scholarly journals Glutamine increases body weight and decreases myocardial damage in Trypanosoma cruzi-infected mice treated with nifurtimox.

2021 ◽  
Vol 23 (1) ◽  
pp. 10-16
Author(s):  
Carmen Marín-Tello ◽  
◽  
César Sánchez-Marín ◽  
Luis Arteaga-Temoche ◽  
◽  
...  
Keyword(s):  
Body Weight ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Rural Areas ◽  
Cardiac Tissue ◽  
Parasitic Infection ◽  
Myocardial Damage ◽  
Glutamine Supplementation ◽  
Histopathological Analysis ◽  
Standard Diet

Chagas disease, a parasitic infection caused by the protist Trypanosoma cruzi, affect the poorest populations, living in remote, rural areas and urban slums. Although this drug is effective against Chagas disease present a number of serious side effects. In residents of high Andean areas with megacolon it can lead to cardiomyopathies. The aim of this study was to investigate whether dietary supplementation with L-glutamine may alleviate some of these symptoms because of its previously observed anti-inflammatory properties. We studied two groups of T. cruzi-infected mice receiving treatment with nifurtimox. One group was fed the standard diet, while the other group’s diet was supplemented with Glutamine. We found that Glutamine supplementation increases body weight (p<0.001), decreases heart mass to body mass ratio (p<0.001), and decreases the number of amastigotes present in cardiac tissue. Additionally, histopathological analysis showed less heart tissue damage in the group that received Glutaminne in their diet. Therefore, our findings suggest that Glutamine supplementation improves nifurtimox treatment outcomes of T. cruzi 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 The epidemiologic profile and prevalence of cardiopathy in Trypanosoma cruzi infected blood donor candidates, Londrina, Paraná, Brazil

2005 ◽  
Vol 47 (6) ◽  
pp. 321-326 ◽  
Author(s):  
Divina Seila de Oliveira-Marques ◽  
Ana Maria Bonametti ◽  
Tiemi Matsuo ◽  
Francisco Gregori Junior
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Blood Donor ◽  
Rural Areas ◽  
Family Income ◽  
State University ◽  
Cardiac Symptoms ◽  
Significant Difference ◽  
Epidemiologic Profile ◽  
The City

To describe the epidemiologic profile and prevalence of cardiopathy in 163 Trypanosoma cruzi serum positive blood donor candidates, a descriptive study was carried out between August, 1996 and November, 1997 at the Londrina State University Chagas Disease Outpatient Clinic. The profile found was: young, average age 42.95 ± 8.62 years; male (65%); Caucasian (84%); low level of schooling; low family income; agricultural worker (26%); born in the state of Paraná (67%); from rural areas (85%); migrated to the city (85%); and the vector as the main mechanism of transmission. During the clinical characterization a chronic cardiac form was found in 38% of the patients and classified as cardiac suggestive form in 21% and little suggestive of Chagas disease in 17%. No significant difference was found among age group distribution, sex and the presence of cardiac symptoms in patients with or without cardiopathy. This study emphasizes the importance of expanding medical services to areas with a greater prevalence of infected individuals, in a hierarchical manner and aiming at decentralization.

scholarly journals Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents Against Trypanosoma cruzi

2021 ◽  
Author(s):  
Jean A. Bernatchez ◽  
Yun-Seo Kil ◽  
Elany Barbosa da Silva ◽  
Diane Thomas ◽  
Laura-Isobel McCall ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasitic Infection ◽  
Antiparasitic Activity ◽  
Gastrointestinal Pathology ◽  
Phenotypic Screen ◽  
Benthic Environment ◽  
Intracellular Amastigote ◽  
Kinetoplastid Parasite

Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid parasite Trypanosoma cruzi, have yet to be developed. Benznidazole and nifurtimox, which are currently the only available drugs against T. cruzi, are associated with severe adverse effects and questionable efficacy in the late stage of the disease. Natural products have proven to be a rich source of new chemotypes for other infectious agents. We utilized a microscopy-based high-throughput phenotypic screen to identify inhibitors of T. cruzi from a library of natural product samples obtained from fungi procured through a Citizen Science Soil Collection Program (https://whatsinyourbackyard.org/), and the Great Lakes (USA) benthic environment. We identified five leucinostatins (A, B, F, NPDG C and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi. Leucinostatin B also showed in vivo efficacy in a mouse model of Chagas disease. Given prior reports that leucinostatins A and B have antiparasitic activity against the related kinetoplastid T. brucei, our findings suggest a potential cross-trypanocidal compound class and provide a platform for further chemical derivatization of a potent chemical scaffold against T. cruzi.

scholarly journals Usefulness of serology for the evaluation of Trypanosoma cruzi transmission in endemic areas of Chagas' disease

1989 ◽  
Vol 22 (3) ◽  
pp. 119-124 ◽  
Author(s):  
Roberto Chuit ◽  
Elisabet Subias ◽  
Analia C. Pérez ◽  
Irene Paulone ◽  
Cristina Wisnivesky-Colli ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Rural Areas ◽  
Culture Media ◽  
Previous Treatment ◽  
Insecticide Treatment ◽  
Tissue Culture Media ◽  
Indirect Hemagglutination ◽  
History Of

Thirteen communities from 7 Argentinian provinces were selected for the evaluation of serology as an indicator of transmission of Chagas disease. Of the communities appraised, 6 did not have a history of previous treatment with insecticides and 7 had received sporadic or continuous insecticide treatment. The inhabitants of 20% of the houses of each locality were studied by serology. The samples were obtained byfinger pricking and 50 fil of blood were mixed with 150μl of 50% glycerine solution in tissue culture media to be assayed by Indirect Hemagglutination and Indirect Immunofluorescence tests. In untreated areas, the prevalence of infection in infants 0-4 years old was 17.5%, reaching to over 22% for the 5-9 year old group, and to 33.3% in 10-14 year old individuals. The prevalence in treated and surveyed areas was 2.6% in 0-4 year old children, 5.4% in 5-9 year old and 6,2% in 10-14 year old youngsters. The differences between both areas were statistically significant (p < 0.005). This study favors serology as a valid indicator for the evaluation of transmission of Chagas disease in rural areas.

scholarly journals Increased heart fibrosis and acute infection in a murine Chagas disease model associated with organophosphorus pesticide metabolite exposure

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dunia Margarita Medina-Buelvas ◽  
Elizabet Estrada-Muñiz ◽  
Miriam Rodríguez-Sosa ◽  
Mineko Shibayama ◽  
Libia Vega
Keyword(s):  
Chagas Disease ◽  
Cardiac Fibrosis ◽  
Acute Infection ◽  
Disease Model ◽  
Parasitic Infection ◽  
Organophosphorus Pesticide ◽  
Parasite Burden ◽  
Myocardial Damage ◽  
Inflammatory Cells ◽  
Inflammatory Macrophages

AbstractSome reports suggest that exposure to organophosphorus (OP) pesticides increases the incidence of infections. Ethylated dialkylphosphates (EtDAPs) are metabolites of OP pesticides widely distributed with immunomodulatory potential. Chagas disease is produced by Trypanosoma cruzi parasites, and resolution of this infection requires the activation of inflammatory macrophages (MΦ), which results in cardiac fibrosis. Some reports indicate that EtDAPs increase the amount of the anti-inflammatory alternatively activated MΦ (M2; CD206+F4/80+). Therefore, we analyzed the course of T. cruzi infection, MΦ profiles from peritoneal exudate cells (PECs), inflammatory cell infiltration and fibrosis in the heart of BALB/c mice exposed to diethyldithiophosphate (DEDTP), diethylthiophosphate (DETP) or diethylphosphate (DEP, 0.01 g/kg), common DAPs produced by OP pesticides, 24 h before infection with T. cruzi. We found that DEDTP increased the parasite burden in blood by 99% at the peak of the infection and enhanced the myocardial damage due to an increase in infiltrated inflammatory cells (induced by DEDTP or DETP) and fibrosis (induced by EtDAPs). In the PECs, exposure to EtDAPs increased the proportion of the MΦ subpopulations of M2a, M2b and M2d, which are associated with tissue repair. These results indicate that exposure to EtDAPs can exacerbate the acute phase of a parasitic infection and increase the long-term damage to the heart.

scholarly journals SB-431542, a Transforming Growth Factor β Inhibitor, Impairs Trypanosoma cruzi Infection in Cardiomyocytes and Parasite Cycle Completion

2007 ◽  
Vol 51 (8) ◽  
pp. 2905-2910 ◽  
Author(s):  
Mariana C. Waghabi ◽  
Michelle Keramidas ◽  
Claudia M. Calvet ◽  
Marcos Meuser ◽  
Maria de Nazaré C. Soeiro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Trypanosoma Cruzi ◽  
Signaling Pathway ◽  
Chagas Disease ◽  
Transforming Growth Factor ◽  
Parasitic Infection ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Cruzi Infection

ABSTRACT The antiinflammatory cytokine transforming growth factor β (TGF-β) plays an important role in Chagas disease, a parasitic infection caused by the protozoan Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-β type I receptor (ALK5), inhibits T. cruzi-induced activation of the TGF-β pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by T. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-β signaling pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our present data demonstrate that small inhibitors of the TGF-β signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.

scholarly journals Acute Pediatric Chagas Disease in Antioquia, Colombia: A Geographic Location of Suspected Oral Transmission

2021 ◽  
Vol 10 (1) ◽  
pp. 8
Author(s):  
Lídia Gual-Gonzalez ◽  
Catalina Arango-Ferreira ◽  
Laura Camila Lopera-Restrepo ◽  
Omar Cantillo-Barraza ◽  
Daniela Velásquez Marín ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Parasitic Infection ◽  
Clinical Manifestations ◽  
Geographic Location ◽  
Myocardial Damage ◽  
Geographic Region ◽  
Structural Barriers ◽  
Oral Transmission ◽  
Physician Awareness ◽  
Epidemiologic Risk

Chagas disease, Trypanosoma cruzi infection, is an insidious cause of heart failure in Latin America. Early diagnosis and treatment are critical to prevent irreversible myocardial damage that progressively accumulates over decades. Several structural barriers account for the less than 1% of cases in Colombia being treated, including poor physician knowledge, especially considering that some regions are considered non-endemic. The two cases reported here represent an emerging epidemiologic scenario associated with pediatric Chagas disease. Both cases are suspected oral transmitted parasitic infection in a geographic region of Colombia (Andean region of Antioquia) where no previous oral transmission of Chagas disease had been reported. Their clinical histories and course of disease are presented here to increase physician awareness of the epidemiologic risk factors and clinical manifestations associated with pediatric oral Chagas disease in Antioquia department, Colombia.

In vitro studies and preclinical evaluation of benznidazole microparticles in the acute Trypanosoma cruzi murine model

Parasitology ◽  
2020 ◽  
pp. 1-10
Author(s):  
Marcela S. Rial ◽  
Katia P. Seremeta ◽  
Mónica I. Esteva ◽  
Jacqueline Búa ◽  
Claudio J. Salomon ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Murine Model ◽  
Morphological Changes ◽  
Quantitative Polymerase Chain Reaction ◽  
Parasitic Infection ◽  
Parasite Load ◽  
Enzyme Linked Immunosorbent Assay ◽  
Significant Difference

Abstract Chagas disease is a serious parasitic infection caused by Trypanosoma cruzi. Unfortunately, the current chemotherapeutic tools are not enough to combat the infection. The aim of this study was to evaluate the trypanocidal activity of benznidazole-loaded microparticles during the acute phase of Chagas infection in an experimental murine model. Microparticles were prepared by spray-drying using copolymers derived from esters of acrylic and methacrylic acids as carriers. Dissolution efficiency of the formulations was up to 3.80-fold greater than that of raw benznidazole. Stability assay showed no significant difference (P > 0.05) in the loading capacity of microparticles for 3 years. Cell cultures showed no visible morphological changes or destabilization of the cell membrane nor haemolysis was observed in defibrinated human blood after microparticles treatment. Mice with acute lethal infection survived 100% after 30 days of treatment with benznidazole microparticles (50 mg kg−1 day−1). Furthermore, no detectable parasite load measured by quantitative polymerase chain reaction and lower levels of T. cruzi-specific antibodies by enzyme-linked immunosorbent assay were found in those mice. A significant decrease in the inflammation of heart tissue after treatment with these microparticles was observed, in comparison with the inflammatory damage observed in both infected mice treated with raw benznidazole and untreated infected mice. Therefore, these polymeric formulations are an attractive approach to treat Chagas disease.

Repositioning of HIV Aspartyl Peptidase Inhibitors for Combating the Neglected Human Pathogen Trypanosoma cruzi

2019 ◽  
Vol 26 (36) ◽  
pp. 6590-6613 ◽  
Author(s):  
Leandro S. Sangenito ◽  
Rubem F.S. Menna-Barreto ◽  
Cláudia M. d'Avila-Levy ◽  
Marta H. Branquinha ◽  
André L.S. Santos
Keyword(s):  
Human Immunodeficiency Virus ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasitic Infection ◽  
Clinical Signs ◽  
Chronic Phase ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Peptidase Inhibitors ◽  
Immunodeficiency Virus

Chagas disease, caused by the flagellate parasite Trypanosoma cruzi, is a wellknown neglected tropical disease. This parasitic illness affects 6-7 million people and can lead to severe myocarditis and/or complications of the digestive tract. The changes in its epidemiology facilitate co-infection with the Human Immunodeficiency Virus (HIV), making even more difficult the diagnosis and prognosis. The parasitic infection is reactivated in T. cruzi/HIV co-infection, with the appearance of unusual manifestations in the chronic phase and the exacerbation of classical clinical signs. The therapeutic arsenal to treat Chagas disease, in all its clinical forms, is restricted basically to two drugs, benznidazole and nifurtimox. Both drugs are extremely toxic and the therapeutic efficacy is still unclear, making the clinical treatment a huge issue to be solved. Therefore, it seems obvious the necessity of new tangible approaches to combat this illness. In this sense, the repositioning of approved drugs appears as an interesting and viable strategy. The discovery of Human Immunodeficiency Virus Aspartyl Peptidase Inhibitors (HIV-PIs) represented a milestone in the treatment of Acquired Immune Deficiency Syndrome (AIDS) and, concomitantly, a marked reduction in both the incidence and prevalence of important bacterial, fungal and parasitic co-infections was clearly observed. Taking all these findings into consideration, the present review summarizes the promising and beneficial data concerning the effects of HIV-PIs on all the evolutionary forms of T. cruzi and in important steps of the parasite’s life cycle, which highlight their possible application as alternative drugs to treat Chagas disease.

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