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Chagas Disease: Celebrating the 115th Anniversary of the Discovery of...
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Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 8194

Special Issue Editor

Dr. Michel Tibayrenc

E-Mail Website
Guest Editor
MIVEGEC (IRD 224-CNRS 5290-UM1-UM2), Institute of Research for the Development, 34394 Montpellier CEDEX 5, France
Interests: genetics and evolution of infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is my pleasure to introduce this Special Issue on Chagas disease, celebrating the 115th anniversary of the discovery of its causative agent. Our knowledge on the disease has made substantial progress in the last 20 years thanks to the impressive development of modern technologies ranging from genomics to megacomputing and artificial intelligence (AI). However, this should not occult the fact that the spread of Chagas disease is chiefly due to socioeconomical factors (poor habitats, sanitary education, access to health systems, etc.). This Special Issue will therefore keep a balance between advanced technology and socioecology. Considering the considerable role played by Latin American scientists, I am very happy to welcome the contribution of many of them in this Special Issue. My hope is that it will constitute a historical landmark in continuing research on this disease, which still poses a considerable public health challenge.

Dr. Michel Tibayrenc
Guest Editor

Manuscript Submission Information

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Keywords

  • parasitology
  • genomics
  • drug development
  • socioeconomical factors
  • public health

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Published Papers (10 papers)

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Research

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13 pages, 1675 KiB  
Article
In Vivo Imaging of Cardiac Attachment of TcI and TcII Variants of Trypanosoma cruzi in a Zebrafish Model
by Victoria E. Rodriguez-Castellanos, Cristhian David Perdomo-Gómez, Juan Carlos Santos-Barbosa, Manu Forero-Shelton, Verónica Akle and John M. González
Pathogens 2025, 14(1), 25; https://doi.org/10.3390/pathogens14010025 - 1 Jan 2025
Viewed by 1066
Abstract
Trypanosoma cruzi, the etiological agent of Chagas disease, is a parasite known for its diverse genotypic variants, or Discrete Typing Units (DTUs), which have been associated with varying degrees of tissue involvement. However, aspects such as parasite attachment remain unclear. It has [...] Read more.
Trypanosoma cruzi, the etiological agent of Chagas disease, is a parasite known for its diverse genotypic variants, or Discrete Typing Units (DTUs), which have been associated with varying degrees of tissue involvement. However, aspects such as parasite attachment remain unclear. It has been suggested that the TcI genotype is associated with cardiac infection, the most common involved site in chronic human infection, while TcII is associated with digestive tract involvement. Traditional models for T. cruzi infection provide limited in vivo observation, making it challenging to observe the dynamics of parasite-host interactions. This study evaluates the cardiac attachment of trypomastigotes from TcI and TcII DTUs in zebrafish larvae. Labeled trypomastigotes were injected in the duct of Cuvier of zebrafish larvae and tracked by stereomicroscopy and light-sheet fluorescence microscopy (LSFM). Remarkably, it was possible to observe TcI parasites adhered to the atrium, atrioventricular valve, and circulatory system, while TcII trypomastigotes demonstrated adhesion to the atrium, atrioventricular valve, and yolk sac extension. When TcI and TcII were simultaneously injected, they both attached to the heart; however, more of the TcII trypomastigotes were observed attached to this organ. Although TcII DTU has previously been associated with digestive tissue infection, both parasite variants showed cardiac tissue attachment in this in vivo model. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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Review

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10 pages, 251 KiB  
Review
Trypanosoma cruzi Transmission Through Blood Samples and Derivatives: Main Routes, Control Strategies, and Recent Advancements in Blood Banks
by Aline Nefertiti Silva da Gama and Maria de Nazaré Correia Soeiro
Pathogens 2025, 14(2), 133; https://doi.org/10.3390/pathogens14020133 - 2 Feb 2025
Viewed by 203
Abstract
Neglected Tropical Diseases are a group of 25 conditions caused by diverse agents. They mostly affect people with poorer health outcomes, particularly preventable diseases. The social determinants of health influence the development and progression of these poverty diseases, with inadequate sanitation presenting chronicity, [...] Read more.
Neglected Tropical Diseases are a group of 25 conditions caused by diverse agents. They mostly affect people with poorer health outcomes, particularly preventable diseases. The social determinants of health influence the development and progression of these poverty diseases, with inadequate sanitation presenting chronicity, high morbidity, and economic impacts. Chagas disease, a prominent Neglected Tropical Disease caused by the intracellular pathogen Trypanosoma cruzi, is endemic in Latin America but is increasing as a global concern due to population migration. It is transmitted through insect vectors, congenitally, orally via contaminated food and beverage, via transfusions and organ donation, and due to laboratory accidents, among other minor relevant routes. As a silent illness, with many infected individuals remaining asymptomatic, it contributes to underdiagnosis, and delayed treatment that involves nitro derivatives is often discontinued due to side effects. Chagas disease spreads in non-endemic areas like the United States of America and Europe. Blood screening practices vary, with endemic regions implementing universal testing, while non-endemic areas rely on selective methods. Recent innovations, such as riboflavin–ultraviolet light treatment and arylimidamide compounds, represent promising alternatives to reduce transfusion transmission. This review presents an analysis of Trypanosoma cruzi transmission through blood and derivatives, addressing the main routes, globally implemented control strategies, and recent advancements in blood bank safety. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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13 pages, 271 KiB  
Review
An Update on Vaccines Against Trypanosoma cruzi and Chagas Disease
by Nisha J. Garg
Pathogens 2025, 14(2), 124; https://doi.org/10.3390/pathogens14020124 - 30 Jan 2025
Viewed by 419
Abstract
Chagas disease (CD) is a global health concern, with no existing therapies to prophylactically treat adults traveling to endemic countries or those who may already be infected with Trypanosoma cruzi. The economic burden of Chagas cardiomyopathy and heart failure, due to healthcare [...] Read more.
Chagas disease (CD) is a global health concern, with no existing therapies to prophylactically treat adults traveling to endemic countries or those who may already be infected with Trypanosoma cruzi. The economic burden of Chagas cardiomyopathy and heart failure, due to healthcare costs and lost productivity from premature deaths, provides a strong rationale for investment in the development of immune therapies against CD. Vaccine efficacy is proposed to depend heavily on the induction of a robust Th1 response for the clearance of intracellular pathogens like T. cruzi. In this review, updated information on the efforts for vaccine development against CD is provided. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
25 pages, 1927 KiB  
Review
Understanding Host–Pathogen Interactions in Congenital Chagas Disease Through Transcriptomic Approaches
by Tatiana M. Cáceres, Luz Helena Patiño and Juan David Ramírez
Pathogens 2025, 14(2), 106; https://doi.org/10.3390/pathogens14020106 - 22 Jan 2025
Viewed by 597
Abstract
Chagas disease, caused by Trypanosoma cruzi, is a parasitic zoonosis with significant health impacts, particularly in Latin America. While traditionally associated with vector-borne transmission, increased migration has expanded its reach into urban and non-endemic regions. Congenital transmission has become a critical route [...] Read more.
Chagas disease, caused by Trypanosoma cruzi, is a parasitic zoonosis with significant health impacts, particularly in Latin America. While traditionally associated with vector-borne transmission, increased migration has expanded its reach into urban and non-endemic regions. Congenital transmission has become a critical route of infection, involving intricate maternal–fetal immune interactions that challenge diagnosis and treatment. This review synthesizes findings from three RNA-seq studies that explore the molecular underpinnings of congenital Chagas disease, emphasizing differentially expressed genes (DEGs) implicated in host–pathogen interactions. The DAVID tool analysis highlighted the overexpression of genes associated with the innate immune response, including pro-inflammatory cytokines that drive chemotaxis and neutrophil activation. Additionally, calcium-dependent pathways critical for parasite invasion were modulated. T. cruzi exploits the maternal–fetal immune axis to establish a tolerogenic environment conducive to congenital transmission. Alterations in placental angiogenesis, cellular regeneration, and metabolic processes further demonstrate the parasite’s ability to manipulate host responses for its survival and persistence. These findings underscore the complex interplay between the host and pathogen that facilitates disease progression. Future research integrating transcriptomic, proteomic, and metabolomic approaches is essential to unravel the molecular mechanisms underlying congenital Chagas disease, with a particular focus on the contributions of genetic diversity and non-coding RNAs in immune evasion and disease pathogenesis. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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25 pages, 393 KiB  
Review
The Body of Chagas Disease Vectors
by Jean-Pierre Dujardin
Pathogens 2025, 14(1), 98; https://doi.org/10.3390/pathogens14010098 - 20 Jan 2025
Viewed by 548
Abstract
Morphometry is an effort to describe or measure the morphology of the body, or parts of it. It also provides quantitative data on the interactions of living organisms with their environment, external or internal. As a discipline, morphometrics has undergone significant developments in [...] Read more.
Morphometry is an effort to describe or measure the morphology of the body, or parts of it. It also provides quantitative data on the interactions of living organisms with their environment, external or internal. As a discipline, morphometrics has undergone significant developments in the last decade, making its implementation more visual and less laborious. Chagas disease vectors, often referred to by the common name of “kissing bugs”, belong to the subfamily Triatominae. Due to their apparent morphological plasticity, they have been the subject of numerous morphometric studies. Most of these have been applied taking into account the particularities of this group of vectors, such as domesticity (synanthropy), food preferences, dispersal ability, insecticide resistance, as well as some taxonomic issues. This brief review over nearly three decades is organized here according to the body organs considered by the authors. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
11 pages, 613 KiB  
Review
Mitochondrial DNA Structure in Trypanosoma cruzi
by Alfonso Herreros-Cabello, Francisco Callejas-Hernández, Manuel Fresno and Núria Gironès
Pathogens 2025, 14(1), 73; https://doi.org/10.3390/pathogens14010073 - 14 Jan 2025
Viewed by 488
Abstract
Kinetoplastids display a single, large mitochondrion per cell, with their mitochondrial DNA referred to as the kinetoplast. This kinetoplast is a network of concatenated circular molecules comprising a maxicircle (20–64 kb) and up to thousands of minicircles varying in size depending on the [...] Read more.
Kinetoplastids display a single, large mitochondrion per cell, with their mitochondrial DNA referred to as the kinetoplast. This kinetoplast is a network of concatenated circular molecules comprising a maxicircle (20–64 kb) and up to thousands of minicircles varying in size depending on the species (0.5–10 kb). In Trypanosoma cruzi, maxicircles contain typical mitochondrial genes found in other eukaryotes. They consist of coding and divergent/variable regions, complicating their assembly due to repetitive elements. However, next-generation sequencing (NGS) methods have resolved these issues, enabling the complete sequencing of maxicircles from different strains. Furthermore, several insertions and deletions in the maxicircle sequences have been identified among strains, affecting specific genes. Unique to kinetoplastids, minicircles play a crucial role in a particular U-insertion/deletion RNA editing system by encoding guide RNAs (gRNAs). These gRNAs are essential for editing and maturing maxicircle mRNAs. In Trypanosoma cruzi, although only a few studies have utilized NGS methods to date, the structure of these molecules suggests a classification into four main groups of minicircles. This classification is based on their size and the number of highly conserved regions (mHCRs) and hypervariable regions (mHVRs). Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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17 pages, 806 KiB  
Review
Molecular Markers for the Phylogenetic Reconstruction of Trypanosoma cruzi: A Quantitative Review
by David Ramírez-Delgado and Carlos Alberto Flores-López
Pathogens 2025, 14(1), 72; https://doi.org/10.3390/pathogens14010072 - 14 Jan 2025
Viewed by 592
Abstract
Trypanosoma cruzi is the parasite responsible for Chagas disease, which has a significant amount of genetic diversification among the species complex. Many efforts are routinely made to characterize the genetic lineages of T. cruzi circulating in a particular geographic area. However, the genetic [...] Read more.
Trypanosoma cruzi is the parasite responsible for Chagas disease, which has a significant amount of genetic diversification among the species complex. Many efforts are routinely made to characterize the genetic lineages of T. cruzi circulating in a particular geographic area. However, the genetic loci used to typify the genetic lineages of T. cruzi have not been consistent between studies. We report a quantitative analysis of the phylogenetic power that is acquired from the commonly used genetic loci that are employed for the typification of T. cruzi into its current taxonomic nomenclature. Based on three quantitative criteria (the number of phylogenetic informative characters, number of available reference sequences in public repositories, and accessibility to DNA sequences for their use as outgroup sequences), we examine and discuss the most appropriate genetic loci for the genetic typification of T. cruzi. Although the mini-exon gene is by far the locus that has been most widely used, it is not the most appropriate marker for the typification of T. cruzi based on the construction of a resolved phylogenetic tree. Overall, the mitochondrial COII-NDI locus stands out as the best molecular marker for this purpose, followed by the Cytochrome b and the Lathosterol oxidase genes. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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23 pages, 1826 KiB  
Review
Trypanosoma cruzi: Genomic Diversity and Structure
by Alfonso Herreros-Cabello, Francisco Callejas-Hernández, Núria Gironès and Manuel Fresno
Pathogens 2025, 14(1), 61; https://doi.org/10.3390/pathogens14010061 - 12 Jan 2025
Viewed by 831
Abstract
Trypanosoma cruzi is the causative agent of Chagas disease, a neglected tropical disease, and one of the most important parasitic diseases worldwide. The first genome of T. cruzi was sequenced in 2005, and its complexity made assembly and annotation challenging. Nowadays, new sequencing [...] Read more.
Trypanosoma cruzi is the causative agent of Chagas disease, a neglected tropical disease, and one of the most important parasitic diseases worldwide. The first genome of T. cruzi was sequenced in 2005, and its complexity made assembly and annotation challenging. Nowadays, new sequencing methods have improved some strains’ genome sequence and annotation, revealing this parasite’s extensive genetic diversity and complexity. In this review, we examine the genetic diversity, the genomic structure, and the principal multi-gene families involved in the pathogenicity of T. cruzi. The T. cruzi genome sequence is divided into two compartments: the core (conserved) and the disruptive (variable in length and multicopy gene families among strains). The disruptive region has also been described as genome plasticity and plays a key role in the parasite survival and infection process. This region comprises several multi-gene families, including trans-sialidases, mucins, and mucin-associated surface proteins (MASPs). Trans-sialidases are the most prevalent genes in the genome with a key role in the infection process, while mucins and MASPs are also significant glycosylated proteins expressed on the parasite surface, essential for its biological functions, as host–parasite interaction, host cell invasion or protection against the host immune system, in both insect and mammalian stages. Collectively, in this review, some of the most recent advances in the structure and composition of the T. cruzi genome are reviewed. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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16 pages, 2016 KiB  
Review
The Functions of Cytokines in the Cardiac Immunopathogenesis of Chagas Disease
by Mariana Citlalli de Alba-Alvarado, Margarita Cabrera-Bravo, Edgar Zenteno, Paz María Salazar-Schetino and Martha Irene Bucio-Torres
Pathogens 2024, 13(10), 870; https://doi.org/10.3390/pathogens13100870 - 3 Oct 2024
Viewed by 1753
Abstract
Chagas disease is a complex zoonosis. Clinically, it presents in two distinct phases, acute and chronic. The ability of patients to respond to Trypanosoma cruzi infection depends on the balance between inflammatory and anti-inflammatory responses, in which cytokines play a key regulatory role. [...] Read more.
Chagas disease is a complex zoonosis. Clinically, it presents in two distinct phases, acute and chronic. The ability of patients to respond to Trypanosoma cruzi infection depends on the balance between inflammatory and anti-inflammatory responses, in which cytokines play a key regulatory role. In this review, we discuss the role of cytokines in regulating the host response and as mediators of cardiac injury by inducing profibrotic alterations. The importance of characterizing cytokine profiles as biomarkers of the evolution of cardiac damage in T.-cruzi-infected individuals is also emphasized. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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Other

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5 pages, 179 KiB  
Perspective
Epidemiology of Chagas Disease in the United States of America: A Short Review and Some Comments
by Stephen A. Klotz
Pathogens 2025, 14(1), 24; https://doi.org/10.3390/pathogens14010024 - 1 Jan 2025
Viewed by 569
Abstract
The epidemiology of Chagas disease in humans has markedly changed within the past several decades in the United States of America. This report discusses autochthonous cases of Chagas disease as well as disease in immigrants from Latin American countries. Suggestions for epidemiology research [...] Read more.
The epidemiology of Chagas disease in humans has markedly changed within the past several decades in the United States of America. This report discusses autochthonous cases of Chagas disease as well as disease in immigrants from Latin American countries. Suggestions for epidemiology research and medical care are discussed given the evolving epidemiology of the disease in the United States of America. Full article
(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)
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