CHRONIC GIARDIASIS

Giardia as a cause of acute diarrhea was discussed in Chapter 6. Diarrhea is the most common clin­ical sign in symptomatic dogs and cats. Until a diagnosis is made and adequate therapy instituted, Giardia may cause intermittent or chronic ongo­ing diarrhea.

Giardia has proven to be a difficult problem both to diagnose definitively and to treat suc­cessfully. For example, despite adequate treatment regimens using both metronidazole (Flagyl) and quinacrine (Atabrine) in the past, some dogs in our practice remained infected and symptomatic. It should be recognized that there may be one or several concurrent intestinal disorders (e.g., intes­tinal bacterial overgrowth, IBD) that complicate resolution of clinical signs. In some cases, even though Giardia is present, it may not be a signifi­cant pathogen. Some other process then may be responsible for the clinical abnormalities.

Individual host immunity factors also play an important role in infection control. Deficiency of secretory IgA has been shown to be a factor in persistent Giardia infection in humans, and the same may be true for animals. A competent cell- mediated immune system is required to resist infection. Also, immunosuppressive doses of cor­ticosteroids can cause recrudescence of Giardia infec­tions in dogs and other species. Noting the prevalence of IBD in dogs and cats and the fre­quent use of corticosteroids to treat the syndrome, every effort should be made to identify the pres­ence of Giardia and to ensure that adequate treat­ment be administered in patients that are also being treated for IBD (either empirically or because a definitive diagnosis has been made).

In dogs, diarrhea may begin as early as 5 days after exposure to infection.The life cycle of Giardia is direct, and the prepatent period lasts between 1 and 2 weeks.

CHAPTER 7

Chronic Diseases of the Small Intestine 213

tine. The cyst form is infective. Trophozoites may also be passed, especially with diarrheic stools, but they are incapable of causing infection and soon die.

Diagnosis

As described in Chapter 6, standard diagnostic tests used in any practice setting should include fresh saline fecal smears and zinc sulfate flotation. Trophozoites are more likely to be found in loose stools, whereas cysts are more often found in semi­formed 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 ?40 magnification. Tropho­zoites are pear shaped and have a characteristic concave ventral disk. They demonstrate wobbly motion, similar to a falling leaf. A drop of Lugol's solution of iodine on the edge of the coverslip enhances the morphologic features of the organisms and makes them easier to find. The iodine kills the parasite, so its motion is no longer seen if this pro­cedure is used. Differentiation of trichomonads from Giardia is based on a different motion pattern (more forward motion with trichomonads), the absence of a concave disk, a single nucleus, and the presence of an undulating membrane. Identification of Giardia trophozoites is diagnostic, but their absence in fecal samples does not rule out giardiasis.

Many studies have now shown that zinc sulfate concentration, with centrifugation is the most reli­able test available for demonstration of Giardia cysts in a fecal sample. The test can be done in any practice setting, or fecal samples can be submitted to a commercial laboratory for detailed evaluation. The technique is described in Box 7-1. Zinc sul­fate concentration is also a very effective method for identifying nematode eggs in feces.

Slides should be examined within 10 minutes of preparation because the cysts may begin to shrink. Because animals shed Giardia on an inter­mittent basis, it is recommended that a series of zinc sulfate concentration tests be run over 3 to 5 days to maximize chances of accurately diagnosing

BOX 7-1

Zinc Sulfate Flotation Technique

Rights were not granted to include this box in electronic media. Please refer to the printed publication.

From Barr SC, Bowman DD: Giardiasis in dogs and cats, Compend Contin Educ Pract Vet 16:605,1994; from Zajac AM: Giardiasis, Compend Contin Educ Pract Vet 14:606, 1992.

or ruling out Giardia in patients with chronic diar­rhea. Diagnostic efficiency increases to 95% when three zinc sulfate examinations are conducted over 3 to 5 days. A positive result on any of the tests warrants treatment for Giardia.

Whether or not any other diagnostic work-up is suspended until a therapeutic response is deter­mined depends on the patient's clinical situation. If it is likely that some other disorder is more responsible for the patient's overall condition (e.g., severe protein-losing enteropathy and significant weight loss that would be highly unlikely to occur solely from a Giardia infection), Giardia might be considered a concurrent but less impor­tant problem. When evaluating a patient for a chronic GI disorder, the clinician must focus on finding the most significant problem. Sometimes a particular diagnostic “lead” is pursued too long while the patient's overall condition continues to decline.

Other diagnostic tests for Giardia include an enzyme-linked immunosorbent assay (ELISA) for Giardia antigen in feces, a direct immunofluores- cent assay, duodenal aspiration under endoscopic guidance, and the peroral string test.

The fecal ELISA detects Giardia antigen that is produced by dividing trophozoites. The test is very sensitive in humans and reportedly detects 30% more cases of Giardia than does zinc sulfate. Studies in dogs, however, have shown that the ELISA appears to be less sensitive than a series of zinc sulfate centrifugal flotation tests. It may be a little more sensitive than a single zinc sulfate test. Keep in mind, however, the quality of the test being run and the accuracy of microscopic inter­pretation in the hands of an inexperienced observer. This is a common problem area in small animal hospital laboratories. One advantage of the ELISA is that, because it detects antigen in the feces, it avoids the problem of intermittent cyst excretion in the feces. This test can be run either in-house or at a commercial laboratory. In human medicine the recognized “gold standard” for diag­nosis of Giardia is to run both a Giardia antigen test and a zinc sulfate assay. This is now a com­monly used approach in veterinary medicine as well.

Treatment

For many years the primary treatment for Giardia in dogs and cats involved metronidazole. For dogs in which metronidazole proved ineffective, quinacrine was often used. It was also used in cats. Although quinacrine has been shown to be more effective than metronidazole, it frequently causes side effects, including lethargy, anorexia, and vom­iting. Quinacrine is no longer available. More recently it was shown that albendazole (Valbazen) is highly effective in controlling Giardia and that it has a high safety factor. However, it was later found that albendazole can cause leukopenia and lethargy, and so its use in dogs and cats is no longer recommended. Fenbendazole (Panacur), well known for its effectiveness against a variety of intestinal parasites, is very effective, as is feban- tel (in the combination product Drontal Plus, which includes febantel, praziquantel, and pyrantel pamoate).

Metronidazole is still a useful drug for treating Giardia, and it has the added advantage of having antibacterial as well as antiinflammatory proper­ties.

Fenbendazole has also been shown to be effec­tive in eliminating Giardia. The same dose that is used to treat roundworms, hookworms, whip­worms, and the tapeworm Taenia pisiformis (22 mg/lb orally once daily for 3 to 5 consecutive days) is used to treat Giardia. Fenbendazole has a proven record for being very safe and is thought not to have any teratogenic effects. Therefore fen- bendazole would be the drug of choice for treat­ment of Giardia in pregnant animals. Fenbendazole is now the preferred treatment for Giardia in cats (Drontal Plus is approved for use only in dogs).

Drontal Plus is now recognized as an excellent drug for treatment of Giardia, as well as nematodes and tapeworms.

Oral furazolidone has proven to be an effective drug for treating Giardia in cats at a dose of 2 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 to minimize chances of reinfec­tion, especially in kennel or cattery situations. Cysts that are present in a cool, wet environment can remain infective for a period. Cages and runs should be thoroughly cleaned of all solid fecal material. Steam cleaning and 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. Finally, patients should be bathed before they are returned to the kennel area to wash out any cysts that may be present in the hair coat. In kennel or cattery environments where Giardia is recognized as a significant problem an additional step that can be undertaken is to use a quaternary ammonium compound topically. The hair in the perineal and perianal regions can be washed with a quaternary ammonium compound once the shampoo has been rinsed out. These compounds do not seem to cause any significant skin irritation as long as they are left on for no more than 3 to 5 minutes and then thoroughly rinsed out and allowed to dry. These compounds can inactivate Giardia cysts within 1 minute at room temperature. In addition, a second 5-day course of treatment for Giardia is administered to ensure that each animal is parasite free before being returned to the kennel or cattery. Any new­comers are treated with fenbendazole or Drontal Plus (dogs) and a topical quaternary ammonium rinse as previously described before being placed in the environment.

In home environment situations bathing the patient at the conclusion of drug therapy may also be helpful. Patients may be reinfected with cysts that are in the hair coat or the environment. Bath­ing will help remove cysts that could be licked from the hair coat by the patient and help reduce the chances of reinfection.

Zoonotic Potential. Zoonotic potential defi­nitely exists with Giardia. Children may be espe­cially at risk due to their proclivity for playing in grass and soil areas where cysts may be present. They also are more likely to put their fingers or hands in their mouths, and this can occur anytime after they have had direct contact with an animal's hair coat, including in the perineal area. This is why it is so important for veterinarians to perform quality laboratory tests to investigate companion animals for parasitic infections, including Giardia, on a routine basis whenever there are children in contact with family pets. 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 patients that are asymp­tomatic carriers of Giardia should be treated is often asked. Giardia cysts have been found in many patients with well-formed feces. Giardia is clearly not pathogenic in some patients, whereas in others it causes significant enteritis. Because the public health considerations must still be considered, it is strongly recommended that all patients with fecal samples that contain Giardia be treated and then retested to ensure that the infection has been cleared.

Vaccination

In 1999 a new vaccine was released for control of Giardia. The vaccine is a killed product containing chemically inactivated trophozoites. Efficacy stud­ies showed that vaccinated dogs were less severely affected clinically and shed cysts for a shorter time following challenge with infective cysts, compared with nonvaccinated dogs. In addition, chronic giardiasis resolved after dogs were vaccinated with this product. In these studies clinical signs of infection were less severe by 21 to 35 days after vaccination, and cysts were no longer detected in the feces by 21 to 70 days. This is not expected to be a “core” vaccine (i.e., recommended for annual

vaccination of all dogs and cats), but there defi­nitely is a place for it in our armamentarium. The vaccine has been approved for use in both dogs and cats.

The following are important points regarding Giardia vaccine:

^• Both cellular and humoral immunity are important for the following purposes:

^• Preventing Giardia infections.

^• Elimination of the parasite.

^• Specific immunity to Giardia is slow to develop in natural infections.

^• Some animals with persistent Giardia infec­tions do not develop a sufficient antibody response.

^• Anti-Giardia IgA and IgG coat the trophozoites in the small intestine, thus preventing adhesion of the parasite to the intestinal mucosa.

^• Anti-Giardia IgG and IgM are cytotoxic to the trophozoites, with or without the presence of complement.

^• Response to vaccine:

^• It was shown in the studies that the Giardia vaccine produced a strong IgG response, whereas saline-treated puppies had a weak or absent response.

^• There was technical difficulty in determining specific IgA in the study puppies, but a spe­cific response was clearly shown in cats.

^• It may be possible for the vaccine to be used to immunostimulate patients with chronic Giardia infections, thus enabling the patients to clear the infection. Further work still needs to be done to confirm this. Of course, it is necessary that a correct diagnosis be made before stating/confirming that a patient has a “chronic infection.”

Which Animals Should Be Considered Candidates for Vaccination?

Pets considered at higher risk of exposure to Giardia (and therefore candidates for vaccination) include dogs that frequently visit parks or play areas frequented by other dogs, dogs and cats liv­ing in multipet households, dogs living in endemic areas, hunting dogs, dogs and cats that travel to pet shows, farm dogs, dogs that board at training kennels, dogs and cats that board frequently at boarding facilities, and animals that have chronic giardiasis with poor response to therapy.