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1.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068436

RESUMO

Extracellular vesicles (EVs) are small lipid vesicles released by either any prokaryotic or eukaryotic cell, or both, with a biological role in cell-to-cell communication. In this work, we characterize the proteomes and nanomechanical properties of EVs released by tissue-culture cell-derived trypomastigotes (mammalian infective stage; (TCT)) and epimastigotes (insect stage; (E)) of Trypanosoma cruzi, the etiologic agent of Chagas disease. EVs of each stage were isolated by differential centrifugation and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), electron microscopy and atomic force microscopy (AFM). Measurements of zeta-potential were also included. Results show marked differences in the surface molecular cargos of EVs between both stages, with a noteworthy expansion of all groups of trans-sialidase proteins in trypomastigote's EVs. In contrast, chromosomal locations of trans-sialidases of EVs of epimastigotes were dramatically reduced and restricted to subtelomeric regions, indicating a possible regulatable expression of these proteins between both stages of the parasite. Regarding mechanical properties, EVs of trypomastigotes showed higher adhesion compared to the EVs of epimastigotes. These findings demonstrate the remarkable surface remodeling throughout the life cycle of T. cruzi, which shapes the physicochemical composition of the extracellular vesicles and could have an impact in the ability of these vesicles to participate in cell communication in completely different niches of infection.


Assuntos
Doença de Chagas/metabolismo , Vesículas Extracelulares/metabolismo , Estágios do Ciclo de Vida , Proteoma/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Animais , Doença de Chagas/parasitologia , Chlorocebus aethiops , Vesículas Extracelulares/parasitologia , Interações Hospedeiro-Parasita , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteoma/análise , Células Vero
2.
Mem Inst Oswaldo Cruz ; 116: e210056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34105689

RESUMO

Vector-borne transmission of Chagas disease in urban areas of Argentina has been an overlooked phenomena. We conducted the first comprehensive cross-sectional study of domestic infestation with Triatoma infestans and vector infection with Trypanosoma cruzi in a metropolitan area of San Juan, Argentina. Our results document the occurrence of T. infestans infected with T. cruzi in human sleeping quarters. In this urban setting, we also show that infestation was associated with construction materials, the presence of chickens, cats and a large number of dogs that can provide blood meals for the vector. Our findings reveal new challenges for vectorial control agencies.


Assuntos
Doença de Chagas , Triatoma , Trypanosoma cruzi , Animais , Argentina , Gatos , Galinhas , Estudos Transversais , Cães , Insetos Vetores
3.
Mem Inst Oswaldo Cruz ; 116: e210015, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076075

RESUMO

Chagas disease persists as one of the most important, and yet most neglected, diseases in the world, and several changes in its epidemiological aspects have been recorded since its discovery. Currently, some of the most relevant changes are related to: (i) the reduction in the incidence of the endemic due to the control of the most important vectors, Triatoma infestans and Rhodnius prolixus, in many countries; (ii) the migration of human populations spreading cases of the disease throughout the world, from endemic to non-endemic areas, transforming Chagas disease into a global threat; and (iii) new acute cases and deaths caused by oral transmission, especially in the north of Brazil. Despite the reduction in the number of cases, new challenges need to be responded to, including monitoring and control activities aiming to prevent house infestation by the secondary vectors from occurring. In 1979, Lent & Wygodzinsky(1) published the most complete review of the subfamily Triatominae, encompassing 111 recognised species in the taxon. Forty-two years later, 46 new species and one subspecies have been described or revalidated. Here we summarise the new species and contextualise them regarding their ecology, epidemiologic importance, and the obstacles they pose to the control of Chagas disease around the world.


Assuntos
Doença de Chagas , Triatoma , Triatominae , Trypanosoma cruzi , Animais , Brasil/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/prevenção & controle , Humanos , Insetos Vetores
4.
Drugs Today (Barc) ; 57(4): 251-263, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33851689

RESUMO

Chagas disease is a vector-borne neglected tropical disease caused by Trypanosoma cruzi. It is a systemic and chronic parasitic infection which is endemic in 21 countries with 10 million cases worldwide and 12,000 annual deaths. Around 70 million people in the Americas are at risk of contracting this disease, and less than 1% of infected people are treated due to low disease awareness and limited access to treatment. The current treatment for Chagas disease consists of benznidazole and nifurtimox under the World Health Organization (WHO) authorization protocol. The current treatment has limitations in terms of efficacy against the chronic phase of infection and side effects associated with prolonged therapy. This review provides an update on nifurtimox progress over the years and its recent approval by the U.S. Food and Drug Administration (FDA) in 2020 for the treatment of Chagas disease in pediatric patients under 18 years of age.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Adolescente , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Criança , Humanos , Nifurtimox/efeitos adversos , Tripanossomicidas/efeitos adversos , Estados Unidos , United States Food and Drug Administration
5.
Medicina (B Aires) ; 81(2): 154-158, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-33906132

RESUMO

Chagas disease is endemic in Latin America and remains a regional problem despite improvements in environmental health conditions that have helped to control its transmission. To know more about its prevalence in heart disease patients, we carried out a survey in our national (El Salvador) reference hospital. We reviewed the Chagas Lab's records 2013-2015 to find out how many of the patients admitted to the Hospital's Heart Unit were serologically positives for Trypanosoma cruzi infection and which the associated diagnoses were. A total of 1472 patients were tested along the 36-month study period. Out of 557 (37.8%) patients with positive serology for Chagas infection, 97 (17.4%) were eventually admitted to the Heart Unit. Among these 97 Chagas infected patients with heart disease, 40 (41.2%) met the criteria for permanent pacemaker placement, while only 13 of 191 (6.8%) patients with non-chagasic heart disease met these criteria. The frequency of heart atrioventricular block associated with Trypanosoma cruzi infection was higher than frequencies reported in South American studies.


Assuntos
Bloqueio Atrioventricular , Doença de Chagas , Trypanosoma cruzi , Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/etiologia , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , El Salvador , Humanos , América Latina
6.
Rev Soc Bras Med Trop ; 54: e0740, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886818

RESUMO

INTRODUCTION: Chagas disease is a health problem that affects approximately 7 million people worldwide, according to the World Health Organization. Vector transmission is one of the most important routes in South and Central American countries. Between 2013 and 2019, municipalities of Sergipe sent 507 triatomines for analysis, unveiling the largest records found in the south in the villages of Poço da Clara, Alagoinhas and Pilões, and the municipality of Tobias Barreto. The high prevalence of infected vectors in these localities motivated this epidemiological study. METHODS: After educational lectures on the vectors and risks of the disease, a structured questionnaire was administered to identify areas and risk factors for transmission of the parasite. The data guided the collection of vectors and blood samples from domestic reservoirs. RESULTS: The studied region is considered endemic for triatomines infected by Trypanosoma cruzi with three species of vectors; the highest prevalence was Panstrongylus lutzi (54.83%), followed by Triatoma pseudomaculata (43.54%), and Triatoma tibiamaculata (1.61%). In the villages in this study, 100% of the vectors were found intradomically. The coexistence of residents with domestic animals was reported by 62.04% (255) of those surveyed. Forty-one small animals that were actively living with humans at home in the localities were evaluated serologically. No infection was observed in the domestic animals. CONCLUSIONS: There are favorable conditions for the domiciliation of triatomines in the evaluated locations, contributing to the risk of vectorial transmission of Chagas disease.


Assuntos
Doença de Chagas , Panstrongylus , Triatoma , Trypanosoma cruzi , Animais , Doença de Chagas/epidemiologia , Humanos , Insetos Vetores
7.
Artigo em Inglês | MEDLINE | ID: mdl-33909845

RESUMO

Chagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel's classification. We selected the simplest combination that most accurately reproduced the panel's results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.


Assuntos
Cardiomiopatia Chagásica , Doença de Chagas , Trypanosoma cruzi , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/epidemiologia , Eletrocardiografia , Estudos Epidemiológicos , Humanos , Retroviridae
8.
Mem Inst Oswaldo Cruz ; 116: e200528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656141

RESUMO

Panstrongylus geniculatus (Latreille, 1811) is the triatomine with the largest geographic distribution in Latin America. It has been reported in 18 countries from southern Mexico to northern Argentina, including the Caribbean islands. Although most reports indicate that P. geniculatus has wild habitats, this species has intrusive habits regarding human dwellings mainly located in intermediate deforested areas. It is attracted by artificial light from urban and rural buildings, raising the risk of transmission of Trypanosoma cruzi. Despite the wide body of published information on P. geniculatus, many knowledge gaps exist about its biology and epidemiological potential. For this reason, we analysed the literature for P. geniculatus in Scopus, PubMed, Scielo, Google Scholar and the BibTriv3.0 databases to update existing knowledge and provide better information on its geographic distribution, life cycle, genetic diversity, evidence of intrusion and domiciliation, vector-related circulating discrete taxonomic units, possible role in oral T. cruzi transmission, and the effect of climate change on its biology and epidemiology.


Assuntos
Doença de Chagas/transmissão , Insetos Vetores/parasitologia , Panstrongylus/genética , Panstrongylus/parasitologia , Triatoma/parasitologia , Trypanosoma cruzi , Animais , Biologia , Ecologia , Genes de Insetos , Variação Genética/genética , Genótipo , Geografia , Humanos , Insetos Vetores/genética , América Latina , Panstrongylus/fisiologia , Filogenia , Trypanosoma cruzi/isolamento & purificação
9.
Artigo em Inglês | MEDLINE | ID: mdl-33681912

RESUMO

INTRODUCTION: This study estimated the seroprevalence and risk factors of Chagas disease (CD) in a population of the Quixeré municipality, Ceará. METHODS: We conducted serological methods to detect the Trypanosoma cruzi infection. The other variables were evaluated by a standardized questionnaire. RESULTS: The estimated prevalence of CD was 3.7%. Male sex, age >40 years, being farmers, low education level, origin from rural areas, and being born in Quixeré were significantly associated with infection. CONCLUSION: CD persists in this rural population of Northeast Brazil. Poverty, low education, and limited information regarding CD are critical issues that need to be addressed.


Assuntos
Doença de Chagas , Trypanosoma cruzi , Adulto , Brasil/epidemiologia , Doença de Chagas/epidemiologia , Humanos , Masculino , Prevalência , Fatores de Risco , População Rural , Estudos Soroepidemiológicos
10.
Artigo em Inglês | MEDLINE | ID: mdl-33681926

RESUMO

INTRODUCTION: Triatomines are insect vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. METHODS: Triatomines were collected from households and by dissecting palm trees in the peri-urban areas of Cruzeiro do Sul (Acre); they were identified using a specific key and via genital analyses. Trypanosomatid infection was determined through microscopy and polymerase chain reaction. RESULTS: In total, 116 triatomines of the species Eratyrus mucronatus, Rhodnius pictipes, R. stali, and R. montenegrensis were collected, of which 13.8% were positive for T. cruzi. CONCLUSIONS: Four species of triatomines presented an infection rate above 13% in the Boca do Moa community.


Assuntos
Doença de Chagas , Rhodnius , Triatominae , Trypanosoma cruzi , Animais , Brasil
11.
Eur J Med Chem ; 216: 113290, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667845

RESUMO

Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de novo, and therefore rely on purine salvage to meet their purine demand. Evaluating purine nucleoside analogs is therefore an attractive strategy to identify antikinetoplastid agents. Several anti-Trypanosoma cruzi and anti-Trypanosoma brucei 7-deazapurine nucleosides were previously discovered, with the removal of the 3'-hydroxyl group resulting in a significant boost in activity. In this work we therefore decided to assess the effect of the introduction of a 3'-fluoro substituent in 7-deazapurine nucleosides on the anti-kinetoplastid activities. Hence, we synthesized two series of 3'-deoxy-3'-fluororibofuranosyl and 3'-deoxy-3'-fluoroxylofuranosyl nucleosides comprising 7-deazaadenine and -hypoxanthine bases and assayed these for antiparasitic activity. Several analogs with potent activity against T. cruzi and T. brucei were discovered, indicating that a fluorine atom in the 3'-position is a promising modification for the discovery of antiparasitic nucleosides.


Assuntos
Nucleosídeos de Purina/química , Purinas/química , Tripanossomicidas/síntese química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nucleosídeos de Purina/síntese química , Nucleosídeos de Purina/farmacologia , Purinas/síntese química , Purinas/farmacologia , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos
12.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669428

RESUMO

Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. METHODS: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. RESULTS: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 × 10-8). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. CONCLUSIONS: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.


Assuntos
Doença de Chagas/tratamento farmacológico , Doença de Chagas/genética , Nitroimidazóis/efeitos adversos , Polimorfismo de Nucleotídeo Único , Transcriptoma , Tripanossomicidas/efeitos adversos , Trypanosoma cruzi/efeitos dos fármacos , Brasil/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/parasitologia , Feminino , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Transdução de Sinais/genética
13.
Rev Soc Bras Med Trop ; 54: e0269-2020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759915

RESUMO

Reactivation of chronic Trypanosoma cruzi infection in solid organ transplant recipients (SOTRs) has been reported. The patient presented with a 2-week history of two painful erythematous, infiltrated plaques with central ulceration and necrotic crust on the left thigh. She had a history of chronic indeterminate Chagas disease (CD) and had received a kidney transplant before 2 months. Skin biopsies revealed lobular panniculitis with intracellular amastigote forms of T. cruzi. The patient was diagnosed with CD reactivation. Treatment with benznidazole significantly improved her condition. CD reactivation should be suspected in SOTRs living in endemic areas with clinical polymorphism of skin lesions.


Assuntos
Doença de Chagas , Transplante de Rim , Paniculite , Trypanosoma cruzi , Doença de Chagas/diagnóstico , Feminino , Humanos , Transplante de Rim/efeitos adversos , Coxa da Perna
14.
Rev Soc Bras Med Trop ; 54: e0873-2020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759934

RESUMO

Chagas disease is caused by the protozoan Trypanosoma cruzi. Seven lineages have been identified based on different molecular markers, namely TcI, TcII, TcIII, TcIV, TcV, TcVI, and TcBat. Dogs play the role of epidemiological sentinels being domestic reservoirs of T. cruzi. The aim of the current study was to report the first case of CD in a domestic dog in Manaus, Amazonas, Brazil, infected with T. cruzi DTU TcIV. We hope our report encourages veterinarians and surveillance professionals to a take a deeper look at T. cruzi infection in domestic animals.


Assuntos
Doença de Chagas , Trypanosoma cruzi , Animais , Brasil , Doença de Chagas/diagnóstico , Doença de Chagas/veterinária , Cães , Genótipo , Trypanosoma cruzi/genética
15.
Mem Inst Oswaldo Cruz ; 116: e200634, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787768

RESUMO

The availability of Trypanosomatid genomic data in public databases has opened myriad experimental possibilities that have contributed to a more comprehensive understanding of the biology of these parasites and their interactions with hosts. In this review, after brief remarks on the history of the Trypanosoma cruzi and Leishmania genome initiatives, we present an overview of the relevant contributions of genomics, transcriptomics and functional genomics, discussing the primary obstacles, challenges, relevant achievements and future perspectives of these technologies.


Assuntos
Genoma de Protozoário/genética , Leishmania/genética , Trypanosoma cruzi/genética , Biologia Computacional , Genômica
16.
Sci Data ; 8(1): 93, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767201

RESUMO

In humans and other eukaryotes, histone post-translational modifications (hPTMs) play an essential role in the epigenetic control of gene expression. In trypanosomatid parasites, conversely, gene regulation occurs mainly at the post-transcriptional level. However, our group has recently shown that hPTMs are abundant and varied in Trypanosoma cruzi, the etiological agent of Chagas Disease, signaling for possible conserved epigenetic functions. Here, we applied an optimized mass spectrometry-based proteomic workflow to provide a high-confidence comprehensive map of hPTMs, distributed in all canonical, variant and linker histones of T. cruzi. Our work expands the number of known T. cruzi hPTMs by almost 2-fold, representing the largest dataset of hPTMs available to any trypanosomatid to date, and can be used as a basis for functional studies on the dynamic regulation of chromatin by epigenetic mechanisms and the selection of candidates for the development of epigenetic drugs against trypanosomatids.


Assuntos
Doença de Chagas/metabolismo , Histonas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Cromatina/metabolismo , Desenvolvimento de Medicamentos , Epigênese Genética , Humanos , Espectrometria de Massas/métodos , Proteômica/métodos , Proteínas de Protozoários/genética , Tripanossomicidas/química , Trypanosoma cruzi/genética
17.
J Med Chem ; 64(7): 4206-4238, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33784107

RESUMO

Chagas disease and visceral leishmaniasis are two neglected tropical diseases responsible for numerous deaths around the world. For both, current treatments are largely inadequate, resulting in a continued need for new drug discovery. As both kinetoplastid parasites are incapable of de novo purine synthesis, they depend on purine salvage pathways that allow them to acquire and process purines from the host to meet their demands. Purine nucleoside analogues therefore constitute a logical source of potential antiparasitic agents. Earlier optimization efforts of the natural product tubercidin (7-deazaadenosine) involving modifications to the nucleobase 7-position and the ribofuranose 3'-position led to analogues with potent anti-Trypanosoma brucei and anti-Trypanosoma cruzi activities. In this work, we report the design and synthesis of pyrazolo[3,4-d]pyrimidine nucleosides with 3'- and 7-modifications and assess their potential as anti-Trypanosoma cruzi and antileishmanial agents. One compound was selected for in vivo evaluation in an acute Chagas disease mouse model.


Assuntos
Nucleosídeos/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/tratamento farmacológico , Desenho de Fármacos , Estabilidade de Medicamentos , Humanos , Leishmania infantum/efeitos dos fármacos , Masculino , Camundongos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Nucleosídeos/síntese química , Nucleosídeos/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia
18.
Acta Trop ; 218: 105908, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33789152

RESUMO

The immunodominant B13 protein of Trypanosoma cruzi is found on the surface of trypomastigotes and exhibits cross-reactivity with the human cardiac myosin heavy chain; for which antibodies against this parasitic antigen may be involved in the development of disease pathology. In a cohort of chronically T. cruzi-infected adults, undergoing trypanocidal treatment, or not, we, therefore, decided to evaluate the levels of anti-B13 antibodies (ELISA-B13) and its eventual relationship with heart complaints. Two hundred twenty-eight serum samples from 76 chronically infected adults with an average follow-up of 24 years were analyzed. Thirty of them had received trypanocidal treatment. Among treated patients, anti-B13 Ab levels in successive samples showed a significant decrease in reactivity as the years after treatment increased (ANOVA test, p = 0.0049). At the end of the follow-up, 36.7% became non-reactive for ELISA B13. Untreated patients did not have significant variations in the level of anti-B13 antibodies during follow-up. None of the treated patients had electrocardiographic changes compatible with chronic chagasic cardiomyopathy, whereas 21.7% of those undergoing no treatment did show such kind of pathological electrocardiogram tracings. ELISA-B13 was reactive in all cases with heart involvement. Among untreated patients, there were no significant differences in anti-B13 antibodies when comparing individuals without proven pathology with those with chronic chagasic cardiomyopathy. Although treatment with trypanocidal drugs was followed by decreased anti-B13 antibody levels, such assessment was unhelpful in differentiating the evolution of chronic chagasic heart disease.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/imunologia , Tripanossomicidas/uso terapêutico , Adulto , Animais , Argentina , Doença Crônica , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Nifurtimox/uso terapêutico , Nitroimidazóis/uso terapêutico , Estudos Retrospectivos , Trypanosoma cruzi , Adulto Jovem
19.
Exp Parasitol ; 224: 108100, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33744229

RESUMO

Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study.


Assuntos
Furanos/farmacologia , Leishmania mexicana/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Linhagem Celular , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Cromatografia em Camada Delgada , Doenças Endêmicas , Furanos/química , Humanos , Concentração Inibidora 50 , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/ultraestrutura , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Macrófagos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Simulação de Acoplamento Molecular , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestrutura
20.
Acta Trop ; 217: 105858, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33582143

RESUMO

Chagas disease is an anthropozoonosis, caused by a flagellated protozoan, Trypanosoma cruzi, in which the enzootic cycle occurs between mammals and triatomines. Two dogs with a history of sudden death were necropsied at the Federal University of Pará (UFPA). One dog had a pale area in the myocardium, which on histopathological examination showed a T. cruzi amastigote nest; immunohistochemistry (IHC) analysis characterized it as acute Chagas disease (ACD). The second dog showed no macroscopic changes. Microscopically, a few cardiomyocytes were replaced by adipocytes, and IHC result was negative for T. cruzi. However, results of polymerase chain reaction (PCR) of the cardiac tissue of both dogs was positive for T. cruzi DNA. After that, an epidemiological study was conducted in the region. For this study, we selected four areas in Castanhal. One of the four areas (Area 1) is where one of the dogs lived. The other three areas were chosen because they were recently deforested for housing. Blood samples were collected from dogs, cats, wild small mammals (marsupials and rodents), and the digestive tract of triatomines. Nested PCR was performed on all the blood samples and the triatomine digestive tracts. In Area 1, T. cruzi DNA was detected in 50% (12/24) of the tested dogs, in the only tested cat (1/1), 50% (1/2) of the tested marsupials (Didelphis marsupials), and 100% of the captured triatomines (Rhodnius pictipes) (2/2). In Area 2, T. cruzi DNA was not detected in any of the 11 (0/11) dogs and two marsupials tested (0/2), and no triatomines were found in this area. In Area 3, T. cruzi DNA was detected in 42.25% (30/71) of the dogs, in 66,6% (2/3) of the cats, the only captured marsupial (D. marsupialis) (1/1), and all three triatomines (3/3) (R. pictipes) tested. In Area 4, the two dogs tested were negative (0/2), 25% (1/4) of the captured marsupials (D. marsupialis) was positive, and no triatomine was captured in this area. The data demonstrate the importance of detecting T. cruzi in dogs, cats, small rodents, and marsupials in the Amazon metropolitan areas, where ecotopes carry reservoirs and vectors capable of participating in the Chagas disease cycle. The proximity between humans and T. cruzi vectors in these places might contribute to increased disease transmission risk and maintenance of agents. It was noted that high-standard condominiums, previously thought to reduce the risk for this disease, presented a new epidemiological risk. The presence of T. cruzi DNA in a dog who, a year earlier had tested negative, when another dog in the same house died of ACD, shows that the transmission cycle is present and active, with a high possibility of disease transmission to animals and humans.


Assuntos
Doença de Chagas/veterinária , Doenças do Cão/parasitologia , Trypanosoma cruzi/genética , Animais , Doenças do Gato/parasitologia , Gatos/parasitologia , Doença de Chagas/transmissão , DNA de Protozoário , Didelphis/parasitologia , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães/parasitologia , Insetos Vetores/parasitologia , Mamíferos/parasitologia , Marsupiais/parasitologia , Reação em Cadeia da Polimerase , Rhodnius/parasitologia , Fatores de Risco , Roedores/parasitologia
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