Clinical aspects of Chagas disease and implications for novel therapies

Abstract

The interaction between the protozoan parasite Trypanosoma cruzi and the human host dates back 9000 years, as demonstrated by molecular analysis of material obtained from Andean mummies indicating the presence of the parasite’s kinetoplast DNA in populations from Chile and Peru. This long-established interaction, which persists today, demonstrates that T. cruzi has established a very well adapted relationship with the human host. From a host-parasite relationship point-of-view this is desirable, however, such a high degree of adaptation is perhaps the foundation for many of the unknowns that surround this disease. Unveiling of the immunological mechanisms that underlie the establishment of pathology, identification of parasite-associated factors that determine strain-differential tissue tropism, discovery of host genetic elements that influence the development of different clinical forms of the disease, and understanding environmental factors that may influence the host-parasite interactions, are some of the key questions remaining to be answered. The response to these questions will aid in addressing some of the current challenges in Chagas disease: fulfilling the need for efficient diagnosis, developing effective prophylactic measures, discovering effective therapeutics, and finding methods to control disease progression.

Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

“…Therefore, one of the most important goals of studying physiopathological mechanisms in Chagas disease is the identification of potential risk factors for the occurrence of major clinical events (sudden death, heart failure, malignant arrhythmias, and stroke) or disease progression among patients still in the indeterminate form or in initial stages of the cardiac form (5,6). Chagas heart disease is characterized by an intense and progressive fibrotic process (4), and the study of biomarkers involved in the establishment and development of fibrosis is essential to identify such potential risk factors (35).…”

Hepatic changes by benznidazole in a specific treatment for Chagas disease

“…BNZ is the treatment of choice given its better treatment efficacy and fewer AEs [ 6 ]. BNZ is a nitroimidazole derivative that acts by interrupting protein synthesis, which impairs the formation of the parasite [ 7 ]. This drug is metabolized in the liver and may cause hepatic toxicity, which has been observed in experiments in which infected mice have elevated liver enzyme levels in the first 15 days of treatment with BNZ.…”

Trypanosoma cruzi Genome 15 Years Later: What Has Been Accomplished?

“…Nonetheless, the information provided by the 2005 publication paved the way for the generation of new diagnostic tools, the discovery of important metabolic routes, the publication of nearly 2000 research papers, and the production of a wealth of information that allows a more systemic approach to T. cruzi biology and a large scale search for druggable targets [ 75 , 76 , 77 ].…”