Myriads of protozoan parasites of the genus Trypanosoma infect plants and animals worldwide. Among these, three are of clinical significance for humans: T. cruzi causes Chagas disease, and T. brucei gambiense and T. brucei rhodesiense cause human African trypanosomiasis (HAT), which is also known as “sleeping sickness.” Despite obvious differences in their geographic distribution, parasitic life cycle, clinical presentation, treatment, and outcome, these vector-borne diseases are archetypal examples of neglected tropical diseases. More broadly, these infectious diseases affect neglected populations of the lowest socioeconomic class who have limited access to care and who live either in remote rural areas of low- or middle-income tropical/subtropical countries or in urban areas of both endemic and nonendemic countries. The drugs to treat these conditions are several decades old, their availability is fragile, and their efficacy and/or safety is suboptimal.
Other trypanosome species (e.g., T. congolense and T. evansi) predominantly cause nonhuman zoonoses and only occasionally cause illness in humans.
CHAGAS DISEASE (AMERICAN TRYPANOSOMIASIS)
First described in 1909 by Carlos Chagas, Chagas disease (American trypanosomiasis) is a zoonosis caused by the flagellated protozoan T. cruzi. After a frequently asymptomatic acute phase, 30–40% of patients develop life-threatening chronic cardiomyopathy and/or digestive-tract dysfunction over the course of decades. Acute reactivation may occur in immunocompromised patients. Chagas disease imposes an important human and social burden in Latin America and has recently spread outside its natural boundaries to become a global public health problem. A vast majority of affected individuals are unaware of being infected and do not have access to appropriate clinical management and counseling.
T. cruzi infection is primarily a zoonosis transmitted to a range of wild and domestic mammals by blood-sucking triatomine bugs. Sylvatic, peridomiciliary, and intradomiciliary vectorial cycles sometimes overlap. Over a large geographic area in the Americas (from northern Argentina to the southern United States), most human infections are intradomiciliary, arising from a triatomine bite during nighttime sleep. Feces released by triatomines during a blood meal contain the infective metacyclic form of T. cruzi that enters the human body through cutaneous breaks, mucosae, or conjunctivae. Despite recent laboratory research showing the potential for transmission by bedbugs, there is no evidence that bedbugs actually transmit T. cruzi to humans.
Other modes of transmission can cause infection in both endemic and nonendemic regions. T. cruzi can be transmitted congenitally from mother to newborn, by transfusion of blood products, by tissue or organ transplantation, or by ingestion of contaminated food or drink. Congenital infection occurs in 1–10% of newborns of infected mothers. The risk of infection from contaminated blood products is low (1.7% overall, 13% for platelet recipients, and close to 0 for recipients of red blood cells and plasma). Transmission by infected organ and tissue transplants mostly ...