American trypanosomiasis (Chagas disease), human African trypanosomiasis (HAT, sleeping sickness), and leishmaniasis are caused by related protozoa of the family Trypanosomatidae, order Kinetoplastida (see Table 200.1). They have a unique mitochondrial structure, the kinetoplast, are transmitted in nature by insect vectors, and exist in multiple morphologic forms in their human hosts and insect vectors. They are important causes of morbidity and mortality in endemic areas of the world: Chagas disease in South and Central America, sleeping sickness in sub-Saharan Africa, and leishmaniasis in scattered areas on every continent except Antarctica. Although uncommon in industrial countries in North America and Europe, these diseases have been the source of increased attention in recent years. Infection with Trypanosoma cruzi, the cause of Chagas disease, is well documented among a subset of Latin American immigrants to the United States and Canada and poses a risk to them and to recipients of contaminated blood or transplanted organs. Cutaneous leishmaniasis is seen among tourists returning from endemic areas in Latin America and the Middle East as well as in military personnel serving in Iraq and Afghanistan. Canine visceral leishmaniasis has been reported in the United States among foxhounds and other dogs, but to date, humans have not been infected.

Despite several important recent advances, the treatment of Chagas disease, African trypanosomiasis, and leishmaniasis leaves much to be desired. Many of the drugs (Table 200.2) used for them are associated with frequent and potentially severe untoward effects, some require parenteral administration, and many must be administered over prolonged periods of time.