Prognosis of chronic Chagas heart disease and other pending clinical challenges

Torres, Rosália Morais; Correia, Dalmo; Nunes, Maria do Carmo Pereira; Dutra, Walderez Ornelas; Talvani, André; Sousa, Andréa Silvestre de; Mendes, Fernanda de Souza Nogueira Sardinha; Scanavacca, Maurício; Pisani, Cristiano; Moreira, Maria da Consolação Vieira; Souza, Dilma do Socorro Moraes de; Oliveira, Wilson de; Martins, Sílvia Marinho; Dias, João Carlos Pinto

doi:10.1590/0074-02760210172

Cited by 18 publications

(22 citation statements)

References 143 publications

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“…In Latin America, the prevalence of the disease has been decreasing and becoming more notable in Europe and the United States due to global immigration ( 2 ). Among clinical disturbances, chronic Chagas cardiomyopathy (CCC) is an important cause of heart failure and sudden death with a mortality rate of approximately 0.2-19.2%, depending on the population studied ( 3 – 5 ). The pathophysiology of CCC is still not completely understood and some hypotheses have been suggested ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…Among clinical disturbances, chronic Chagas cardiomyopathy (CCC) is an important cause of heart failure and sudden death with a mortality rate of approximately 0.2-19.2%, depending on the population studied ( 3 – 5 ). The pathophysiology of CCC is still not completely understood and some hypotheses have been suggested ( 5 ). Myocyte destruction by the protozoan does not appear to be a dominant mechanism because parasite loads seem to be inadequate to induce the degree of observed tissue injury.…”

Section: Introductionmentioning

confidence: 99%

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Functional antibodies against G-protein coupled receptors in Beagle dogs infected with two different strains of Trypanosoma cruzi

et al. 2022

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The interaction of the anti-beta1-adrenergic receptor autoantibodies (β1ARAb) and the anti-muscarinic M2 receptor autoantibodies (M2RAb) with cardiac neurotransmitter receptors were identified in human chronic Chagas cardiomyopathy (CCC) related to the ECG and dysautonomia disturbances. Dogs are considered gold model to the study of Trypanosoma cruzi infection due the clinical similarities with CCC. This study aims to evaluate whether anti-β1ARAb, anti-β2ARAb, and anti-muscarinic M2RAb are generated in Beagle dogs infected by T. cruzi using Y and Berenice-78 strains of T. cruzi. Animals were infected with 4.0 x 103 bloodstream trypomastigotes/kg of body weight and, after 25 months of infection, blood sample was collected, and serum stored at -80°C. Dog serum was treated by ammonium sulphate precipitation and the IgG antibodies isolated and added to the beating neonatal rats’ cardiomyocytes. All T. cruzi-infected dogs developed agonistic β1ARAb, β2ARAb, and M2RAb. Animals infected by Berenice strain presented less β2ARAb and M2RAb activities than dogs infected by Y strain of the parasite. In cardiomyocytes culture, the antibodies recognized an epitope on the second extracellular loop of the receptors which were similar to findings in human Chagas disease. There was no detection of antibody against G protein-coupled receptor in serum from uninfected dogs. In conclusion, both Y and Berenice-78 strains of T. cruzi induced dog antibodies, whose targets located in the second extracellular loop of the adrenergic and muscarinic receptors were similar to those observed in individuals with CCC. Therefore, our findings highlight dogs as a promisor model to investigate pathogenic roles of functional Ab against G-protein coupled receptors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional antibodies against G-protein coupled receptors in Beagle dogs infected with two different strains of Trypanosoma cruzi

et al. 2022

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“…There is a bulk of evidence that parasite persistence in tissues associated with ill-adapted homeostatic mechanisms, such as oxidative/anti-oxidative and pro-inflammatory/anti-inflammatory processes, are critical for the pathogenesis and progression of organ dysfunction in CD. 18 , 19 …”

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confidence: 99%

“… 19 In Chagas’ heart disease, low-level cardiac inflammation is linked to low-grade parasite persistence, tissue injury, progressive fibrosis, electrical abnormalities, and dysfunction, potentially evolving to heart failure. 18 , 19 The progression from IND to CARD form, and its severity (mild, moderate, severe), have been directly associated with the levels of the systemic inflammatory profile, revealed as increased serum levels of inflammatory (TNF, IL-6, IL-17, IFNγ, CCL2/MCP1) and regulatory/anti-inflammatory (IL-4, IL-10, TGFβ) cytokines, inflammatory mediators as nitric oxide, and reduced anti-oxidant enzymes as superoxide dismutase (SOD) and glutathione peroxidase (GPx), supporting inflammatory/anti-inflammatory and oxidant/anti-oxidant imbalance. 62 , 63 This is a quite relevant trait.…”

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confidence: 99%

Anxiety, depression, and memory loss in Chagas disease: a puzzle far beyond neuroinflammation to be unpicked and solved*

Lannes‐Vieira

Vilar-Pereira

Barrios

et al. 2023

Mem. Inst. Oswaldo Cruz

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Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke. The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation; however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy, parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and molecular basis of the central nervous system commitment in chronic CD.

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“…The challenge of risk assessment in the riddle of Chagas heart disease Morais-Torres et al recently provided us with an extensive review on several pending challenges the scientific community still faces in order to decipher the conundrum of diagnosis, prognosis and the adequate treatment of patients with chronic Chagas cardiomyopathy (CCC). (1) Among other no less conspicuous aspects of their review, it is relevant to emphasise that it is right on prognosis that substantial advances have been made over the last two decades of continuous progress in the understanding of the clinical issues concerning the management of CCC patients. And the authors of that important review in the Memórias do Instituto Oswaldo Cruz, in fact, did not fail to mention several relevant clinical aspects of CCC that connote plausible prognostic information.…”

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confidence: 99%