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Advances in Chagas Disease Control

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A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Vector-Borne Diseases".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 24139

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Prof. Dr. Marta Helena Branquinha

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Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Interests: trypanosomatids; biochemistry; enzymes; protease inhibitors
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Dr. Leandro Stefano Sangenito

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Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Interests: peptidases; mechanisms of action of drugs; pathogen-host interaction; Trypanosoma cruzi ; Leishmania spp.; neglected diseases

Prof. Dr. André Luis Souza dos Santos

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1. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
2. Rede Micologia RJ – Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
Interests: chemotherapy; antifungal resistance; biochemistry; cell biology; enzymes; biofilm; virulence
Special Issues, Collections and Topics in MDPI journals

Dr. Simone Santiago Carvalho de Oliveira

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Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil
Interests: leishmania; leishmaniasis; trypanosoma; antiprotozoal chemotherapy; drug resistance

Dr. Claudia Masini d’Avila-Levy

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Laboratory of Integrated Studies in Protozoology, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil
Interests: trypanosomatids; Monoxenic trypanosomatids; host-parasite interaction; peptidases; taxonomy; phylogeny; chemotherapy

Special Issue Information

Dear Colleagues,

Chagas disease is an emerging and neglected tropical disease caused by the parasite Trypanosoma cruzi, which is estimated to infect 8 to 10 million people worldwide, according to World Health Organization. The tropical aspect of this disease refers to its prevalence in Latin American countries, and the emergence issue is due to its expansion over recent decades to non-endemic areas owing to immigration to urban regions and hence increased globalization. Despite being a zoonotic disease, transmission of the parasite can also occur through blood transfusion, organ donation, congenital infection and via the oral route, reinforcing its emerging character. The acute phase of the disease is relatively mild, but the chronic phase, occurring years after infection, may be responsible for severe manifestations, such as cardiomyopathies and digestive complications, leading to disability and higher mortality rates. However, as a neglected disease, the only options for treatment nowadays are benznidazole and nifurtimox, both developed several decades ago, with questionable efficacy and high toxicity. In this regard, what can be envisioned in terms of Chagas disease treatment in the near future? This Special Issue intends to embrace the different aspects that may be explored with the intention of controlling Chagas disease, from the development of novel options for treatment and prevention to the repurposing of drugs and the discovery of novel cell targets.

Dr. Marta Helena Branquinha
Dr. Leandro Stefano Sangenito
Dr. André Luis Souza dos Santos
Dr. Simone Santiago Carvalho de Oliveira
Dr. Claudia Masini d’Avila-Levy
Guest Editors

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Keywords

chagas disease
Trypanosoma cruzi
chemotherapy
neglected disease
antitrypanosomal therapy
drug repurposing

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 214 KiB

Open AccessEditorial

Chagas Disease Control—Many Approaches to Prospect

by Marta H. Branquinha, Leandro S. Sangenito, Simone S. C. Oliveira, Claudia M. d’Avila-Levy and André L. S. Santos

Trop. Med. Infect. Dis. 2023, 8(8), 395; https://doi.org/10.3390/tropicalmed8080395 - 2 Aug 2023

Viewed by 1172

Abstract

Chagas disease is an emerging and neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, estimated to infect 8 to 10 million people worldwide, according to the World Health Organization [...] Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

Research

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11 pages, 1472 KiB

Open AccessArticle

Acute Phase Proteins in Dogs with Natural Infection by Trypanosoma cruzi

by Pilar Rivadeneira-Barreiro, Roberto Montes-de-Oca-Jiménez, Pablo Zambrano-Rodríguez, Juan Carlos Vázquez-Chagoyán, Adriana del Carmen Gutiérrez-Castillo, Luis Pardo-Marin, Lorena Franco-Martínez, José Joaquín Cerón and Silvia Martínez-Subiela

Trop. Med. Infect. Dis. 2023, 8(6), 299; https://doi.org/10.3390/tropicalmed8060299 - 31 May 2023

Cited by 2 | Viewed by 1874

Abstract

Acute phase proteins have been used as tools for the diagnosis, monitoring, and prognosis of several diseases in domestic animals. However, the dynamics of these proteins in infection by Trypanosoma cruzi, the causative agent of Chagas disease in dogs, is still unknown. The aim of this study was to determine concentrations of acute phase proteins (C-reactive protein, haptoglobin, ferritin and paraoxonase-1) in dogs in a coastal town of Ecuador, with natural Trypanosoma cruzi infection with or without seroreactivity of Ehrlichia canis, Ehrlichia ewingii, Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi and Dirofilaria immitis. For the detection of Trypanosoma cruzi serum antibodies, two different antigen-based enzyme-linked immunosorbent assay tests were implemented. For the detection of seroreactivity of Ehrlichia canis, Ehrlichia ewingii, Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi and Dirofilaria immitis, an IDEXX SNAP^® 4Dx^® test was used. To determine the concentration of C-reactive protein and ferritin, an immunoturbidimetric assay was used; haptoglobin concentration was measured using a commercial colorimetric method validated in dogs; a spectrophotometric method was used to determine the serum concentration of paraoxonase-1. Results showed a reduction in the serum levels of paraoxonase-1 in Trypanosoma cruzi-seroreactive dogs, either with or without seroreactivity to other vector-borne diseases. A serum ferritin increment was observed in Trypanosoma cruzi-seroreactive dogs with seroreactivity to any other vector-borne diseases. Our findings suggest that paraoxonase-1 levels are reduced in Trypanosoma cruzi-seroreactive dogs without evident clinical signs of Chagas disease, despite their seroreactivity to the other vector-borne diseases studied. These findings could indicate an oxidative stress response in Trypanosoma cruzi-seroreactive dogs with no evident signs of inflammation. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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12 pages, 721 KiB

Open AccessArticle

Chagas Disease: Medical and ECG Related Findings in an Indigenous Population in Colombia

by Simone Kann, Gustavo Andrés Concha Mendoza, Maria Hartmann, Hagen Frickmann and Lothar Kreienbrock

Trop. Med. Infect. Dis. 2023, 8(6), 297; https://doi.org/10.3390/tropicalmed8060297 - 29 May 2023

Cited by 4 | Viewed by 1869

Abstract

Chagas Disease (CD) is highly prevalent among the indigenous populations in the Sierra Nevada de Santa Marta, Colombia. Villages examined show prevalence rates ranging from 43.6% up to 67.4%. In the present study, associated medical conditions were assessed with a particular focus on ECG alterations. CD diagnosis was based on a rapid test, two different ELISAs, and a specific and highly sensitive Chagas real-time PCR. In both CD positive and CD negative patients, relations of the status and medical (physical examination-based, questionnaire-based) and/or electrocardiogram-based findings were investigated. As expected, CD-associated symptoms and complaints were predominantly found in CD-positive patients. Interestingly, ECG-findings were found to show the potential of leading to early CD diagnosis because ECG alterations were already seen in early stagechanges of the disease. In conclusion, although the observed ECG changes are unspecific, they should be considered as an indicator for a CD screening and, in case of positive results, an associated early treatment of the disease. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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15 pages, 3136 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Effects of Aminopyridyl Ligands Complexed to Copper(II) on the Physiology and Interaction Process of Trypanosoma cruzi

by Rafaela Silva-Oliveira, Leandro S. Sangenito, Andrew Reddy, Trinidad Velasco-Torrijos, André L. S. Santos and Marta H. Branquinha

Trop. Med. Infect. Dis. 2023, 8(5), 288; https://doi.org/10.3390/tropicalmed8050288 - 21 May 2023

Cited by 2 | Viewed by 2495

Abstract

Chagas disease is derived from the infection by the protozoan Trypanosoma cruzi. In many countries, benznidazole is the only drug approved for clinical use despite several side effects and the emergence of resistant parasite strains. In this context, our group has previously pointed out that two novel aminopyridine derivatives complexed with Cu²⁺, namely, cis-aquadichloro(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamino)copper (3a) and its glycosylated ligand cis-dichloro (N-{[4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)pheny]lmethyl}-2-pyridinemethamino)copper (3b), are effective against T. cruzi trypomastigote forms. With this result in mind, the present work aimed to investigate the effects of both compounds on trypomastigotes physiology and on the interaction process with host cells. Apart from loss of plasma membrane integrity, an increased generation of reactive oxygen species (ROS) and decreased mitochondrial metabolism were observed. Pretreatment of trypomastigotes with these metallodrugs inhibited the association index with LLC-MK₂ cells in a typical dose-dependent manner. Both compounds showed low toxicity on mammalian cells (CC₅₀ > 100 µM), and the IC₅₀ values calculated for intracellular amastigotes were determined as 14.4 µM for 3a and 27.1 µM for 3b. This set of results demonstrates the potential of these aminopyridines complexed with Cu²⁺ as promising candidates for further antitrypanosomal drug development. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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9 pages, 1317 KiB

Open AccessCommunication

Microencapsulation of a Native Strain of the Entomopathogenic Fungus Beauveria bassiana and Bioinsecticide Activity against Pyrethroid-Resistant Triatoma infestans to Vector Control of Chagas Disease in the Argentine Gran Chaco Region

by Linda Vanesa Baldiviezo, Lucía Beatriz Nieva, Nicolás Pedrini and Rubén Marino Cardozo

Trop. Med. Infect. Dis. 2023, 8(5), 245; https://doi.org/10.3390/tropicalmed8050245 - 24 Apr 2023

Cited by 2 | Viewed by 1788

Abstract

The blood-sucking bug Triatoma infestans is the main Chagas disease vector in the Southern Cone of Latin America. Populations resistant to pyrethroid insecticides have been detected in the early 2000s and then expanded to the endemic area of northern Salta province, Argentina. In this context, the entomopathogenic fungus Beauveria bassiana has been shown to be pathogenic to pyrethroid-resistant T. infestans. In this study, both the bioinsecticidal activity and the residual effect of an alginate-based microencapsulation of a native strain of B. bassiana (Bb-C001) were tested under semi-field conditions against pyrethroid-resistant T. infestans nymphs. Fungal microencapsulated formulation caused higher nymph mortality than the unmicroencapsulated fungus and contributed to maintaining the conidial viability throughout the period evaluated under the tested conditions. These results suggest that alginate microencapsulation is an effective, simple, low-cost method that could be incorporated into the formulation of a bioinsecticide as a strategy to reduce the vector transmission of Chagas disease. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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8 pages, 2720 KiB

Open AccessCommunication

Characterization of External Female Genitalia in Five Triatoma Laporte Species of South America (Hemiptera: Reduviidae: Triatominae)

by João Paulo Sales Oliveira-Correia, Hélcio Reinaldo Gil-Santana, Jacenir Reis dos Santos-Mallet and Cleber Galvão

Trop. Med. Infect. Dis. 2023, 8(5), 240; https://doi.org/10.3390/tropicalmed8050240 - 23 Apr 2023

Cited by 2 | Viewed by 1406

Abstract

Currently, there are 158 valid species of triatomines, all of which are potential vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. The correct taxonomic identification of triatomines is essential since each species hos a different epidemiological importance. The aim of the study is to compare five species of South American Triatoma. Here we present a comparative study of terminal abdominal segments in females by scanning electron microscopy (SEM) of the species Triatoma delpontei, T. jurbergi, T. infestans var. melanosoma, T. platensis, and T. vandae. The results showed diagnostic characters for the studied species. The dorsal view featured more valuable characters, with seven informative characters. Similarities were observed among T. delpontei, T. infestans var. melanosoma, and T. platensis, and between T. jurbergi and T. vandae, correlating with previous studies. Thus, female genital characters proved to be reliable and useful in the diagnosis of the Triatoma species studied here; additional studies, along with other sets of behavioral, morphological, and molecular data, helped to reinforce the hypotheses found here. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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14 pages, 3125 KiB

Open AccessEditor’s ChoiceArticle

Chagas Disease Maternal Seroprevalence and Maternal–Fetal Health Outcomes in a Parturition Cohort in Western El Salvador

by Mary K. Lynn, Marvin Stanley Rodriguez Aquino, Pamela Michelle Cornejo Rivas, Mufaro Kanyangarara, Stella C. W. Self, Berry A. Campbell and Melissa S. Nolan

Trop. Med. Infect. Dis. 2023, 8(4), 233; https://doi.org/10.3390/tropicalmed8040233 - 20 Apr 2023

Cited by 5 | Viewed by 2867

Abstract

Congenital Chagas disease is a growing concern, prioritized by the World Health Organization for public health action. El Salvador is home to some of the highest Chagas disease (Trypanosoma cruzi infection) burdens in the Americas, yet pregnancy screening remains neglected. This pilot investigation performed a maternal T. cruzi surveillance study in Western El Salvador among women presenting for labor and delivery. From 198 consented and enrolled pregnant women, 6% were T. cruzi positive by serology or molecular diagnosis. Half of the infants born to T. cruzi-positive women were admitted to the NICU for neonatal complications. Geospatial statistical clustering of cases was noted in the municipality of Jujutla. Older women and those knowing an infected relative or close friend were significantly more likely to test positive for T. cruzi infection at the time of parturition. In closing, maternal T. cruzi infections were significantly higher than national HIV or syphilis maternal rates, creating an urgent need to add T. cruzi to mandatory pregnancy screening programs. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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15 pages, 470 KiB

Open AccessArticle

Identifying Barriers and Facilitators for Home Reconstruction for Prevention of Chagas Disease: An Interview Study in Rural Loja Province, Ecuador

by Benjamin R. Bates, Majo Carrasco-Tenezaca, Angela M. Mendez-Trivino, Luis E. Mendoza, Claudia Nieto-Sanchez, Esteban G. Baus and Mario J. Grijalva

Trop. Med. Infect. Dis. 2023, 8(4), 228; https://doi.org/10.3390/tropicalmed8040228 - 18 Apr 2023

Cited by 2 | Viewed by 2155

Abstract

Background: Chagas disease (CD) is a tropical parasitic disease spread by triatomine bugs, which are bugs that tend to infest precarious housing in rural and impoverished areas. Reducing exposure to the bugs, and thus the parasite they can carry, is essential to preventing CD in these areas. One promising long-term sustainable solution is to reconstruct precarious houses. Implementing home reconstruction requires an understanding of how householders construct barriers and facilitators they might encounter when considering whether to rebuild their homes. Methods: To understand barriers and facilitators to home reconstruction, we performed in-depth qualitative interviews with 33 residents of Canton Calvas, Loja, Ecuador, a high-risk endemic region. Thematic analysis was used to identify these barriers and facilitators. Results: The thematic analysis identified three facilitators (project facilitators, social facilitators, and economic facilitators) and two major barriers (low personal economy and extensive deterioration of existing homes). Conclusions: The study findings provide important loci for assisting community members and for agents of change in home reconstruction projects to prevent CD. Specifically, the project and social facilitators suggest that collective community efforts (minga) are more likely to support home reconstruction intentions than individualist efforts, while the barriers suggest that addressing structural issues of economy and affordability are necessary. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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13 pages, 1868 KiB

Open AccessArticle

Trypanosoma cruzi Parasite Burdens of Several Triatomine Species in Colombia

by Natalia Velásquez-Ortiz, Carolina Hernández, Omar Cantillo-Barraza, Nathalia Ballesteros, Lissa Cruz-Saavedra, Giovanny Herrera, Luz Stella Buitrago, Hugo Soto, Manuel Medina, Jatney Palacio, Marina Stella González, Andrés Cuervo, Gustavo Vallejo, Liliana Zuleta Dueñas, Plutarco Urbano, Marina Muñoz and Juan David Ramírez

Trop. Med. Infect. Dis. 2022, 7(12), 445; https://doi.org/10.3390/tropicalmed7120445 - 19 Dec 2022

Cited by 8 | Viewed by 2333

Abstract

Trypanosoma cruzi, the causal agent of Chagas disease, is mainly transmitted by insects of the Triatominae subfamily. In Colombia, there are 26 triatomine species, and 16 of them are naturally infected with the parasite. The parasite loads of naturally infected vectors can be significant in targeting specific species that can affect the epidemiology of the disease. Studying their ecology and behavior is vital to understand their role in T. cruzi transmission dynamics. We evaluated the parasite loads of 182 field-collected triatomines corresponding to 10 species in 13 departments across Colombia. We standardized a methodology to quantify T. cruzi DNA in these insects. We obtained a LOD (limit of detection) of 3.05 p-eq/mL. The 82% of triatomines we evaluated were positive for T. cruzi infection, with loads ranging from hundreds to millions of equivalent parasites per milliliter. Panstrongylus geniculatus, Rhodnius prolixus, and Triatoma dimidiata were the species with the highest loads of T. cruzi; however, other species whose role as vectors is still unknown were also found with high loads of parasites. Our results suggest the relevance of secondary species for T. cruzi transmission in Colombia. We hope our data can help improve entomological surveillance and vector control programs in the country and the region. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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Review

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19 pages, 10581 KiB

Open AccessEditor’s ChoiceReview

What Do You Need to Know before Studying Chagas Disease? A Beginner’s Guide

by José A. De Fuentes-Vicente, Nancy G. Santos-Hernández, Christian Ruiz-Castillejos, Eduardo E. Espinoza-Medinilla, A. Laura Flores-Villegas, Mariana de Alba-Alvarado, Margarita Cabrera-Bravo, Adriana Moreno-Rodríguez and Dolores G. Vidal-López

Trop. Med. Infect. Dis. 2023, 8(7), 360; https://doi.org/10.3390/tropicalmed8070360 - 10 Jul 2023

Cited by 10 | Viewed by 4803

Abstract

Chagas disease is one of the most important tropical infections in the world and mainly affects poor people. The causative agent is the hemoflagellate protozoan Trypanosoma cruzi, which circulates among insect vectors and mammals throughout the Americas. A large body of research on Chagas disease has shown the complexity of this zoonosis, and controlling it remains a challenge for public health systems. Although knowledge of Chagas disease has advanced greatly, there are still many gaps, and it is necessary to continue generating basic and applied research to create more effective control strategies. The aim of this review is to provide up-to-date information on the components of Chagas disease and highlight current trends in research. We hope that this review will be a starting point for beginners and facilitate the search for more specific information. Full article

(This article belongs to the Special Issue Advances in Chagas Disease Control)

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