Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi that infects a broad range of triatomines and mammalian species, including man. It afflicts 8 million people in Latin America, and its incidence is increasing in nonendemic countries owing to rising international immigration and nonvectorial transmission routes such as blood donation. Since the 1960s, the only drugs available for the clinical treatment of this infection have been benznidazole (BZ) and nifurtimox (NFX). Treatment with these trypanocidal drugs is recommended in both the acute and chronic phases of CD. These drugs have low cure rates mainly during the chronic phase, in addition both drugs present side effects that may result in the interruption of the treatment. Thus, more efficient and better-tolerated new drugs or pharmaceutical formulations containing BZ or NFX are urgently needed. Here, we review the drugs currently used for CD chemotherapy, ongoing clinical assays, and most-promising new experimental drugs. In addition, the mechanism of action of the commercially available drugs, NFX and BZ, the biodistribution of the latter, and the potential for novel formulations of BZ based on nanotechnology are discussed. Taken together, the literature emphasizes the urgent need for new therapies for acute and chronic CD.

Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8⁺ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4⁺/CD8⁺ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4⁺ and CD8⁺ T-lymphocytes and IL-4 by CD8⁺ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

Studies showed the positive effects of omega-3 fatty acid (n-3 FA) for the treatment of inflammatory bowel disease as it alleviated the symptoms and promoted better mucosal integrity. The objective of this study was to determine whether a diet with the addition of n-3 FA helps control the inflammation observed in 5-fluorouracil (5-FU) induced mucositis. BALB/c mice were randomly divided into four groups as follows: 1: control (CTL), fed a standard chow diet; 2: CTL + n-3 FA – n-3 FA, fed a diet with n-3; 3: mucositis (MUC), fed a standard chow diet and subjected to mucositis; and 4: MUC+ n-3 FA, fed a diet with n-3 FA and subjected to mucositis. On the 8th day, the animals of the MUC and MUC + n-3 FA groups received an intraperitoneal injection of 300 mg/kg 5-FU for mucositis induction. After 24 h or 72 h, all mice were euthanized and evaluated for intestinal permeability, bacterial translocation, intestinal histology and apoptosis. Mice that received the diet with n-3 FA and a 5-FU injection showed less weight loss compared to the animals of the MUC group (p < 0.005). Decreased intestinal permeability and bacterial translocation were also observed in animals fed n-3 FA, and these mice underwent mucositis compared to the MUC group (p < 0.005). These data were associated with mucosal integrity and a reduced number of apoptotic cells in the ileum mucosa compared to the mice that received the control diet and 5-FU injection. Together, these results show that omega-3 fatty acid decreases the mucosal damage caused by 5-FU-induced mucositis.

Chagas disease is a so-called “neglected disease” and endemic to Latin America. Nifurtimox and benznidazole are drugs that have considerable efficacy in the treatment of the acute phase of the disease but cause many significant side effects. Furthermore, in the Chronic Phase its efficiency is reduced and their therapeutic effectiveness is dependent on the type of T. cruzi strain. For this reason, the present work aims to drive basic research towards the discovery of new chemical entities to treat Chagas disease. Differently substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines were synthesized by cyclocondensation of substituted flavones with ethylenediamine and tested as anti-Trypanosoma cruzi candidates. Epimastigotes of the Y strain from T. cruzi were used in this study and the number of parasites was determined in a Neubauer chamber. The most potent diaryldiazepine that reduced epimastigote proliferation exhibited an IC₅₀ value of 0.25 μM, which is significantly more active than benznidazole.

A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration.

The present study aims at establishing whether the diversity in pathogenesis within a genetically diverse host population infected with a single polyclonal strain of Trypanosoma cruzi is due to selection of specific subpopulations within the strain. For this purpose we infected Swiss mice, a genetically diverse population, with the polyclonal strain of Trypanosoma cruzi Berenice-78 and characterized via LSSP-PCR the kinetoplast DNA of subpopulations isolated from blood samples collected from the animals at various times after inoculation (3, 6 and 12 months after inoculation). We examined the biological behavior of the isolates in acellular medium and in vitro profiles of infectivity in Vero cell medium. We compared the characteristics of the isolates with the inoculating strain and with another strain, Berenice 62, isolated from the same patient 16 years earlier. We found that one of the isolates had intermediate behavior in comparison with Berenice-78 and Berenice-62 and a significantly different genetic profile by LSSP-PCR in comparison with the inoculating strain. We hereby demonstrate that genetically distinct Trypanosoma cruzi isolates may be obtained upon experimental murine infection with a single polyclonal Trypanosoma cruzi strain.