Chapter 349. Giardiasis

Giardia lamblia or Giardia intestinalis is a protozoan flagellate that is among the most common disease-causing parasites in the United States and the most frequently identified agent of waterborne diarrhea.1 Cases are especially common in areas with inadequate water and sanitation facilities. Humans are the major reservoir of infection, although other mammals, such as dogs, cats, and beavers, may be colonized and excrete cysts. Massive epidemics have occurred after the contamination of reservoirs, lakes, and streams, especially when community water supplies are not adequately filtered.

Although giardiasis affects persons of all age groups, the populations at highest risk are children ages 0 to 5 years and adults ages 31 to 40. In developing countries, Giardia infection has been reported in almost 100% of children who were followed prospectively from birth until age 2 years. In the United States and other developed countries, Giardia is prevalent in childcare centers and custodial institutions, among backpackers and others spending time in wooded areas, and among travelers to disease-endemic areas. Among children in daycare centers, Giardia cyst carriage has been documented to be as high as 50%, and many of these are asymptomatic carriers who can spread infection to household contacts. Person-to-person spread via fecal-oral route and ingestion of contaminated water are the most common modes of transmission; infection through food is less common.

Giardia cysts, present in the stool of infected persons, are the infective form. After ingestion, they excyst in the small intestine, yielding trophozoites that subsequently multiply. The trophozoites remain limited to the mucosa, mucus, or lumen of the intestine and are rarely, if ever, invasive (Fig. 349-1). Encystation normally occurs prior to expulsion in the feces. Contamination of oneself and the environment with cysts is common. The number of cysts excreted varies, but it may reach as many as 10 million per gram. Infections are relatively frequent, because as few as 10 cysts can infect 30% of inoculated humans.

The exact pathophysiology of the diarrhea is not known. The most severe cases are characterized by malabsorption and lactose intolerance, with varying degrees of inflammation and villous blunting. Host factors are also determinants of disease outcome; only 40% of humans infected with the same inoculum develop diarrhea. Patients with hypogammaglobulinemia frequently suffer from particularly severe cases of giardiasis. The observation that asymptomatic infections are more common in persons previously infected with Giardia also suggests partial immunity.

Clinical Manifestations

Clinical manifestations and duration of symptoms vary. Infections range from asymptomatic cases to severe, life-threatening diarrhea accompanied by malabsorption and dehydration. Infections may last from a few days to years. In naturally occurring infections, symptoms usually appear approximately 12 to 14 days after presumed exposure. Passage of cysts usually begins 7 to 10 days after inoculation (range 5 to 21 days). Symptoms include watery, foul-smelling diarrhea, which can be sudden in onset and accompanied by abdominal distension, epigastric cramping, flatus, nausea, vomiting, anorexia, and fatigue. Systemic symptoms such as fever and chills are uncommon. Blood and mucus in the stools do not occur in giardiasis. Urticaria and arthritis have been anecdotally associated. In its most florid manifestations, giardiasis results in symptoms and signs associated with severe small-intestinal malabsorption and weight loss. Although some patients have severe symptoms at the onset of illness and seek medical care shortly after becoming ill, the majority who seek medical attention complain of remitting abdominal pain, nausea, or weight loss lasting weeks to months.

Diagnosis

Giardiasis is confirmed by detecting the parasite or its antigens in the stool or intestinal lining. Cysts are oval, 8 to 10 μm long by 7 to 10 μm wide, and contain four nuclei. When viewed dorsally, the trophozoite has a characteristic pear shape and contains two similar nuclei. Trophozoites vary in size from 9 to 21 μm in length and 5 to 15 μm in width. Other features include four paired flagella and a ventral sucking disc with which the trophozoite attaches to the intestinal mucosa.

Cysts are the most commonly detected form in the feces, and trophozoites are almost entirely limited to liquid stools. Merthiolate-iodine-formalin (MIF) concentration improves the detection of cysts. The number of cysts excreted vary, and they may not be detected on any single examination. If initial stool examination is negative, three stool examinations spaced 2 days apart are recommended. Careful fecal examination detects over 90% of infected individuals but requires an experienced microscopist.

Occasionally, cysts are not detected in the feces, and sampling small-intestinal fluid by intubation or by the “string test” is useful. For the string test, a capsule attached to an absorbent string is swallowed, and trophozoites attach as the capsule proceeds through the jejunum. After 4 hours, the string is withdrawn and duodenal fluid on the string is examined for trophozoites. Esophagogastroduodenoscopy with biopsy may be diagnostic.

Commercially available assays for detecting Giardia antigen in the stool may be useful when microscopy is negative.2 In general, these tests are more sensitive than stool examination, with similar specificity and with the added benefit of being much less time-consuming than microscopy. Giardia antigens may be detected by immunofluorescent ELISAs, nonenzymatic immunoassays (some of which combine detection of Giardia and Cryptosporidium in a single kit), and direct fluorescent antibody tests. These commercial detection tests are similar in cost to microscopy but with better reproducibility and more rapid return of results. Overall, antigen detection tests have a sensitivity of 85% to 98% and a specificity of 90% to 100% as compared to microscopy. Antibody detection assays are rarely clinically useful, as the relationship between serum antibody and clinical disease is unclear.

Treatment and Prevention

Because many people are asymptomatically infected, the decision to treat should be based upon presence of symptoms such as diarrhea, malabsorption, and failure to thrive. Asymptomatic cyst excreters are generally not treated except in unusual circumstances—for example, when attempting to prevent or control infections in a family with high-risk individuals such as pregnant women or patients with hypogammaglobulinemia or cystic fibrosis.

Furazolidone (Furoxone) was the first anti-Giardia drug to become available as a suspension in the United States, thus making it particularly useful in infants and younger children. There are mixed reports on the effectiveness of furazolidone, with cure rates ranging from 77% to 92%. The dose for children is 6 mg/kg per day, divided into four doses for 7 to 10 days.

Metronidazole (Flagyl) is frequently prescribed for giardiasis and is a highly effective drug for this indication (80–95% efficacy after 7 days of treatment), but it remains unlicensed in the United States for this purpose.3 Metronidazole is administered in doses of 250 mg three times a day for 5 to 7 days for adults and in doses of 5 mg/kg three times a day for 5 to 7 days in children.4 Tinidazole (Tindamax) is FDA approved for giardiasis and is considered by some to be first-line therapy, because it is highly effective against Giardia with single-dose treatment (90–95% efficacy when given as a 2-gm dose to adults). Treatment failures with metronidazole or tinidazole can be treated with another drug, with longer durations of therapy and with increased amounts of drug when metronidazole is used. Treatment failures with metronidazole are seen more commonly in immunodeficient patients, including those with AIDS.

Nitazoxanide (Alinia) is a broad-spectrum antiparasitic drug active against a wide range of protozoa and intestinal helminthes, as well as some bacteria.5 It is also FDA approved for treating giardiasis in adults and children, and a liquid formulation for pediatric patients is available. The drug interferes with anaerobic energy metabolism by inhibiting some enzyme-dependent electron transfer reactions. Clinical trials in children showed efficacy rates of 70% to 85%, similar to those seen with metronidazole therapy. Nitazoxanide is usually administered for 3-day treatment courses, making it an attractive alternative to other treatments that require longer courses of therapy.

Anthelminthic benzimidazole drugs such as albendazole and mebendazole have recently been shown to have efficacy against Giardia similar to that of metronidazole but with fewer adverse effects. Albendazole was given for 5 days or longer in clinical trials for this indication, so the efficacy of single-dose albendazole (as it is frequently given for helminth infections) for giardiasis is not known.

The most effective treatment is quinacrine hydrochloride (Atabrine), although it is no longer available in the United States because of concerns related to toxicity. Combined therapy with metronidazole and quinacrine is effective in the rare patient who is refractory to multiple courses of therapy. Paromomycin, a nonabsorbable aminoglycoside, has limited efficacy (50–70%) but is recommended for treating symptomatic giardiasis in pregnant women because of its lack of systemic absorption.

Food or drinks that are likely contaminated should be avoided. Hand-washing and attention to personal hygiene are important preventative measures. Potentially contaminated water should be boiled or filtered, because chlorination, freezing, and disinfection by ultraviolet light are not effective against Giardia.