Human American trypanosomiasis, commonly called Chagas disease, is one of the most neglected
illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with
thousands of new cases every year. The only treatments available have been introduced five decades ago.
They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease – a characteristic
and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused
their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and
lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This
fragility has been recently exposed by the failure of two candidates; posaconazole and E1224, to sterilely cure
patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug
discovery and development efforts to discover better and safer treatments.
In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by
academic research groups, industry and other research organizations over the last half century. We also analyze
the current research landscape that is now better placed than ever to deliver alternative treatments for
Chagas disease in the near future.