Background Trypanosoma cruzi, the etiologic agent of Chagas Disease, is a major vector borne health problem in Latin America and an emerging infectious disease in the United States.MethodsWe tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine (TcVac1) against experimental T. cruzi infection in a canine model. Dogs were immunized with antigen-encoding plasmids and cytokine adjuvants, and two weeks after the last immunization, challenged with T. cruzi trypomastigotes. We measured antibody responses by ELISA and haemagglutination assay, parasitemia and infectivity to triatomines by xenodiagnosis, and performed electrocardiography and histology to assess myocardial damage and tissue pathology.ResultsVaccination with TcVac1 elicited parasite-and antigen-specific IgM and IgG (IgG2>IgG1) responses. Upon challenge infection, TcVac1-vaccinated dogs, as compared to non-vaccinated controls dogs, responded to T. cruzi with a rapid expansion of antibody response, moderately enhanced CD8+ T cell proliferation and IFN-γ production, and suppression of phagocytes’ activity evidenced by decreased myeloperoxidase and nitrite levels. Subsequently, vaccinated dogs controlled the acute parasitemia by day 37 pi (44 dpi in non-vaccinated dogs), and exhibited a moderate decline in infectivity to triatomines. TcVac1-immunized dogs did not control the myocardial parasite burden and electrocardiographic and histopatholgic cardiac alterations that are the hallmarks of acute Chagas disease. During the chronic stage, TcVac1-vaccinated dogs exhibited a moderate decline in cardiac alterations determined by EKG and anatomo-/histo-pathological analysis while chronically-infected/non-vaccinated dogs continued to exhibit severe EKG alterations.ConclusionsOverall, these results demonstrated that TcVac1 provided a partial resistance to T. cruzi infection and Chagas disease, and provide an impetus to improve the vaccination strategy against Chagas disease.
Here we describe clinical and pathologic evidence of Chagas disease caused in dogs by circulating Trypanosoma cruzi from a newly recognized endemic area in Mexico. We show that the Zumpahuacan isolate, although less virulent than the Sylvio-X10 reference strain that caused acute myocarditis and death, was pathogenic in dogs. Dogs infected with the Zumpahuacan isolate exhibited electrocardiographic alterations, left- and right-ventricle dilation, and hydropericardium. Histologically, diffused perimysial and endomysial lymphoplasmacytic cell infiltration, cardiomyocyte necrosis, and amastigote nests were noted in Zumpahuacan-infected dogs. These findings suggest that the risk of T. cruzi infection and Chagas disease is present in the State of Mexico, and further research is needed to identify the T. cruzi bio-types circulating in southern State of Mexico.
Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.
Vanilla juice has been shown empirically to have antifungal activity against some fungal strains; however, there are no activity reported against Alternaria genre. In this work, the chemical profile of vanilla juice was obtained and its antifungal activity against fungal strains from the family Pleosporaceae, isolated from sorghum-and barley-diseased plants, was tested. The strains were identified as Alternaria alternata by their molecular and morphological characteristics. The vanilla juice characterization from Vanilla planifolia pods showed the presence of vanillin, vanillic acid, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, guaiacol, glucovanillin, vanillyl alcohol, and furfural. Vanilla juice showed a fungistatic effect against all A. alternata strains tested in this study and increased the lag time from 50 to 112 h, and no conidia were produced. This result indicates the possible application of vanilla juice as an alternative to control agricultural crops such as barley and sorghum in Mexico.
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