IgG Isotypes Targeting a Recombinant Chimeric Protein of Trypanosoma cruzi in Different Clinical Presentations of Chronic Chagas Disease.

Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, which leads to a spectrum of clinical presentations that range from asymptomatic to severe cardiac involvement. The host immune response plays a pivotal role in disease progression. Ig isotypes may contribute to disease pathogenesis. Investigating these components can provide insights into the immunopathogenic mechanisms underlying CD. This cross-sectional study aims to establish a correlation between the Ig profile of individuals infected with T. cruzi with the clinical forms of chronic CD. Serum samples were collected from partner institutions in different states of Brazil. Individuals diagnosed with chronic CD were categorized based on the clinical form of the disease. The indirect ELISA method using the recombinant chimeric Molecular Biology Institute of Paraná membrane protein 8.4 as the antigen was used to determine the Ig profile, including total IgG, IgG1, IgG2, IgG3, and IgG4. Ninety-seven serum samples from patients classified as negative (NEG, n = 38), indeterminate (IND, n = 24), mild cardiac (MC, n = 20), and severe cardiac (SC, n = 15) forms were analyzed. IgG1 exhibited greater levels compared with the other isotypes, showing a significant difference between the MC and IND groups. IgG3 levels were greater in individuals from the MC group compared with the SC group. IgG1 and IgG3 isotypes can serve as biomarkers to evaluate the progression of CD because they exhibit variations across clinical groups. Additional longitudinal studies are necessary to explore the relationship between antibody kinetics and the development of tissue damage.

Technological advances in the serological diagnosis of Chagas disease in dogs and cats: a systematic review.

BACKGROUND: Chagas disease (CD) is caused by Trypanosoma cruzi, which is transmitted mainly through the feces/urine of infected triatomine bugs. The acute phase lasts 2-3 months and is characterized by high parasitemia and nonspecific symptoms, whereas the lifelong chronic phase features symptoms affecting the heart and/or digestive tract occurring in 30-40% of infected individuals. As in humans, cardiac abnormalities are observed in T. cruzi-infected dogs and cats. We reviewed the technological advances in the serological diagnosis of CD in dogs and cats. METHODS: A review of the published literature during the last 54 years (1968-2022) on the epidemiology, clinical features, diagnosis, treatment and prevention of CD in dogs and cats was conducted. RESULTS: Using predefined eligibility criteria for a search of the published literature, we retrieved and screened 436 publications. Of these, 84 original studies were considered for inclusion in this review. Dogs and cats are considered as sentinels, potentially indicating an active T. cruzi transmission and thus the risk for human infection. Although dogs and cats are reputed to be important for maintaining the T. cruzi domestic transmission cycle, there are no commercial tests to detect past or active infections in these animals. Most published research on CD in dogs and cats have used in-house serological tests prepared with native and/or full-length recombinant antigens, resulting in variable diagnostic performance. In recent years, chimeric antigens have been used to improve the diagnosis of chronic CD in humans with encouraging results. Some of them have high performance values (> 95%) and extremely low cross-reactivity rates for Leishmania spp., especially the antigens IBMP-8.1 to IBMP-8.4. The diagnostic performance of IBMP antigens was also investigated in dogs, showing high diagnostic performance with negligible cross-reactivity with anti-Leishmania infantum antibodies. CONCLUSIONS: The development of a commercial immunodiagnostic tool to identify past or active T. cruzi infections in dogs and cats is urgently needed. The use of chimeric recombinant T. cruzi antigens may help to fill this gap and is discussed in this review.

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.

Chagas disease (CD) affects at least 6 million people in 21 South American countries besides several thousand in other nations all over the world. It is estimated that at least 14,000 people die every year of CD. Since vaccines are not available, chemotherapy remains of pivotal relevance. About 30% of the treated patients cannot complete the therapy because of severe adverse reactions. Thus, the search for novel drugs is required. Here we tested the benznidazole (BZ) combination with the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) upon Trypanosoma cruzi in vitro and in vivo. DETC-BZ combination was synergistic diminishing epimastigote proliferation and enhancing selective indexes up to over 10-fold. DETC was effective upon amastigotes of the BZ- partially resistant Y and the BZ-resistant Colombiana strains. The combination reduced proliferation even using low concentrations (e.g., 2.5 µM). Scanning electron microscopy revealed membrane discontinuities and cell body volume reduction. Transmission electron microscopy revealed remarkable enlargement of endoplasmic reticulum cisternae besides, dilated mitochondria with decreased electron density and disorganized kinetoplast DNA. At advanced stages, the cytoplasm vacuolation apparently impaired compartmentation. The fluorescent probe H2-DCFDA indicates the increased production of reactive oxygen species associated with enhanced lipid peroxidation in parasites incubated with DETC. The biochemical measurement indicates the downmodulation of thiol expression. DETC inhibited superoxide dismutase activity on parasites was more pronounced than in infected mice. In order to approach the DETC effects on intracellular infection, peritoneal macrophages were infected with Colombiana trypomastigotes. DETC addition diminished parasite numbers and the DETC-BZ combination was effective, despite the low concentrations used. In the murine infection, the combination significantly enhanced animal survival, decreasing parasitemia over BZ. Histopathology revealed that low doses of BZ-treated animals presented myocardial amastigote, not observed in combination-treated animals. The picrosirius collagen staining showed reduced myocardial fibrosis. Aminotransferase de aspartate, Aminotransferase de alanine, Creatine kinase, and urea plasma levels demonstrated that the combination was non-toxic. As DSF and DETC can reduce the toxicity of other drugs and resistance phenotypes, such a combination may be safe and effective.

Principais complicações cardíacas em idosos infectados pelo SARS-CoV-2: uma revisão sistemática / Principales complicaciones cardíacas en ancianos infectados por SARS-CoV-2: una revisión sistemática / Main cardiac complications in elderly infected by SARS-CoV-2: a systematic review

Objetivo: compreender as principais complicações ocasionadas pelo vírus SARS-CoV-2 no sistema cardíaco do público idoso. Métodos: trata-se de uma revisão sistemática da literatura de abordagem qualitativa e característica descritivo-exploratória realizada no ano de 2020. Resultados: as complicações cardíacas mais prevalentes na população idosa foram miocardite, arritmias, insuficiência cardíaca, infarto agudo, choque cardiogênico, lesão miocárdica aguda e parada cardiorrespiratória. O principal biomarcador cardíaco foi a troponina, apresentando elevação superior ao percentil 99°, evidenciando a necessidade de tratamento em Unidade de Terapia Intensiva. Considerações Finais: o aparecimento desse vírus causou grande prejuízo no campo da saúde, especialmente a população idosa, que apresenta risco elevado de óbito ao contrair essa doença. Destarte, é de extrema importância se ater a mensuração da troponina sérica no público alvo e realizar monitorização longitudinal, utilizando para tal a telecardiologia, uma vez que diminuem as chances de contaminação entre infectado e profissional de saúde

Objective: to understand the main complications of SARS-CoV-2 in the elderly cardiac system. Methods: systematic literature review conducted in 2020. Results: the most prevalent cardiac complications in the elderly population were myocarditis, arrhythmias, heart failure, acute infarction, cardiogenic shock, acute myocardial injury and cardiorespiratory arrest. The main cardiac biomarker was troponin, showing an elevation above the 99th percentile, evidencing the need for treatment in the Intensive Care Unit. Final Considerations: the appearance of this virus has caused great damage in the health field, especially the elderly population, who is at high risk of death when contracting this disease. Therefore, it is important to stick to the measurement of serum troponin in the target audience and perform longitudinal monitoring, using telecardiology for this purpose, since they reduce the chances of contamination between infected and health professionals

Objetivo: comprender las principales complicaciones del SARS-CoV-2 en el sistema cardíaco anciano. Métodos: revisión sistemática de la literatura realizada en 2020. Resultados: las complicaciones cardíacas más prevalentes en la población anciana fueron miocarditis, arritmias, insuficiencia cardíaca, infarto agudo, shock cardiogénico, lesión miocárdica aguda y parada cardiorrespiratoria. El principal biomarcador cardíaco fue la troponina, mostrando una elevación por encima del percentil 99, evidenciando la necesidad de tratamiento en la Unidad de Cuidados Intensivos. Consideraciones finales: la aparición de este virus ha provocado un gran daño en el campo de la salud, especialmente en la población anciana, que se encuentra en alto riesgo de muerte al contraer esta enfermedad. Por tanto, es importante ceñirse a la medición de troponina sérica en el público objetivo y realizar un seguimiento longitudinal, utilizando para ello la telecardiología, ya que reducen las posibilidades de contaminación entre los infectados y los profesionales sanitarios

Avaliação da associação do quimioterápico benzonidazol a outros fármacos com ação anti-T. cruzi no tratamento da doença de Chagas experimental / Evaluation of the association of benznidazole to other chemotherapeutic drugs with action anti-T cruzi in the treatment of experimental Chagas disease

A doença de Chagas (DC) é causada pelo protozoário hemoflagelado Trypanosoma cruzi. Estima-se que ainda existam 10 milhões de pessoas infectadas na América Latina. Para a quimioterapia específica da DC o benzonidazol (BZ) é o medicamento de escolha. A eficácia terapêutica dos compostos atualmente em uso clínico tem sido questionada, tendo em conta os diferentes índices de cura já registrados na literatura. A associação do BZ, com medicamentos que apresentem um efeito anti-T. cruzi poderá potencializar a ação antiparasitária do mesmo e possivelmente permitirá o uso de doses menores e consequentemente diminuição dos efeitos tóxicos. O objetivo da presente investigação é avaliar o efeito do tratamento com o BZ associado aos medicamentos nifurtimox (NF) e cetoconazol (CETO)...

Chagas’disease (CD) is caused by the hemoflagelate protozoa Trypanosoma cruzi. It is estimated that 10 million infected people are still living in Latin America. For the specific chemotherapy of CD, the Benznidazole (BZ) is the drug of choice. However, the therapeutic efficacy of the compounds now in clinical use is not confirmed, taking into account that different cure rates have been registered. It is possible that the association of BZ with other drugs with an anti-T. cruzi action could improve its anti-parasitic effect, with the use of lower dose and consequent decrease of the toxic effects. The objective of the present investigation is to evaluate the effect of the treatment with BZ in association with the drugs Nifurtimox (NF) and Ketoconazole (CETO)...

Biological, biochemical and molecular features of Trypanosoma cruzi strains isolated from patients infected through oral transmission during a 2005 outbreak in the state of Santa Catarina, Brazil: its correspondence with the new T. cruzi Taxonomy Consensus (2009)

We examined strains of Trypanosoma cruzi isolated from patients with acute Chagas disease that had been acquired by oral transmission in the state of Santa Catarina, Brazil (2005) and two isolates that had been obtained from a marsupial (Didelphis aurita) and a vector (Triatoma tibiamaculata). These strains were characterised through their biological behaviour and isoenzymic profiles and genotyped according to the new Taxonomy Consensus (2009) based on the discrete typing unities, that is, T. cruzi genotypes I-VI. All strains exhibited the biological behaviour of biodeme type II. In six isolates, late peaks of parasitaemia, beyond the 20th day, suggested a double infection with biodemes II + III. Isoenzymes revealed Z2 or mixed Z1 and Z2 profiles. Genotyping was performed using three polymorphic genes (cytochrome oxidase II, spliced leader intergenic region and 24Sα rRNA) and the restriction fragment length polymorphism of the kDNA minicircles. Based on these markers, all but four isolates were characterised as T. cruzi II genotypes. Four mixed populations were identified: SC90, SC93 and SC97 (T. cruzi I + T. cruzi II) and SC95 (T. cruzi I + T. cruzi VI). Comparison of the results obtained by different methods was essential for the correct identification of the mixed populations and major lineages involved indicating that characterisation by different methods can provide new insights into the relationship between phenotypic and genotypic aspects of parasite behaviour.

Biological, biochemical and molecular features of Trypanosoma cruzi strains isolated from patients infected through oral transmission during a 2005 outbreak in the state of Santa Catarina, Brazil: its correspondence with the new T. cruzi Taxonomy Consensus (2009).

We examined strains of Trypanosoma cruzi isolated from patients with acute Chagas disease that had been acquired by oral transmission in the state of Santa Catarina, Brazil (2005) and two isolates that had been obtained from a marsupial (Didelphis aurita) and a vector (Triatoma tibiamaculata). These strains were characterised through their biological behaviour and isoenzymic profiles and genotyped according to the new Taxonomy Consensus (2009) based on the discrete typing unities, that is, T. cruzi genotypes I-VI. All strains exhibited the biological behaviour of biodeme type II. In six isolates, late peaks of parasitaemia, beyond the 20th day, suggested a double infection with biodemes II + III. Isoenzymes revealed Z2 or mixed Z1 and Z2 profiles. Genotyping was performed using three polymorphic genes (cytochrome oxidase II, spliced leader intergenic region and 24Sα rRNA) and the restriction fragment length polymorphism of the kDNA minicircles. Based on these markers, all but four isolates were characterised as T. cruzi II genotypes. Four mixed populations were identified: SC90, SC93 and SC97 (T. cruzi I + T. cruzi II) and SC95 (T. cruzi I + T. cruzi VI). Comparison of the results obtained by different methods was essential for the correct identification of the mixed populations and major lineages involved indicating that characterisation by different methods can provide new insights into the relationship between phenotypic and genotypic aspects of parasite behaviour.