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INTRODUCTION

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Humans host a wide variety of protozoal parasites that can be transmitted by insect vectors, directly from other mammalian reservoirs or from one person to another. The immune system plays a crucial role in protecting against the pathological consequences of protozoal infections. Thus, opportunistic infections with protozoa are prominent in infants, individuals with cancer, transplant recipients, those receiving immunosuppressive drugs or extensive antibiotic therapy, and persons with advanced human immunodeficiency virus (HIV) infection. Because effective vaccines are unavailable, chemotherapy has been the only practical way to both treat infected individuals and reduce transmission. Many effective antiprotozoal drugs are toxic at therapeutic doses, a problem exacerbated by increasing drug resistance.

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INTRODUCTION TO PROTOZOAL INFECTIONS OF HUMANS

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AMEBIASIS. Amebiasis affects ~10% of the world's population, commonly individuals living in poverty, crowded conditions, and areas with poor sanitation. Three morphologically identical but genetically distinct species of Entamoeba (i.e., E. histolytica, E. dispar, and E. moshkovskii) have been isolated from infected persons, with E. histolytica responsible for ~10% of human infections. Only E. histolytica causes disease and requires treatment.

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Humans are the only known hosts for these protozoa, which are transmitted almost exclusively by the fecal-oral route. Ingested E. histolytica cysts from contaminated food or water survive acid gastric contents and transform into trophozoites that reside in the large intestine. The outcome of E. histolytica infection is variable. Many individuals remain asymptomatic but excrete the infectious cyst form, making them a source for further infections. In other individuals, E. histolytica trophozoites invade into the colonic mucosa with resulting colitis and bloody diarrhea (amebic dysentery). In a smaller proportion of patients, E. histolytica trophozoites invade through the colonic mucosa, reach the portal circulation, and travel to the liver, where they establish an amebic liver abscess.

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The cornerstone of therapy for amebiasis is metronidazole or its analogs tinidazole and ornidazole. Because metronidazole is so well absorbed in the gut, levels may not be therapeutic in the colonic lumen, and the drug is less effective against cysts. Hence patients with amebiasis (amebic colitis or amebic liver abscess) also should receive a luminal agent to eradicate any E. histolytica trophozoites residing within the gut lumen. Luminal agents are also used to treat asymptomatic individuals found to be infected with E. histolytica. The nonabsorbed aminoglycoside paromomycin and the 8-hydroxyquinoline compound iodoquinol are effective luminal agents. Diloxanide furoate, previously considered the luminal agent of choice for amebiasis, is no longer available in the U.S. Nitazoxanide (Alinia), approved in the U.S. for treatment of cryptosporidiosis and giardiasis, is also active against E. histolytica.

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GIARDIASIS. Giardiasis, caused by the flagellated protozoan Giardia intestinalis, is prevalent worldwide and is the most commonly reported intestinal protozoal infection in the U.S. Infection results from ingestion of the cyst form of the parasite, which is found in fecally contaminated water or food.

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Infection with Giardia results ...

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