Current Challenges and Obstacles to Drug Development for Chagas Disease

Abstract

Chagas disease is one of the 17 neglected diseases and was identified 109 years ago by the Brazilian physician and researcher Carlos Justiniano Ribeiro Chagas. Also known as American trypanosomiasis, Chagas disease is endemic in 21 Latin American countries [1][2][3][4][5]. Due to an increasingly globalized world, this parasite has spread to the United States, Japan, Australia, Canada, and even across the European continent [6,7]. It is caused by the hemoflagellate protozoan from the Kinetoplastida order of the Trypanosamatidae family, called Trypanosoma cruzi [2,8,9]. Treatment is restricted to two nitroheterocyclic drugs: nifurtimox (1) and benznidazole (2) (Figure 1). These were discovered during the 1960s and 1970s, respectively [10,11]. Both drugs are more effective in the acute phase of the disease than in the indeterminate and chronic phases [12][13][14][15][16][17][18][19][20][21]. Furthermore, there are differences in the efficacies of these drugs in relation to the several strains of T. cruzi [22] (Figure 1).

Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi

“…Moreover, BZN can induce genome-wide mutagenesis and multi-drug resistance in T. cruzi [21]. Thus, limited efficacy and toxicity represent major challenges to be overcome if new treatments for CD are to be developed against this neglected disease, which remains a major public health issue in many areas of Latin America [22,23].…”