Etiology

The life cycle of G. lamblia (also known as Giardia intestinalis or Giardia duodenalis) is composed of 2 stages: trophozoites and cysts. Giardia infects humans after ingestion of as few as 10-100 cysts (which measure 8-10 mm in diameter). Each ingested cyst produces 2 trophozoites in the duodenum. After excystation, trophozoites colonize the lumen of the duodenum and proximal jejunum, where they attach to the brush border of the intestinal epithelial cells and multiply by binary fission. The body of the trophozoite is teardrop shaped, measuring 10-20 mm in length and 5-15 mm in width. Giardia trophozoites contain 2 oval nuclei anteriorly, a large ventral disk, a curved median body posteriorly, and 4 pairs of flagella. As detached trophozoites pass down the intestinal tract, they encyst to form oval cysts that contain 4 nuclei. Cysts are passed in stools of infected individuals and may remain viable in water for as long as 2 mo. Their viability often is not affected by the usual concentrations of chlorine used to purify water for drinking.

Giardia strains that infect humans are diverse biologically, as shown by differences in antigens, restriction endonuclease patterns, DNA fingerprinting, isoenzyme patterns, and pulsed-field gel electrophoresis. Studies suggest that different Giardia genotypes may cause unique clinical manifestations, but these findings appear to vary according to the geographic region tested.

Epidemiology

Giardia occurs worldwide and is the most common intestinal parasite identified in public health laboratories in the USA, where it is estimated that up to 2 million cases of giardiasis occur annually. Giardia infection usually occurs sporadically but is a frequently identified etiologic agent of outbreaks associated with drinking water. The age-specific prevalence of giardiasis is high during childhood and begins to decline after adolescence. The asymptomatic carrier rate of G. lamblia in the USA is as high as 20-30% in children younger than 36 mo of age attending child-care centers. Asymptomatic carriage may persist for several months.

Transmission of Giardia is common in certain high-risk groups, including children and employees in child-care centers, consumers of contaminated water, travelers to certain areas of the world, men who have sex with men, and persons exposed to certain animals. The major reservoir and vehicle for spread of Giardia appears to be water contaminated with Giardia cysts, but food-borne transmission occurs. The seasonal peak in age-specific case reports coincides with the summer recreational water season and might be a result of the extensive use of communal swimming venues by young children, the low infectious dose, and the extended periods of cyst shedding that can occur. In addition, Giardia cysts are relatively resistant to chlorination and to ultraviolet light irradiation. Boiling is effective for inactivating cysts.

Person-to-person spread also occurs, particularly in areas of low hygiene standards, frequent fecal-oral contact, and crowding. Individual susceptibility, lack of toilet training, crowding, and fecal contamination of the environment all predispose to transmission of enteropathogens, including Giardia, in child-care centers. Child-care centers play an important role in transmission of urban giardiasis, with secondary attack rates in families as high as 17-30%. Children in child-care centers may pass cysts for several months. Campers who drink untreated stream or river water, particularly in the western USA, and residents of institutions for the developmentally delayed are also at increased risk for infection.

Humoral immunodeficiencies, including common variable hypogammaglobulinemia and X-linked agammaglobulinemia, predispose humans to chronic symptomatic Giardia infection, suggesting the importance of humoral immunity in controlling giardiasis. Selective immunoglobulin A (IgA) deficiency is also associated with Giardia infection. Although many individuals with AIDS have relatively mild Giardia infections, some reports suggest that severe Giardia infection, often refractory to treatment, may occur in a subset of individuals with AIDS. There is a higher incidence of Giardia infection in patients with cystic fibrosis, probably owing to local factors such as the increased amount of mucus, which may protect the organism against host factors in the duodenum. Human milk contains glycoconjugates and secretory IgA antibodies that may provide protection to nursing infants.

Clinical Manifestations

The incubation period of Giardia infection usually is 1-2 wk but may be longer. A broad spectrum of clinical manifestations occurs, depending on the interaction between G. lamblia and the host. Children who are exposed to G. lamblia may experience asymptomatic excretion of the organism, acute infectious diarrhea, or chronic diarrhea with persistent gastrointestinal tract signs and symptoms, including failure to thrive and abdominal pain or cramping. Giardia was the cause of 15% of nondysenteric diarrhea in children examined in U.S. outpatient clinics in 1 study. Most infections in both children and adults are asymptomatic. There usually is no extraintestinal spread, but occasionally trophozoites may migrate into bile or pancreatic ducts.

Symptomatic infections occur more frequently in children than in adults. Most symptomatic patients usually have a limited period of acute diarrheal disease with or without low-grade fever, nausea, and anorexia; in a small proportion of patients, an intermittent or more protracted course characterized by diarrhea, abdominal distention and cramps, bloating, malaise, flatulence, nausea, anorexia, and weight loss develops (Table 274-1). Stools initially may be profuse and watery and later become greasy and foul smelling and may float. Stools do not contain blood, mucus, or fecal leukocytes. Varying degrees of malabsorption may occur. Abnormal stool patterns may alternate with periods of constipation and normal bowel movements. Malabsorption of sugars, fats, and fat-soluble vitamins has been well documented and may be responsible for substantial weight loss. Giardia has been associated with iron deficiency in internationally adopted children. Giardiasis has been associated with growth stunting and repeated Giardia infections with a decrease in cognitive function in children in endemic areas.

Table 274-1 CLINICAL SIGNS AND SYMPTOMS OF GIARDIASIS

Diagnosis

Giardiasis should be considered in children who have acute nondysenteric diarrhea, persistent diarrhea, intermittent diarrhea and constipation, malabsorption, chronic crampy abdominal pain and bloating, failure to thrive, or weight loss. It should be particularly high in the differential diagnosis of children in child care, children in contact with an index case, children with a history of recent travel to an endemic area, and children with humoral immunodeficiencies. Testing for giardiasis should be standard for internationally adopted children from Giardia-endemic areas, and screening for iron deficiency should be considered in internationally adopted children with giardiasis.

Stool enzyme immunoassay (EIA) or direct fluorescent antibody tests for Giardia antigens are now the tests of choice for giardiasis in most situations. EIA is less reader dependent and more sensitive for detection of Giardia than microscopy. Some studies have reported that a single stool is sufficiently sensitive for detection of Giardia by EIA, while others suggest that sensitivity is increased with testing of 2 samples. Traditionally, a diagnosis of giardiasis has been established by microscopy documentation of trophozoites or cysts in stool specimens, but 3 stool specimens are required to achieve a sensitivity of >90%. In patients in whom other parasitic intestinal infections are in the differential diagnosis, microscopy examination of stool allows evaluation for these infections in addition to Giardia. Laboratories can reduce reagent and personnel costs by pooling specimens submitted for detection of Giardia before evaluation by microscopy or EIA. Polymerase chain reaction (PCR) and gene probe–based detection systems specific for Giardia have been used in environmental monitoring but at present remain research tools. Multiplex PCR testing for multiple parasitic pathogens may become a viable option for testing in the future.

In patients with chronic symptoms in whom giardiasis is suspected but in whom testing of stool specimens for Giardia yields a negative result, aspiration or biopsy of the duodenum or upper jejunum should be considered. In a fresh specimen, trophozoites usually can be visualized by direct wet mount. An alternate method of directly obtaining duodenal fluid is the commercially available Entero-Test (Hedeco Corp, Mountain View, CA), but this method is less sensitive than aspiration or biopsy. The biopsy can be used to make touch preparations and tissue sections for identification of Giardia and other enteric pathogens and also to visualize changes in histology. Biopsy of the small intestine should be considered in patients with characteristic clinical symptoms, negative stool and duodenal fluid specimen findings, and 1 or more of the following: abnormal radiographic findings (such as edema and segmentation in the small intestine); abnormal lactose tolerance test result; absent secretory IgA level; hypogammaglobulinemia; or achlorhydria. Duodenal biopsy may show findings consistent with chronic inflammation, including eosinophilic infiltration of the lamina propria.

Radiographic contrast studies of the small intestine may show nonspecific findings such as irregular thickening of the mucosal folds. Blood cell counts usually are normal. Giardiasis is not tissue invasive and is not associated with peripheral blood eosinophilia.

Treatment

Children with acute diarrhea in whom Giardia organisms are identified should receive therapy. In addition, children who manifest failure to thrive or exhibit malabsorption or gastrointestinal tract symptoms such as chronic diarrhea should be treated.

Asymptomatic excreters generally are not treated except in specific instances such as in outbreak control, for prevention of household transmission by toddlers to pregnant women and patients with hypogammaglobulinemia or cystic fibrosis, and in situations requiring oral antibiotic treatment where Giardia may have produced malabsorption of the antibiotic.

The U.S. Food and Drug Administration (FDA) has approved tinidazole and nitazoxanide for the treatment of Giardia in the USA. Both medications have been used to treat Giardia in thousands of patients in other countries and have excellent safety and efficacy against Giardia (Table 274-2). Tinidazole has the advantage of single-dose treatment and very high efficacy (>90%), while nitazoxanide has the advantage of a suspension form, high efficacy (80-90%), and very few adverse effects. Metronidazole, though never approved by the FDA for treatment of Giardia, is also highly effective (80-90% cure rate), and the generic form is considerably less expensive than tinidazole or nitazoxanide. Frequent adverse effects are seen with metronidazole therapy, and it requires 3 times a day dosing for 5-7 days. Suspension forms of tinidazole and metronidazole must be compounded by a pharmacy; neither drug is sold in suspension form.

Table 274-2 DRUG TREATMENT FOR GIARDIASIS

* All pediatric dosages are up to a maximum of the adult dose.

^† Not commercially available. Can be compounded by Medical Center Pharmacy in New Haven, CT (203-785-6818) or Panorama Compounding Pharmacy in Van Nuys, CA (800-247-9767).

Second line alternatives for the treatment of patients with giardiasis include furazolidone, albendazole, paromomycin, and quinacrine (see Table 274-2). Furazolidone, albendazole, and paromomycin are less effective than tinidazole, nitazoxanide, and metronidazole. Furazolidone has been prescribed for children because it is available in liquid form. Albendazole has few adverse effects and is effective against many helminths, making it useful for treatment when multiple intestinal parasites are identified or suspected. Paromomycin is a nonabsorbable aminoglycoside and is less effective than other agents but is recommended for treatment of pregnant women with giardiasis because of potential teratogenic effects of other agents. Quinacrine is effective and inexpensive but is not available commercially and must be obtained from compounding pharmacies (see Table 274-2). Refractory cases of giardiasis have been successfully treated with nitazoxanide, prolonged courses of tinidazole, or a 3-week course of metronidazole and quinacrine.

Prognosis

Symptoms recur in some patients in whom reinfection cannot be documented and in whom an immune deficiency such as an immunoglobulin abnormality is not present, despite use of appropriate therapy. Several studies have demonstrated that variability in antimicrobial susceptibility exists among strains of Giardia, and in some instances resistant strains have been demonstrated. Combined therapy may be useful for infection that persists after single-drug therapy, assuming reinfection has not occurred and the medication was taken as prescribed.

Prevention

Infected persons and persons at risk should practice strict handwashing after any contact with feces. This point is especially important for caregivers of diapered infants in child-care centers, where diarrhea is common and Giardia organism carriage rates are high.

Methods to purify public water supplies adequately include chlorination, sedimentation, and filtration. Inactivation of Giardia cysts by chlorine requires the coordination of multiple variables such as chlorine concentration, water pH, turbidity, temperature, and contact time. These variables cannot be appropriately controlled in all municipalities and are difficult to control in swimming pools. Individuals, especially children in diapers, should avoid swimming if they have diarrhea. Individuals should also avoid swallowing recreational water and drinking untreated water from shallow wells, lakes, springs, ponds, streams, and rivers.

Travelers to endemic areas are advised to avoid uncooked foods that might have been grown, washed, or prepared with water that was potentially contaminated. Purification of drinking water can be achieved by a filter with a pore size of <1 mm or that has been National Sanitation Foundation rated for cyst removal, or by brisk boiling of water for at least 1 min. Treatment of water with chlorine or iodine is less effective but may be used as an alternate method when boiling or filtration is not possible.