20 research outputs found
Trypanosoma cruzi co-infections with other vector borne diseases are frequent in dogs from the pacific coast of Ecuador
Este articulo describe la presentación de infecciones múltiples con Trypnosoma cruzi, Anaplasma spp., Dirofilaria immitis y Ehrlichia spp. (transmitidas por vector) en perros de una región de la costa del PacÃfico de EcuadorDogs are a reservoir for Chagas disease, caused by Trypanosoma cruzi (T. cruzi), and other companion vectorborne
diseases, including ehrlichiosis (Ehrlichia canis and Ehrlichia ewingii), anaplasmosis (Anaplasma phagocytophilum
and Anaplasma platys), dirofilariasis (Dirofilaria immitis) and Lyme disease (Borrelia burgdorferi). This
study has two key objectives: 1) to determine seroreactivity against T. cruzi in dogs from the town of Col´on, in
Portoviejo city, in the central coast of Ecuador; and 2) to establish the coinfection frequency of other companion
vector-borne diseases in dogs positive for T. cruzi. Antibodies against T. cruzi were detected using two enzymelinked
immunosorbent assays. Diagnostic consensus between ELISA tests was established using the Cohen’s
Kappa coefficient. Other haemoparasitic diseases were detected using the IDEXX SNAP® 4Dx® kit in dogs
previously diagnosed as T. cruzi-seropositive. From 84 dogs sampled, 57.14% (48/84) tested positive for T. cruzi.
Co-infection analysis of 25 dogs positive for T. cruzi revealed antibodies also against Ehrlichia spp. (48%),
Anaplasma spp. (28%), and Dirofilaria immitis (12%). These results provide a novel perspective regarding the
status of these pathogens which co-infect dogs in Col´on. Since all these pathogens are zoonotic, our findings
should warn regional health authorities to implement sanitary programs, to better prevent and control vectors
associated to these pathogens. On the other hand, human and veterinarian doctors, should consider that patients
with a cardiac infection condition could be suffering co-infections with two or more vector transmitted
pathogens.RMJ The research was funded by the Universidad Autónoma del Estado de México (UAEM) Project (4351/2017/CI).
NJG National Institute of Allergy and Infectious Diseases (R01AI136031) of the National Institutes of Health
Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs
Immunization of dogs with DNA-prime/DNA-boost vaccine (TcVac1) enhanced the
Trypanosoma cruzi-specific type 1 antibody and
CD8+ T cell responses that resulted in an early control of
acute parasitemia and a moderate decline in pathological symptoms during chronic
phase. Further improvement of vaccine-induced immunity would be required to
achieve clinical and epidemiological benefits and prevent transmission of
parasites from vaccinated/infected dogs to triatomines
Effects of astaxanthin in mice acutely infected with
During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX) were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4–6 weeks old) infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day) and/or nifurtimox (NFMX; 100 mg/kg/day). Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days), while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox
Effects of astaxanthin in mice acutely infected with Trypanosoma cruzi
During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX) were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4–6 weeks old) infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day) and/or nifurtimox (NFMX; 100 mg/kg/day). Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days), while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox
Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.
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
TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice
Trabajo de investigación doctoral de Wael Hegazy Hassan Moustafa bajo la dirección de Juan Carlos Vázquez ChagoyánThe efforts for the development and testing of vaccines against Trypanosoma cruzi infection have
increased during the past years. We have designed a TcVac series of vaccines composed of T. cruzi derived,
GPI-anchored membrane antigens. The TcVac vaccines have been shown to elicit humoral and cellular
mediated immune responses and provide significant (but not complete) control of experimental infection
in mice and dogs. Herein, we aimed to test two immunization protocols for the delivery of DNA-prime/
DNA-boost vaccine (TcVac1) composed of TcG2 and TcG4 antigens in a BALB/c mouse model. Mice were
immunized with TcVac1 through intradermal/electroporation (IDE) or intramuscular (IM) routes, challenged
with T. cruzi, and evaluated during acute phase of infection. The humoral immune response
was evaluated through the assessment of anti-TcG2 and anti-TcG4 IgG subtypes by using an ELISA.
Cellular immune response was assessed through a lymphocyte proliferation assay. Finally, clinical and
morphopathological aspects were evaluated for all experimental animals. Our results demonstrated that
when comparing TcVac1 IDE delivery vs IM delivery, the former induced significantly higher level of
antigen-specific antibody response (IgG2a + IgG2b > IgG1) and lymphocyte proliferation, which
expanded in response to challenge infection. Histological evaluation after challenge infection showed
infiltration of inflammatory cells (macrophages and lymphocytes) in the heart and skeletal tissue of all
infected mice. However, the largest increase in inflammatory infiltrate was observed in TcVac1_IDE/Tc
mice when compared with TcVac1_IM/Tc or non-vaccinated/infected mice. The extent of tissue inflammatory
infiltrate was directly associated with the control of tissue amastigote nests in vaccinated/
infected (vs. non-vaccinated/infected) mice. Our results suggest that IDE delivery improves the protective
efficacy of TcVac1 vaccine against T. cruzi infection in mice when compared with IM delivery of the
vaccine.Universidad Autónoma de Estado de
México (proyecto No. 3326/2012C), Consejo Nacional de Ciencia y TecnologÃa (Proyecto No. 156701) . Beca CONACyT a M.Sc. Wael Hegazy Hassan Moustafa (Beca numero No. 518232/291117)
T cell and cytokine response in vaccinated dogs.
<p>(<b>A</b>) Spleen cells were obtained from vaccinated and
non-vaccinated dogs at one year after challenge infection with <i>T.
cruzi</i>. Spleen cells were incubated for 30 min with
FITC-conjugated anti-CD8 and PE-conjugated anti-CD4 antibodies and
CD4<sup>+</sup> and CD8<sup>+</sup> T cell subsets monitored
by flow cytometry. (<b>B</b>) The circulatory IFN-γ level was
measured by an ELISA. Data are presented as mean ± SD
(*<i>p</i><0.05).</p
The antibody response to <i>T. cruzi</i> infection was polarized to type 1 in vaccinated dogs.
<p>Dogs were vaccinated as above, and infected with <i>T. cruzi</i>.
An ELISA was performed to evaluate sera levels (1∶100-dilution) of
<i>T. cruzi</i>-specific IgM (<b>A</b>), IgG
(<b>B</b>), IgG1 (<b>C</b>), and IgG2 (<b>D</b>)
antibodies at 0, 15, 30, 45, and 60 days post-infection.</p
Histological analysis of hearts.
<p>Dogs were vaccinated, and challenged with <i>T. cruzi</i>. Heart
tissue sections (5-ìM) from left ventricle, septum, and right
ventricle were obtained at 60 days post-infection (acute phase), and stained
with hematoxylin-eosin. Shown are representative micrographs of dogs
injected with vector only (<b>B,B1,B2</b>) or immunized with TcVac1
(<b>C,C1,C2</b>). Micrographs from normal/uninfected dogs
(<b>A,A1,A2</b>) are shown for comparison. Vertical arrows show
amastigote nests and horizontal arrows show lymphocyte infiltration, and
cardiomyocytes destruction.</p
Shown are plasma levels of myeloperoxidase activity (A) and nitrite content (B) in dogs immunized with vector only or TcVac1 vaccine during the course of 0–60 days post-infection.
<p>Data are presented as mean ± SD (*<i>p</i><0.05).</p