More than One Hundred Years after It Was First Discovered by Carlos Ribeiro Justiniano

Chagas, the disease bearing his name remains one of the most neglected topical diseases in the world. Trypanosoma cruzi, the causative agent of Chagas disease, is a protozoan parasite which has become unable to synthesize purines and pteridines instead salvaging them from its human host. It is mainly transmitted by the feces of the Kissing bug, but it is also spread by organ transplant, blood transfusion, and from mother to child by breastfeeding. Trypanosoma cruzi has a sophisticated life cycle with four stages each with unique metabolism. Once in the body the metacyclic trypomastigote penetrates a cell and transforms into an amastigote. The amastigote divides by binary fission in cells of infected tissue then transform into a trypomastigote which burst out from cells into the blood stream, the trypomastigote can infect other cells (usually cells of the heart or gastrointestinal tract) and transform back into an intracellular amastigote in a new infection cycle, leading to chronic infection. Benznidazole and nifurtimox have been the only drugs used to treat Chagas disease for 40 years. They work well to treat the infection in the acute stages but their potency diminishes the longer a person has been infected, becoming ineffective at chronic stages of infection. The 2 month duration of treatment, adverse effect rate of 40%, and increase in drug resistance are top reasons why a safer, polypharmacological drug is needed [1]. Currently an estimated 10 million people, mostly in Latin America, are infected with Trypanosoma Cruzi, and it will kill about 50,000 people this year. Although, Chagas was once only seen in South and Central America with the rise in globalization it has spread to other countries and might become a worldwide problem [2]. New drugs with specificity to multiple targets and potency at chronic stages of infection are desperately needed.