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.

Correlation of Parasite Burden, kDNA Integration, Autoreactive Antibodies, and Cytokine Pattern in the Pathophysiology of Chagas Disease.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi (T. cruzi), is the main parasitic disease in the Western Hemisphere. Unfortunately, its physiopathology is not completely understood, and cardiomegaly development is hard to predict. Trying to explain tissue lesion and the fact that only a percentage of the infected individuals develops clinical manifestations, a variety of mechanisms have been suggested as the provokers of CD, such as parasite persistence and autoimmune responses. However, holistic analysis of how parasite and host-related elements may connect to each other and influence clinical outcome is still scarce in the literature. Here, we investigated murine models of CD caused by three different pathogen strains: Colombian, CL Brener and Y strains, and employed parasitological and immunological tests to determine parasite load, antibody reactivity, and cytokine production during the acute and chronic phases of the disease. Also, we developed a quantitative PCR (qPCR) protocol to quantify T. cruzi kDNA minicircle integration into the mammalian host genome. Finally, we used a correlation analysis to interconnect parasite- and host-related factors over time. Higher parasite load in the heart and in the intestine was significantly associated with IgG raised against host cardiac proteins. Also, increased heart and bone marrow parasitism was associated with a more intense leukocyte infiltration. kDNA integration rates correlated to the levels of IgG antibodies reactive to host cardiac proteins and interferon production, both influencing tissue inflammation. In conclusion, our results shed light into how inflammatory process associates with parasite load, kDNA transfer to the host, autoreactive autoantibody production and cytokine profile. Altogether, our data support the proposal of an updated integrative theory regarding CD pathophysiology.

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.

Congenital Chagas disease: alert of research negligence.

INTRODUCTION: Chagas disease (CD), a neglected endemic disease in Latin America, has acquired new epidemiological characteristics with an increase in the importance of alternative transmission routes such as congenital transmission. We evaluated the scientific research on this subject. METHODS: We searched the Scielo, BVS, and PubMed databases from 2006 to 2017. RESULTS: We identified a small number of published articles, mostly in journals with an impact factor less than 3.0. Studies on human congenital transmission of CD were carried out in only seven different countries. CONCLUSIONS: Our data highlight the lack of research on congenital CD.

Congenital Chagas disease: alert of research negligence

Abstract INTRODUCTION: Chagas disease (CD), a neglected endemic disease in Latin America, has acquired new epidemiological characteristics with an increase in the importance of alternative transmission routes such as congenital transmission. We evaluated the scientific research on this subject. METHODS: We searched the Scielo, BVS, and PubMed databases from 2006 to 2017. RESULTS: We identified a small number of published articles, mostly in journals with an impact factor less than 3.0. Studies on human congenital transmission of CD were carried out in only seven different countries. CONCLUSIONS: Our data highlight the lack of research on congenital CD.