scholarly journals Experimental Vaccines against Chagas Disease: A Journey through History

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Olivia Rodríguez-Morales ◽  
Víctor Monteón-Padilla ◽  
Silvia C. Carrillo-Sánchez ◽  
Martha Rios-Castro ◽  
Mariana Martínez-Cruz ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Chagas Disease ◽  
Latin American ◽  
Protozoan Parasite ◽  
Immune Protection ◽  
Transmission Control ◽  
American Trypanosomiasis ◽  
Control Programs ◽  
Primary Prevention Strategy ◽  
Latin American Countries

Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasiteTrypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented,T. cruzihas not been eradicated. The development of an anti-T. cruzivaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection withT. cruzihas been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms “Chagas disease” and “American trypanosomiasis” together with “vaccines” or “immunization”. In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed.

Major Kinds of Drug Targets in Chagas Disease or American Trypanosomiasis

2019 ◽  
Vol 20 (11) ◽  
pp. 1203-1216 ◽  
Author(s):  
Vilma G. Duschak
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Drug Targets ◽  
Defense Mechanisms ◽  
Cysteine Proteinase ◽  
Parasitic Infection ◽  
Etiologic Agent ◽  
World Health ◽  
American Trypanosomiasis ◽  
Group I

American Trypanosomiasis, a parasitic infection commonly named Chagas disease, affects millions of people all over Latin American countries. Presently, the World Health Organization (WHO) predicts that the number of international infected individuals extends to 7 to 8 million, assuming that more than 10,000 deaths occur annually. The transmission of the etiologic agent, Trypanosoma cruzi, through people migrating to non-endemic world nations makes it an emergent disease. The best promising targets for trypanocidal drugs may be classified into three main groups: Group I includes the main molecular targets that are considered among specific enzymes involved in the essential processes for parasite survival, principally Cruzipain, the major antigenic parasite cysteine proteinase. Group II involves biological pathways and their key specific enzymes, such as Sterol biosynthesis pathway, among others, specific antioxidant defense mechanisms, and bioenergetics ones. Group III includes the atypical organelles /structures present in the parasite relevant clinical forms, which are absent or considerably different from those present in mammals and biological processes related to them. These can be considered potential targets to develop drugs with extra effectiveness and fewer secondary effects than the currently used therapeutics. An improved distinction between the host and the parasite targets will help fight against this neglected disease.

scholarly journals Imidazole Derivatives as Promising Agents for the Treatment of Chagas Disease

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Julianna Siciliano de Araújo ◽  
Alfonso García-Rubia ◽  
Victor Sebastián-Pérez ◽  
Titilola D. Kalejaiye ◽  
Patrícia Bernardino da Silva ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Protozoan Parasite ◽  
Aqueous Solubility ◽  
Content Type ◽  
Cellular Effects ◽  
Transmission Electron ◽  
Phenotypic Screen ◽  
Current Therapies ◽  
Potential Inhibitors

ABSTRACT More than 100 years after being first described, Chagas disease remains endemic in 21 Latin American countries and has spread to other continents. Indeed, this disease, which is caused by the protozoan parasite Trypanosoma cruzi, is no longer just a problem for the American continents but has become a global health threat. Current therapies, i.e., nifurtimox and benznidazole (Bz), are far from being adequate, due to their undesirable effects and their lack of efficacy in the chronic phases of the disease. In this work, we present an in-depth phenotypic evaluation in T. cruzi of a new class of imidazole compounds, which were discovered in a previous phenotypic screen against different trypanosomatids and were designed as potential inhibitors of cAMP phosphodiesterases (PDEs). The confirmation of several activities similar or superior to that of Bz prompted a synthesis program of hit optimization and extended structure-activity relationship aimed at improving drug-like properties such as aqueous solubility, which resulted in additional hits with 50% inhibitory concentration (IC50) values similar to that of Bz. The cellular effects of one representative hit, compound 9, on bloodstream trypomastigotes were further investigated. Transmission electron microscopy revealed cellular changes, after just 2 h of incubation with the IC50 concentration, that were consistent with induced autophagy and osmotic stress, mechanisms previously linked to cAMP signaling. Compound 9 induced highly significant increases in both cellular and medium cAMP levels, confirming that inhibition of T. cruzi PDE(s) is part of its mechanism of action. The potent and selective activity of this imidazole-based PDE inhibitor class against T. cruzi constitutes a successful repurposing of research into inhibitors of mammalian PDEs.

scholarly journals The ubiquinone synthesis pathway is a promising drug target for Chagas disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0243855
Author(s):  
Takeshi Nara ◽  
Yukari Nakagawa ◽  
Keiko Tsuganezawa ◽  
Hitomi Yuki ◽  
Katsuhiko Sekimata ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Drug Target ◽  
Culture Medium ◽  
Protozoan Parasite ◽  
Redox Balance ◽  
New Drugs ◽  
Key Enzyme ◽  
2D And 3D ◽  
Similarity Searches

Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi). It was originally a Latin American endemic health problem, but now is expanding worldwide as a result of increasing migration. The currently available drugs for Chagas disease, benznidazole and nifurtimox, provoke severe adverse effects, and thus the development of new drugs is urgently required. Ubiquinone (UQ) is essential for respiratory chain and redox balance in trypanosomatid protozoans, therefore we aimed to provide evidence that inhibitors of the UQ biosynthesis have trypanocidal activities. In this study, inhibitors of the human COQ7, a key enzyme of the UQ synthesis, were tested for their trypanocidal activities because they were expected to cross-react and inhibit trypanosomal COQ7 due to their genetic homology. We show the trypanocidal activity of a newly found human COQ7 inhibitor, an oxazinoquinoline derivative. The structurally similar compounds were selected from the commercially available compounds by 2D and 3D ligand-based similarity searches. Among 38 compounds selected, 12 compounds with the oxazinoquinoline structure inhibited significantly the growth of epimastigotes of T. cruzi. The most effective 3 compounds also showed the significant antitrypanosomal activity against the mammalian stage of T. cruzi at lower concentrations than benznidazole, a commonly used drug today. We found that epimastigotes treated with the inhibitor contained reduced levels of UQ9. Further, the growth of epimastigotes treated with the inhibitors was partially rescued by UQ10 supplementation to the culture medium. These results suggest that the antitrypanosomal mechanism of the oxazinoquinoline derivatives results from inhibition of the trypanosomal UQ synthesis leading to a shortage of the UQ pool. Our data indicate that the UQ synthesis pathway of T. cruzi is a promising drug target for Chagas disease.

scholarly journals The control of Latin American trypanosomiasis

1997 ◽  
Vol 30 (6) ◽  
pp. 521-527 ◽  
Author(s):  
Philip D. Marsden
Keyword(s):  
Latin America ◽  
Trypanosoma Cruzi ◽  
Disease Control ◽  
Chagas Disease ◽  
Latin American ◽  
Present Situation ◽  
Point Of View ◽  
American Trypanosomiasis ◽  
Triatomine Bugs ◽  
Latin America Countries

The author presents his personal point of view on the present situation of Chagas' disease control in Latin America countries. He compares the situation with African trypanosomiasis. He comments on the existence of cases in other Continents. He emphazises the success of the fighting against domiciliated triatomine bugs by using residual inseticides. He discusses other forms of Trypanosoma cruzi transmission.

scholarly journals Taxonomy, Evolution, and Biogeography of the Rhodniini Tribe (Hemiptera: Reduviidae)

Diversity ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 97 ◽  
Author(s):  
Carolina Hernández ◽  
João Aristeu da Rosa ◽  
Gustavo A. Vallejo ◽  
Felipe Guhl ◽  
Juan David Ramírez
Keyword(s):  
Latin American ◽  
Control Strategies ◽  
Protozoan Parasite ◽  
Molecular Techniques ◽  
Fossil Species ◽  
Wide Geographical Distribution ◽  
Vector Capacity ◽  
Five Tribes ◽  
Latin American Countries ◽  
Shed Light

The Triatominae subfamily includes 151 extant and three fossil species. Several species can transmit the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, significantly impacting public health in Latin American countries. The Triatominae can be classified into five tribes, of which the Rhodniini is very important because of its large vector capacity and wide geographical distribution. The Rhodniini tribe comprises 23 (without R. taquarussuensis) species and although several studies have addressed their taxonomy using morphological, morphometric, cytogenetic, and molecular techniques, their evolutionary relationships remain unclear, resulting in inconsistencies at the classification level. Conflicting hypotheses have been proposed regarding the origin, diversification, and identification of these species in Latin America, muddying our understanding of their dispersion and current geographic distribution. Clarifying these factors can help for the design of vector control strategies. The aim of this review is to depict the different approaches used for taxonomy of the Rhodniini and to shed light on their evolution and biogeography.

scholarly journals Clinical forms and diagnosis of Chagas disease and immunosuppressants

2019 ◽  
pp. 11-14
Author(s):  
Darío Scublinsky ◽  
M. V. Pinoni ◽  
F. Ibelli ◽  
A. Valledor ◽  
E.R. Soriano
Keyword(s):  
Diagnostic Criteria ◽  
Chagas Disease ◽  
Latin American ◽  
Severe Infection ◽  
Clinical Forms ◽  
High Prevalence ◽  
Latin American Countries ◽  
Made In

Chagas disease constitutes a severe infection of high prevalence in Argentina and other Latin American countries. The administration of immunosuppressive rheumatic drugs in these patients is often necessary but the implication that this may have on the reactivation of Chagas disease is not yet known. In this update, general diagnostic criteria in this group of patients, and available evidence and recommendations made in this context are reviewed.

scholarly journals Chagas Disease: Where to now?

2016 ◽  
Vol 7 ◽  
Author(s):  
Louise Gabrielle Shewan ◽  
Andrew Coats ◽  
Michael Henein ◽  
Reinaldo Bestetti
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Imaging Techniques ◽  
Chagas Cardiomyopathy ◽  
Wide Range ◽  
The Usa ◽  
End Stage Heart Failure ◽  
End Stage ◽  
Latin American Countries ◽  
Emerging Topics

<p class="normal">This special issue includes expert reviews on the neglected cardiological syndrome – Chagas Disease<ins cite="mailto:Andrew%20Coats" datetime="2016-07-11T15:49"> (CD)</ins>, also known as American trypanosomiasis.   First described in 1909 this syndrome is endemic in several Latin American countries. This specially commissioned themed issue of the International Cardiovascular Forum Journal brings together notable experts who discuss a wide range of emerging topics in CD.  These include the changing, and challenging, epidemiology of CD in migrants and visitors to the Europe and the USA.  We also review what treatments exist for the primary infective aetiology, and how to manage Chagas cardiomyopathy when it has reached its end-stage heart failure form.  We have expert reviews on advanced imaging techniques and their role in the assessment and care of Chagas’ patients and the opportunity to protect against sudden death in this enigmatic condition.  </p>

Use of clomipramine as chemotherapy of the chronic phase of Chagas disease

Parasitology ◽  
2013 ◽  
Vol 140 (7) ◽  
pp. 917-927 ◽  
Author(s):  
ROMINA FAURO ◽  
SILVINA LO PRESTI ◽  
CAROLINA BAZAN ◽  
ALEJANDRA BAEZ ◽  
MARIANA STRAUSS ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Chronic Phase ◽  
Tricyclic Antidepressant ◽  
Trypanothione Reductase ◽  
Parasite Intensity ◽  
Collateral Effects ◽  
Inflammatory Infiltrates ◽  
Latin American Countries ◽  
Chronic Chagas Disease

SUMMARYChagas infection is a major endemic disease affecting Latin American countries. The persistence ofTrypanosoma cruzigenerates a chronic inflammatory reactivity that induces an immune response directed to the host's tissues. The effectiveness of the treatment in the chronic phase is still unsatisfactory due, amongst other reasons, to the collateral effects of the drugs used. We investigated the effect of clomipramine, a tricyclic antidepressant that, when used as a treatment ofT. cruzi-chronically infected mice, inhibits trypanothione reductase, an exclusive and vital enzyme ofT. cruzi. Clomipramine improved survival (P<0·05) by diminishing the parasite intensity as demonstrated by PCR studies in the heart and skeletal muscle, and significantly prevented the evolution to fibrosis of the inflammatory infiltrates. Clomipramine could be a good candidate for the treatment of chronic Chagas disease.

scholarly journals Predictions of Future Geographical Distribution of Two Vectors of American Trypanosomiasis: Implications for Endemic Chagas disease in Texas, USA

Fine Focus ◽  
2017 ◽  
Vol 3 (2) ◽  
pp. 129-138
Author(s):  
Helen G. Scott ◽  
Catherine A. Wakeman
Keyword(s):  
Chagas Disease ◽  
Protozoan Parasite ◽  
Environmental Niche ◽  
American Trypanosomiasis ◽  
Vector Borne Diseases ◽  
Bioclimatic Variables ◽  
Vector Distribution ◽  
The Face ◽  
Vector Borne ◽  
Environmental Niche Models

It is known that climate has a direct effect on vectorborne and zoonotic diseases, and in the face of climate change, understanding this link has become more urgent. Many such vector-borne diseases primarily afflict impoverished populations and have therefore been previously understudied. One major focus of our research is to understand the influence that climate has on the distribution of disease causing microorganisms and their vectors, especially those in relation to American trypanosomiasis (Chagas disease). Chagas disease is caused by the hemoflagellate protozoan parasite, Trypanosoma cruzi. For this study, we hypothesized that the increasing prevalence Chagas in the state of Texas is due to expanding distributions of vectors. To test this hypothesis, historical data on vector distribution and climate was used to determine the probable locations of prevalent vectors in Texas. Predictions for the future distributions were made using environmental niche models for bioclimatic variables with a maximum entropy algorithm. Of the two Triatominae species studied, the range and concentration of both decreased under a global warming scenario, a finding that is consistent with the current research of risk of Chagas disease in Venezuela. In future, this same procedure will be used on more Chagas vectors to better understand if there is a northward shift for vectors, or if Texas is becoming more inhospitable to all vectors of Chagas.

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