Manifestations Of Chagas Disease Research Articles

Gastrointestinal Manifestations of Chagas Disease: A Systematic Review with Meta-Analysis.

The aims of this study were to estimate the prevalence of gastrointestinal manifestations among individuals with positive serology for Chagas disease (ChD) and to describe the clinical gastrointestinal manifestations of the disease. A systematic review with meta-analysis was conducted based on the criteria and recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Scopus, Virtual Health Library, Web of Science, and Embase databases were used to search for evidence. Two reviewers independently selected eligible articles and extracted data. RStudio® software was used for the meta-analysis. For subgroup analysis, the studies were divided according to the origin of the individuals included: 1) individuals from health units were included in the health care service prevalence analysis, and 2) individuals from the general population were included in the population prevalence analysis. A total of 2,570 articles were identified, but after removal of duplicates and application of inclusion criteria, 24 articles were included and 21 were part of the meta-analysis. Most of the studies were conducted in Brazil. Radiological diagnosis was the most frequent method used to identify the gastrointestinal clinical form. The combined effect of meta-analysis studies showed a prevalence of gastrointestinal manifestations in individuals with ChD of 12% (95% CI, 8.0-17.0%). In subgroup analysis, the prevalence for studies involving health care services was 16% (95% CI, 11.0-23.0%), while the prevalence for population-based studies was 9% (95% CI, 5.0-15.0%). Megaesophagus and megacolon were the main forms of ChD presentation in the gastrointestinal form. The prevalence of gastrointestinal manifestations of ChD was 12%. Knowing the prevalence of ChD in its gastrointestinal form is an important step in planning health actions for these patients.

Sudden Cardiac Death Risk Stratification and Prevention in Chagas Disease: A Non-systematic Review of the Literature.

Chagas disease is an important public health problem in Latin America. However, migration and globalisation have resulted in the increased presence of Chagas disease worldwide. Sudden cardiac death is the leading cause of death in people with Chagas disease, most often due to ventricular fibrillation. Although more common in patients with documented ventricular arrhythmias, sudden cardiac death can also be the first manifestation of Chagas disease in patients with no previous symptoms or known heart failure. Major predictors of sudden cardiac death include cardiac arrest, sustained and non-sustained ventricular tachycardia, left ventricular dysfunction, syncope and bradycardia. The authors review the predictors and risk stratification score developed by Rassi et al. for death in Chagas heart disease. They also discuss the evidence for anti-arrhythmic drugs, catheter ablation, ICDs and pacemakers for the prevention of sudden cardiac death in these patients. Given the widespread global burden, understanding the risk stratification and prevention of sudden cardiac death in Chagas disease is of timely concern.

Chagas Cardiomyopathy: Evidence in Medical and Nutritional Management

Chagas cardiomyopathy (CC) is a prevalent manifestation of Chagas disease, responsible for high mortality. Treatment and management have not changed significantly, and there is still a lack of consensus about the proper approach. Particular characteristics in the pathogenesis and clinical manifestations of CC cause inadequate treatment. This review aims to describe the treatment and management of CC currently indicated and describe topics of discussion and future medical and nutritional interventions. New evidence suggests benznidazole (BZ) is beneficial in the treatment of CC. Also, posaconazole as adjuvant treatment could be beneficial. ECA inhibitors, β-blockers, and ivabradine show benefit in CC. Amiodarone as treatment of ventricular arrhythmias but also inhibiting Trypanosoma cruzi infection is described. Nutritional supplementation prevents progression of CC as adjuvant therapy. Treatment in CC cardiomyopathy has not changed over the years; use of benznidazole may be beneficial reducing parasitemia although there is no consistent survival improvement. Novel therapies failed to produce promising results in animal models to human models. Nutritional supplementation plays an important role in reducing proinflammatory cytokines and could be in the in the future adjuvant therapy. Investigation in CC is needed to address important topics.

Analyses of 32 Loci Clarify Phylogenetic Relationships among Trypanosoma cruzi Lineages and Support a Single Hybridization prior to Human Contact

BackgroundThe genetic diversity of Trypanosoma cruzi, the etiological agent of Chagas disease, has been traditionally divided in two major groups, T. cruzi I and II, corresponding to discrete typing units TcI and TcII-VI under a recently proposed nomenclature. The two major groups of T. cruzi seem to differ in important biological characteristics, and are thus thought to represent a natural division relevant for epidemiological studies and development of prophylaxis. To understand the potential connection between the different manifestations of Chagas disease and variability of T. cruzi strains, it is essential to have a correct reconstruction of the evolutionary history of T. cruzi.Methodology/Principal FindingsNucleotide sequences from 32 unlinked loci (>26 Kilobases of aligned sequence) were used to reconstruct the evolutionary history of strains representing the known genetic variability of T. cruzi. Thorough phylogenetic analyses show that the original classification of T. cruzi in two major lineages does not reflect its evolutionary history and that there is only strong evidence for one major and recent hybridization event in the history of this species. Furthermore, estimates of divergence times using Bayesian methods show that current extant lineages of T. cruzi diverged very recently, within the last 3 million years, and that the major hybridization event leading to hybrid lineages TcV and TcVI occurred less than 1 million years ago, well before the contact of T. cruzi with humans in South America.Conclusions/SignificanceThe described phylogenetic relationships among the six major genetic subdivisions of T. cruzi should serve as guidelines for targeted epidemiological and prophylaxis studies. We suggest that it is important to reconsider conclusions from previous studies that have attempted to uncover important biological differences between the two originally defined major lineages of T. cruzi especially if those conclusions were obtained from single or few strains.

Stroke in Asymptomatic Trypanosoma cruzi-Infected Patients

Background: The knowledge about the natural history of stroke in Chagas disease is incomplete. Methods: Vascular risk factors and stroke subtypes of asymptomatic Trypanosoma cruzi-infected patients with no clinical evidence of heart failure were assessed. They were compared with chronic chagasic cardiomyopathy patients who suffered a stroke and with a control group of 60 T. cruzi-noninfected stroke patients. Eighty-six consecutive chagasic stroke patients (mean age: 57.4 years; 64% females) were studied. Results: 38.4% of chagasic stroke patients had asymptomatic T. cruzi infection. Smoking was more frequent in asymptomatic chagasic stroke patients (21.2 vs. 5.7%; p = 0.04). Prevalence of hypertension, diabetes and prior stroke was similar in both groups. Small-vessel infarction (15.6 vs. 3.8%) and large-vessel atherosclerosis (9.4 vs. 3.8%) were significantly more frequent in asymptomatic than in symptomatic T. cruzi-infected stroke patients (p = 0.001). Nevertheless, their frequency was even higher in T. cruzi-noninfected stroke patients (36.7 and 13.3%, respectively). Apical aneurysm (27.3%), left atrial dilatation (12.1%), left ventricle hypokinesia (9.4%) and right bundle branch block (36.4%) were also detected in asymptomatic T. cruzi-infected stroke patients. Conclusions: Ischemic stroke may be the first manifestation of Chagas disease in asymptomatic patients with mild left ventricle dysfunction. Other noncardioembolic stroke subtypes can occur in asymptomatic T. cruzi-infected patients.

Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke

American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.

Lack of association betweenIL-6−174G/C gene polymorphism and Chagas disease

The aim of this study was to investigate the role of the IL-6-174G/C gene polymorphism in susceptibility/resistance to Trypanosoma cruzi infection in two independent cohorts from Colombia and Peru. We determined the IL-6-174G/C genotypes in a sample of 399 seronegative individuals and 317 serologically positive patients from Colombia and Peru. All individuals are from regions where T. cruzi infection is endemic. No statistically significant differences in the frequency of IL-6-174G/C gene polymorphism between chagasic patients and controls or between asymptomatic and individuals with cardiomyopathy were observed. Our results do not support an evidence for a major role contribution of this IL-6 gene polymorphism in the susceptibility to or clinical manifestations of Chagas disease in these studied cohorts.

Transmission ofTrypanosoma cruziby Heart Transplantation

Trypanosoma cruzi infection (i.e., Chagas disease) is an unusual complication that can occur after solid-organ transplantation and that can result in severe illness or death. In 2006, there were 2 heart transplant recipients in Los Angeles, California, reported to have acute trypanosomiasis during the same month. We conducted an investigation to determine the source of these infections. We reviewed the medical, organ procurement, and donor transfusion and transplantation records of these 2 heart transplant recipients. The 2 heart transplant recipients were interviewed regarding any kind of natural exposure and were screened for parasites by obtaining blood and other tissue samples for buffy coat, culture, and polymerase chain reaction. Serum samples from the heart transplant recipients, organ donors, and blood donors were tested for T. cruzi antibodies by use of immunofluorescence assay and radioimmunoprecipitation assay. Tissue samples from the organ donors were examined by use of polymerase chain reaction and immunohistochemical staining. Other recipients of organs from the same donors were monitored for T. cruzi infection by use of polymerase chain reaction and immunofluorescence assay. Both heart transplant recipients had no apparent risk factors for preexisting T. cruzi infection. Both were seronegative but tested positive for the parasite, indicating recent infection. Both recipients died despite medical treatment. The organ donors tested positive for T. cruzi antibodies by use of radioimmunoprecipitation assay; the blood donors were seronegative. Six other patients had received a liver or kidney from these organ donors. None showed evidence of T. cruzi infection. To our knowledge, this is the first report of T. cruzi transmission associated with heart transplantation. Clinicians and public health authorities should be aware that manifestations of Chagas disease can occur after transplantation, requiring rapid evaluation, diagnosis, and treatment.

Parasitic Diseases, Diagnostic Approaches, and Therapies

The diagnosis and treatment of parasitic diseases has undergone major changes because of increased awareness and technological advances that now allow for more rapid and accurate diagnosis of parasitic diseases. These advances are critically important for the continuing diagnosis of these infections as there has been a steady decline in the quantity and quality of laboratory technicians who are expert in the classical techniques of examining stool and blood smears for parasites. The majority of laboratories have an increased reliance on nonclassical parasitological techniques for the accurate diagnosis of these infections. Dr. Ndao from McGill University has given an overview of many of these newer diagnostic methods. Malaria is a major pathogen in most of the world, and Drs Murray and Bennett from the US Army provide a timely review of the current status of rapid diagnosis of malaria using nontraditional methods. These rapid techniques have been a great advance since, in many laboratories; there are now few individuals that are expert in examining smears. In addition, these rapid techniques can be used by field workers and military personnel. These new methods make the diagnosis more rapid and accurate leading to a more rapid institution of appropriate treatment. Amebiasis continues to be an important cause of morbidity and mortality worldwide. Drs. Singh, Haupt, and Petri, in their review provide an update on the rapid diagnosis of Entamoeba histolytica. Diseases caused by Microsporidia are found in both immune-competent and immune-compromised hosts such as those with HIV/AIDS. The diagnosis is often difficult to make. In their article, Drs. Ghosh and Weiss review the state of molecular diagnostics for microsporidian infections. Human infections caused by free-living amoebas have not received sufficient attention in literature despite the fact that they may cause disabilities and death. Dr. Marciano-Cabral's group has reviewed the current state of the diagnosis of these important organisms. The review by Vannier and Krause provides an excellent update on the status of the diagnosis and treatment of babesiosis. Importantly, this infection still poses a threat not only from natural infection via the bite of a tick but also through blood transfusion. New diagnostic techniques have been developed for metazoan as well as protozoan infections. Neurocysticercosis has received increasing attention as a cause of seizures worldwide. There has also been an awareness of this disease because of the immigration of individuals from endemic areas to non-endemic areas of the world. Drs. Coyle and Tanowitz provide a review of the diagnostic and therapeutic options for management of this infection. Another helmintic disease of humans with complex management issues is that caused by Echinococcus and this is reviewed by Siracusano and colleagues. The articles by Dr. Baccchi and Dr. de Souza deal with the chemotherapy of trypanosomiasis, both African and American. Drs. Hochman and Kim explore the recent data on the HIV-malaria interaction. Since both HIV and malaria coexist in sub-saharan Africa, this review is timely. Dr. Petersen examines canine leishmaniasis and it implications for human disease. This year 2009 marks the 100th anniversary of the discovery of Chagas disease. This disease caused by the parasite Trypanosoma cruzi continues to be an important cause of cardiomyopathic heart disease in endemic areas of Latin America and is being increasingly recognized in non-endemic areas such as North America and Europe. The article by Dr. Gupta et al. from the Garg group in the University of Texas has offered a unique insight into the role of oxidative stress in the pathogenesis of chagasic cardiomyopathy. Adipose tissue is the largest endocrine organ in the body and its role in infection has only recently been appreciated. The laboratory group at the Albert Einstein College of Medicine offers a review of the role of adipose tissue in the pathogenesis of Chagas diseases, providing a new perspective on this overlooked facet of pathogen host interaction. There has been little success in changing the chronic manifestations of Chagas Disease by using antiparasitic therapy. A new approach to this problem is discussed in the article by Dr. Campos de Carvalho et al. who provide data suggesting that stem cell therapy may be useful in the treatment of the cardiomyopathy caused by T. cruzi infection. We have obtained articles on a range of topics which highlight many of the new issues in the field of parasitological diagnosis and treatment. It is our belief that this collection of articles provides an important summary of these issues and will be of use to both clinicians and researchers working on parasitic diseases. Herbert B. Tanowitz Louis M. Weiss

Interstitial cells of Cajal in chagasic megaesophagus

Chagasic visceromegalies are the most important digestive manifestations of Chagas disease and are characterized by motor disorders and dilation of organs such as esophagus and colon. One of the theories raised to explain the physiopathogenesis of chagasic megas is the plexus theory. Recent studies have shown a reduction of interstitial cells of Cajal (ICCs) in the colon of chagasic patients. These cells are present throughout the gastrointestinal tract and are considered to be pacemaker cells, that is, they are responsible for coordinating peristalsis and for mediating nerve impulses. In view of the lack of studies on these cells in megaesophagus and the previous observation of a reduction of ICCs in chagasic megacolons, we compared the distribution of ICCs in the esophagus of chagasic and nonchagasic patients to contribute to a better understanding of the physiopathogenesis of this esophageal disease. Esophageal biopsy samples from 10 chagasic and 5 nonchagasic patients were used. Cells were identified with the anti-CD117 antibody. The number of ICCs was quantified in longitudinal and circular muscle layers and myenteric plexus. The results were analyzed statistically by comparison of means. An intense reduction in the number of ICCs was observed in muscle layers and in the myenteric plexus of patients with megaesophagus. We conclude that there is an intense reduction of ICCs in the esophagus of chagasic patients when compared to nonchagasic patients, a finding supporting the important role of these cells in gastrointestinal tract motility. A deficiency in these cells might be implied in the genesis of megaesophagus.

O megaesôfago tratado cirurgicamente: perfil epidemiológico dos pacientes operados no Hospital de Clínicas da Universidade Estadual de Campinas entre 1989 e 2005

Megaesophagus is one of the manifestations of Chagas disease and surgical treatment is the approach that presents the best results. In this retrospective study, the epidemiological profile of patients operated in the Clinical Hospital of University of Campinas between 1989 and 2005 was evaluated with regard to: place of birth, place of residence, probable place of infection, age, degree of megaesophagus, etiology, duration and evolution of dysphagia, other diseases in association and the type of surgery chosen. The method used was to analyze the 390 medical files of these patients, at the hospitals medical archive service. The results made it possible to establish the endemic regions, place of birth and place of residence of the patients with Chagas disease attended at our clinic, and to characterize the group. After detailed analysis, it was found that the mean age was 47 years and the mean duration of dysphagia was 9.47 years. It was observed that: a) in 84.4% of the patients, dysphagia took hold progressively; b) 306 (78.5%) patients presented Chagas disease etiology; c) grade 2 was prevalent in 48%; d) 89.8% of the patients underwent cardiomyotomy; and e) there were frequent associations with gastritis, esophagitis, megacolon, arterial hypertension and cardiopathy.

Manifestations of Chagas disease (American trypanosomiasis) in patients with HIV/AIDS

Between June 1989 and December 2005, an observational study of adults co-infected with HIV and Trypanosoma cruzi was conducted, to investigate the spectrum of manifestations of chronic Chagas disease (American trypanosomiasis) in the HIV-positive. The 31 men and 22 women investigated were aged 23-59 years. Each subject was investigated by ambulatory (Holter) and non-ambulatory electrocardiography, chest X-ray, oesophagography and echocardiography (to determine the clinical form of trypanosomiasis), by xenodiagnosis, blood culture and the microscopical examination of blood (to explore their T. cruzi parasitaemia), and by counting their CD4 T cells (to stage their HIV infection). The subjects were followed-up for 1-190 months (median = 58 months) and checked for re-activation of their Chagas disease, which was usually defined by the occurrence of unusual clinical manifestations and/or the detection, by microscopical examination, of trypanosomes in the blood or cerebrospinal fluid. Eleven (20.8%) of the subjects showed re-activation, another nine (17.0%) were found to have developed high T. cruzi parasitaemias but these were only detected by xenodiagnosis or culture, and 15 (28.3%) had illnesses typical of chronic Chagas disease in HIV-negative individuals, with low parasitaemias. Anti-T. cruzi therapy (benznidazole), recommended for 17 patients, resulted in the sustained reduction of parasitaemia in 11 of the 12 subjects who completed treatment. Chagas disease was the cause of death of eight of the 14 subjects who died during the study. Four of the women investigated gave birth, each to a single child, during follow-up, and three of the four babies showed evidence of the congenital transmission of T. cruzi.