Exploring the parasite load and molecular diversity of Trypanosoma cruzi in patients with chronic Chagas disease from different regions of Brazil

Rodrigues-dos-Santos, Ícaro; Melo, Myllena F. A. D.; Castro, L. de; Hasslocher‐Moreno, Alejandro Marcel; Brasil, Pedro Emmanuel Alvarenga Americano do; Sousa, Andréa Silvestre de; Britto, Constança; Moreira, Otacílio C.

doi:10.1371/journal.pntd.0006939

Cited by 46 publications

(55 citation statements)

References 37 publications

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“…Finally, although we believe that the chronic CD patients of the state of Paraná might be representative of countries from the Southern Cone, further investigation in other regions of Brazil is desirable as the clinical forms may also be influenced by genetically diverse T. cruzi according to discrete typing units (DTUs) 81 . Thus, it is imperative to improve our understanding of the epidemiologic background and pathophysiologic aspects of this neglected disease.…”

Section: Discussionmentioning

confidence: 99%

Clinical and epidemiological aspects of chronic Chagas disease from Southern Brazil

Lidani

Sandri

Castillo-Neyra

et al. 2020

Rev. Soc. Bras. Med. Trop.

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Introduction: Patients with Chagas disease (CD), caused by Trypanosoma cruzi, present a higher risk of developing other chronic diseases, which may contribute to CD severity. Since CD is underreported in the southern state of Paraná, Brazil, we aimed to characterize clinical and epidemiological aspects of individuals chronically infected with T. cruzi in Southern Brazil. Methods: A community hospital-based study was performed, recording clinical/demographic characteristics of 237 patients with CD from Southern Brazil. To estimate the association between different forms of CD and sociodemographic and clinical variables, multiple logistic regression models were built using the Akaike information criterion. Results: Mean age was 57.5 years and 59% were females. Most patients' (60%) place of origin/birth was within Paraná and they were admitted to the CD outpatient clinic after presenting with cardiac/digestive symptoms (64%). The predominant form of CD was cardiac (53%), followed by indeterminate (36%), and digestive (11%). The main electrocardiographic changes were in the right bundle branch block (39%) and left anterior fascicular block (32%). The average number of comorbidities per patient was 3.9±2.3; systemic arterial hypertension was most common (64%), followed by dyslipidemia (34%) and diabetes (19%); overlapping comorbidities were counted separately. Male sex was associated with symptomatic cardiac CD (OR=2.92; 95%CI: 1.05-8.12; p=0.040). Conclusions: This study provided greater understanding of the distribution and clinical profile of CD patients in Southern Brazil, indicating a high prevalence of comorbidities among these patients who are a vulnerable group due to advanced age and substantial risk of morbidity.

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Section: Discussionmentioning

confidence: 99%

Clinical and epidemiological aspects of chronic Chagas disease from Southern Brazil

Lidani

Sandri

Castillo-Neyra

et al. 2020

Rev. Soc. Bras. Med. Trop.

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“…While parasite persistence is required for progression to chronic CD 24 , only a minority of infected patients progress to symptomatic disease 4 , and parasite load does not fully predict disease severity ( e.g. 25 ), indicating that disease tolerance mechanisms also regulate CD progression, although these are not well understood. Our novel finding that carnitine modulation determines infection outcome ( Fig.…”

Section: Discussionmentioning

confidence: 99%

3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

Hossain

Khanam

et al. 2019

Preprint

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Chagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi protozoa. Over 8 million people worldwide are T. cruzi-positive, 20-30% of which will develop cardiomyopathy, megaoesophagus and/or megacolon. The mechanisms leading to gastrointestinal (GI) symptom development are however poorly understood. To address this issue, we systematically characterized the spatial impact of experimental T. cruzi infection on the microbiome and metabolome across the GI tract. The largest microbiota perturbations were observed in the proximal large intestine in both acute and chronic disease, with chronic-stage effects also observed in the cecum. Strikingly, metabolomic impact of acute-to-chronic stage transition differed depending on the organ, with persistent large-scale effects of infection primarily in the oesophagus and large intestine, providing a potential mechanism for GI pathology tropism in CD. Infection particularly affected acylcarnitine and lipid metabolism. Building on these observations, treatment of infected mice with carnitine-supplemented drinking water prevented acute-stage mortality with no changes in parasite burden. Overall, these results identified a new mechanism of disease tolerance in CD, with potential for the development of new therapeutic regimens. More broadly, these results highlight the potential of spatially-resolved metabolomic approaches to provide insight into disease pathogenesis, with translational applications for infectious disease drug development.

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“…Chagas disease is an endemic zoonosis in some countries of Central and South America that has Trypanosoma cruzi as its etiological agent, which affects 6-7 million individuals and still remains a major public health problem (World Health Organization [WHO], 2017). T. cruzi is represented by a group of isolates that shows distinct levels of sensitivity to drugs, disease prognosis and pathogenicity (Macedo and Pena, 1998;Campbell et al, 2004), as well as eco-epidemiological complexity (Miles et al, 2009;Brenière et al, 2016;Rodrigues-dos-Santos et al, 2018). The chemotherapy currently used is based on antiparasitics such as, nifurtimox and benznidazole, which cause many side effects and present a lack of effectiveness on the chronic phase of the disease (Bern, 2011;Morillo et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Knocking Down TcNTPDase-1 Gene Reduces in vitro Infectivity of Trypanosoma cruzi

Silva-Gomes

Rampazzo

Moreira³

et al. 2020

Front. Microbiol.

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Ecto-Nucleoside Triphosphate Diphosphohydrolases are enzymes that hydrolyze tri-and/or diphosphate nucleosides. Evidences pointed out to their participation in Trypanosoma cruzi virulence, infectivity, and purine acquisition. In this study, recombinant T. cruzi knocking out or overexpressing the TcNTPDase-1 gene were built, and the role of TcNTPDase-1 in the in vitro interaction with VERO cells was investigated. Results show that epimastigote forms of hemi-knockout parasites showed about 50% lower level of TcNTPDase-1 gene expression when compared to the wild type, while the T. cruzi overexpressing this gene reach 20 times higher gene expression. In trypomastigote forms, the same decreasing in TcNTPDase-1 gene expression was observed to the hemi-knockout parasites. The in vitro infection assays showed a reduction to 51.6 and 59.9% at the adhesion and to 25.2 and 26.4% at the endocytic indexes to the parasites knockout to one or other allele (Hygro and Neo hemiknockouts), respectively. In contrast, the infection assays with T. cruzi overexpressing TcNTPDase-1 from the WT or Neo hemi-knockout parasites showed an opposite result, with the increasing to 287.7 and 271.1% at the adhesion and to 220.4 and 186.7% at the endocytic indexes, respectively. The parasitic load estimated in infected VERO cells by quantitative real time PCR corroborated these findings. Taken together, the partial silencing and overexpression of the TcNTPDase-1 gene generated viable parasites with low and high infectivity rates, respectively, corroborating that the enzyme encoded for this gene plays an important role to the T. cruzi infectivity.

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Exploring the parasite load and molecular diversity of Trypanosoma cruzi in patients with chronic Chagas disease from different regions of Brazil

Cited by 46 publications

References 37 publications

Clinical and epidemiological aspects of chronic Chagas disease from Southern Brazil

Clinical and epidemiological aspects of chronic Chagas disease from Southern Brazil

3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

Knocking Down TcNTPDase-1 Gene Reduces in vitro Infectivity of Trypanosoma cruzi

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