Chapter Three - Drugs and Drug Resistance in African and American Trypanosomiasis

Diseases caused by several (sub)species of parasites from the genus Trypanosoma are a major concern for public and animal health. Trypanosomes have a digenetic life cycle that involves an insect host that acts as the vector for transmission to different mammals, some of which are natural reservoirs. The zoonotic nature of the disease together with the capacity of the parasites to evade the host immune response or become dormant hampers pathogen eradication and immunoprophylactic control. A handful of drugs are available for the treatment, although none of them has been specifically designed toward these pathogens. The drugs are efficacious when applied at very early stages of the infections, but display high toxicity, require a long or assisted administration, present a limited efficacy against late stages of the diseases and are prone to develop resistance. Here we review the state-of-the-art for the drugs used to treat trypanosomiasis that causes African sleeping sickness and Chagas’ disease in humans. The state-of-the-art on drug uptake, mode of action, and resistance is here reviewed. The prospects for developing new molecules that circumvent the current challenges for treating trypanosomiasis are also discussed.