Surgical risk for patients with Chagasic achalasia and its correlation with the degree of esophageai dilation

AIM： To analyze the risk of cardiovascular complications in patients with indication for surgical treatment of Chagasic esophageal achalasia and to correlate the surgical risks with the degree of esophageal dilation, thereby proposing a risk scale index. METHODS： One hundred and twenty-four patients with Chagasic esophageal achalasia, who received surgical treatment at the Hospital das Clinicas of the Federal University of Goiás, were included in this study. The patients were mostly related to the postoperative complications due to the cardiovascular system. All the patients were submitted to： （1） clinical history to define the cardiac functional class （New York Heart Association）; （2） conventional 12-lead electrocardiogram at rest; and （3） contrast imaging of the esophagus to determine esophageal dilatation according to Rezende＇s classification of Chagasic megaesophagus. RESULTS： An assessment of the functional classification （FC） of heart failure during the preoperative period determined that 67 patients （54.03%） were assigned functional class Ⅰ （FC Ⅰ）, 46 patients （37.09%） were assigned functional class Ⅱ （FC Ⅱ）, and 11 patients （8.87%） were assigned functional class Ⅲ （FC Ⅲ）. None of the patients were assigned to functional class Ⅳ （FC Ⅳ）. There was a positive correlation between the functional class and the postoperative complications （FC Ⅰ×FC Ⅱ： P〈0.001; FC Ⅰ×FC Ⅲ： P〈0.001）. The ECG was normal in 44 patients （35.48%） and presented abnormalities in 80 patients （64.52%）. There was a significant statistical correlation between abnormal ECG （arrhythmias and primary change in ventricular repolarization） and postoperative complications （P〈0.001）. With regard to the classification of the Chagasic esophageal achalasia, the following distribution was observed： group Ⅱ, 53 patients （42.74%）; group Ⅲ, 37 patients （29.83%）; and group Ⅳ, 34 patients （27.41%）. There was a positive correlation between the degree of esophageal dilation and the increase in postoperative complications （grade Ⅱ×grade Ⅲ achalasia： P〈0.001; grade Ⅱ×grade Ⅳ achalasia： P〈0.001; and grade Ⅲ×grade Ⅳ achalasia： P = 0.017）. Analyzing these results and using a multivariate regression analysis associated with the probability decision analysis, a risk scale was proposed as follows： up to 21 points （mild risk）; from 22 to 34 points （moderate risk）; and more than 34 points （high risk）. The scale had 82.4% accuracy for mild risk patients and up to 94.6% for the high risk cases. CONCLUSION： The preoperative evaluation of the cardiovascular system, through a careful anamnesis, an ECG and contrast imaging of the esophagus, makes possible to estimate the surgical risks for Chagas＇ disease patients who have to undergo surgical treatment for esophageal achalasia.

Clinicopathological alterations in wild mammals from the reservoir system of Trypanosoma cruzi:a scoping review

Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.

Plasma Lysophosphatidylcholine and Phospholipase A2 Activity in Chagas Disease Patients: A Comparative Analysis

Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.

Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole

Objective:To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.Methods:Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole.Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment.Results:Thirty-two participants were recruited and treated with benznidazole,and 20 were followed-up.Adverse events(AE)were observed in 22 out of 29 participants that had safety data(76%),and dermatological alterations were the most frequently observed AE.Of the 20 participants analyzed,13 and 7 completed 12 and 18 months follow-up after the treatment,respectively.12 Months after the final treatment,Trypanosoma cruzi was detectable in 3 patients by qPCR;18 months after the final treatment,Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants.Thus,between 12 and 18 months,7 participants of the 20 initial follow-up cases showed positive qPCR,indicating treatment failures.Conclusions:qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD,and can be applied to analyze early therapeutic failures.The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients,thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.

Chagas心脏病研究现状

Chagas病即查加斯病,是一个古老的热带寄生虫病。该病由克氏锥虫感染引起,可累及皮肤、心脏和消化道等全身多个系统,因其广泛流行于墨西哥及拉丁美洲国家的贫穷地区也被称为美洲锥虫病（American trypanosomiasis）。

Chagas氏病的诊断:重组ELISA与传统ELISA和血凝反应实验的比较分析

背景和目的 南美血库Chagas氏病(南美锥虫病)血清学筛查是通过两种不同的检测方法进行的,这两种方法往往会有大量不确定的结果。解决这一难题,作者比较了重组ELISA法和这两种传统方法。材料与方法 分别用重组EIJISA(Re-

Unlocking the in vitro anti-Trypanosoma cruzi activity of halophyte plants from the southern Portugal

Objective:To evaluate the in vitro anti-Trypanosoma cruzi（T.cruzi） activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal（Algarve）,and chemically characterize the most active samples.Methods:Acetone,dichloromethane and methanol extracts were prepared from 31 halophyte species and tested in vitro against trypomastigotes and intracellular amastigotes of the Tulahuen strain of T.cruzi.The most active extract was fractionated by preparative HPLC-DAD,affording 11 fractions.The most selective fraction was fully characterized by 1H-NMR.Results:From 94 samples tested,one was active,namely the root dichloromethane extract of Juncus acutus(IC50 < 20 μg/mL).This extract was fractionated by HPLC,affording 11 fractions,one of them containing only a pure compound（juncunol）,and tested for anti-parasitic activity.Fraction 8(IC50 = 4.1 μg/mL) was the most active,and was further characterized by 1H-NMR.The major compounds were phenanthrenes,9,10-dihydrophenanthrenes and benzocoumarins.Conclusion:Our results suggest that the compounds identified in fraction 8 are likely responsible for the observed anti parasitic activity.Further research is in progress aiming to isolate and identify the specific active molecules.To the best of our knowledge,this is the first report on the in vitro anti T.cruzi activity of halophyte species.

Chagas heart disease:An overview of diagnosis,manifestations,treatment,and care

Chagas heart disease(CHD)affects approximately 30%of patients chronically infected with the protozoa Trypanosoma cruzi.CHD is classified into four stages of increasing severity according to electrocardiographic,echocardiographic,and clinical criteria.CHD presents with a myriad of clinical manifestations,but its main complications are sudden cardiac death,heart failure,and stroke.Importantly,CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies,and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies.Among patients with CHD,approximately 90%of deaths can be attributed to complications of Chagas disease.Sudden cardiac death is the most common cause of death(55%–60%),followed by heart failure(25%–30%)and stroke(10%–15%).The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with.Therefore,the management of CHD is challenging,and in this review,we present the most updated available data to help clinicians and cardiologists in the care of these patients.We describe the clinical manifestations,diagnosis and classification criteria,risk stratification,and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Modulation of immune response in experimental Chagas disease

Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response(modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection.

Preclinical stem cell therapy in Chagas Disease: Perspectives for future research

Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity and mortality in Central and Latin America. Chagas disease disrupts blood microcirculation via various autoimmune mechanisms, causing loss of cardiomyocytes and severe impairment of heart function. Different cell types and delivery approaches in Chagas Disease have been studied in both preclinical models and clinical trials. The main objective of this article is to clarify the reasons why the benefits that have been seen with cell therapy in preclinical models fail to translate to the clinical setting. This can be explained by crucial differences between the cellular types and pathophysiological mechanisms of the disease, as well as the differences between human patients and animal models. We discuss examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration therapies. Future research should focus, not only on studying the best cell type to use but, very importantly, understanding the levels of safety and cellular interaction that can elicit efficient therapeutic effects in human tissue. Addressing the challenges associated with future research may ensure the success of stem cell therapy in improving preclinical models and the treatment of Chagas disease.

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.

Emerging and under-recognized Chagas cardiomyopathy in non-endemic countries

Due to recent population emigration movements,an epidemic of Chagas disease is currently menacing most developed countries.The authors report the case of a 53-year-old Brazilian woman living in Europe for the last 10 years who developed heart failure symptoms,having a previous symptomatic sinus node disease with a pacemaker implant at age of 40 years.The diagnosis was based on serology and myocardial biopsy and the patient was treated with nifurtimox.The authors emphasize the need of a high level of suspicion in patients with suggestive epidemiology and the needof populational screening of specific high risk groups.New treatment options are also discussed.

The association of Triatoma maculata(Ericsson 1848) with the gecko Thecadactylus rapicauda(Houttuyn 1782)(Reptilia:Squamata:Gekkonidae):a strategy of domiciliation of the Chagas disease peridomestic vector in Venezuela?

Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and electric vacuum cleaner search in and outside the building.Then,age structure of the captured Triatoma maculata(T.maculata) were identified and recorded.Reptiles living in sympatric with the triatomines were also searched.Results:T.maculata were found living sympatric with geckos(Thecadactylus rapicauda) and they bit residents of the apartment building in study.A total of 1 448 individuals of T.maculata were captured within three days,of which 74.2%(1 074 eggs) were eggs,21.5%were nymphs at different stages,and 4.3%were adults.Conclusions:The association of T.maculata and T.rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present;and therefore,could have implications of high importance in the intradomiciliary transmission of Chagas disease.

High resolution manometric findings in patients with Chagas' disease esophagopathy

Objective:To describe high resolution manometry features of a population of symptomatic- patients with Chagas’ disease esophagopathy(CDE).Methods:Sixteen symptomatic dysphagic patients with CDE[mean age(54.81±13.43) years,10 women]were included in this study.All patients underwent a high resolution manometry.Results:Mean lower esophageal sphincter(LES) extension was(3.02±1.17) cm with a mean basal pressure of(15.25±7.00) mmHg.Residual pressure was(14.31±9.19) mmHg.Aperistalsis was found in all 16 patients.Achalasia with minimal esophageal pressurization(type I) was present in 25%of patients and achalasia with esophageal compression(type 2) in 75%,according to the Chicago Classification.Upper esophageal sphincter(UES) mean basal pressure was(97.96±54.22) mmHg with a residual pressure of(12.95±6.42) mmHg.Conclusions:Our results show that LES was hypotensive or normotensive in the majority of the patients.Impaired relaxation was found in a minority of our patients.Aperistalsis was seen in 100%of patients.UES had impaired relaxation in a significant number of patients. Further clinical study is needed to investigate whether manometric features can predict outcomes following the studies of idiopathic achalasia..

Trypanosoma cruzi invasion in non-phagocytic cells:an ultrastructural study

Trypanosoma cruzi is the causative agent of Chagas disease.This parasite requires the intracellular niche in order to proliferate and disseminate the infection.After invasion,T.cruzi resides temporarily in an acidic vacuole which is lysed by a not well-understood mechanism.Transmission electron microscopy was used to describe the process of T.cruzi escape from the parasitophorous vacuole over the time.Using HeLa(non-professional phagocytic cells)as host cell,we observed that recently internalized parasites reside in a membrane-bounded vacuole.A few hours later,the first sign of vacuole disruption appeared as membrane discontinuities.This observation was followed by a progressive vacuole swelling as evidenced by an electron-lucent halo between the parasite and the vacuole membrane.Apparently,the vacuole membrane remnants reorganized as small vesicles that eventually disappeared from the vicinity of the parasites.Finally,parasites reach the host cell cytosol where replication takes place.The thorough ultrastructural description of this process set the base for a comprehensive understanding of the parasite-host cell interaction and,thus open the possibility of new therapeutic intervention strategies.

Regulation of RNA binding proteins in trypanosomatid protozoan parasites

Posttranscriptional mechanisms have a critical role in the overall outcome of gene expression. These mechanisms are especially relevant in protozoa from the genus Trypanosoma, which is composed by death threatening parasites affecting people in Sub-saharan Africa or in the Americas. In these parasites the classic view of regulation of transcription initiation to modulate the products of a given gene cannot be applied. This is due to the presence of transcription start sites that give rise to long polycistronic units that need to be processed costranscriptionally by trans-splicing and polyadenylation to give mature monocistronic mRNAs. Posttranscriptional mechanisms such as mRNA degradation and translational repression are responsible for the final synthesis of the required protein products. In this context, RNA-binding proteins(RBPs) in trypanosomes have a relevant role as modulators of mRNA abundance and translational repression by associating to the 3' untranslated regions in mRNA. Many different RBPs have been proposed to modulate cohorts of mRNAs in trypanosomes. However, the current understanding of their functions lacks a dynamic view on the different steps at which these RBPs are regulated. Here, we discuss different evidences to propose regulatory events for different RBPs in these parasites. These events vary from regulated developmental expression, to biogenesis of cytoplasmic ribonucleoprotein complexes in the nucleus, and condensation of RBPs and mRNA into large cytoplasmic granules. Finally, we discuss how newly identified posttranslational modifications of RBPs and mRNA metabolism-related proteins could have an enormous impact on the modulation of m RNA abundance. To understand these modifications is especially relevant in these parasites due to the fact that the enzymes involved could be interesting targets for drug therapy.

Chagas Disease: Proposal of Health Education for Community Health Workers in the City of Petrolina, Pernambuco, Brazil

The Education for Health at PET Work Program (PET-Health) is focused on education as a pre-supposition. Actions are directed towards to the integration of service-learning and community. Interdisciplinary principle is directed from fusion of work of graduate students, academics and professionals of health services for the benefit of strengthening primary care and health surveillance. This work aimed to carry out educational activities with Community Health Agents (ACS) of the health facilities of PET-health, with the theme of Chagas disease. This descriptive cross-sectional study was carried out from January to May 2013, and the sample consisted of 25 active ACS in six Basic Health Units in the city of Petrolina, Brazil. In spite of actuation of ACS in primary care for over 10 years, a limited knowledge has been developed about this pathology. The health education workshops developed by the PET group clarified the ACS on Chagas disease allowing them to have an expansion of knowledge about the vector, habitat Barber, transmission, clinical manifestations… After the workshop, it was found that the ACS expanded their knowledge about the disease cycle, expanding the possibilities for action in the prevention of this pathology in their respective coverage areas. This work shows an important form of integration between education, service and community that can govern the new direction of health education.

Synthesis and Trypanocidal Evaluation of Some Novel 2-(Substituted Benzylidene)-5, 7-Dibromo-6-Hydroxy-1-Benzofuran-3(2<i>H</i>)-Ones

Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a new series of aurones using 3’,5’-dibromo-2’,4’-dihydroxychalcones and copper bromide in presence of DMF-water mixture (8:2, v/v) for the first time. Preliminary bioassay shows that most of compounds have good trypanocidal activity against Trypanosoma cruzi at 10 μg/mL. Few compounds are equally potent to the standard drugs Benznidazole and Nifurtimox. The structures of the newly synthesized products 2a-n were established by elemental analysis, FTIR, 1H NMR, 13C NMR and mass spectroscopic studies.

Effects of Parasitic Diseases on the Cardiovascular System

The parasitic disease can significantly affect the cardiovascular system through various mechanisms;even though it is traditionally regarded as a disease characterized by parasitic sites’ mechanical damage and some immune responses. Recent studies have shown that the role of parasitic factors in the cause of death due to cardiovascular events cannot be ignored. Considering the worldwide prevalence of parasitic diseases, exploring the effects of parasitic diseases on the cardiovascular system becomes increasingly essential. Here we summarize the latest understanding of common parasitic infections, explore the possible mechanisms of cardiovascular responses to parasitic infections, and propose feasible strategies for preventing and treating parasite-induced cardiac reactions.