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 Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanchi Malhotra ◽  
Imran Masood ◽  
Noberto Giglio ◽  
Jay D. Pruetz ◽  
Pia S. Pannaraj
Keyword(s):  
United States ◽  
Differential Diagnosis ◽  
Heart Disease ◽  
Chagas Disease ◽  
Latin American ◽  
Current Knowledge ◽  
Parasitic Infection ◽  
The United States ◽  
Cardiac Complications ◽  
The U.S

Abstract Background Chagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S. Methods We prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience. Results Of 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture. Conclusions Pediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

scholarly journals Trypanosoma cruzi Genome 15 Years Later: What Has Been Accomplished?

2020 ◽  
Vol 5 (3) ◽  
pp. 129
Author(s):  
Jose Luis Ramirez
Keyword(s):  
Trypanosoma Cruzi ◽  
Latin American ◽  
Drug Targets ◽  
Leishmania Major ◽  
Etiologic Agent ◽  
Neglected Diseases ◽  
Adaptive Capabilities ◽  
Genome Draft ◽  
Work Done

On 15 July 2020 was the 15th anniversary of the Science Magazine issue that reported three trypanosomatid genomes, namely Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. That publication was a milestone for the research community working with trypanosomatids, even more so, when considering that the first draft of the human genome was published only four years earlier after 15 years of research. Although nowadays, genome sequencing has become commonplace, the work done by researchers before that publication represented a huge challenge and a good example of international cooperation. Research in neglected diseases often faces obstacles, not only because of the unique characteristics of each biological model but also due to the lower funds the research projects receive. In the case of Trypanosoma cruzi the etiologic agent of Chagas disease, the first genome draft published in 2005 was not complete, and even after the implementation of more advanced sequencing strategies, to this date no final chromosomal map is available. However, the first genome draft enabled researchers to pick genes a la carte, produce proteins in vitro for immunological studies, and predict drug targets for the treatment of the disease or to be used in PCR diagnostic protocols. Besides, the analysis of the T. cruzi genome is revealing unique features about its organization and dynamics. In this work, I briefly summarize the actions of Latin American researchers that contributed to the first publication of the T. cruzi genome and discuss some features of the genome that may help to understand the parasite’s robustness and adaptive capabilities.

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.

Chagas disease: A Latin American health problem becoming a world health problem

Acta Tropica ◽  
2010 ◽  
Vol 115 (1-2) ◽  
pp. 14-21 ◽  
Author(s):  
Gabriel A. Schmunis ◽  
Zaida E. Yadon
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Health Problem ◽  
World Health

scholarly journals Benzopyrazine-Based Small Molecule Inhibitors As Trypanocidal and Leishmanicidal Agents: Green Synthesis, In Vitro, and In Silico Evaluations

2021 ◽  
Vol 9 ◽  
Author(s):  
Jonathan Rock ◽  
Daniel Garcia ◽  
Omar Espino ◽  
Shaila A. Shetu ◽  
Manuel J. Chan-Bacab ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Drug Targets ◽  
Leishmania Major ◽  
Neglected Tropical Diseases ◽  
Catalyst Support ◽  
Trna Synthetase ◽  
World Health ◽  
Lead Compound ◽  
Lipinski’S Rule

World Health Organization (WHO) identified twenty tropical disease categories as neglected tropical diseases (NTDs)1. Chagas’ disease (also known as American trypanosomiasis) and leishmaniasis are two major classes of NTDs. The total number of mortality, morbidity, and disability attributed each year due to these two categories of diseases in magnitudes is much higher than the so-called elite diseases like cancer, diabetes, AIDS, cardiovascular and neurodegenerative diseases. Impoverished communities around the world are the major victim of NTDs. The development of new and novel drugs in the battle against Chagas’ disease and leishmaniasis is highly anticipated. An easy and straightforward on-water green access to synthesize benzopyrazines is reported. This ultrasound-assisted procedure does not require any catalyst/support/additive/hazardous solvents and maintains a high atom economy. A series of eleven benzopyrazines has been synthesized, and most of the synthesized compounds possess the drug-likeness following Lipinski’s “Rule of 5”. Benzopyrazines 3 and 4 demonstrated moderate leishmanicidal activity against L. mexicana (M378) strain. The selective lead compound 1 showed good leishmanicidal, and trypanocidal activities (in vitro) against both L. mexicana (M378) and T. cruzi (NINOA) strains compared to the standard controls. The in vitro trypanocidal and leishmanicidal activities of the lead compound 1 have been validated by molecular docking studies against four biomolecular drug targets viz. T. cruzi histidyl-tRNA synthetase, T. cruzi trans-sialidase, leishmanial rRNA A-site, and leishmania major N-myristoyl transferase.

scholarly journals Public policy for controlling the taeniasis/cysticercosis complex in Colombia

Case reports ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. 5-7
Author(s):  
Luis Reinel Vásquez-Arteaga ◽  
Julio César Giraldo-Forero
Keyword(s):  
Latin American ◽  
Social Protection ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Developed Countries ◽  
Tissue Level ◽  
World Health ◽  
Immigrant Communities ◽  
C Complex ◽  
Health Organization

The teniosis/cysticercosis (T/C) complex is a parasitic disease caused by the cestodes Taenia solium and Taenia saginata, and is considered as a neglected zoonosis by the World Health Organization (WHO) and the Colombian Ministry of Health and Social Protection. (1-3) This parasitic infection is a public health and environmental problem in Latin-American, African and Asian countries, and is currently being introduced to developed countries through immigrant communities. Estimates are that 2 500 000 people are infected with this complex and that twice as many individuals develop the parasite at the tissue level. This disease is associated to 50 000 deaths every year, but these figures need to be updated. (4-8)

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.

scholarly journals Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

2020 ◽  
Author(s):  
Sanchi Malhotra ◽  
Imran Masood ◽  
Noberto Giglio ◽  
Jay D. Pruetz ◽  
Pia S. Pannaraj
Keyword(s):  
United States ◽  
Differential Diagnosis ◽  
Heart Disease ◽  
Chagas Disease ◽  
Latin American ◽  
Current Knowledge ◽  
Parasitic Infection ◽  
The United States ◽  
Cardiac Complications ◽  
The U.S

Abstract BackgroundChagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S.MethodsWe prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience.ResultsOf 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture.ConclusionsPediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

scholarly journals Fatal Chagas Disease Among Solid-Organ Transplant Recipients in Colombia

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Carlos Fernando Gómez-P ◽  
Julio César Mantilla-H ◽  
Alfonso J. Rodriguez-Morales
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Parasitic Infection ◽  
Organ Transplant ◽  
The United States ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Abstract Chagas disease continues to cause substantial morbidity and mortality in endemic areas in Latin America. Although there have been some well documented successes in halting the transmission of Chagas disease through preventive interventions to decrease vector-borne and blood-transfusion cases, this parasitic infection continues to be transmitted through these routes in some areas as well through perinatal and foodborne routes. In addition, transmission through solid-organ transplantation has been described in nonendemic settings due to the increasing globalization of Chagas disease to the United States of America, Europe, and other areas. Because there has been a concomitant increase in the number of solid-organ transplantations performed in Latin American settings endemic for American trypanosomiasis, there is increasing concern for the potential reactivation of Trypanosoma cruzi in a previously infected recipient and as a result of aggressive immunosuppression; or via transmission from organs donated by a latently infection donor transplanted onto an uninfected recipient. In this study, we report 2 cases of Chagas disease reactivation in 2 solid-organ transplant recipients in Northeastern Colombia, and we discuss the implications for screening as a crucial strategy for preventing transmission in endemic settings.

scholarly journals Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Rito Santo Pereira ◽  
Aparecida Donizette Malvezi ◽  
Maria Isabel Lovo-Martins ◽  
Bruno Fernando Cruz Lucchetti ◽  
Jussevania Pereira Santos ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Chagas Disease ◽  
Latin American ◽  
Acute Phase ◽  
Chronic Phase ◽  
World Health ◽  
Low Doses ◽  
Cardiovascular Dysfunction ◽  
Content Type ◽  
Cardiac Lesions

ABSTRACT Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than BZ-treated mice. These results were associated with an increase in numbers of eosinophils and reticulocytes and levels of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the lipoxin A4 (LXA4) receptor antagonist Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of the acute phase of Chagas disease that are beneficial for patients with chronic disease.

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