Chapter 50: Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis, Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other Protozoal Infections

INTRODUCTION

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. Because protozoa multiply rapidly in their hosts and effective vaccines are unavailable, chemotherapy has been the only practical way to both treat infected individuals and reduce transmission. 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. Treatment of protozoal infections in immunocompromised individuals is especially difficult, and the outcome is often unsatisfactory.

Most antiprotozoal drugs have been in use for years despite major advances in bioscience relevant to parasite biology, host defenses, and mechanisms of disease. Satisfactory agents for treating important protozoal infections such as African trypanosomiasis (sleeping sickness) and chronic Chagas' disease still are lacking. Many effective antiprotozoal drugs are toxic at therapeutic doses, a problem exacerbated by increasing drug resistance. Development of drug resistance also poses a serious threat to better tolerated antiprotozoal agents in current use. Unfortunately, many of these diseases afflict the poor in developing countries, and there is little economic incentive for pharmaceutical companies to develop new antiparasitic drugs. Scientists and physicians working in this field must be creative and have turned to drugs developed originally for other indications (e.g., amphotericin and miltefosine for leishmaniasis), to investigational drugs made available directly from the Centers for Disease Control and Prevention (CDC), or to agents developed for veterinary use to discover new antiparasitic therapies.

This chapter describes important human protozoal infections other than malaria and the drugs used to treat them.

INTRODUCTION TO PROTOZOAL INFECTIONS OF HUMANS

Amebiasis. Amebiasis affects ~10% of the world's population, causing invasive disease in ~50 million people and death in ~100,000 of these annually (Stanley, 2003). In the U.S., amebiasis is seen most commonly in the states that border Mexico and among 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. Although the proportions vary worldwide, E. dispar and E. moshkovskii account for ~90% of human infections, with E. histolytica responsible for only 10%. However, only E. histolytica is capable of causing disease and thus requires treatment.