Infectious diseases of the feline GI system (Proceedings)

Clinical problem and differentials

Vomiting is the forceful ejection of stomach and proximal duodenal contents through the mouth. Vomiting can be induced by vestibular, vagal, chemoreceptor trigger zone, or direct input to the emetic center. Diarrhea is a characterized by increased frequency of defecation, increased fluid content of the stool, or increased volume of stool. Markedly increased frequency of defecation, small volume stools, tenesmus, urgency, hematochezia, and mucus are consistent with large bowel diarrhea. Slight increase in frequency of defecation, large volume, melena, steatorrhea, and polysystemic clinical signs are more consistent with small bowel diarrhea. Mixed bowel diarrhea is a combination of characteristics or clinical signs. Gastrointestinal (GI) signs can be the result of primary diseases of the GI system or secondary GI diseases. The secondary GI diseases are generally those of the kidneys, liver, pancreas (pancreatitis or exocrine pancreatic insufficiency), endocrine system (hypoadrenocorticism; diabetic ketoacidosis; hyperthyroidism), or central nervous system. Differential diagnoses for primary GI diseases are often grouped into obstruction (masses, foreign body, and intussusception), dietary intolerance, drugs/toxins (garbage gut), inflammatory gastric and bowel diseases, neoplasia, infectious diseases, and parasites. The primary bacteria associated with gastrointestinal tract disease in cats include Salmonella spp., Campylobacter jejuni, Clostridium perfringens, Helicobacter spp., bacterial overgrowth syndrome, bacterial peritonitis, and bacterial cholangiohepatitis. The primary viral agents include feline coronaviruses, feline leukemia virus, feline immunodeficiency virus, and feline panleukopenia virus. The primary nematodes are Ancylostoma/Uncinaria,Strongyloides cati, Dirofilaria immitis (vomiting), Toxocara cati, Toxascaris leonina, Ollulanus tricuspis, and Physaloptera spp. Enteric protozoans include Giardia spp., Cystoisospora spp., Cryptosporidium spp., Entamoeba histolytica, and Tritrichomonas foetus. The cestodes Taenia, Dipylidium, and Echinococcus generally cause subclinical infection.

Diagnostic procedures for infectious diseases

Direct smear

Liquid feces or feces that contains large quantities of mucus should be microscopically examined immediately for the presence of protozoal trophozoites, including those of Giardia spp. and Tritrichomonas foetus. A direct saline smear can be made to potentiate observation of these motile organisms. The amount of feces required to cover the head of a match is mixed thoroughly with one drop of 0.9% NaCl. Following application of a coverslip, the smear is evaluated for motile organisms by examining it under 100X magnification. The sample should be fresh. The material for evaluation should be collected from the surface of the fecal material, preferably mucous if present. Alternately, a rectal scraping can be used.

Stained smear

A thin smear of feces should be made from all cats with large or small bowel diarrhea. Material should be collected by rectal swab if possible to increase chances of finding white blood cells. A cotton swab is gently introduced 3-4 cm through the anus into the terminal rectum, directed to the wall of the rectum, and gently rotated several times. Placing a drop of 0.9% NaCl on the cotton swab will facilitate passage through the anus, but not adversely affect cell morphology. The cotton swab is rolled on a microscope slide gently multiple times to give areas with varying smear thickness. Following air drying, the slide can be stained. White blood cells and bacteria morphologically consistent with Campylobacter jejuni or Clostridium perfringens can be observed after staining with Diff-Quick or Wright's-Giemsa stains. Histoplasma capsulatum or Prototheca may be observed in the cytoplasm of mononuclear cells. Methylene blue in acetate buffer (pH 3.6) stains trophozoites of the enteric protozoans. Iodine stains and acid methyl green are also used for the demonstration of protozoans. Acid-fast or monoclonal antibody staining of a fecal smear should be performed in cats with diarrhea to aid in the diagnosis of cryptosporidiosis. Cryptosporidium parvum is the only enteric organism of approximately 4 to 6 µ in diameter that will stain pink to red with acid-fast stain. Presence of neutrophils on rectal cytology can suggest inflammation induced by Salmonella spp., Campylobacter spp., or Clostridium perfringens; fecal culture is indicated in these cases. Fecal enterotoxin measurement should be considered for cats with spore-forming rods morphologically consistent with C. perfringens.

Fecal flotation

Cysts, oocysts, and eggs in feces can be concentrated to increase sensitivity of detection. Most eggs, oocysts, and cysts are easily identified after sugar or zinc sulfate centrifugal flotation. These procedures are considered by many to be optimal for the demonstration of protozoan cysts, in particular, Giardia spp. and so is a good choice for a routine flotation technique in practice. Sugar centrifugation can be used for routine parasite evaluation and may be superior to many techniques for the demonstration of oocysts of Toxoplasma gondii and Cryptosporidium spp.. Giardia cysts are distorted by sugar centrifugation but can still be easily identified. Fecal sedimentation will recover most cysts and ova, but will also contain debris. This technique may be superior to flotation procedures for the documentation of Eurytrema procyonis, the pancreatic fluke. Strongyloides cati larva may be easier to identify after concentration using the Baerman funnel technique.

Culture

Culture of feces for Salmonella spp., Campylobacter spp., and Clostridium perfringens is occasionally indicated in small animal practice. Approximately 2-3 grams of fresh feces should be submitted to the laboratory immediately for optimal results, however, Salmonella and Campylobacter are often viable in refrigerated fecal specimens for 3-7 days. Appropriate transport media should be available through your laboratory. The laboratory should be notified of the suspected pathogen so appropriate culture media can be used. More than 1 culture may be needed to prove infection. Tritrichomonas foetus can be cultured from feces of cats in general practice using a commercially available kit (InpouchTM, Biomed Diagnostics). Some Giardia spp. isolated from cats will grow on culture media, but this technique is not generally performed in small animal practice.

Immunologic techniques

Parvovirus, Cryptosporidium parvum, and Giardia spp. antigen detection procedures are available for use with feces. Canine parvovirus antigen assays appear to detect feline parvovirus antigen. A fluorescein-labeled monoclonal antibody system is available that contains monoclonal antibodies that react with Cryptosporidium spp. oocysts and Giardia spp. cysts. However, the assay was developed for detection of human isolates and it is possible that cat isolates may not always be detected. In addition, a fluorescence microscope is required and so the assay can only be performed in diagnostic laboratories. Antigens of Giardia spp. or Cryptosporidium spp. can be detected in feces by enzyme-linked immunosorbent assays. Most fecal antigen studies in cats have evaluated with kits developed for use with human feces and so it is possible that cat isolates may not always be detected. This appears to be true for Cryptosporidium spp. assays and they should not be used with cat feces. Recently, an in clinic Giardia spp. antigen test for use with dog and cat feces was released and seems to detect feline isolates. Serum antibodies against D. immitis can be measured in cat serum but positive test results do not prove current infection or disease induced by D. immitis. FeLV can cause lymphoma and induces the panleukopenia-like syndrome. FIV has been associated with lymphoma and can cause enteritis. Detection of FIV antibodies or FeLV antigen in serum documents exposure, but does not prove that clinical disease is due to the virus. The only way to document that gastrointestinal signs are due to FeLV or FIV is to exclude other known causes.

Electron microscopy

Electron microscopy can be used to detect viral particles in feces of cats with gastrointestinal signs of disease. Approximately 1-3 grams of feces without fixative should be transported to the laboratory by overnight mail on cold packs.

Endoscopy or exploratory laparotomy

Ollulanus and Physaloptera rarely pass ova in feces and so frequently are diagnosed only by endoscopy. Diagnosis of diffuse inflammatory diseases can be made by evaluation of endoscopy or surgically obtained tissue samples. Endoscopically obtained biopsies are small; I generally take at least 8-10 biopsies from stomach, duodenum, colon, and ileum if possible. Even if a lesion is present, endoscopically obtained biopsies can be falsely negative requiring full thickness biopsies. Gastric biopsies should be placed on urea slants to assess for urease which is found in the cell wall of Helicobacter spp.. The combination of inflammation, exclusion of other causes of inflammation, presence of gastric spiral bacteria, and positive urease testing can be used as a presumptive diagnosis of gastric helicobacteriosis. There is no benefit to performing duodenal aspirates for quantitative bacterial cultures or Giardia trophozoite evaluations in cats; the normal bacterial count range is very broad in cats and Giardia is found in the distal small intestine. Regional enteritis due to feline infectious peritonitis can be confirmed by documenting the organism in tissue after immunohistochemical staining.

Polymerase chain reaction

Polymerase chain reaction (PCR) is currently available to detect Giardia spp., Cryptosporidium spp., and T. foetus in feline feces. For Cryptosporidium spp., PCR is 10 to 1,000 fold more sensitive than IFA. Reverse-transcriptase PCR can be used to detect coronavirus RNA in feces of cats but is not specific for feline infectious peritonitis.

Infectious disease treatment options

There are multiple drugs used in the treatment of gastrointestinal parasitic infections. For all kittens, the strategic deworming recommendations for the control of hookworm and roundworm infections from the Centers for Disease Control and the American Association of Veterinary Parasitologists should be followed by veterinary practitioners. (http://www.cdc.gov/ncidod/dpd/parasites/ascaris/prevention.htm). Kittens should be administered an anthelmintic at 3, 5, 7, and 9 weeks of age and then periodically monitored or treated. If the kitten is not presented to the clinic until 6-8 weeks of age, administer the anthelmintic at least 2-3 times, 2-3 weeks apart. Pyrantel pamoate and fenbendazole are usually effective drugs for use in strategic deworming programs and for the treatment of nematodes causing gastrointestinal tract disease. Albendazole is more likely to cause hematologic side-effects than fenbendazole and so should not be used in cats. Even if anthelmintics for hookworms and roundworms are administered, a fecal flotation should be performed to evaluate for other parasites.

Monthly D. immitis preventatives can help control or eliminate some nematode infections as well as prevent heartworm infection. Ivemectin at heartworm preventative doses is effective for control of hookworms but not roundworms. Thus, selamectin or milbemycin should be used in regions where roundworm infections are common. Selamectin has the advantage of controlling fleas as well and so may lessen the potential for Bartonella spp., Rickettsia felis, and Haemobartonella (Mycoplasma) spp. infections. Dipylidium and T. taeniaformis infestations usually are eliminated by praziquantel or espiprantel; fenbendazole is effective for Taeniataeniaformis. Since Echinococcus multilocularis can be a significant zoonosis transmitted to cats by carnivorism, hunting cats in endemic areas should be treated up to monthly. Administration of a pyrantel/praziquantel combination may be effective in these cats since praziquantel is approved for the treatment of Echinococcus and roundworms are also transmitted by carnivorism.

Withholding food for 24 to 48 hours is indicated in cats with acute vomiting or diarrhea. Highly digestible, bland diets are used most frequently if vomiting and small bowel diarrhea are the primary manifestations of disease. High fiber diets are generally indicated if large bowel diarrhea is occurring. Diarrhea associated with Giardia spp. generally resolves during or after administration of metronidazole. In a recent study, cyst shedding resolved in 26 cats after the administration of metronidazole benzoate at 25 mg/kg, PO, q12hr for 7 days. Metronidazole also helps correct the anaerobic bacterial overgrowth that commonly accompanies giardiasis. If inflammatory changes exist, metronidazole may also be beneficial due to inhibition of lymphocyte function. Central nervous system toxicity occasionally occurs with this drug; it is unlikely if no more than 50 mg/kg, PO, total daily dose is given. Fenbendazole has not been studied extensively for treatment of giardiasis in cats. In one experiment study of cats coinfected with Giardia spp. and Cryptosporidium spp., four of eight cats treated with fenbendazole at 50 mg/kg, PO, daily for 5 days stopped shedding Giardia cysts. The combination product of febantel, pyrantel, and praziquantel has been shown to have anti-Giardia activity in dogs. When given at the febantel dose of approximately 56 mg/kg, PO, daily for 5 days, Giardia cyst shedding was eliminated in some cats. Albendazole has been evaluated for treatment of giardiasis in a limited number of dogs, but has been associated with neutropenia. Furazolidone (4 mg/kg, PO, q12hr, for 7 days) and paromomycin (appropriate dosing interval for cats is unknown) are other drugs with anti-Giardia effects but have not been evaluated extensively in cats. Lastly, because use of the commercially available Giardia spp. vaccines as immunotherapy has given variable treatment responses in dogs and cats, the use of the feline product should be reserved for resistant infections in cats.

Multiple drugs have been evaluated for the treatment of cats with T. foetus infections; until recently no drug eliminated infection and diarrhea rarely resolves during the treatment period. Recently ronidazole at 30 mg/kg, PO, q12hr, for 14 days eliminated clinical signs of disease and trophozoites from cats infected with one strain of the organism. Ronidazole is more neurotoxic than metronidazole and so should be used carefully. In another one small study, administration of metronidazole and enrofloxacin lessened diarrhea in kittens but it is unknown if the organisms infecting those cats was T. foetus. It is possible that some cats with T. foetus have other enteric coinfections and so antihelmintics or drugs with activity against Giardia spp., Cryptosporidium spp., and enteric bacteria like Campylobacter spp. are often prescribed. Paromomycin should be avoided cats with bloody stools because of the potential for being absorbed and inducing renal disease or deafness. In one study, 23 of 26 cats with diarrhea and T. foetus infection had complete resolution of diarrhea a median of 9 months after initial diagnosis. Cryptosporidium spp. associated diarrhea sometimes resolves after administration of tylosin (10-15 mg/kg, PO, BID for at least 14 days) or azithromycin (10 mg/kg, PO, daily for at least 14 days). If the cat is responding to therapy, continue treatment for 1 week past clinical resolution. Some cats may require several weeks of treatment.

The Toxoplasma gondii oocyst shedding period can be shortened by administration of clindamycin or sulfadimethoxine. Cystoisospora spp. generally responds to the administration of sulfadimethoxine or other sulfa-containing drugs. Clindamycin, trimethoprim-sulfa, or ponazuril are also options.

Since many of the gastrointestinal parasites that infect cats are transmitted by carnivorism, cats should not be allowed to hunt or be fed raw meats. Additionally, infection of cats by many feline parasites results from ingestion of contaminated water. Clinical disease in some parasitized cats can be lessened by eliminating stress and providing a quality diet and clean environment.

Clostridium perfringens and bacterial overgrowth generally respond to treatment with tylosin, metronidazole, ampicillin, amoxicillin, or tetracyclines. The drug of choice for campylobacteriosis is erythromycin; however, oral administration of quinolones is often less likely to potentiate vomiting. Salmonellosis should only be treated parenterally due to rapid resistance that occurs following oral administration of antibiotics. Appropriate antibiotics for the empirical treatment of salmonellosis while awaiting susceptibility testing results include chloramphenicol, trimethoprim-sulfa, amoxicillin; quinolones are also effective. Helicobacter spp. infections are usually treated with the combination of metronidazole and tetracycline or amoxicillin and metronidazole in dogs. Clarithromycin or azithromycin may be logical choices in cats since the species is often difficult to treat with multiple drugs. Whether to concurrently administer an antacid like famotidine is controversial but seems to lessen vomiting in some cats.

Cats with apparent bacteremia due to enteric bacteria should be treated with parenteral antibiotics with a spectrum against anaerobic and gram negative organisms. The combination of enrofloxacin with a penicillin or first generation cephalosporin is generally effective. Second generation cephalosporins or imipenem are also appropriate choices.

Cats that have hepatic infections and signs of bacteremia should be treated with antibiotics that kill gram positive, gram negative and anaerobic bacteria as discussed before. Non septic hepatic infections generally respond to amoxicillin, amoxicillin-clavulanate, first-generation cephalosporins, or chloramphenicol. Decreasing numbers of enteric flora by oral administration of penicillins, metronidazole, or neomycin can lessen the clinical signs of hepatic encephalopathy.

Table 1. Common gastrointestinal parasites of cats.

Panleukopenia virus, feline leukemia virus, feline immunodeficiency virus, and coronaviruses are the most common viral causes of gastrointestinal tract disease in cats. Viral diseases are managed by supportive treatment. Make sure to maintain hydration, correct hypoglycemia, and maintain normal potassium concentrations. Use of jugular catheters is superior to leg veins since blood samples can be drawn and CVP can be measured. Based on results in dogs with parvovirus infection, administration of plasma or serum (1 ml/kg) from your hyperimmune blood donor cat may lessen morbidity in cats with panleukopenia due to passive transfer of immunity. This is effective because parvoviruses induce a viremic state; virus particles are complexed by the antibodies transferred passively. Adminstration of interferon alpha at 10,000 U/kg, SQ, once daily may have anti-viral effects. Antibiotics effective against gram negative and anaerobic bacteria are commonly indicated. Vaccines are available for the prevention of parvovirus, coronaviruses, and feline leukemia virus infection.

Histoplasma capsulatum infection is the most common fungal infection of the gastrointestinal tract of cats in the United States. Treatment with itraconazole can be effective.

Table 2. Drugs commonly used in the management feline gastrointestinal diseases

Zoonotic considerations

Infection of people by feline enteric agents is usually from contact with feces in the environment, by ingestion of contaminated food or water, or by ingestion of undercooked meat (T. gondii). Contact with infected cats is an unlikely way for humans to acquire infection. The following guidelines may lessen the risk of transfer of feline enteric zoonotic agents to people.

• Perform a thorough physical examination and zoonoses risk assessment on all new cats.

• Perform a physical examination and fecal examination at least once or twice yearly.

• Take all cats with vomiting or diarrhea to a veterinarian for evaluation.

• Fecal material produced in the home environment should be removed daily, preferably by someone

• other than an immunocompromised individualUse litterbox liners and periodically lean the litterbox with scalding water and detergent.

• Do not allow cats to drink from the toilet.

• Follow the CDC strategic deworming guidelines.

• Wear gloves when gardening and wash hands thoroughly when finished.

• Filter or boil water from sources in the environment.

• Wash your hands after handling cats.

• Maintain cats within the home environment to lessen exposure to other animals and their feces.

• Feed cats only commercially processed food.

• Do not share food utensils with cats.

• Avoid being licked by cats.

• Control potential transport hosts like flies, rodents, and cockroaches.

• Cook meat for human consumption to 80 C for 15 minutes minimum (medium-well).

• Wear gloves when handling meat and wash hands thoroughly with soap and water when finished.

References available on request