Diarrhea Caused by Giardia and Clostridium Perfringens Enterotoxicosis
Todd R. Tams, DVM, Dipl ACVIM
Diagnosis and Management of Giardia
Standard diagnostic tests used in any practice setting should include fresh saline fecal smears and zinc sulfate flotation. Zinc sulfate flotation with centrigugation, rather than flotation alone, is the most effective means of testing for Giardia Trophozoites are more likely to be found in loose stools, while cysts are more often found in semi-formed or formed stools.
A fresh saline smear is made by mixing a drop of feces with a drop of saline on a glass slide. A coverslip is applied and the preparation is examined immediately under 40x magnification. Trophozoites are pear-shaped and have a characteristic concave ventral disk. They demonstrate rapid forward motion. A drop of Lugol's solution of iodine on the edge of the coverslip will enhance the morphologic features of the organisms and make them easier to find. The iodine kills the parasite, so their motions will no longer be seen if this procedure is used. Differentiation of trichomonads from Giardia is based on a different motion pattern (more rolling with trichomonads versus forward motion with Giardia), the absence of a concave disk, a single nucleus, and the presence of an undulating membrane. Identification of Giardia trophozoites is diagnostic, while their absence in fecal samples does not rule out presence of infection.
Many studies have now shown that zinc sulfate concentration with centrifugation is the most reliable test available for demonstration of Giardia cysts in fecal samples. The test can be done in any practice setting. Zinc sulfate concentration is also a very effective method for identifying nematode eggs in feces. It is therefore now used as the standard test for screening for intestinal parasites in most academic and many private practices. Studies have shown that approximately 70 percent of Giardia positive dogs can be identified on a single zinc sulfate concentration test (as opposed to approximately 40 percent of dogs after 3 separate saline smear preparations). Slides should be examined within 10 minutes of preparation because the cysts may begin to shrink. Since animals shed Giardia on an intermittent basis it is recommended that a series of zinc sulfate concentration tests be run over a 3 to 5 day period in order to maximize chances of accurately diagnosing or ruling out Giardia in animals with chronic diarrhea. Diagnostic efficiency increases to 95 percent when 3 zinc sulfate examinations are conducted over a 3 to 5 day period.2 A positive result on any of the tests warrants treatment for Giardia.
Caution: It is not uncommon for plant spores, yeast bodies, and other amorphous debris to be mistaken for Giardia cysts. In fact, Giardia is frequently misdiagnosed - either it is being diagnosed incorrectly, or the wrong tests are being run and animals with Giardia are being missed. Giardia cysts are 11-13 u in size, and the subtle characteristics of the nuclei, axostyles, and median bodies are often more easily observed under 100X oil immersion magnification. Sometimes there are crescent shaped indentations of the cyst wall. Yeast bodies are similar to Giardia in size, shape, and color. Yeast bodies appear to be far more common that Giardia.
Other diagnostic tests for Giardia include an enzyme-linked immunosorbent assay (ELISA) test for Giardia antigen in feces, a direct immunofluorescent assay, duodenal aspiration under endoscopic guidance, and the peroral string test. The latter two tests are impractical for routine use in small animal practice, especially when the effectiveness of serial zinc sulfate examinations is recognized. The fecal ELISA test detects Giardia antigen that is produced by trophozoites. The test is very sensitive in humans and reportedly detects 30 percent more cases of Giardia than does zinc sulfate. Studies have now confirmed that this is also an excellent test for use in animals. A rapid assay for in-house use is now available and is technically easy to perform (ProSpecT Giardia Rapid Assay, Alexon). One advantage of the ELISA test is that, since it detects Giardia specific antigen in the feces, it avoids the problem of intermittent cyst excretion in the feces. This test can be a significant aid in accurate diagnosis of Giardia in any private practice setting, and I highly recommend that veterinarians utilize this test in order to more consistently make an accurate diagnosis of giardiasis in their small animal patients.
For many years the primary treatment for Giardia in dogs and cats has involved metronidazole. For dogs in which metronidazole proved ineffective, quinacrine was often used in the past. However, although quinacrine has been shown to be more effective than metronidazole, it frequently causes side effects, including lethargy, anorexia, and vomiting. It was also used in cats. Quinacrine is no longer available, however. More recently it was shown that albendazole (Valbazen) is highly effective in controlling Giardia. I recommended albendazole as an effective treatment for Giardia from 1993-1997, but experience with albendazole in dogs and cats has shown that it can cause bothersome side effects; including leukopenia, lethargy, and inappetence. Therefore, I no longer recommend albendazole for treatment for giardiasis in dogs and cats.
Fenbendazole (Panacur), well known for its effectiveness against a variety of intestinal parasites, also appears to be very effective against Giardia. In a controlled trial at Cornell 6/6 dogs were effectively treated. The same dose that is used to treat roundworms, hookworms, whipworms, and the tapeworm Taenia pisiformis (22 mg/lb orally once daily for 3 consecutive days) is used to treat Giardia. If the infection is not cleared on this regimen, a longer course of therapy is used (5 to 7 days). Fenbendazole has a proven track record for being very safe and is thought to not have any teratogenic effects. Fenbendazole is therefore the drug of choice for treatment of Giardia in pregnant animals.
Drontal Plus is also be an excellent choice for treatment of Giardia. This product includes febantel in addition to praziquantel and pyrantel pamoate). Drontal Plus is administered once daily for 3 consecutive days for treatment of Giardia.
Metronidazole is still a useful drug for treating Giardia, and it has the added advantage of having antibacterial as well as antiinflammatory properties. In situations in which it is unclear whether diarrhea is due to giardiasis, bacterial overgrowth, or mild inflammatory bowel disease, metronidazole is an excellent choice, especially when a client requests empirical therapy rather than definitive diagnostic testing. Metronidazole is only 67-74 percent effective in eliminating Giardia from dogs, however, and if a positive diagnosis is made fenbendazole would also be a reasonable choice. Potential side effects of metronidazole include anorexia, vomiting, and neurologic problems (ataxia, vestibular problems, seizures). In my experience these side effects are not common. They are more likely to occur when the anti-Giardia dose is used (11.5 to 15 mg/lb orally every 12 hours for 5 to 7 days). The total dose of metronidazole should not exceed 30 mg/lb per day (65 mg/kg per day). A lower dose (5 to 10 mg/lb every 12 hours) is used in treatment of intestinal bacterial overgrowth and inflammatory bowel disease. Side effects are infrequent at this dose. In the past, if a 5 to 7 day course of metronidazole failed to eliminate Giardia, a longer follow-up course (10 to 14 days) was often used. With the availability of fenbendazole and Drontal Plus it is recommended that one of these drugs be used instead in this situation.
Oral furazolidone has proven to be an effective drug for treating Giardia in cats at a dose of 1.8 mg/lb orally twice daily for 5 to 10 days. Furazolidone causes vomiting and/or diarrhea in some cats. It should not be used in pregnant queens.
In addition to use of pharmacotherapy to eradicate Giardia, it is important to consider environmental control so as to minimize chances of reinfection, especially in kennel or cattery situations. Cysts present in a cool environment can remain infective for a long period of time. Cages and runs should be thoroughly cleaned of all solid fecal material. Steam cleaning or treatment with a quaternary ammonium compound are both very effective measures for killing cysts. Allowing time for thorough drying is important, to desiccate any remaining cysts.
Whether Giardia is truly transmissible from animals to humans is still a question. Current information indicates that zoonotic potential definitely exists. When both animals and humans living in the same environment become infected, a common source of infection rather than direct transmission must also be considered.
The question whether animals that are asymptomatic carriers of Giardia should be treated is often asked. Giardia cysts have been found in many animals with well-formed feces. Giardia is clearly not pathogenic in some animals, while in others it causes significant enteritis. Because the public health considerations must still be considered, it is recommended that all animals with fecal samples that contain Giardia be treated.
Vaccination: New Giardia Vaccine (GiardiaVax)
In 1999 a new vaccine was released by Ft. Dodge for control of Giardia. I have reviewed the published papers which described the vaccine development studies and have discussed the vaccine with several of my colleagues in gastroenterology as well as infectious disease specialists. The vaccine is a sound product and definitely can be very effective in controlling Giardia. Certainly this is not expected to be a Tier 1 vaccine (i.e., recommended for annual vaccination of all dogs), but there definitely is a place for it in our armamentarium.
Clostridium Perfringens Enterotoxicosis
Over the last 11 years Clostridium perfringens enterotoxicosis (CPE) has emerged as a frequently recognized cause of chronic intermittent diarrhea in dogs. Although it is likely a less common cause of diarrhea in cats it is still diagnosed frequently enough that it should be considered in the diagnosis of diarrhea in cats as well. This is not a new disease. Frequent use of the definitive test (enterotoxin assay) for this disorder has revealed that CPE is seen relatively commonly in clinical practice and that CPE is a disorder that should be considered in any dog or cat with intermittent or chronic persistent diarrhea.
C. perfringens is a normal vegetative enteric organism. Simply identifying C. perfringens on a fecal culture is meaningless. The pathogenesis of CPE is through an enterotoxin that is produced after certain strains of C. perfringens sporulate. The toxin damages epithelial cells of the distal ileum and colon. Inciting factors that promote sporulation are not clearly understood but may include stress, diet changes, concurrent disease, or inherent immune status.
The most common clinical signs are chronic intermittent or persistent diarrhea. In some animals acute diarrhea is the primary sign. In fact, some of the cases of hemorrhagic gastroenteritis (HGE syndrome), characterized by acute bloody diarrhea and an increased packed cell volume that most practitioners have seen over the years, may have been due to CPE. Many animals exhibit signs of large bowel diarrhea, but small bowel signs may be seen as well. In some cases signs may be seen for only a day or two at a time, with persistent recurrences on a weekly, monthly, or on a less frequent basis. Stressful events or diet changes may incite flare-ups of clinical signs. In other cases C. perfringens enterotoxicosis is one of several problems that an animal may have concurrently and diarrhea may be persistent.
CPE must be considered whenever more than one animal in the environment has diarrhea (e.g., household, kennel, cattery). Transmission from animal to animal can occur. A presumptive diagnosis can be made on fecal cytology in which more than 3-4 spores per high power oil immersion field are observed (the spores have a safety pin appearance and are larger than most bacteria). Definitive diagnosis is by identification of enterotoxin which is currently done via a reverse passive latex agglutination assay. Clinicians should be aware that simply seeing spores on fecal cytology does not establish a definitive diagnosis (see JAVMA February 1, 1999). Stool is submitted to the lab for enterotoxin analysis. Laboratories that run the assay include Antech Diagnostics, Colorado State University, Cornell University, and the University of California Davis. Fecal samples that will be shipped off from the hospital directly to a laboratory should be sent on ice via overnight express. If a courier service will be picking up samples for transport to the laboratory it is sufficient to keep the sample refrigerated until pick-up. The minimum amount of stool that should be submitted is the size of a pea. Typically I submit samples in a red top tube, without serum separator. In animals with intermittent diarrhea the chances of a positive toxin finding are greater when abnormal rather than a normal stool is examined. A negative result does not definitively rule-out CPE.
Several antibacterial drugs are effective in controlling CPE. Acute cases often respond well to amoxicillin (10 mg/lb BID) or metronidazole (5-10 mg/lb BID) for 7-28 days. Many clinicians have likely treated CPE with these medications empirically without knowing what they were treating. Chronic cases tend to respond best to tylosin powder. The recommended dose is: Animals greater than 50 pounds ¼ tsp BID, 26-50 lb 1/8 tsp BID, 11-25 lb 1/12 tsp BID, and less than 10 lb 1/16 tsp BID (a "pinch"). Cats definitely do not accept the powder well at all, even when it is mixed in very tasty foods. It is best to have the powder reconstituted to capsule form for administration to cats. The medication is very safe. Some animals require treatment for several to many months (3-12 or more). Over time the dose may in some cases be successfully reduced to SID and then every other day dosage (after several months or more on a BID schedule). Dietary fiber supplementation may also help control CPE. Probable mechanisms include decreased C. perfringens fecal concentration, lower colonic pH which prevents sporulation, and increased concentrations of SCFA.
Follow-up testing at 3-6 months can be done to determine if toxin persists. It is best to continue treatment if the test remains positive, even if there is no diarrhea. Once daily to every other day tylosin in conjunction with dietary fiber supplementation are used in chronic cases.