scholarly journals Effects of betamethasone on the course of experimentai. Infection with Trypanosoma cruzi

1986 ◽  
Vol 19 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Frederico G.C. Abath ◽  
Yara M. Gomes ◽  
Eridan M. Coutinho ◽  
Silvia M.L. Montenegro ◽  
Maria E.B. Melo ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Bacterial Infections ◽  
Acute Infection ◽  
Chronic Phase ◽  
Control Group ◽  
Cumulative Mortality ◽  
Histopathological Findings ◽  
Experimental Group

In this experiment, the effect of betamethasone administered in the early post- acute infection of mice by Trypanosoma cruzi was studied. This drug was administered during 30 days after the 42nd day of infection in a dose of 0.15 mg/day. The betamethasone treatment did not cause fresh outbreaks of parasitemia and the histopathological findings in the chronic phase were not different from those in the control group. The higher cumulative mortality after treatment in the experimental group was due to superimposed bacterial infections. Outbred albino mice infected with low numbers ofY strain Trypanosoma cruzi trypomastigotes were not suitable models for Chagas' disease, since after 7 months of observation only mild histological lesions developed in all the animais. Prolonged betamethasone treatment of mice infected with low numbers o/Trypanosoma cruzi of the Y strain, during the post-acute phase did not aggravate the course of infection.

Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
Author(s):  
Adriana Egui ◽  
Paola Lasso ◽  
Elena Pérez-Antón ◽  
M. Carmen Thomas ◽  
Manuel Carlos López
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Clinical Status ◽  
Chronic Phase ◽  
Parasite Load ◽  
Chronic Patients ◽  
Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

scholarly journals Trypanosoma cruzi and experimental Chagas' disease: characterization of a stock isolated from a patient with associated digestive and cardiac form

1993 ◽  
Vol 26 (1) ◽  
pp. 25-33 ◽  
Author(s):  
E.C. Oliveira ◽  
M.M.A. Stefani ◽  
A.O. Luquetti ◽  
E.F. Vêncio ◽  
M.A.R. Moreira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Digestive Tract ◽  
Chagas Disease ◽  
Acute Phase ◽  
Experimental Infection ◽  
Post Infection ◽  
Chronic Phase ◽  
Igg Antibodies ◽  
Histopathology Examination

A new Trypanosoma cruzi stock isolated from a patient in the chronic phase of Chagas' disease with the digestive and cardiac fortn of the disease was characterized by experimental infection in isogenic, susceptible, A/Sn strain mice. Parasitemia curves showed up to 1.7x10(6) parasites/ml and no mortality was observed up to 300 days post infection. Specific IgM was found in mice in the acute phase up to 40 days and also in the chronic phase. IgG antibodies yvere detected in the acute and chronic phase. Histopathology examination demonstrated myotropism to the digestive tract muscle layers and to the heart.

scholarly journals Trypanosoma cruzi infection associated with atypical clinical manifestation during the acute phase of the Chagas disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucia Rangel-Gamboa ◽  
Lirio López-García ◽  
Francisco Moreno-Sánchez ◽  
Irma Hoyo-Ulloa ◽  
María Elisa Vega-Mémije ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Clinical Manifestations ◽  
Chronic Phase ◽  
Clinical History ◽  
Skin Lesions ◽  
Small Subunit ◽  
Serological Tests ◽  
Cutaneous Manifestations

Abstract Background Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi and is transmitted by triatomine insects. Clinical manifestations vary according to the phase of the disease. Cutaneous manifestations are usually observed in the acute phase (chagoma and Romaña’s sign) or after reactivation of the chronic phase by immunosuppression; however, a disseminated infection in the acute phase without immunosuppression has not been reported for CD. Here, we report an unusual case of disseminated cutaneous infection during the acute phase of CD in a Mexican woman. Methods Evaluation of the patient included a complete clinical history, a physical exam, and an exhaustive evaluation by laboratory tests, including ELISA, Western blot and PCR. Results Skin biopsies of a 50-year-old female revealed intracellular parasites affecting the lower extremities with lymphangitic spread in both legs. The PCR tests evaluated biopsy samples obtained from the lesions and blood samples, which showed a positive diagnosis for T. cruzi. Partial sequencing of the small subunit ribosomal DNA correlated with the genetic variant DTU II; however, serological tests were negative. Conclusions We present a case of CD with disseminated skin lesions that was detected by PCR and showed negative serological results. In Mexico, an endemic CD area, there are no records of this type of manifestation, which demonstrates the ability of the parasite to initiate and maintain infections in atypical tissues.

BloodstreamTrypanosoma cruziparasites from mice simultaneously express antigens that are markers of acute and chronic human Chagas disease

Parasitology ◽  
1991 ◽  
Vol 102 (3) ◽  
pp. 379-385 ◽  
Author(s):  
M. S. Leguizamon ◽  
O. E. Campetella ◽  
M. B. Reyes ◽  
C. F. Ibañez ◽  
M. A. Basombrio ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Early Period ◽  
Chronic Phase ◽  
Blood Parasites ◽  
Expression Library ◽  
Antibody Specificities ◽  
Human Infections ◽  
Parasite Strains

Several recombinantTrypanosoma cruziproteins previously isolated were used as antigens to analyse antibody specificities present in sera from human infections. Some parasite proteins such as SAPA (Shed Acute Phase Antigen) are antigenic early after infection. Others, like antigens 1 and 30, are antigenic mainly during the chronic phase of the infection. To understand why different proteins are antigenic at different periods of infection, specificities of antibodies present in the sera of infected mice were compared with the antigens expressed by parasites collected directly from blood. Parasites collected during the acute parasitaemia peak expressed not only antigen SAPA, but also antigens 1 and 30. However, only antibodies against SAPA were frequently observed during the early period and also in the chronic phase of murine infection. Long-lasting antibodies against SAPA were detected regardless of the mouse and parasite strains used. Furthermore, all 8 recombinant clones detected in aT. cruziexpression library with pooled sera from acutely infected mice were homologous to the SAPA gene. These results show that even though parasites from the acute parasitaemia peak in mice may express simultaneously several proteins known to be antigenic, only antibodies against SAPA were consistently detected.

scholarly journals The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role

2021 ◽  
Vol 11 ◽  
Author(s):  
Jorge Nihei ◽  
Fabiola Cardillo ◽  
Jose Mengel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Chagas Disease ◽  
Acute Phase ◽  
Acute Infection ◽  
Dependent Manner ◽  
Tissue Specific

Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection progresses to a chronic stage. The parasite infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart muscle, among many others. It is evident now that tissue-specific immune responses may develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity and to ensure tissue-specific tolerance are operating during the infection. Studying those immunoregulatory mechanisms is fundamental to improve host protection or control inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection is not established. IL-2 production by T cells is strongly down-modulated early in the disease by unknown mechanisms and remains low during the chronic phase of the disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity development. Also, the expansion and maintenance of regulatory T cells require IL-2. Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune responses, probably in a dose-dependent manner. This study blocked IL-2 during the acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that parasitemia and mortality rate was lower in animals treated with anti-IL-2. The percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T cells increased during the acute infection. T cells producing IFN-γ, TNF-α and IL-10 also augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17 produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation through the expansion/maintenance of regulatory T cells and regulating IL-17 production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes in acute and chronic phases of Chagas’ disease.

scholarly journals Recombinant Enolase of Trypanosoma cruzi as a Novel Vaccine Candidate against Chagas Disease in a Mouse Model of Acute Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Minerva Arce-Fonseca ◽  
María Cristina González-Vázquez ◽  
Olivia Rodríguez-Morales ◽  
Verónica Graullera-Rivera ◽  
Alberto Aranda-Fraustro ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Acute Infection ◽  
Parasite Burden ◽  
Protozoan Parasite ◽  
World Health ◽  
Protective Effects ◽  
Th2 Immune Response

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, which is considered by the World Health Organization to be a neglected tropical disease. Two drugs exist for the treatment of Chagas disease, nifurtimox and benznidazole; they are only effective in the acute phase, and a vaccine is currently not available. In this study, we used the recombinant enolase from T. cruzi H8 strain (MHOM/MX/1992/H8 Yucatán) (rTcENO) and its encoding DNA (pBKTcENO) to immunize mice and evaluate their protective effects in an experimental murine model of acute phase infection. Our results showed that mice vaccinated with rTcENO or its encoding DNA were able to generate typical specific antibodies (IgG1, IgG2a, and IgG2b), suggesting that a mixed Th1/Th2 immune response was induced. The parasite burden in the blood was reduced to 69.8% and 71% in mice vaccinated with rTcENO and pBKTcENO, respectively. The group vaccinated with rTcENO achieved 75% survival, in contrast to the group vaccinated with pBKTcENO that showed no survival in comparison to the control groups. Moreover, rTcENO immunization elevated the production of IFN-γ and IL-2 after the parasite challenge, suggesting that the Th1-type immune response was polarized. These results indicated that rTcENO could be used as a vaccine against Chagas disease.

scholarly journals In VitroandIn VivoStudies of the Antiparasitic Activity of Sterol 14α-Demethylase (CYP51) Inhibitor VNI against Drug-Resistant Strains of Trypanosoma cruzi

2013 ◽  
Vol 57 (9) ◽  
pp. 4151-4163 ◽  
Author(s):  
Maria de Nazaré Correia Soeiro ◽  
Elen Mello de Souza ◽  
Cristiane França da Silva ◽  
Denise da Gama Jaen Batista ◽  
Marcos Meuser Batista ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Infection ◽  
Chronic Phase ◽  
Antifungal Drugs ◽  
Drug Candidate ◽  
Mammalian Host ◽  
Severe Toxicity ◽  
Mutagenic Potential ◽  
Content Type

ABSTRACTChagas disease affects more than 10 million people worldwide, and yet, as it has historically been known as a disease of the poor, it remains highly neglected. Two currently available drugs exhibit severe toxicity and low effectiveness, especially in the chronic phase, while new drug discovery has been halted for years as a result of a lack of interest from pharmaceutical companies. Although attempts to repurpose the antifungal drugs posaconazole and ravuconazole (inhibitors of fungal sterol 14α-demethylase [CYP51]) are finally in progress, development of cheaper and more efficient, preferablyTrypanosoma cruzi-specific, chemotherapies would be highly advantageous. We have recently reported that the experimentalT. cruziCYP51 inhibitor VNI cures with 100% survival and 100% parasitological clearance both acute and chronic murine infections with the Tulahuen strain ofT. cruzi. In this work, we further explored the potential of VNI by assaying nitro-derivative-resistantT. cruzistrains, Y and Colombiana, in highly stringent protocols of acute infection. The data show high antiparasitic efficacy of VNI and its derivative (VNI/VNF) against both forms ofT. cruzithat are relevant for mammalian host infection (bloodstream and amastigotes), with thein vivopotency, at 25 mg/kg twice a day (b.i.d.), similar to that of benznidazole (100 mg/kg/day). Transmission electron microscopy and reverse mutation tests were performed to explore cellular ultrastructural and mutagenic aspects of VNI, respectively. No mutagenic potential could be seen by the Ames test at up to 3.5 μM, and the main ultrastructural damage induced by VNI inT. cruziwas related to Golgi apparatus and endoplasmic reticulum organization, with membrane blebs presenting an autophagic phenotype. Thus, these preliminary studies confirm VNI as a very promising trypanocidal drug candidate for Chagas disease therapy.

scholarly journals Resting and Dynamic Electrocardiography in Dogs with Experimental Chagas Cardiomyopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
R. Oliveira Alves ◽  
A. A. Camacho ◽  
D. P. Junior
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Sinus Tachycardia ◽  
Chronic Phase ◽  
Left Ventricular ◽  
Sinus Arrest ◽  
Chagas Cardiomyopathy ◽  
Electrocardiographic Monitoring ◽  
Electrocardiographic Changes

In the present protocol, adult dogs were infected with Trypanosoma cruzi, Bolivian strain, in order to show electrocardiographic changes by means of resting and dynamic (Holter) methods during acute and chronic phases of Chagas disease. In the acute phase there were sinus tachycardia, atrial and left ventricular overload, millivoltage suppression, electric alternance, and episodes of sinus arrest. At the parasitemia peak, atrium-ventricular block, junctional escape complexes, and atrium-ventricular dissociation were observed. Dogs that presented the most serious arrhythmias died suddenly. The increase in supraventricular and ventricular arrhythmic events, concentrated in the 4th postinoculation week, was visible at electrocardiographic monitoring. In the chronic phase, the events were restricted to first-degree atrium-ventricular blocks, premature ventricular complexes, ventricular bigeminy, and electrical alternation. It was concluded that the computerized and dynamic electrocardiography allowed to diagnose transient arrhythmia and to observe that the main tachyarrhythmic changes are concentrated at the acute phase concomitantly to the parasitemia peak.

scholarly journals Alterations of the myenteric plexus of the ileum and the descending colon caused by Toxoplasma gondii (genotype III)

2008 ◽  
Vol 66 (3a) ◽  
pp. 516-523 ◽  
Author(s):  
Elaine Yae Yamashita Sugauara ◽  
Débora de Mello Gonçales Sant'Ana ◽  
Elton Carlos de Almeida ◽  
Anderson Brunetti Reis ◽  
Aristeu Vieira da Silva ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Acute Phase ◽  
Terminal Ileum ◽  
Neuronal Loss ◽  
Chronic Phase ◽  
Control Group ◽  
Nacl Solution ◽  
Genotype Iii ◽  
Descending Colon ◽  
Experimental Group

Alterations caused by a genotype III strain of Toxoplasma gondii were assessed with respect to the number and the morphometry of the myenteric neurons in the terminal ileum and the descending colon. Eighteen rats were divided into four groups: Acute Control Group (ACG, n=4); Acute Experimental Group (AEG, n=4); Chronic Control Group (CCG, n=5) and Chronic Experimental Group (CEG, n=5). NaCl solution was administered through gavage to the animals in the ACG and CCG. Toxoplasma gondii tachyzoites (10(4)) from a genotype III strain were orally administered to the AEG and CEG. Acute Groups were died after 24 hours, and the Chronic Groups after 30 days. Neuronal loss was not observed in both organs. The neurons atrophied in the terminal ileum as the opposite occurred with the neurons at the descending colon during the chronic phase of infection. In the terminal ileum, the neurons atrophied during the chronic phase of the infection as no alteration was found during the acute phase. For the descending colon, the neurons became hypertrophic during the chronic infection in opposition to the atrophy found during the acute phase.

Assessing the effectiveness of AS-48 in experimental mice models of Chagas’ disease

2020 ◽  
Vol 75 (6) ◽  
pp. 1537-1545 ◽  
Author(s):  
Rubén Martín-Escolano ◽  
Rubén Cebrián ◽  
Mercedes Maqueda ◽  
Desirée Romero ◽  
Maria José Rosales ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Enterococcus Faecalis ◽  
Chagas Disease ◽  
Chronic Infection ◽  
Acute Infection ◽  
Chronic Phase ◽  
Aetiological Agent ◽  
Promising Alternative ◽  
Parasitic Load

Abstract Objectives We report the in vivo trypanocidal activity of the bacteriocin AS-48 (lacking toxicity), which is produced by Enterococcus faecalis, against the flagellated protozoan Trypanosoma cruzi, the aetiological agent of Chagas’ disease. Methods We determined the in vivo activity of AS-48 against the T. cruzi Arequipa strain in BALB/c mice (in both acute and chronic phases of Chagas’ disease). We evaluated the parasitaemia, the reactivation of parasitaemia after immunosuppression and the nested parasites in the chronic phase by PCR in target tissues. Results AS-48 reduced the parasitaemia profile in acute infection and showed a noteworthy reduction in the parasitic load in chronic infection after immunosuppression according to the results obtained by PCR (double-checking to demonstrate cure). Conclusions AS-48 is a promising alternative that provides a step forward in the development of a new therapy against Chagas’ disease.

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