Current trends in the pharmacological management of Chagas disease.

Chagas disease (CD) is a tropical neglected illness, affecting mainly populations of low socioeconomic status in Latin America. An estimated 6 to 8 million people worldwide are infected with Trypanosoma cruzi, the etiological agent of CD. Despite being one of the main global health problems, this disease continues without effective treatment during the chronic phase of the infection. The limitation of therapeutic strategies has been one of the biggest challenges on the fight against CD. Nifurtimox and benznidazole, developed in the 1970s, are still the only commercial options with established efficacy on CD. However, the efficacy of these drugs have a proven efficacy only during early infection and the benefits in the chronic phase are questionable. Consequently, there is a growing need for new pharmacological alternatives, either by optimization of existing drugs or by the formulation of new compounds. In the present study, a literature review of the currently adopted therapy, its concomitant combination with other drugs, and potential future treatments for CD was performed, considering articles published from 2012. The revised articles were selected according to the protocol of treatment: evaluation of drug association, drug repositioning and research of new drugs. As a result of the present revision, it was possible to conclude that the use of benznidazole in combination with other compounds showed better results when compared with its use as a single therapy. The search of new drugs has been the strategy most used in pursuing more effective forms of treatment for CD. However, studies have still focused on basic research, that is, they are still in a pre-clinical stage, using methodologies based on in vitro or in animal studies.

Intestinal microbiota - A modulator of the Trypanosoma cruzi-vector-host triad.

Chagas disease affects millions of people, and it is a major cause of death in Latin America. Prevention and development of an effective treatment for this infection can be favored by a more thorough understanding of T. cruzi interaction with the microbiome of vectors and hosts. Next-generation sequencing technology vastly broadened the knowledge about intestinal bacteria composition, showing that microbiota within each host (triatomines and mammals) is composed by high diversity of species, although few dominant phyla. This fact may represent an ecological balance that was acquired during the evolutionary process of the microbiome-host complex, and that serves to perpetuate this system. In this context, commensal microbiota is also essential to protect hosts, conferring them resistance to pathogens colonization. However, in some situations, the microbiota is not able to prevent infection but only modulate it. Here we will review the role of the microbiota on the parasite-vector-host triad with a focus on the kinetoplastida of medical importance Trypanosoma cruzi. Novel strategies to control Chagas disease based on intestinal microbiome will also be discussed.