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.

Figure 1

Regardless of the route of infection, it is critical to detect Trypanosoma cruzi infection early on in order to provide immediate treatment to the patients. It is estimated that treatment efficacy is observed in at least of 80% of the treated acute patients. Lack of detection of the acute phase, or treatment failure lead to disease chronification. During the chronic phase of Chagas disease, most individuals remain in an asymptomatic clinical form, named indeterminate. However, approximately 30% of the patients will develop severe clinical forms of Chagas disease, which often lead to death. The reasons why patients progress from the indeterminate to the symptomatic forms of Chagas disease are not completely understood, although host and parasite factors are involved. The search of prognostic markers of disease progression is a critical aspect for preventing pathology and introducing better clinical measures. The figure highlights three challenges in Chagas disease: better diagnosis, better treatment and discovery of prognostic factors.