Etiology and Epidemiology

Giardia duodenalis is a protozoan parasite with worldwide distribution that infects a variety of mammals. Molecular genetic studies report that G. duodenalis is a species complex comprising seven assemblages (A to G). Some of the assemblages have been detected in animals and humans, but some others are species-specific. Dogs usually harbor the species-specific C-D assemblages, and cats usually harbor the cat-specific assemblage F (Table 77-2 and Fig. 77-1). In some situations, DNA of assemblages A and B have been amplified from feces of dogs and cats; these genotypes have mainly been detected in humans.^13,161,161 Results of one morphologic study were that area, length, width and eccentricity of Giardia cysts were significantly different between assemblages, with B and F being most different from assemblages A and C or D.²⁹⁵

Giardia spp. infections in dogs and cats have been reported in many prevalence studies, case reports, and treatment studies (Web Tables 77-1 and 77-2). Giardia spp. occur in two forms, the trophozoite and the cyst form. The trophozoite is the active, motile form that is found in the intestinal tract. It is approximately 15 µm long and 8 µm wide and has a tear-drop shape (Fig. 77-2). The trophozoites can be identified under light microscopy by the smiling-face appearance, which is formed by the two nuclei in the anterior third forming the eyes, the axonemes passing longitudinally between the nuclei forming the nose, and the median bodies located transversely in the posterior third forming the mouth; four pairs of flagella complete the shape.¹⁵ Trophozoites are susceptible to inactivation by many environmental conditions, and they are usually not responsible for spread among animals.

The cyst form (12 µm long and 7 µm wide) is the resistant stage mainly responsible for transmission. The cyst actually contains two incompletely separated but formed trophozoites, their axonemes, fragments of the ventral disks, and as many as four nuclei (Fig. 77-3, A and B). The cyst is resistant to some environmental conditions and can survive for several months outside the host in wet, cold conditions, but is susceptible to desiccation in dry and hot conditions. Giardia spp. are transmitted through the fecal-oral route by direct or indirect ingestion of contaminated water, food, or fomites. Transmission can also occur through carnivorism if the organisms are present in the intestines of the prey species.¹⁵⁷ Many infected hosts shed fecal cysts for months, but infections may also be self-limited in 27 to 35 days in dogs and cats.

The life cycle of Giardia within the host is summarized in Figure 77-4. After cysts are ingested by a susceptible host, excystation occurs in the duodenum after exposure to gastric acid and pancreatic enzymes. The two trophozoites contained in the cyst separate, mature quickly, and attach to the brush border of the villous epithelium (Fig. 77-5). The distribution of Giardia in the intestinal tract varies according to the host and its diet. In dogs, trophozoites are found from the duodenum to the ileum, and in cats, trophozoites predominate in the jejunum and ileum.¹⁵² Trophozoites multiply by binary fission in the intestinal tract and then encyst by an unknown mechanism.^230a Cysts are passed in the feces within days after primary infection. Trophozoites can also be passed, especially in watery feces in cats, but rarely survive for a significant period outside the host.¹⁵

The prepatent period of giardiasis in cats ranges from 5 to 16 days (mean of approximately 10 days) and in dogs ranges from 4 to 12 days (mean of approximately 8 days). Shedding of Giardia cysts by cats may fluctuate from undetectable to concentrations greater than 1,000,000 cysts pre gram of feces.⁶ Peaks of cyst shedding occur sporadically rather than cyclically, and the duration between any two given peaks is generally from 2 to 7 days.¹⁵² Young dogs shed an average of 2000 cysts per gram of feces, and in one study the mean cyst count per gram of feces for all infected dogs was 705.8.²⁶⁷ The reported range in another study was between 26 and 114,486 cysts per gram of feces.²⁷

Pathogenesis

Although the pathogenesis of Giardia is not completely understood, studies done in vitro and in vivo reveal that the mechanism producing clinical illness is multifactorial. It appears that a combination of intestinal malabsorption and hypersecretion are the primary mechanisms associate with Giardia diarrhea. The host-parasite interaction leads to the upregulation of genes involved in the apoptotic cascade and in the formation of reactive oxygen species within the intestinal cells.³⁹ Results of studies indicate a novel biological mechanism in which a sodium-coupled-glucose-transporter-1 (SGLT-1) activation may rescue enterocytes from apoptosis by enhancing glucose uptake.³⁹ This cellular response may be a nonspecific host defense mechanism to enhance cell survival against enteropathogens such as Giardia.³⁹ The induction of apoptosis increases gastrointestinal (GI) permeability, allowing luminal antigens to activate host immune-dependent pathologic pathways. Loss of the epithelial barrier function may also result from disruption of F-actin and the tight junctional proteins (ZO-1). Giardia also alters epithelial claudin proteins that are components of sealing properties of the tight junctions.³⁹ Despite these permeability changes, Giardia can cause clinical symptoms in the absence of light microscopic changes such as villous atrophy or mucosal injury.³⁹

Diarrhea is caused by a combination of malabsorption and hypersecretion of electrolytes. Giardia infection stimulates chloride secretion and results in a diffuse loss of brush border microvillus length, leading to epithelial maldigestion and malabsorption of glucose, sodium, and water and to reduced disaccharidase activity. Increased numbers of intraepithelial lymphocytes can be observed microscopically in association with the sodium/glucose malabsorption. Mast cell hyperplasia may be in part responsible in the loss of epithelial barrier function. The loss of epithelial barrier function may lead to chronic intestinal disorders, but the mechanisms remain unclear.³⁹ Giardia infection may elicit clinical signs similar to irritable bowel syndrome in humans, and giardiasis is associated with histopathologic changes similar to food allergies or inflammatory bowel disease. It is unknown how some humans and animals maintain chronic, subclinical infections.

Clinical Findings

Although most of the cats and dogs shedding Giardia do not show clinical signs of disease, Giardia infection can induce illness in some animals. Younger, immunosuppressed animals and those living in crowded environments are at the highest risk of showing clinical disease.71a,131,150,153 The primary clinical signs of giardiasis include chronic diarrhea and weight loss. The diarrhea is usually mucoid, pale, and soft and has a strong odor; steatorrhea may be present as well.* The organism is not usually enteroinvasive, and so blood is uncommon. Most infected cats and dogs are afebrile, do not vomit, and have serum total protein concentration and complete blood count values within reference limits. Although some cats and dogs with giardiasis have only Giardia detected on diagnostic evaluation, co-infection with other parasites is common. Giardia and Cryptosporidium co-infection may often be found in association with diarrhea.^216,236 Results of another study were combined Tritrichomonas foetus and Giardia infection in cats.¹⁰⁶ It is unknown if the different assemblages vary in their disease-producing properties and induce respective range of severity of clinical signs in cats and dogs.

Diagnosis

Giardia is one of the most commonly misidentified (over- and underidentified) parasites.⁶⁸ Pseudoparasites or yeasts are easily mistaken for Giardia, leading to false-positive fecal detection results. Giardia cysts are shed intermittently, and repeated fecal analysis may be needed to detect cysts. In addition, cysts can deteriorate in fecal flotation solutions, leading to false-negative results.⁶⁸ A variety of different Giardia-detection tests have been evaluated for use in cats and dogs. Despite the improved specificity, there is no one test that can be performed on a single fecal sample that has 100% sensitivity. Even more problematic is the lack of an assay with high positive predictive value for clinical giardiasis. This problem arises from the high background prevalence of infection in clinically healthy animals. The following is a discussion of the advantages and disadvantages of available diagnostic methods.

Therapy

In human medicine, a combination of nutritional intervention and phytotherapy is often the first line of approach for treating symptomatic giardiasis.¹¹⁸ In veterinary medicine, dietary manipulation is often combined with antiprotozoal chemotherapy. Although there is no licensed veterinary drug specific for Giardia, many are effective in reducing the level of infecting organisms in attempts to speed resolution of clinical signs (Table 77-3).

Drugs in the nitroimidazole class have anti-Giardia effects. The suggested dosages of drugs listed here are summarized in Table 77-3. Although metronidazole has been widely used for the treatment of giardiasis in naturally and experimentally infected cats and dogs, controlled studies are lacking.* Unfortunately, central nervous system toxicity had been associated with the administration of metronidazole in some dogs⁶⁷ and kittens.⁴⁵ Neurologic toxicity was reported after either chronic therapy or acute high doses.⁴⁵ The optimal dose and duration for metronidazole when used for the treatment of clinical giardiasis is unknown. The CAPC suggests a maximum dose of 25 mg/kg, orally (PO), twice daily for 5 days.⁵⁵ Therapy longer than 7 days should never exceed 30 mg/kg/day (see the Drug Formulary in the Appendix). Metronidazole hydrochloride is the United States Pharmacopeia (USP) formulations in tablets, which causes cats to salivate, while the benzoate form available in some countries is less likely to cause this problem. However, products containing metronidazole benzoate are available in some countries, and the drug is available for formulation in the United States. When metronidazole benzoate was administered to cats with subclinical giardiasis in one study, cyst shedding ceased over the time period of the study, and signs of toxicity did not develop.²³⁵ Other nitroimidazoles including ipronidazole, ronidazole, and tinidazole had been used for the treatment of giardiasis in a small number of animals. Ipronidazole added to water was effective for the treatment of giardiasis in two dogs.⁵ Use of drugs in the nitroimidazole class also may have the added benefit of correcting bacterial overgrowth, which may also contribute to diarrhea, in some dogs and cats with clinical giardiasis. See Table 77-3 and the Drug Formulary in the Appendix for further details on each of these drugs.

Fenbendazole has been evaluated for the treatment of giardiasis in a number of studies of dogs and cats.20,147,182,300 An additional benefit for the use of this drug is its effect against ascarid hookworms and Taenia infections that can occur as co-infections with Giardia spp. The CAPC recommends the administration of fenbendazole (50 mg/kg, once daily, for 5 days) to cats and dogs or a combination of this same dosage of fenbendazole and metronidazole (25 mg/kg, every 12 hours, for 5 days). However, when fenbendazole was administered to cats concurrently infected with Giardia and Cryptosporidium parvum, only 4 of 8 cats stopped shedding Giardia cysts.¹⁴⁷ When fenbendazole was administered to naturally infected shelter dogs, the percent persistence of cyst counts per gram of feces were 84% and 78% when feces were rechecked 9 and 16 days, respectively, after treatment.¹⁸² In cats, fenbendazole was safe when administered to healthy, adult, nonpregnant cats at a dosage 5 times higher than the approved dosage.²³³ Other benzimidazoles used in some studies of giardiasis are albendazole, oxfendazole, and febantel. Albendazole was effective in one study involving dogs; however, because of bone marrow suppression, it is not recommended for use.^18,263 Administration of oxfendazole when used in conjunction with other control measures led to resolution of diarrhea and cyst shedding in one study of kenneled dogs with giardiasis.²⁸⁸

A combination of febantel, pyrantel, and praziquantel (FPP) (Drontal Plus Tablets, Bayer, Shawnee Mission, KS), using a variety of dosage protocols, has had variable results in the treatment of giardiasis in dogs and cats.* Two different formulations of the drug exist (see Table 77-3), and dosage differences may be responsible for some of the discrepancies between results of efficacy studies. In one report involving seven healthy Giardia-infected dogs, organisms were not detected again in 3 days after 3 consecutive days of treatment with the Drontal Plus Tablets.³⁴ However, 6 days after the last treatment, some dogs began to shed organisms again, and this was hypothesized as being from reinfection.³⁴ Another study reported that the efficacy of the treatment of dogs naturally infected with Giardia spp. for 5 consecutive days with the European formulation was not significantly better than treatment for 3 consecutive days.¹⁸⁹ Results of an additional study implied that when Drontal Plus Tablets were used to treat dogs with giardiasis, bathing the animal and changing its environment after treatment may be more important for preventing reinfection than duration of treatment.²¹⁵ When Drontal Plus Tablets were administered at the empiric dosage of two small dog-tablets per cat, orally, for 5 days, to 6 cats, a significant decrease in cyst shedding was observed in the treated group in comparison to the untreated control group.²³⁹ In addition, 4 of the 6 treated cats had evidence of infection after two doses of repositol glucocorticoids at immunosuppressive levels.²³⁹

Azithromycin was used for the treatment of an 8-month-old dog that had persistent diarrhea after being treated with fenbendazole and metronidazole for giardiasis.³⁰⁹ Azithromycin was administered at a dose of 10 mg/kg once a day for 5 days, and after treatment the diarrhea stopped and no adverse reactions were observed. Giardia cysts and DNA were not detected after examination of fecal smears and PCR of fecal samples on days 2, 4, and 6 after therapy.³⁰⁹ However, azithromycin has failed to lessen Giardia attachment or growth in vivo, and so use of this drug for treatment of giardiasis in animals needs additional study.¹⁴⁴

Other drugs used historically to treat giardiasis in dogs or cats included quinacrine and furazolidone; however, controlled efficacy studies are lacking. Other drugs with potential use for the treatment of giardiasis include paromomycin and nitazoxanide. See Chapter 70 and the Drug Formulary in the Appendix for a discussion of these drugs.

Although controlled studied in dogs and cats are generally lacking, other adjunctive therapies, including fiber, silymarin, and probiotics, have been administered to some dogs or cats with giardiasis on the basis of work with other species. Addition of insoluble fiber in a Giardia model in gerbils was proposed to lessen trophozoite adherence and colonization to the microvillus.¹⁶⁶ Silymarin was evaluated for the treatment of canine giardiasis.⁵¹ Although all dogs who received metronidazole, with or without silymarin, stopped shedding Giardia cysts, the addition of silymarin appeared to help to compensate for weight loss and increased the levels of serum total proteins and albumin when compared to dogs administered metronidazole alone.⁵¹ In a rodent model, the administration of the probiotic Enterococcus faecium strain SF68 lessened Giardia spp. shedding.²⁶ However, positive effects on Giardia spp. cyst shedding, fecal antigen shedding, fecal IgA concentrations, or leukocyte phagocytic activity were not recognized in adult dogs with chronic giardiasis fed this probiotic.²⁴⁴ Further work is required before these adjunctive therapies can be routinely recommended.

Because Giardia infection may be difficult to eliminate in dogs and cats, the primary goal is to resolve diarrhea. The treatment protocol used may need to be varied according to each individual patient. Additionally, control measures should be instituted to attempt to avoid reinfection. In dogs and cats with persistent diarrhea and detection of Giardia in feces, an extensive work-up should be undertaken to evaluate for other underlying disorders that may aid in the perpetuation of clinical disease.