Resting and Dynamic Electrocardiography in Dogs with Experimental Chagas Cardiomyopathy

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.

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

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821986000300006 ◽

1986 ◽

Vol 19 (3) ◽

pp. 161-164 ◽

Cited By ~ 5

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.

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

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821993000100006 ◽

1993 ◽

Vol 26 (1) ◽

pp. 25-33 ◽

Cited By ~ 7

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.

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

Parasites & Vectors ◽

10.1186/s13071-019-3766-3 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

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.

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

Parasitology ◽

10.1017/s0031182000064337 ◽

1991 ◽

Vol 102 (3) ◽

pp. 379-385 ◽

Cited By ~ 8

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.

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Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma Cruzi Seropositive Individuals

Circulation ◽

10.1161/circulationaha.121.055112 ◽

2021 ◽

Author(s):

Maria Carmo P. Nunes ◽

Lewis F. Buss ◽

Jose Luiz P. da Silva ◽

Larissa Natany Almeida Martins ◽

Claudia Di Lorenzo Oliveira ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Clinical Epidemiology ◽

Outpatient Service ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Blood Collection ◽

Ventricular Ejection Fraction ◽

Chagas Cardiomyopathy

Background: There are few contemporary cohorts of Trypanosoma cruzi -seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi -seropositive blood donors. T. cruzi -seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, electrocardiogram, and echocardiogram at enrollment (2008 to 2010) and at follow-up (2018 to 2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% and/or QRS complex duration ≥ 120 ms. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. Results: We enrolled 499 T. cruzi -seropositive donors (age 48 ± 10 years, 52% male), 488 T. cruzi -seronegative donors (age 49 ± 10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48 ± 8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000py (17/114, 15%) in T. cruzi -seropositives with cardiomyopathy at baseline. Among T. cruzi -seropositive donors without cardiomyopathy at baseline mortality was 3.7 events/1000py (15/385, 4%), which was no different from T. cruzi -seronegative donors with 3.6 deaths/1000py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi -seropositive donors was 13.8 (95% CI 9.5-19.6) events/1000py (32/262, 12%) compared with 4.6 (95% CI 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI 3.6 - 15.0) events/1000py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted OR of 1.4, 95% CI 1.1-1.8). Conclusions: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti- T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.

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Wnt Signalling Orchestrates the Immune Response and Cardiac Damage During Trypanosoma cruzi Infection

10.1101/2020.05.27.119107 ◽

2020 ◽

Author(s):

Ximena Volpini ◽

Laura Fernanda Ambrosio ◽

Agustina Brajín ◽

María Belen Brugo ◽

María Pilar Aoki ◽

...

Keyword(s):

Immune Response ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Acute Phase ◽

Wnt Signalling ◽

Signalling Pathways ◽

Chagas Cardiomyopathy ◽

Cardiac Lesions ◽

Parasite Replication ◽

Chronic Chagas Disease

AbstractChagas’ cardiomyopathy is the consequence of a compromised electrical and mechanical cardiac function, with parasite persistence, unbalanced inflammation and pathological tissue remodelling, being intricately related to the myocardial aggression and the impaired function. Recent studies have shown that Wnt signalling pathways, which are important for developmental processes, play a critical role in the pathogenesis of cardiac and vascular diseases. In addition, we have reported that Trypanosoma cruzi infection activates Wnt signalling pathways in macrophages to promote their intracellular replication, with treatment of mice with IWP-L6 (an inhibitor of the O-acyl-transferase, PORCN, responsible for the post-translational modifications necessary for Wnt proteins secretion) being able to diminish parasitaemia and tissue parasitism. Therefore, Wnt signalling may contribute to the development of Chagas’ cardiomyopathy. In this work we have evaluated the effectiveness of Wnt secretion inhibition to control the parasite replication, modulate the adaptive immune response, and prevent the development of cardiac lesions in an experimental model of chronic Chagas disease. The IWP-L6 treatment, administered to T. cruzi infected BALB/c mice in a time window during the acute phase of the infection, was able to control the parasitaemia and heart parasitism together with the amelioration of the electrical, mechanical and histopathological cardiac alterations observed in chronically infected mice. Moreover, we demonstrated that during the acute phase of the infection Wnt signalling activation contributes to promote specific Th2-type immune response and to maintain the suppressive activity of Treg cells. Our data provide evidence that inhibition of Wnt signalling during the acute phase of T. cruzi infection controls the parasite replication, inhibits the development of parasite-prone and fibrosis-prone Th2-type immune response and prevents the development of cardiac lesions characteristics of chronic Chagas disease. Our study suggests that Wnt signalling pathway might be a potential target to prevent the development of T. cruzi-induced cardiomyopathy.

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The effect of memantine, an antagonist of the NMDA glutamate receptor, in in vitro and in vivo infections by Trypanosoma cruzi

10.1101/546861 ◽

2019 ◽

Author(s):

Higo Fernando Santos Souza ◽

Sandra Carla Rocha ◽

Flávia Silva Damasceno ◽

Ludmila Nakamura Rapado ◽

Elisabeth Mieko Furusho Pral ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Side Effects ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Glutamate Receptor ◽

Acute Phase ◽

Chronic Phase ◽

Parasitic Load ◽

Inflammatory Infiltrates

AbstractChagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease that affects 5-6 million people in endemic areas of the Americas. Presently, chemotherapy relies on two compounds that were proposed as trypanocidal drugs four decades ago: nifurtimox and benznidazole. Both drugs are able to eliminate parasitemia and to avoid seroconversion in infected people when used in the acute phase; however, their use in the chronic phase (the time when the majority of cases are diagnosed) is limited due to their serious side effects. Memantine is a glutamate receptor antagonist in the central nervous system of mammals that has been used for the treatment of Alzheimer’s disease. Our group previously reported memantine as a trypanocidal drug that is able to induce apoptosis-like death in T. cruzi. In the present work, we further investigated the effects of memantine on the infection of RAW 264.7 macrophages in vivo (in BALB/c mice). Here, we showed that memantine is able to diminish NO and Ca2+ entry in both LPS-activated and non-activated cells. These results, together with the fact that memantine was also able to reduce the infection of macrophages, led us to propose that this drug is able to activate a pro-oxidant non-NO-dependent cell defense mechanism. Finally, infected mice that were treated with memantine had diminished parasitemia, cardiac parasitic load, and inflammatory infiltrates. In addition, the treated mice had an increased survival rate. Taken together, these results indicate memantine to be a candidate drug for the treatment of Chagas disease.Author summaryChagas disease affects approximately 5 million people and is caused by the protist parasite Trypanosoma cruzi. Until now, there are no vaccines to prevent the human infection, and the therapy relies on the use of two drugs discovered more than 50 years ago, nifurtimox and benznidazole. Both drugs are efficient during the acute phase of the disease, however their efficacy in the chronic phase, when most of patients are diagnosed is controversial. In addition, both drugs are toxic, causing severe side effects during the treatment. For these reasons, new drugs against T. cruzi are urgently needed. In this work, we report a series of experiments supporting the repositioning of memantine, a drug used for treating Alzheimer’s disease, to treat the T. cruzi infection in an experimental infection model. Our data show that infected mice treated with memantine have diminished their parasitemia, cardiac parasitic load and inflammatory infiltrates and more importantly, they have diminished their mortality. Taken together, these results prompt memantine as a promising drug for treating Chagas disease.

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

Current Medicinal Chemistry ◽

10.2174/0929867325666181101111819 ◽

2019 ◽

Vol 26 (36) ◽

pp. 6519-6543 ◽

Cited By ~ 1

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.

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Immunoblotting analyses using two-dimensional gel electrophoresis of Trypanosoma cruzi excreted-secreted antigens

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822004000600005 ◽

2004 ◽

Vol 37 (6) ◽

pp. 454-459

Author(s):

Adriano Gomes Silva ◽

Elisangela Paula Silveira-Lacerda ◽

Jair Pereira Cunha-Júnior ◽

Maria Aparecida de Souza ◽

Silvio Favoreto Junior

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Gel Electrophoresis ◽

Complex Mixture ◽

Chronic Phase ◽

Disease Diagnosis ◽

Basic Knowledge ◽

Two Dimensional ◽

Two Dimensional Gel Electrophoresis ◽

Secreted Antigens

Trypanosoma cruzi trypomastigotes excrete-secrete a complex mixture of antigenic molecules. This antigenic mixture denominated trypomastigote excreted-secreted antigens contains a 150-160 kDa band that shows excellent performance in Chagas' disease diagnosis by immunoblotting. The present study partially characterized by two-dimensional gel electrophoresis the immunoreactivity against the 150-160kDa protein using sera samples from chagasic patients in different phases of the disease. Trypomastigote excreted-secreted antigen preparations were subjected to high-resolution two-dimensional (2D) gel electrophoresis followed by immunoblotting with sera from chagasic and non-chagasic patients. The 150-160kDa protein presented four isoforms with isoelectric focusing ranging from 6.2 to 6.7. The four isoforms were recognized by IgM from acute phase and IgG from chronic phase sera of chagasic patients. The 150-160kDa isoform with IF of approximately 6.4 became the immunodominant spot with the progression of the disease. No cross-reactivity was observed with non-chagasic or patients infected with Leishmania sp. In this study we provide basic knowledge that supports the validation of trypomastigote excreted-secreted antigens for serological diagnosis of Chagas' disease.

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