted carefully for cardiac murmurs, muffled heart or lung sounds, or pulmonary crackles or wheezes and the chest should be gently compressed to evaluate for mediastinal masses. Bartonella spp. have recently been associated with bacterial endocarditis and myocarditis in cats. The external lymph nodes and spleen should be palpated for enlargement that may indicate immune-stimulation or neoplasia. Cats showing clinical signs of stiffness should have the muscles, long bones, spinal column, and joints palpated separately. The joints should be gently extended and flexed while evaluating for swelling, pain, or redness. The abdomen should be palpated for evidence of organomegaly, peritoneal effusion, or pain.

A thorough ophthalmic examination should be performed to evaluate for evidence of anterior or posterior segment inflammation. Uveitis occurs with several infectious agents associated with fever in cats, including T. gondii, FeLV, FIV, FIP, B. henselae, feline herpesvirus 1, Ehrlichia spp., and the systemic mycoses. However, the lack of uveitis does not exclude these differentials.

Diagnostic plan

After the physical examination and history are completed, obvious causes of fever like subcutaneous abscessation or bite wounds are treated appropriately. The further diagnostic plan is directed by results of the history and physical examination. A complete blood cell count, serum biochemical panel, urinalysis, FeLV antigen test, and FIV antibody test are indicated as the minimal diagnostic plan in most cats with fever without a readily apparent cause.

Complete blood cell count

The presence of neutrophilic leukocytosis with or without a left shift and toxic neutrophil changes are nonspecific but may indicate an inflammatory condition. Monocytosis is commonly present with chronic inflammatory diseases. Neutrophilia and monocytosis do not prove presence of an infectious disease. Neutropenia in cats results from consumption of neutrophils at a site of inflammation or decreased production of neutrophils. Extreme neutropenia is most commonly associated with panleukopenia, FeLV, FIV, and acute salmonellosis. Eosinophilia is commonly present with Type I hypersensitivity reactions and metazoan parasites including gastrointestinal parasites and dirofilariasis. Recently, lymphocytosis has been reported with toxoplasmosis and bartonellosis. In contrast, cats with fever and FIP usually have lymphopenia.

Anemia may occur with some causes of fever including primary or secondary immune-mediated hemolytic anemia, hemoplasmosis, and feline leukemia virus infection. Hemopathology may also provide information concerning primary causes. Red cell parasites like hemoplasmas or Cytauxzoon felis (USA only) may be seen; spherocytes and microagglutination may indicate immune-mediated hemolytic anemia. Cats with hemolytic anemia but without hemoplasmas on red blood cells that were collected into EDTA should have fresh blood smears made from blood collected from an ear margin vein. In many countries including the United States, whole blood from cats can be assessed for hemoplasmas using polymerase chain reaction (PCR) assays. Thrombocytopenia develops with many immune-mediated, neoplastic, and infectious diseases.

Serum biochemical panel

Serum biochemical findings are usually non-specific for the cause of fever but may provide clues for the further diagnostic plan. Azotemia with a suboptimal urine specific gravity (< 1.035 in the cat) combined with bacteriuria and pyuria may indicate pyelonephritis. However, some cats with fever from pyelonephritis have not been azotemic. Increases in activities of liver cytosolic enzymes (ALT and AST) may indicate bacterial or immune-mediated cholangiohepatitis, hepatic abscessation, primary hepatic infections like feline infectious peritonitis virus (FIP), or neoplastic diseases of the liver. Pancreatitis in cats can result in fever but is difficult to diagnose due to poor correlation with lipase and amylase concentrations. If suspected, the combination of laboratory data, TLI, ultrasound, and comparison of lipase concentrations in serum and abdominal fluid can be used to make a tentative diagnosis. Hyperglobulinemia occurs commonly with chronic primary immune-mediated diseases, infectious diseases, and neoplasia. Lymphoma, plasmacytic stomatitis, bartonellosis, and FIP are common causes of hyperglobulinemia in cats. Protein electrophoresis should be used to determine whether the gammopathy is monoclonal or polyclonal. Measurement of total T4 concentration may be indicated in some cats with elevated body temperature but is an uncommon cause.

Urinalysis

Pyuria and bacteriuria noted on urinalysis performed on urine obtained by cystocentesis indicate upper or lower urinary tract infection; if fever is present, pyelonephritis is likely. All cats with pyuria or bacteriuria should have urine culture and sensitivity performed. Proteinuria may indicate immune complex deposition in the glomeruli from immune-mediated diseases like systemic lupus erythematosus or chronic inflammatory infectious diseases like FIP, FeLV, ehrlichiosis or dirofilariasis. The urine protein to creatinine ratio can be used to semi-quantitate protein amounts and to monitor therapy in animals with proteinuria without an inflammatory sediment.

Cytology

Cytology can be used to help confirm the presence of inflammation and occasionally, infectious agents with characteristic morphologic form may be detected. Cats with radiographic evidence of alveolar or bronchial lung patterns not associated with cardiac failure should be evaluated with transtracheal wash or bronchoalveolar wash for cytology, culture, and antimicrobial susceptibility. Enlarged peripheral lymph nodes should be aspirated to differentiate neoplastic causes from hyperplasia due to primary immune-mediated diseases or infectious diseases. Submandibular lymph nodes from cats with fever or signs of pneumonia living in states endemic for Yersinia pestis should be aspirated carefully, stained, and examined for characteristic bipolar rods. Fluorescent antibody staining can be used to confirm the diagnosis. Fungal or protozoal agents can be detected cytologically in some cats.

Abdominal paracentesis or thoracocentesis are indicated in cats with fever and pleural or peritoneal effusions, respectively. Bacterial peritonitis or pyothorax have high protein concentration and extremely high numbers of neutrophils and macrophages. There is usually a mixed population of degenerative and nondegenerate neutrophils; bacteria may or may not be seen. Cats with pancreatitis can have peritoneal or the combination of peritoneal and pleural effusion. The fluid cytologically is similar to the bacterial diseases but the fluid is usually not septic. Detection of abdominal fluid lipase concentrations greater than serum can be used to confirm the diagnosis of pancreatitis. Fluid induced by FIP usually have high protein concentration and increased numbers of neutrophils and macrophages but the neutrophils are usually non-degenerate. Determination of the albumin to globulin ratio of peritoneal or pleural effusions can aid in the diagnosis of FIP. Cats with fluid albumin/globulin ratio > 0.8 are unlikely to have FIP; ratios < 0.4 are usually associated with FIP.

Arthrocentesis can be used to confirm neutrophilic infiltrates in synovial fluid which supports a diagnosis of immune-mediated or infectious polyarthritis even if joint effusion or pain is not readily apparent. Calicivirus, Anaplasma phagocytophilum, Mycoplasma, and L-form bacterial infection are several infectious agents associated with polyarthritis in cats.

Fecal tests

Rectal cytology is indicated in cats with fever and diarrhea. Fecal culture for Salmonella and Campylobacter is generally indicated for the evaluation of cats with neutrophils detected on rectal cytology, particularly if other risk factors are present. Clostridium perfringens can produce enterotoxin which can be measured in feces and is usually performed in cats with spore-forming rods detected cytologically. Cats with hemorrhagic gastroenteritis and neutropenia can be further evaluated for the presence of parvovirus infection by fecal ELISA if they are not vaccinated for panleukopenia and for salmonellosis if they are vaccinated. Fecal PCR panels have little predictive value and so I usually do not perform them in cats with fever.

Culture and sensitivity

Culture and sensitivity of body fluids, aspirates or biopsies of tissue, or feces can be used to help confirm infectious causes of fever. Bacteremia is best confirmed by blood culture but polymerase chain reaction (PCR) may be used in the future. At least 3 bacterial blood cultures over 2 hours should be collected from the jugular vein following sterile preparation of the skin. Aerobic and anaerobic bacterial cultures and fungal cultures may be indicated in some cases. Special media is required to support the growth of some organisms like Mycobacterium spp., Bartonella spp., and Mycoplasma. L-form bacteria will not be cultured on routine culture media.

Serologic testing

Serologic testing is indicated in some cats with fever; choices are based on the combination of clinical and routine laboratory findings. A FeLV antigen test and a FIV antibody test are indicated in cats with fever of unknown origin. Fever is rarely induced by FeLV infection and when due to FIV is present most commonly in the acute phase of infection. However, both viruses cause immuodeficiency and so predispose to infection by other infectious agents.

Clinical features and diagnostic tests for FeLV have been extensively researched and were recently reviewed in the American Association of Feline Practitioner's Feline Retrovirus Management Guidelines (www.catvets.com). It is now believed that most exposed cats become infected. Cats with progressive infection generally succumb to FeLV associated illness within months to several years. Some cats with initial positive ELISA results will occasionally regress to negative results (regressive infection) and the virus cannot be detected in blood by culture or antigen tests. However, the FeLV provirus can be amplified from blood or bone marrow by real time PCR assays (Torres and colleagues, 2005). Some experimentally infected cats had abortive exposure characterized by negative test results for culturable virus, antigen, viral RNA, and proviral DNA after FeLV exposure. In addition, focal infections, where the FeLV virus appears to be restricted to certain tissues like the spleen, lymph node, small intestine or mammary glands, rarely have been reported.

Most cats with suspected FeLV infection are screened for FeLV antigens in neutrophils and platelets by immunofluorescent antibody (IFA) or in whole blood, plasma, serum, saliva, or tears by enzyme-linked immunosorbent assay (ELISA). IFA is not positive until the bone marrow has been infected. Results of IFA are accurate 98.3% of the time. False-negative reactions may occur when leukopenia or thrombocytopenia prevents evaluation of an adequate number of cells. False-positive reactions can occur if the blood smears submitted for evaluation are too thick. A positive IFA indicates that the cat is viremic and contagious; 90-97% of cats with positive IFA results will be viremic for life. The rare combination of IFA positive and ELISA negative results suggests technique-related artifact. Negative ELISA results correlate well with negative IFA results and an inability to isolate FeLV.

The virus can be detected in serum by ELISA prior to infection of bone marrow and so can be positive in some cats during early stages of infection, or during self-limiting infection even though IFA results are negative. Other possibilities for discordant results (ELISA positive, IFA negative) are false positive ELISA results or false negative IFA results. Cats with positive ELISA results and negative IFA results are probably not contagious at that time, but should be isolated until retested 4-6 weeks later since progression to persistent viremia and epithelial cell infection may be occurring.

ELISA-positive cats that revert to negative have developed neutralizing antibodies, latent infection, or localized (focal) infection. Virus isolation, IFA performed on bone marrow cells, immunohistochemical staining of tissues, and polymerase chain reaction can be used to confirm localized or latent infection. Cats with localized or latent infection are not likely contagious to other cats, but infected queens may pass the virus to kittens during gestation, parturition, or by milk. Cats with localized or latent infection can have immunodeficiency and may become viremic (IFA and ELISA positive) after receiving of corticosteroids or following extreme stress.

There is generally a delay of 1 to 2 weeks after the onset of viremia before ELISA tear and saliva tests become positive, so these tests can be negative even when results using serum are positive. Antibody titers to FeLV envelope antigens (neutralizing antibody) and against virus-transformed tumor cells (FOCMA antibody) are available in some research laboratories but the prognostic significance of results from these tests is unknown. Cats with suspected focal FeLV infection can be evaluated for the presence of the virus in bone marrow by IFA, polymerase chain reaction, or virus isolation.

Antibodies against FIV are detected in serum in clinical practice most frequently by ELISA. Seroconversion occurs 2-4 weeks post-inoculation in experimentally infected cats; thus, false-negative reactions can occur during peracute infection. False-positive reactions are common using ELISA. Positive ELISA results should be confirmed using Western blot immunoassay or IFA, especially if the positive cat is healthy or is from a low-risk population for infection. Kittens can have detectable colostrum-derived antibodies until 12-14 weeks of age and should not be tested until > 14 weeks of age. Detection of antibodies against FIV in the serum of cats documents exposure and correlates well with persistent infection but does not correlate to disease induced by the virus. Since many of the clinical syndromes associated with FIV can be due to opportunistic infections, further diagnostic procedures may determine treatable etiologies. For example, most FIV-seropositive cats with uveitis are coinfected by T gondii and often respond to the administration of anti-Toxoplasma drugs. Cats in the primary phase of FIV can have fever but be seronegative; the antibody test should be repeated in 6 to 8 weeks in cats with a high index of suspicion for FIV infection. A killed FIV vaccine is currently available. This vaccine induces antibodies detectable in both ELISA and western immunoblot that are indistinguishable from those induced by natural infection. Too date, PCR has not been 100% accurate in discriminating vaccinated cats from those infected with FIV.

Detection of serum antibodies is of limited benefit in the evaluation of cats for FIP. Infection of cats by any coronavirus can cause cross-reacting antibodies, so a positive antibody titer does not diagnose FIP, protect against disease, or predict when a cat may develop clinical FIP. Coronavirus antibody tests are not standardized, so results from different laboratories commonly do not correlate. Antibodies in serum against bovine serum products that result from vaccination can cause false-positive results in some coronavirus antibody tests. Cats with FIP are occasionally serologically negative because of rapidly progressive disease with a delayed rise in titer, disappearance of antibody in terminal stages of the disease, or immune complex formation. Maternal antibodies decline to undetectable concentrations by 4 to 6 weeks of age; kittens infected in the postnatal period become seropositive at 8 to 14 weeks of age. Thus, serologic testing of kittens can be used to prevent spread of coronaviruses. Serologic testing is indicated as a screening procedure in breeding colonies that are coronavirus antibody-negative. A test to detect the 7B protein of coronaviruses has been introduced and purported to correlate to FIP. However, not all cats that are positive develop FIP. Thus, all positive coronavirus tests should be interpreted with other clinical factors including signalment (generally young cats), appropriate clinical signs and physical examination abnormalities, and appropriate laboratory abnormalities like lymphopenia and hyperglobulinemia. Definitive diagnosis of FIP still requires documentation of characteristic histopathologic findings or the organism in inflamed tissues by immunohistochemistry or PCR.

Toxoplasma gondii serologic testing should be considered in cats with fever, particularly if muscle hyperesthesia or uveitis are concurrently present. Toxoplasmosis is also most common in cats that are allowed outdoors and so are more likely to ingest infected rodents. Presence of IgM in serum correlates better to clinical toxoplasmosis than IgG. Detection of T. gondii antibodies by ELISA or the organism in aqueous humor or CSF by PCR are the most accurate methods of proving ocular or CNS toxoplasmosis.

The only antigen test validated for systemic fungal infections in cats is for Cryptococcusneoformans. This organism can usually be detected cytologically. However, antigen testing is also used to follow efficacy of treatment and so is indicated in most cases. Only antibody tests are available for the other mycoses. Presence of antibodies are not indicative of current infection.

Ehrlichiosis (E. canis and possibly another related organism) and anaplasmosis (Anaplasma phagocytophilum; previously E. equi) have been shown to cause fever in cats of multiple countries around the world including France, Brazil, Sweden, Africa, Thailand, and the United States. Serologic testing is available in some countries. Like results of most other antibody tests, positive Ehrlichia spp. serology only correlates to exposure not clinical disease. Some cats with E. canis DNA in serum were seronegative; in contrast, all A. phagocytophilum cats were seropositive. However, infection by A. phagocytophilum will not be detected by E. canis antibody tests and vice versa. Thus, cats with suspected ehrlichiosis or anaplasmosis must be screened for both antibodies and PCR.

Polymerase chain reaction

DNA of infectious agents can be detected in body fluids, feces, and tissues by PCR; this technique is being used to aid in the diagnosis of multiple infectious causes of fever. The following are several examples. All 3 hemoplasmas of cats, Mycoplasma haemofelis, 'Candidatus M. haemominutum', and 'Candidatus M. turicensis, can all be amplified from the blood of cats with PCR and the technique is more sensitive than cytology. Bartonella spp. can be amplified from blood and sensitivity may be equal to that of culture in cats, but not dogs. Ehrlichia canis and A. phagocytophilum (previously E. equi) infection of cats has been amplified from the blood of cats by PCR. Coronavirus polymerase chain reaction (PCR) can document the organism in effusions and whole blood; while positive results from effusions correlate fairly well with FIP those from whole blood do not. Even the new mRNA based assay can be positive in as many as 50% of healthy cats. As more PCR are introduced to the marketplace, request information concerning sensitivity, specificity, positive predictive value, and negative predictive value of each assay.

Diagnostic imaging.

Thoracic and abdominal radiographs are commonly utilized in the search for the cause of fever; infections or neoplasia not obvious on physical examination can often be identified. For example, cats with unilateral pyothorax may not have a restrictive breathing patterns. Not all cats with pyelonephritis have painful kidneys; an irregularly shaped kidney could be detected on abdominal radiographs. Radiographs of the axial or appendicular skeleton can be used to evaluate for neoplasia or osteomyelitis. Contrast studies, ultrasonography, nuclear scintigraphy, and both CT and MRI can be used to evaluate different organ systems for disease resulting in fever.

Primary immune tests

Tests used most frequently in cats to aid in the diagnosis of primary immune-mediated diseases include direct Coomb's and antinuclear antibody tests. The laboratory should be consulted to determine whether the assays and controls have been validated for use with cats. Positive test results combined with appropriate clinical or laboratory evidence of disease may support a diagnosis of immune-mediated disease. Both of these tests can be positive secondary to chronic inflammatory diseases independent of primary immune disease.

Other tests

Bone marrow aspiration and cytology may aid in the identification of immune-mediated, infectious, or neoplastic diseases. For example, macrophages with ingested platelets or red blood cells may be noted and Histoplasma capsulatum is commonly detected in the bone marrow of infected cats.

Protein electrophoresis can be used to determine whether a gammopathy is monoclonal or polyclonal; immunoelectrophoresis can be used to detemine which antibody class is being produced in excess. Monoclonal gammopathy is most commonly associated with neoplasia but has been detected with ehrlichiosis as well. Results of protein electrophoresis of serum are not beneficial for documentation of feline infectious peritonitis virus (see cytology section). The polyclonal gammopathy that occur with FIP cannot be distinguished from that induced by other chronic inflammatory diseases.

Treatment plan

Empirical treatment is frequently used in cats with elevated body temperature. If hyperthermia is suspected, the cause should be removed if possible (seizures, increased environmental temperature etc.).

In cats with suspected infectious, neoplastic, or primary immune-mediated causes of fever, multiple specific and non-specific therapeutic options are available. Intravenous administration of room temperature fluids is often all that is required to maintain body temperature at safe levels. Using a cool cage or directing a fan towards the patient may also be effective. Since fever in general is biologically helpful, artificial lowering of body temperature is usually not indicated. Thus, the use of drugs like dipyrone is usually contraindicated. If chronic fever is present that results in morbidity (depression, inappetance), aspirin at 5 mg/kg, orally once daily can be used. Multiple non-steroidal anti-inflammatory agents are available that can be used to transiently decrease body temperature if indicated. Once infectious and neoplastic causes of fever are excluded, use of glucocorticoids may be indicated for the treatment of primary immune-mediated diseases.

Antibiotics should be given to cats with presumed bacterial, rickettsial, protozoal, or mycoplasmal infections. Ultimately, treatment should be based on results of culture and sensitivity if possible. Empirical antibiotic choices can be based on the organ system involved or the organism suspected. Feline hemoplasmas, Bartonella spp., and Ehrlichia/Anaplasma infections generally respond to doxycycline at 10 mg/kg, PO, once daily. I attempt to treat for at least 28 days to lessen chance for recurrence. I personally liquefy doxycyline at 50 mg/ml in tuna flavoring which lowers the volume needed. You can also give water after pilling or put butter or Nutrical on the tablet to lessen odds of developing esophageal strictures. We have also shown that placement of tablets and capsules in flavored treats result in rapid passage to the stomach. For Bartonella spp. infections of cats, the AAFP Panel (aafponline.org) recommended doxycycline as the first drug of choice. Fluoroquinolones are suggested as rescue drugs for hemoplasmosis and bartonellosis if doxycycline fails. Toxoplasma gondii infections generally respond to clindamycin at 10 mg/kg, PO, twice daily or trimethoprim sulfa at 15 mg/kg, PO, twice daily. If responding, try to treat for 28 days. Azithromycin can be a rescue drug for bartonellosis and toxoplasmosis but is ineffective for hemoplasmosis.

Most fungal infections in cats are ultimately treated with amphotericin B, itraconazole, or fluconazole. Ketaconazole should not be used in cats due to risk of toxicity. Amphotericin B should be used if life-threatening disease is present so a cidal drug is needed. Liposomal or lipid encapsulated amphotericin B are preferred because these drugs are less likely than regular amphotericin B to induce fever or nephrotoxicity but are expensive. Recently, subcutaneous administration of regular amphotericin B has been reported for treatment of cryptococcosis and is a less expensive alternative. Intraconazole or fluconazole are the drugs used most frequently for chronic therapy. Due to superior penetration, fluconazole should be used in cats with ocular or central nervous system involvement.

Fever induced by viral infections is rarely treated primarily since most are acute. AZT has been used successfully to improve quality of life in some cats infected with FeLV or FIV. I currently use 5 mg/kg, PO, q12 hours. Controlled studies are lacking that document efficacy of propriobacterium acnes, Staphylococcus protein A, acemannan, Pind-dorf, or interferon alpha for the treatment of retroviral infections of cats.

Glucocorticoids are used for the treatment of noneffusive FIP, primary immune-mediated diseases, and some neoplasia. Prednisolone is more effective than prednisone in some cats and so is the first glucocorticoid of choice for many clinicians. Cats with primary immune diseases thought to have resistance to prednisolone should be treated with dexamethasone or triamcinolone prior to use of cytotoxic drugs. If cytotoxic drugs are needed, chlorambucil is apparently safer than azathioprine for long term administration.

Feline blood borne agents

The purpose of this part of the manuscript is to provide a brief review of the emerging clinical issues associated with Bartonella spp, Ehrlichia spp., haemoplasma, Anaplasma spp. and Rickettsia spp. infections of cats.

Please also see the AAFP Panel report on feline bartonellosis www.catvets.com, the ACVIM Consensus Statement on blood donor testing (www.acvim.org), and the ACVIM Ehrlichia Consensus Statement (www.acvim.org).

Feline bartonellosis

Cats have proven by culture or DNA amplification to be infected by Bartonella henselae, B. clarridgeiae, B. koehlerae, B. quintana and B. bovis. Cats are the main reservoir hosts for B. henselae and B. clarridgeiae and are likely to be the reservoir for B. koehlerae.

Bartonella henselae is the most common cause of Cat Scratch Disease as well as bacillary angiomatosis, and peliosis hepatis, common disorders in humans with AIDS. Bartonella spp. are thought to have both intra-endothelial and intra-erythrocytic phases of infection. Based on results of seroprevalence studies, culture, or polymerase chain reaction (PCR) assay, cats are commonly exposed to or infected by Bartonella spp.. Recently, B. henselae has been documented as a cause of chronic disease syndromes like fever, headaches and chronic fatigue in immunocompetent veterinary health care providers (Breitschwerdt et al, 2008). Most medical doctors may not recognize this differential and should be informed if you are exhibiting these problems.

The organisms are transmitted between cats by Ctenocephalides felis and so prevalence is greatest in cats from regions where fleas are common. In a recent study in the United States, we collected fleas from cats and attempted to amplify Bartonella spp. DNA from flea digests as well as the blood of the cat. The prevalence rates for B. henselae in cats and their fleas were 34.8% and 22.8%, respectively. The prevalence rates for B. clarridgeiae in cats and their fleas were 20.7% and 19.6%, respectively. Results are similar in other studies performed around the world including recent studies completed in England and Australia. In Scotland, we showed the Bartonella spp. seroprevalence and DNA prevalence rates to be 15.3% and 5.8%, respectively (Bennett et al, 2010).

Bartonella henselae survives in flea feces for days after being passed by infected C. felis. Infected flea feces are likely to contaminate cat claws during grooming and then Bartonella are inoculated into the human when scratched. It is also possible that open wounds are contaminated with infected flea feces. Thus, administration of flea control products, avoiding bites and scratches, and thorough cleansing of wounds or areas contaminated with flea feces is indicated to potentially decrease risk of acquiring bartonellosis.

We recently completed a study in which SPF cats were exposed naturally to C. felis (100 fleas added to each cat in R2 monthly) allowed to feed on cats with B. henselae administered IV. The barriers between R1, R2, and R3 were mesh so the fleas could move amongst the cats but the cats could not touch each other. The oblong circles represent the cat perches that were placed next to the mesh to encourage movement of fleas from group to group.

Cats in R3 were administered imidacloprid-moxidectin monthly and the other cats were not treated. At the end of the study, all cats in R1 had become infected but none of the cats in R3. We believe this data supports the Colorado State University recommendation that all cats used as blood donors be housed indoors when possible and be maintained on flea control products year round. At this time only imidacloprid-moxidectin has been shown to block transmission of Bartonella spp. amongst cats.

Most cats with serological evidence of exposure to a Bartonella spp., a Bartonella spp. cultured from blood, or microbial DNA amplified from blood by PCR assay are clinically normal. However, Bartonella spp. infection of cats has also been associated directly or indirectly with a variety of clinical manifestations like fever, lethargy, lymphadenopathy, uveitis, gingivitis, and neurological diseases. How often cats become ill from Bartonella spp. infections is unknown and more information is needed. For example, the association of B. henselae infection to uveitis in a cat was first made in an individual case with uveitis that ultimately responded to doxycycline therapy. We subsequently found Bartonella antibody production and DNA in the aqueous humor of cats previously presumed to have idiopathic uveitis. A series of clinical cases of feline ocular disease that were responsive to antibiotic therapy was recently reported. Thus, it appears likely that Bartonella spp. causes ocular disease in some cats. However, it can be difficult to determine which cats have been exposed and which cats are diseased. For example, in recent studies in my laboratory, the prevalence rates for Bartonella spp. antibodies in feline sera were not significantly different for cats with and without ocular disease, cats with or without seizures, or cats with or without stomatitis. It is also still also still unclear as to why some cats develop Bartonella associated illness and others do not. For example, we failed to induce Toxoplasmagondii or Bartonella spp. uveitis when we inoculated Bartonella IV into cats with chronic toxoplasmosis.

Blood culture, PCR assay on blood, and serologic testing can be used to assess individual cats for Bartonella infection. Cats that are culture-negative or PCR-negative and antibody-negative and cats that are culture-negative or PCR-negative and antibody-positive are probably not a source of flea, cat, or human infection. However, bacteremia can be intermittent and false-negative culture or PCR results can occur, limiting the predictive value of a single battery of tests. With PCR, false positive results can occur and positive results do not necessarily indicate that the organism is alive. While serologic testing can be used to determine whether an individual cat has been exposed, both seropositive and seronegative cats can be bacteremic, limiting the diagnostic utility of serologic testing. Thus, testing healthy, client-owned cats for Bartonella spp. infection is not currently recommended in the United States. Testing should be reserved for cats with suspected clinical bartonellosis. In our laboratory (http://www.dlab.colostate.edu/) we offer a combination of Bartonella spp. serology and PCR which I believe gives the best combined positive predictive values. If the results of Bartonella tests are negative in a clinically ill cat, the organism is not likely the cause of the clinical syndrome unless the infection was peracute and serological testing was used as the diagnostic test. If the results of Bartonella tests are positive, the agent remains on the differential list, but other causes of the clinical syndrome must also be excluded.

For blood donor cats, the ACVIM Panel was equivocal on their recommendation concerning blood donor testing of cats. In a recent study in our laboratory, we showed that Bartonella is not killed by CPDA-1 solution (Bradbury et al, 2010). Because of these findings and the fact that some cats become ill after IV inoculation with the organism, Colorado State University recommends only using Bartonella spp. PCR or culture negative and Bartonella spp. seronegative cats as blood donors.

In experimental studies, administration of doxycycline, tetracycline, erythromycin, amoxicillin-clavulanate, or enrofloxacin can limit bacteremia but does not cure infection in all cats. To date, use of antibiotics in healthy cats has not been shown to lessen the risk of cat scratch disease. Thus in the United States, treatment is generally recommended for clinically ill cats. If clinical bartonellosis is suspected, the AAFP Panel Report recommends doxycycline at 10 mg/kg, PO, daily for 7 days as the initial therapeutic trial. In the United States, I have my doxycycline prescriptions formulated into a flavored suspension to avoid esophageal strictures. Using the drug twice daily as labeled in Australia is also acceptable and may increase the chance of eliminating bacteremia. If a positive response is achieved, continue treatment for 2 weeks past clinical resolution of disease or for a minimum of 28 days. If a poor response is achieved by day 7 or doxycycline is not tolerated and I still believe bartonellosis is a valid differential diagnosis, I consider azithromycin or a fluoroquinolones as second choices. In my experience, Bartonella spp. positive cats that have failed to respond after administration of 2 different drugs with presumed anti-Bartonella activity generally have another cause of the clinical syndrome. There is no clinical utility in rechecking Bartonella serological test results in cats.

To lessen the likelihood of acquiring a Bartonella spp. infection from a cat, the following are adaptations of what is recommended to HIV-infected people and other cat owners by the Centers for Disease Control and the American Association of Feline Practitioners.

• Flea control should be initiated and maintained year-round.

• If a family member is immunocompromised and a new cat is to be acquired, adopt a healthy cat > 1 year of age and free of fleas.

• Immunocompromised individuals should avoid contact with cats of unknown health status.

• Declawing of cats is generally not required but claws should be trimmed regularly.

• Bites and scratches should be avoided (including rough play with cats).

• Cat-associated wounds should be washed promptly and thoroughly with soap and water and medical advice sought.

• While Bartonella spp. have not been shown to be transmitted by saliva, cats should not be allowed to lick open wounds.

• Keep cats indoors to minimize hunting and exposure to fleas and other possible vectors.

Feline granulocytotropic anaplasmosis

Cats have shown to be susceptible to A. phagocytophilum infection after experimental inoculation. In naturally exposed cats, DNA of A.phagocytophilum has been amplified from several countries including Sweden, Denmark, Ireland, and the United States (Bjoersdorff and colleagues, 1999; Shaw and colleagues, 2001; Lappin and colleagues, 2004). Morulae consistent with A. phagocytophilum have been detected cytologically in neutrophils of naturally infected cats in other countries including Brazil, Kenya, and Italy. Cats living in endemic areas are commonly seropositive. As in dogs, A. phagocytophilum is transmitted by Ixodes ticks and so infections of cats are likely to be most common in these areas. While rodents are commonly infected with A. phagocytophilum, it is currently unknown whether ingestion or direct contact with rodents plays a role in A. phagocytophilum infection of cats. While the pathogenesis of disease associated with A. phagocytophilum in cats is unknown, some cats experimentally inoculated with A. phagocytophilum developed anti-nuclear antibodies and increased IFN-gamma mRNA suggesting that an immune pathogenesis of disease may contribute to the clinical findings.

Fever, anorexia, and lethargy were the most common clinical abnormalities. Tachypnea has also been detected. Ticks may or may not currently be infesting infected cats. Overall, clinical signs associated with A. phagocytophilum infection in cats were mild and resolved quickly after initiating tetracycline therapy.

Approximately 50% of cats with proven clinical infections induced by A. phagocytophilum have a mild thrombocytopenia (66,000-118,000/µl). Neutrophilia with a left shift, lymphocytosis, lymphopenia, and hyperglobulinemia have been detected in some cats. Morulae are less commonly detected than in dogs. The abnormalities resolved quickly after doxycycline treatment was initiated (Bjoersdorff and colleagues, 1999; Lappin and colleagues, 2004). Biochemical and urinalysis abnormalities are unusual. Some commercial laboratories offer serologic testing. Infected cats are negative for antibodies against E. canis and so A. phagocytophilum IFA slides should be used. Approximately 30% of cats with proven clinical infections induced by A. phagocytophilum are seronegative when first assessed serologically, but all proven cases to date have ultimately seroconverted. Some mountain lions with A. phagocytophilum DNA amplified from blood have been serum antibody negative (Foley and colleagues, 1999) and so a single negative antibody result in an acutely infected cat does not exclude infection. Therefore, cats with suspected anaplasmosis may need convalescent serum samples to prove infection. Alternately, antibody testing could be combined with PCR testing of whole blood in acute cases (Lappin and colleagues, 2004).

Supportive care should be administered as needed. Several antibiotics have been administered to naturally infected cats, but all cats in 2 studies became clinically normal within 24 to 48 hours after initiation of tetracycline or doxycycline administration and recurrence was not reported (Bjoersdorff and colleagues, 1999; Lappin and colleagues, 2004). While clinically normal, 2 cats were still PCR positive 17 days and 90 days after treatment (of 21 to 30 days duration) which suggests that treatment with tetracyclines for 21 to 30 days may be inadequate for eliminating the organism from the body (Lappin and colleagues, 2004)..

To prevent A. phagocytophilum infection in cats, acaricidal products that are approved for use on cat should be used. It is likely that A. phagocytophilum can be transmitted by blood; therefore, cats used as blood donors in endemic areas should be screened for infection by use of serum antibody tests or PCR assay and positive cats should be excluded as donors.

Feline monocytotropic ehrlichiosis.

Ehrlichia-like bodies or morulae have been detected in peripheral lymphocytes or monocytes of naturally exposed cats in a number of countries including the United States, Kenya, France, Brazil, and Thailand. Two studies of naturally infected cats have amplified DNA consistent with E.canis (Breitschwerdt et al, 2002, Beaufils et al, 2002). Other studies of cats in endemic areas (Florida and Arizona) have failed to amplify Ehrlichia spp. DNA from the blood of cats (Luria and colleagues, 2004; Eberhardt and colleagues, 2006). To our knowledge, there have only been two experimental inoculation studies of cats with monocytotropic Ehrlichia spp.(Dawson and colleagues, 1988; Lappin and Breitschwerdt, unpublished observations, 2007). Morulae of N.risticii were detected in mononuclear cells from two of six cats inoculated IV (but not SQ); diarrhea developed in one cat, and depression, anorexia, and lymphadenomegaly developed in the other. When cats were inoculated SQ with an E. canis strain (North Carolina State University canine isolate) maintained in cell culture, microbial DNA or antibodies that reacted to E. canis morulae were not detected in an 8 week follow-up period. (Lappin and Breitschwerdt, unpublished observations, 2007). These results indicate the E. canis-like DNA amplified from naturally-infected cats may be from a different Ehrlichia spp. more infective to cats, not all E. canis stains will infect cats, not all cats are susceptible to infection by E. canis, or SQ inoculation is not an effective method for infecting cats with E. canis.

Sera from cats have been assessed for Ehrlichia spp. antibodies using IFA or western immunoblot. However, standardization of methodologies between laboratories has not been performed, the most appropriate cutoff values have not been determined, and there is variable serological cross-reactivity among Ehrlichia spp. Neorickettsia spp. and Anaplasma spp.. Therefore, results of serological studies should be interpreted cautiously. By use of IFA, serum antibodies that react with E. canis morulae have been detected in cats from multiple states in the United States, France, Italy, and Kenya. While antibodies have been commonly detected in naturally exposed cats, DNA of Ehrlichia spp. are rarely amplified from blood. When taken together, these results suggest that cats are less susceptible to monocytotropic ehrlichial infections that dogs.

It is currently unknown how cats are exposed to monocytotropic ehrlichial agents. Documentation of arthropod exposure in proven cases has been variable. Pathogenesis of disease associated with monocytotropic ehrlichiosis in cats is unknown but is likely to be similar to that for E. canis infection of dogs.

All ages of cats have been infected; most cats were domestic short haired, and both males and females have been affected. Anorexia, fever, inappetence, lethargy, weight loss, hyperesthesia or joint pain, pale mucous membranes, splenomegaly, dyspnea, and lymphadenomegaly were the most common historical and physical examination abnormalities. Dyspnea, petechiae, retinal detachments, vitreous hemorrhages, and pale mucous membranes were other reported physical examination abnormalities. Concurrent diseases are rarely reported but have included hemoplasmas (previously Haemobartonella felis), Cryptococcus neoformans, feline leukemia virus and feline immunodeficiency virus infections, and lymphoma.

Anemia is common and is usually nonregenerative. Leukopenia; leukocytosis characterized by neutrophilia, lymphocytosis, monocytosis; and intermittent thrombocytopenia were reported in some cats. Bone marrow evaluation of cats with cytopenias has revealed primarily hypoplasia of the effected cell line. However, one cat had bone marrow cytologic characteristics consistent with myeloid leukemia (Breitschwerdt and colleagues, 2002). Hyperglobulinemia was reported in multiple cats; protein electrophoresis usually reveals a polyclonal gammopathy. An epidemiologic link has been made between the presence of Ehrlichia spp. antibodies in serum and monoclonal gammopathy (Stubbs and colleagues, 2000). Based on the cases reported to date, ehrlichiosis should be considered on the differential list for cats with unexplained leukocytosis, cytopenias, and hyperglobulinemia. Biochemical abnormalities were infrequently reported in cats with suspected monocytotropic ehrlichiosis and were non-specific. The three cats with E. canis-like DNA in blood also had antinuclear antibodies, similar to results reported for infected dogs (Breitschwerdt and colleagues, 2002).

Some cats with suspected clinical ehrlichiosis seroreacted to E. canis or N. risticii morulae. Antibodies that seroreact to more than one ehrlichia are sometimes detected. Some cats with E. canis-like DNA in blood were seronegative (Breitschwerdt and colleagues, 2002). In contrast, most A phagocytophilum infected cats have strongly positive antibody test results. Positive serologic test results occur in both healthy and clinically ill cats, and so a diagnosis of clinical ehrlichiosis should not be based on serologic test results alone. A tentative diagnosis of clinical feline ehrlichiosis can be based on the combination of positive serologic test results, clinical signs of disease consistent with Ehrlichia infection, exclusion of other causes of the disease syndrome, and response to anti-rickettsial drugs. Ehrlichia spp. has been cultured from some cats on monocyte cell cultures. PCR and gene sequencing can also be used to confirm infection and should be considered the tests of choice at this time. However, as for dogs no standardization exists among laboratories providing Ehrlichia spp. PCR assays.

Clinical improvement after therapy with tetracycline, doxycycline, or imidocarb dipropionate was reported for most cats. However, for some cats a positive response to therapy was a criterion for the diagnosis of ehrlichiosis. The current recommendation of the ACVIM Infectious Disease Study Group is to give doxycycline (10 mg/kg PO q24h for 28 days). For cats with treatment failure or those intolerant of doxycycline, imidocarb diproprionate can be given safely (5 mg/kg IM or SQ twice, 14 days apart). Salivation and pain at the injection site are the common adverse effects and imidocarb efficacy is in question for the treatment of canine monocytotropic ehrlichiosis. While cats and people can both being infected E. canis, direct transmission is not known to occur. Care should be taken when removing ticks, and arthropod control should be maintained at all time for cats, particularly if allowed outdoors.

Feline hemoplasmosis

The new names for Haemobartonella felis are Mycoplasma haemofelis (Mhf), 'Candidatus Mycoplasma haemominutum' (Mhm), and 'Candidatus M. turicensis'. Strains evaluated in the United States, Australia, and the United Kingdom are genetically similar. In at least two studies of experimentally infected cats, Mhf is apparently more pathogenic than Mhm; all Mhf inoculated cats became clinical ill whereas Mhm inoculated cats were generally subclinically infected. Cats with chronic Mhm infection had more severe anemia and longer duration of anemia when experimentally infected with Mhf when compared to cats infected with Mhf alone.

In a recent study, we collected fleas from cats and attempted to amplify hemoplasma DNA from flea digests as well as the blood of the cat. The prevalence rates for Mhf in cats and their fleas were 7.6% and 2.2%, respectively. The prevalence rates for Mhm in cats and their fleas were 20.7% and 23.9%, respectively. Results from our collaborative study in Australia were similar (Barrs et al, 2008).

Ctenocephalides felis ingest Mhm and Mhf from infected cats when feeding. In one cat, we documented flea feeding to transfer Mhf. However, when we fed Mhf or Mhm infected fleas to cats, infection was not documented. In other studies, hemoplasmas have been transmitted experimentally by IV, IP, and oral inoculation of blood. Clinically ill queens can infect kittens; whether transmission occurs in utero, during parturition, or from nursing has not been determined. Transmission by biting has been hypothesized. DNA of the hemoplasmas has been amplified from the mouths of cats, the salivary glands, and the tonsils. We are currently studying the role mosquitoes may play in the transmission of these agents.

Red blood cell destruction is due primarily to immune-mediated events; direct injury to red blood cells induced by the organism is minimal. Clinical signs of disease depend on the degree of anemia, the stage of infection, and the immune status of infected cats. Coinfection with FeLV can potentiate disease associated with Mhm. Clinical signs and physical examination abnormalities associated with anemia are most common and include pale mucous membranes, depression, inappetence, weakness, and occasionally, icterus and splenomegaly. Fever occurs in some acutely infected cats and may be intermittent in chronically infected cats. Evidence of coexisting disease may be present. Weight loss is common in chronically infected cats. Cats in the chronic phase can be subclinically infected only to have recurrence of clinical disease following periods of stress.

The anemia associated with hemoplasmosis is generally macrocytic, normochromic. Chronic non-regenerative anemia is unusual in cats with hemoplasmosis. Neutrophilia and monocytosis have been reported in some hemoplasma-infected cats. Diagnosis is based on demonstration of the organism on the surface of erythrocytes on examination of a thin blood film or PCR assay. Organism numbers fluctuate and so blood film examination can be falsely negative up to 50% of the time. The organism may be difficult to find cytologically, particularly in the chronic phase. Thus, PCR assays are the tests of choice due to sensitivity. Primers are available that amplify a segment of the 16S rRNA gene common to both hemoplasmas. Real time PCR to quantify hemoplasma DNA has now been titrated and can be used to monitor response to treatment. Since hemoplasmosis and primary immune hemolytic anemia are difficult to differentiate, cats with severe, regenerative hemolytic anemia are often treated with glucocorticoids and antibiotics.

Doxycycline has fewer side-effects than other tetracyclines in cats and so is preferred. I usually administer doxycycline as a flavored suspension (to avoid esophageal strictures) at 10 mg/kg, PO, every 24 hours for 7 days. If there is a positive response and the cat is tolerating the drug, I continue treatment for 28 days. If autoagglutination is evident, I generally prescribe prednisolone at 1 mg/kg, PO, every 12 hours for the first 7 days or until autoagglutination is no longer evident. Tetracyclines utilized to date appear to lessen parasitemia and clinical signs of disease but probably do not always clear the organism from the body and so recurrence is possible. In cats intolerant of doxycycline, enrofloxacin given at 5 mg/kg, PO, every 24 hours for 14 days was tolerated by cats and is equally effective or more effective than doxycycline. Administration of marbofloxacin or orbifloxacin gives similar results. Azithromycin was not effective for the treatment of hemoplasmosis in one study. Imidocarb administered at 5 mg/kg, IM, every 2 weeks for at least 2 injections was used successfully in the management of five naturally-infected cats that had failed treatment with other drugs. Blood transfusion should be given if clinically indicated. Most drug protocols have failed to eliminate infection and so at this time there is no clinical utility to repeat PCR testing. The owners should be warned that recurrences may occur.

To attempt to prevent hemoplasma infections, it might be prudent to control fleas. Cats should be housed indoors to avoid other potential vectors and fighting. Blood donor cats should be screened by PCR assay prior to use.

Feline rickettsiosis

Rickettsia spp. are obligate intracellular gram negative bacteria that are divided into two distinct groups, the spotted fever group (SFG) and the typhus group. Cats can be infected by Rickettsia felis and have been shown to have antibodies against R. rickettsii. Rickettsia felis was originally detected in a commercial cat flea (Ctenocephalides felis) colony and was has been shown to belong in the SFG. Fever, headache, myalgia, and macular rash in humans have been attributed to R. felis infection in several countries around the world. In addition, one person in Mexico developed neurological symptoms following R. felis infection, suggesting that the organism may be the cause of severe debilitating disease in some people. The organism has been detected in C. felis, C. canis, and Pulex irritans; these fleas have a worldwide distribution. Ctenocephalides felis is a biological vector for R. felis; the organism can be transmitted transovarially and transtadially within the flea. Rickettsia felis DNA has been amplified from C. felis collected from cats in the United Kingdom, France, Israel, New Zealand, Australia, Thailand, and the United States.

In recent study in our laboratory, we assayed 92 pairs of cat blood and flea extracts from Alabama, Maryland and Texas, using PCR assays that amplify a region of the citrate synthase gene (gltA) and the outer membrane protein B gene (ompB). Of the 92 pairs, 62 of 92 (67.4%) flea extracts and none of the cat blood samples were positive for R. felis DNA. We have now documented R. felis DNA in fleas from cats in Australia (Barrs et al, 2008). In another study, we showed R. felis and R. rickettsii antibody prevalence rates in cats in the USA with fever to be 5.6% and 6.6%, respectively but neither organism was amplified from blood. These results prove that cats are sometimes exposed but further data are needed to determine significance of diseases associations. Because clinical illness in cats has not been documented, optimal treatment is unknown. However, based on results in dogs, doxycycline or a fluoroquinolone would be logical choices. Prevention in cats and people should include flea control. Since cats are generally not PCR positive for these organisms in blood, it is not currently recommended by Colorado State University to test blood donor cats.

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