Treatment Options for the Eradication of Intestinal Protozoa

Michael JG Farthing

Disclosures

Nat Clin Pract Gastroenterol Hepatol. 2006;3(8) 

In This Article

Giardia Intestinalis

G. intestinalis (syn. G. lamblia, G. duodenalis), the most common human protozoan enteropathogen, is a noninvasive organism that generally remains within the intestinal lumen, often within the adherent mucus layer in close apposition to intestinal epithelial cells. The parasite is responsible for both acute and chronic diarrhea.[1,2,3] The resulting intestinal malabsorption can be severe, such that chronic infection in children can be associated with retardation of growth and development. The most common form of giardiasis, however, is asymptomatic carriage. This form is common in highly endemic areas in the developing world, although it also occurs in Europe and North America.

In many healthy, immunocompetent individuals G. intestinalis will be eradicated by host defense mechanisms without the need for specific antimicrobial chemotherapy. Administration of an antigiardial drug will generally reduce the severity of symptoms and the duration of the illness.[2,4] Although symptomatic patients with giardiasis are usually offered antimicrobial chemotherapy, the question as to whether asymptomatic patients (particularly those in an endemic area) should be treated remains controversial. Since the development of in vitro culture techniques for G. intestinalis isolates, methods have been developed to assess drug sensitivity in vitro.[5] The precise relationship between indices of drug susceptibility in vitro and the subsequent behavior of the drug in vivo, however, has not been clearly established. Treatment failures do occur, and it is thought that at least some of these episodes are related to drug resistance.[6,7]

Various antiparasitic agents have been shown to be effective in the treatment of the symptoms of giardiasis and in the eradication of the parasite.[8] A recent meta-analysis involving 34 trials performed by the Cochrane collaboration indicates that the preferred treatment regimen is an ultra-short course (i.e. a single dose regimen taken on 1 day) of a nitroimidazole derivative.[9]

Nitroimidazole derivatives act by causing DNA damage, with loss of the helical structure, impaired template function and strand breakage. Metronidazole is commonly given as 2 g single dose on three successive days (efficacy 60–100%, median 92%), or tinidazole is given as a 2 g single dose (efficacy 80–100%, median 92%). Other nitroimidazole derivatives, including ornidazole and secnidazole, are also effective as single-dose therapies.[10]

Nitrofuran compounds can also be used to treat G. intestinalis infection. Furazolidone damages intracellular components, including DNA. It has a lower efficacy than the nitroimidazole derivatives, but is popular for the treatment of giardiasis in children because it has relatively few adverse effects and is available as a suspension. Efficacy rates of 80–96% are reported, but the drug needs to be administered for 7–10 days, which can result in problems with compliance.[8]

The benzimidazole drugs (albendazole and mebendazole) have antigiardial activity, which relates at least in part to their ability to bind to β-tubulin and inhibit cytoskeletal function. Albendazole has been shown to have antigiardial activity in vitro and clinical trial data support its therapeutic efficacy in adults (400 mg daily for 5 days) and children.[8]

Nitrazoxanide has broad-spectrum antiparasitic activity. Clinical trials in children and adults indicate that this is an effective antigiardial agent with similar efficacy to the nitroimidazole derivatives. Nitazoxanide 100–200 mg twice daily (efficacy 85%) has been shown to be as effective as a 5-day course of metronidazole (efficacy 80%) in children.[11] Similar results have been reported in a trial in adults.[12] Nitazoxanide has also been shown to be effective in the treatment of combined metronidazole-resistant and albendazole-resistant giardiasis.[6] The efficacy of nitazoxanide has since been confirmed by a systematic review.[13]

Mepacrine has a similar efficacy to the nitroimidazole derivatives, but is generally less well tolerated, and is no longer widely available because of concerns about toxicity. The drug of choice for the treatment of giardiasis in pregnancy is paromomycin (500 mg three times daily for 5–10 days), as it is poorly absorbed by the intestine and excreted virtually unmetabolized.[8]

A vaccine for giardiasis has been developed for use in dogs[14,15] and cats,[16] which suggests that it might eventually be possible to prevent infection with Giardia in humans.

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