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Microorganisms
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Chagas Disease (American Trypanosomiasis)
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Chagas Disease (American Trypanosomiasis)

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Parasitology".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 13236

Special Issue Editors

Prof. Joaquim Gascon

E-Mail Website
Guest Editor
Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - University of Barcelona, 08036 Barcelona, Spain
Interests: Chagas disease; Trypanosoma cruzi; diagnosis; treatment; biomarkers; drug discovery; social impact; vaccine development
Dr. Julio Alonso-Padilla

E-Mail Website
Guest Editor
Barcelona Institute for Global Health (ISGlobal), 08036 Barcelona, Spain
Interests: Chagas disease; Trypanosoma cruzi; epitope-based vaccines; diagnostics; immune-informatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chagas disease (or American trypanosomiasis), which is caused by infection with the protozoan parasite Trypanosoma cruzi, continues to be a major public health problem in Latin America, where the majority of the more than 6 million people affected live. Historically neglected, the increasing research interest in the disease in the last few decades has permitted notable advances towards knowledge-driven control of the disease. These have been ultimately evidenced through the performance of several drug clinical trials, which have consisted of the evaluation of new drugs (azole derivatives) as well as the assessment of new regimes of existing drugs (benznidazole and nifurtimox). Nonetheless, the reality is that only a small fraction of those chronically infected by T. cruzi have access to diagnosis and treatment, and so many challenges remain.

From a diagnosis perspective, the use of point-of-care diagnostics, which are better suited to the field conditions found in many highly endemic areas, could be further explored. Looking at the treatment possibilities, although shorter and intermittent regimes with reduced dosages of benznidazole and nifurtimox are being pursued, the search for new drugs and vaccines should also be further promoted with the hope of identifying safer and more efficacious treatments. In relation to this, the discovery of biomarkers for the early assessment of treatment efficacy and/or to anticipate clinical progression represents a research subject of utmost relevance in terms of controlling the disease impact. Finally, the social impact of Chagas disease is a field of investigation that is gaining pace, as it overarches all previous subjects, both on the scale of the individual, and the scale of population-level health economics.

In this Special Issue, we invite you to contribute with original research articles, letters, or reviews related to Chagas disease, with a focus on the evaluation of point-of-care diagnostics, elucidation of the mechanisms of pathogenesis, assessment of biomarkers to assess treatment efficacy and disease prognosis, but also with manuscripts dealing with recent advances in drug and vaccine development and those related to the social and societal impact of the disease.

Prof. Joaquim Gascon
Dr. Julio Alonso-Padilla
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Chagas disease
  • Trypanosoma cruzi
  • diagnosis
  • point-of-care
  • treatment
  • efficacy assessment
  • biomarkers
  • prognosis
  • social impact evaluation
  • pharmacovigilance
  • drugs discovery
  • vaccine

Published Papers (6 papers)

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19 pages, 4606 KiB  
Article
Temporal and Wash-Out Studies Identify Medicines for Malaria Venture Pathogen Box Compounds with Fast-Acting Activity against Both Trypanosoma cruzi and Trypanosoma brucei
by Melissa L. Sykes, Emily K. Kennedy, Kevin D. Read, Marcel Kaiser and Vicky M. Avery
Microorganisms 2022, 10(7), 1287; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10071287 - 25 Jun 2022
Cited by 2 | Viewed by 1705
Abstract
Chagas disease caused by the protozoan Trypanosoma cruzi is endemic to 21 countries in the Americas, effects approximately 6 million people and on average results in 12,000 deaths annually. Human African Trypanosomiasis (HAT) is caused by the Trypanosoma brucei sub-species, endemic to 36 [...] Read more.
Chagas disease caused by the protozoan Trypanosoma cruzi is endemic to 21 countries in the Americas, effects approximately 6 million people and on average results in 12,000 deaths annually. Human African Trypanosomiasis (HAT) is caused by the Trypanosoma brucei sub-species, endemic to 36 countries within sub-Saharan Africa. Treatment regimens for these parasitic diseases are complicated and not effective against all disease stages; thus, there is a need to find improved treatments. To identify new molecules for the drug discovery pipelines for these diseases, we have utilised in vitro assays to identify compounds with selective activity against both T. cruzi and T.b. brucei from the Medicines for Malaria Venture (MMV) Pathogen Box compound collection. To prioritise these molecules for further investigation, temporal and wash off assays were utilised to identify the speed of action and cidality of compounds. For translational relevance, compounds were tested against clinically relevant T.b. brucei subspecies. Compounds with activity against T. cruzi cytochrome P450 (TcCYP51) have not previously been successful in clinical trials for chronic Chagas disease; thus, to deprioritise compounds with this activity, they were tested against recombinant TcCYP51. Compounds with biological profiles warranting progression offer important tools for drug and target development against kinetoplastids. Full article
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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12 pages, 2837 KiB  
Article
Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis
by Héctor O. Rodríguez-Angulo, Diana Colombet-Naranjo, María C. Maza, Cristina Poveda, Alfonso Herreros-Cabello, Iván Mendoza, Juan C. Perera, Juan D. Goyo, Núria Gironès and Manuel Fresno
Microorganisms 2021, 9(11), 2208; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9112208 - 23 Oct 2021
Cited by 2 | Viewed by 2044
Abstract
Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who [...] Read more.
Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger than 60 years old. HCN4 channels, one of the principal elements responsible for pacemaker currents, are associated with cardiac fetal reprogramming and supraventricular and ventricular arrhythmias, but their role in chagasic arrhythmias is not clear. We found that a single-dose administration of ivabradine, which blocks HCN4, caused QTc and QRS enlargement and an increase in P-wave amplitude and was associated with ventricular and supraventricular arrhythmias in mice challenged with isoproterenol, a chronotropic/ionotropic positive agent. Continuous treatment with ivabradine did not alter the QTc interval, but P-wave morphology was deeply modified, generating supraventricular arrhythmias. In addition, we found that repolarization parameters improved with ivabradine treatment. These effects could have been caused by the high HCN4 expression observed in auricular and ventricular tissue in infected mice. Thus, we suggest, for the first time, that molecular remodeling by overexpression of HCN4 channels may be related to supraventricular arrhythmias in acute Chagas disease, causing ivabradine over-response. Thus, ivabradine treatment should be administered with caution, while HCN4 overexpression may be an indicator of heart failure and/or sudden death risk. Full article
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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12 pages, 1750 KiB  
Article
Chagas Disease-Related Mortality in Spain, 1997 to 2018
by Jose-Manuel Ramos-Rincon, Jara Llenas-García, Hector Pinargote-Celorio, Veronica Sánchez-García, Philip Wikman-Jorgensen, Miriam Navarro, Concepción Gil-Anguita, Violeta Ramos-Sesma and Diego Torrus-Tendero
Microorganisms 2021, 9(9), 1991; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091991 - 20 Sep 2021
Cited by 4 | Viewed by 1827
Abstract
Background. Chagas disease (CD) is associated with excess mortality in infected people in endemic countries, but little information is available in non-endemic countries. The aim of the study was to analyze mortality in patients admitted to the hospital with CD in Spain. Methods. [...] Read more.
Background. Chagas disease (CD) is associated with excess mortality in infected people in endemic countries, but little information is available in non-endemic countries. The aim of the study was to analyze mortality in patients admitted to the hospital with CD in Spain. Methods. A retrospective, observational study using the Spanish National Hospital Discharge Database. We used the CD diagnostic codes of the 9th and 10th International Classification of Diseases to retrieve CD cases from the national public registry from 1997 to 2018. Results. Of the 5022 hospital admissions in people with CD, there were 56 deaths (case fatality rate (CFR) 1.1%, 95% confidence interval (CI) 0.8%, 1.4%), 20 (35.7%) of which were considered directly related to CD. The median age was higher in those who died (54.5 vs. 38 years; p < 0.001). The CFR increased with age, peaking in the 70–79-year (7.9%, odds ratio (OR) 6.27, 95% CI 1.27, 30.90) and 80–89-year (16.7%, OR 14.7, 95% CI 2.70, 79.90) age groups. Men comprised a higher proportion of those who died compared to survivors (50% vs. 22.6%; p < 0.001). Non-survivors were more likely to have neoplasms (19.6% vs. 3.4%; p < 0.001), heart failure (17.9% vs. 7.2%; p = 0.002), diabetes (12.5% vs. 3.7%; p = 0.001), chronic kidney failure (8.9% vs. 1.6%; p < 0.001), and HIV (8.9% vs. 0.8%; p < 0.001). In the multivariable analysis, the variables associated with mortality were age (adjusted OR (aOR) 1.05; 95% CI: 1.03, 1.07), male sex (aOR 1.79, 95% CI 1.03, 3.14), cancer (aOR: 4.84, 95% CI 2.13, 11.22), and HIV infection (aOR 14.10 95% CI 4.88, 40.73). Conclusions. The case fatality rate of CD hospitalization was about 1%. The mortality risk increased with age, male sex, cancer, and HIV infection. Full article
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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12 pages, 938 KiB  
Article
Feasibility of a Combined Mobile-Health Electrocardiographic and Rapid Diagnostic Test Screening for Chagas-Related Cardiac Alterations
by Michele Spinicci, Carlo Fumagalli, Niccolò Maurizi, Enrico Guglielmi, Mimmo Roselli, Herlan Gamboa, Marianne Strohmeyer, Veronica Poma, Roberto Vargas, Iacopo Olivotto and Alessandro Bartoloni
Microorganisms 2021, 9(9), 1889; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091889 - 06 Sep 2021
Cited by 5 | Viewed by 1793
Abstract
Background: Chronic Chagas cardiomyopathy (CChC) is the most common cause of death related to Chagas disease (CD). The aim of this study was to assess the feasibility of a combined rapid diagnostic test (RDT) and electrocardiographic (ECG) screening in a remote rural village [...] Read more.
Background: Chronic Chagas cardiomyopathy (CChC) is the most common cause of death related to Chagas disease (CD). The aim of this study was to assess the feasibility of a combined rapid diagnostic test (RDT) and electrocardiographic (ECG) screening in a remote rural village of the Bolivian Chaco, with a high prevalence of CChC. Methods: Consecutive healthy volunteers > 15 years were enrolled in the community of Palmarito (municipality of Gutierrez, Santa Cruz Department, Bolivia) in February 2019. All patients performed an RDT with Chagas Stat-Pak® (CSP, Chembio Diagnostic System, Medford, NY, USA) and an ECG by D-Heart® technology, a low-cost, user-friendly smartphone-based 8-lead Bluetooth ECG. RDTs were read locally while ECGs were sent to a cardiology clinic which transmitted reports within 24 h from recording. Results: Among 140 people (54 men, median age 38(interquartile range 23–54) years), 98 (70%) were positive for Trypanosoma cruzi infection, with a linear, age-dependent, increasing trend (p < 0.001). Twenty-five (18%) individuals showed ECG abnormalities compatible with CD. Prevalence of ECG abnormalities was higher in infected individuals and was associated with higher systolic blood pressure and smoking. Following screening, 22 (16%) individuals underwent clinical evaluation and chest X-ray and two were referred for further evaluation. At multivariate analysis, positive CSP results (OR = 4.75, 95%CI 1.08–20.96, p = 0.039) and smoking (OR = 4.20, 95%CI 1.18–14.92, p = 0.027) were independent predictors of ECG abnormalities. Overall cost for screening implementation was <10 $. Conclusions: Combined mobile-Health and RDTs was a reliable and effective low-cost strategy to identify patients at high risk of disease needing cardiologic assessment suggesting potential future applications. Full article
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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19 pages, 2196 KiB  
Article
Early Post-Prandial Regulation of Protein Expression in the Midgut of Chagas Disease Vector Rhodnius prolixus Highlights New Potential Targets for Vector Control Strategy
by Radouane Ouali, Larissa Rezende Vieira, Didier Salmon and Sabrina Bousbata
Microorganisms 2021, 9(4), 804; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9040804 - 11 Apr 2021
Cited by 6 | Viewed by 2387
Abstract
Chagas disease is a vector-borne parasitic disease caused by the flagellated protozoan Trypanosoma cruzi and transmitted to humans by a large group of bloodsucking triatomine bugs. Triatomine insects, such as Rhodnius prolixus, ingest a huge amount of blood in a single meal. [...] Read more.
Chagas disease is a vector-borne parasitic disease caused by the flagellated protozoan Trypanosoma cruzi and transmitted to humans by a large group of bloodsucking triatomine bugs. Triatomine insects, such as Rhodnius prolixus, ingest a huge amount of blood in a single meal. Their midgut represents an important interface for triatomine–trypanosome interactions. Furthermore, the development of parasites and their vectorial transmission are closely linked to the blood feeding and digestion; thus, an understanding of their physiology is essential for the development of new strategies to control triatomines. In this study, we used label-free quantitative proteomics to identify and analyze the early effect of blood feeding on protein expression in the midgut of Rhodnius prolixus. We both identified and quantified 124 proteins in the anterior midgut (AM) and 40 in the posterior midgut (PM), which vary significantly 6 h after feeding. The detailed analysis of these proteins revealed their predominant involvement in the primary function of hematophagy, including proteases, proteases inhibitors, amino acids metabolism, primary metabolites processing, and protein folding. Interestingly, our proteomics data show a potential role of the AM in protein digestion. Moreover, proteins related to detoxification processes and innate immunity, which are largely accepted to be triggered by blood ingestion, were mildly modulated. Surprisingly, one third of blood-regulated proteins in the AM have unknown function. This work contributes to the improvement of knowledge on the digestive physiology of triatomines in the early hours post-feeding. It provides key information for selecting new putative targets for the development of triatomine control tools and their potential role in the vector competence, which could be applied to other vector species. Full article
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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9 pages, 1622 KiB  
Case Report
Acute Pediatric Chagas Disease in Antioquia, Colombia: A Geographic Location of Suspected Oral Transmission
by Lídia Gual-Gonzalez, Catalina Arango-Ferreira, Laura Camila Lopera-Restrepo, Omar Cantillo-Barraza, Daniela Velásquez Marín, Natalia Restrepo Bustamante, Omar Triana-Chavez and Melissa S. Nolan
Microorganisms 2022, 10(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010008 - 22 Dec 2021
Cited by 2 | Viewed by 2335
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chagas Disease (American Trypanosomiasis))
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