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Sample records for chagas departamento general

  1. [Chronic Chagas cardiomyopathy detected in patients at the Regional General Hospital O'Horan, Merida, Yucatan, Mexico].

    PubMed

    Zavala-Castro, J E; Gutiérrez-Flota, H; Barrera-Pérez, M A; Bolio-Solís, A de J; Zavala-Velázquez, J E

    1995-01-01

    The purpose of this study was to determine the frequency of cardiopathy due to Chagas' disease in 36 patients of the cardiology department at the Regional General Hospital O'Horan in Merida, Yucatan. All patients included in the study had cardiac involvement compatible with acute or chronic stages of Chagas' disease. Medical records prepared for each one of the patients included a Chagas' disease targeted clinical history, chest X-ray, electrocardiogram, blood culture and serology using indirect immunofluorescence test. Out of the 36 patients studied, 7 were diagnosed as having Chagas' disease cardiopathy. Grade II cardiomegaly was established in 2 patients while the remaining 5 had grade III cardiomegaly. Conduction abnormalities were established in 6 patients while 2 of these had evidence of necrosis and/or ischemia. Chagas' disease cardiopathy, as our results suggest, is not a rare event in the cardiology ward at the O'Horan Hospital.

  2. Chagas Disease

    MedlinePlus

    Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...

  3. American Trypanosomiasis (Also Known as Chagas Disease) Diagnosis

    MedlinePlus

    ... The CDC Parasites - American Trypanosomiasis (also known as Chagas Disease) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Chagas Disease General Information Detailed FAQs Blood Screening FAQs ...

  4. Chagas' disease.

    PubMed Central

    Tanowitz, H B; Kirchhoff, L V; Simon, D; Morris, S A; Weiss, L M; Wittner, M

    1992-01-01

    Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS. Images PMID:1423218

  5. Chagas disease in prehistory.

    PubMed

    Ferreira, Luiz F; Jansen, Ana M; Araújo, Adauto

    2011-09-01

    The classical hypothesis proposes that Chagas disease has been originated in the Andean region among prehistoric people when they started domesticating animals, changing to sedentary habits, and adopting agriculture. These changes in their way of life happened nearly 6,000 years ago. However, paleoparasitological data based on molecular tools showed that Trypanosoma cruzi infection and Chagas disease were commonly found both in South and North American prehistoric populations long before that time, suggesting that Chagas disease may be as old as the human presence in the American continent. The study of the origin and dispersion of Trypanosoma cruzi infection among prehistoric human populations may help in the comprehension of the clinical and epidemiological questions on Chagas disease that still remain unanswered.

  6. Treatment of Chagas Cardiomyopathy

    PubMed Central

    Botoni, Fernando A.; Ribeiro, Antonio Luiz P.; Marinho, Carolina Coimbra; Lima, Marcia Maria Oliveira; Nunes, Maria do Carmo Pereira; Rocha, Manoel Otávio C.

    2013-01-01

    Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities. PMID:24350293

  7. Carlos Chagas: biographical sketch.

    PubMed

    Moncayo, Alvaro

    2010-01-01

    Carlos Chagas was born on 9 July 1878 in the farm "Bon Retiro" located close to the City of Oliveira in the interior of the State of Minas Gerais, Brazil. He started his medical studies in 1897 at the School of Medicine of Rio de Janeiro. In the late XIX century, the works by Louis Pasteur and Robert Koch induced a change in the medical paradigm with emphasis in experimental demonstrations of the causal link between microbes and disease. During the same years in Germany appeared the pathological concept of disease, linking organic lesions with symptoms. All these innovations were adopted by the reforms of the medical schools in Brazil and influenced the scientific formation of Chagas. Chagas completed his medical studies between 1897 and 1903 and his examinations during these years were always ranked with high grades. Oswaldo Cruz accepted Chagas as a doctoral candidate and directed his thesis on "Hematological studies of Malaria" which was received with honors by the examiners. In 1903 the director appointed Chagas as research assistant at the Institute. In those years, the Institute of Manguinhos, under the direction of Oswaldo Cruz, initiated a process of institutional growth and gathered a distinguished group of Brazilian and foreign scientists. In 1907, he was requested to investigate and control a malaria outbreak in Lassance, Minas Gerais. In this moment Chagas could not have imagined that this field research was the beginning of one of the most notable medical discoveries. Chagas was, at the age of 28, a Research Assistant at the Institute of Manguinhos and was studying a new flagellate parasite isolated from triatomine insects captured in the State of Minas Gerais. Chagas made his discoveries in this order: first the causal agent, then the vector and finally the human cases. These notable discoveries were carried out by Chagas in twenty months. At the age of 33 Chagas had completed his discoveries and published the scientific articles that gave him world

  8. Current situation and perspectives regarding human Chagas disease in midwestern of the state of Minas Gerais, Brazil

    PubMed Central

    Matos, Christiane Santos; dos Santos, José Eloy; Medeiros, Fernanda Alvarenga Cardoso; Furtado, Eliana; Dias, João Carlos Pinto

    2014-01-01

    Recognising the importance of Chagas disease in Brazil, Bambuí set up epidemiological surveillance for Chagas disease in 1974 and was the first municipality to do so. To ascertain the current epidemiology of Chagas disease in this municipality, 1.782 blood samples from the general population were analysed; 7.7% of samples were found to be seropositive for Chagas disease. A strong positive correlation between increasing age and Chagas disease was evident in both genders, with the highest prevalence in individuals aged over 60 years. Clinically, the cardiodigestive form of Chagas disease was the most common in these samples. These data confirm the interruption of Trypanosoma cruzi transmission, in parallel with a still important residual morbidity of Chagas disease in the county, thus supporting political decisions that will prioritise epidemiological surveillance and medical treatment of Chagas disease in the coming years. PMID:24831551

  9. Immunology of Chagas' disease*

    PubMed Central

    1974-01-01

    After reviewing present knowledge of the morphology, multiplication, and transmission of Trypanosoma cruzi, this Memorandum discusses the animal models that may be of value in understanding the immune mechanisms operating in Chagas' disease. The role of both circulating antibody and cell-mediated immunity in protection against the parasite is discussed, together with the possibility that immunopathological mechanisms may be responsible for some of the lesions found in patients with Chagas' disease. The immunodiagnostic methods at present available are also reviewed, and the possibility of producing a vaccine for human use is considered in the light of recent findings in experimental animals. A series of recommendations for further research is included. PMID:4218137

  10. Immunity in Chagas’ Disease.

    DTIC Science & Technology

    This is the final report on the immunity in Chagas ’ disease contract and it summarizes the results of a diversity of studies directed toward...antibody test for Chagas ’ disease. Also mentioned are the facts that the cell membranes of live trypomastigotes are not immunoreactive with the...humoral immune response of an infected host and that suppression of parasitemias in chronic Chagas ’ disease is probably a function of the cell immune system of the host. (Author)

  11. The history of Chagas disease

    PubMed Central

    2014-01-01

    The ancestor of Trypanosome cruzi was probably introduced to South American via bats approximately 7-10 million years ago. When the first humans arrived in the New World, a sylvatic cycle of Chagas disease was then already well established. Paleoparasitological data suggests that human American trypanosomiasis originated in the Andean area when people founded the first settlements in the coastal region of the Atacama Desert. Identification of T. cruzi as the etiological agent and triatome bugs as the transmission vector of Chagas disease occurred within a few years at the beginning of the 20th century. History also teaches us that human activity leading to environmental changes, in particular deforestation, is the main cause for the spread of Chagas disease. Recently, migration of T. cruzi-infected patients has led to a distribution of Chagas disease from Latin America to non-endemic countries in Europe, North America and western Pacific region. PMID:25011546

  12. [Chagas disease in Brazil].

    PubMed

    Vinhaes, M C; Dias, J C

    2000-01-01

    This article presents the current situation for Chagas disease vectors in Brazil, based on data from the Brazilian National Health Foundation (FNS). Over the course of the last 20 years, continuous chemical control has resulted in a clear reduction of triatomine densities and Trypanosoma cruzi in Brazilian dwellings. Results have been particularly promising in relation to Triatoma infestans and Panstrongylus megistus, considered the most important species in the past. In parallel, data from school serological surveys, hospitalized patients, and mortality records show an important decrease in the disease. Nevertheless, some areas of the Brazilian Northeast and some residual foci of Triatoma infestans and Panstrongylus megistus remain as major challenges for public health authorities, requiring effective epidemiological surveillance. States and municipalities are required to assume this task at present, as the traditional Brazilian National Health Foundation is undergoing decentralization.

  13. Chagas Cardiomyopathy: Clinical Presentation and Management in the Americas.

    PubMed

    Benziger, Catherine Pastorius; do Carmo, Gabriel Assis Lopes; Ribeiro, Antonio Luiz Pinho

    2017-02-01

    The initial infection of Chagas disease is typically asymptomatic, but approximately 30% of people will progress to a chronic cardiac form, and others develop the gastrointestinal form. Death is often sudden due to arrhythmias or progressive heart failure. Prevention through vector control programs and blood bank screening, along with strengthened surveillance systems and rapid information sharing, are key to decreasing disease burden globally. The epidemiology, diagnostic evaluation, diagnosis, and treatment of acute and chronic Chagas cardiac disease are discussed with focus on educating the primary care professionals and general cardiologists in nonendemic areas who have limited experience treating this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Chagas' disease after bone marrow transplantation.

    PubMed

    Altclas, J; Jaimovich, G; Milovic, V; Klein, F; Feldman, L

    1996-08-01

    Chagas' disease is caused by Trypanosoma cruzi. It is endemic in Latin America where 16 to 18 million people are infected. Immunocompromised patients such as BMT recipients are at risk of Chagas' disease either due to reactivation or transfusion. We report a case of acute Chagas' disease in the setting of BMT.

  15. Acute Chagas Disease in a Returning Traveler

    PubMed Central

    Carter, Yvonne L.; Juliano, Jonathan J.; Montgomery, Susan P.; Qvarnstrom, Yvonne

    2012-01-01

    Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas. PMID:23091192

  16. Control of Chagas disease.

    PubMed

    Yamagata, Yoichi; Nakagawa, Jun

    2006-01-01

    The Southern Cone Initiative (Iniciativa de Salud del Cono Sur, INCOSUR) to control domestic transmission of Trypanosoma cruzi is a substantial achievement based on the enthusiasm of the scientific community, effective strategies, leadership, and cost-effectiveness. INCOSUR triggered the launch of other regional initiatives in Central America and in the Andean and Amazon regions, which have all made progress. The Central American Initiative targeted the elimination of an imported triatomine bug (Rhodnius prolixus) and the control of a widespread native species (Triatoma dimidiata), and faced constraints such as a small scientific community, the difficulty in controlling a native species, and a vector control programme that had fragmented under a decentralized health system. International organizations such as the Japan International Cooperation Agency (JICA) have played an important role in bridging the gaps between fragmented organizational resources. Guatemala achieved virtual elimination of R. prolixus and ;reduction of Tri. Dimidiata and El Salvador and Honduras revitalized their national programmes. The programme also revealed new challenges. Tri. dimidiata control needs to cover a large geographic area efficiently with stratification, quality control, community mobilization, and information management. Stakeholders such as the National Chagas Program, the local health system and their communities, as well as local government must share responsibilities to continue comprehensive vector control.

  17. Chagas Heart Disease: An Update.

    PubMed

    Malik, Lindsey H; Singh, Gagan D; Amsterdam, Ezra A

    2015-11-01

    Chagas disease, also known as American trypanosomiasis, results from infection by the protozoan Trypanosoma cruzi, and is a major cause of cardiac disease worldwide. Until recently, Chagas disease was confined to those areas of South and Central America where Trypanosoma cruzi is endemic. With the migration of infected individuals, however, the disease has spread, and it is estimated that 6-7 million people worldwide are infected. In the US alone, more than 7 million people from Trypanosoma cruzi-endemic countries became legal US residents by the turn of the century, resulting in a surge of Chagas disease in this country. According to preliminary estimates, the US now ranks seventh in the Western Hemisphere in number of individuals infected with Trypanosoma cruzi, and the disease has become a major public health concern due to limited awareness in the medical community. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Heart Transplantation for Chagas Cardiomyopathy.

    PubMed

    Benatti, Rodolfo D; Oliveira, Guilherme H; Bacal, Fernando

    2017-06-01

    Chagas cardiomyopathy (CC) is one of the chronic manifestations of Trypanosoma cruzi (T. cruzi) infection and is a major public health disease in Latin America. Since it is a chronic systemic infection, Chagas disease was long considered a potential contraindication for transplantation because of the risk of recurrence with immunosuppression. However, early South American experience in the 1980's established the feasibility of heart transplantation (HT) in patients with Chagas disease. Indeed, the first cardiac transplant for a recipient with CC was performed in 1985 in Brazil. Chagas etiology of heart failure has become the third most common indication for HT in South America. T. cruzi reactivation post-transplant is a common issue that requires prophylactic surveillance but responds well to appropriate therapy. Chagas reactivation has been associated with the potency of the immunosuppressive protocol and occurs more frequently after rejection episodes. Yet, many important questions regarding the management of Chagas HT candidates and recipients remain unanswered. For example, biventricular systolic failure is frequent in end-stage CC, but its impact on the modality of mechanical circulatory bridging has not been described. Also, there is no consensus regarding the most adequate immunosuppressive regimen that balances the risk of graft rejection and disease reactivation. The real efficacy and safety of HT for end-stage CC will only be appreciated when a Latin American transplant registry is established. This review covers the current state of the art of HT for CC. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Transfusion-transmitted Chagas' disease.

    PubMed

    Wendel, S

    1998-11-01

    Transfusion-transmitted Chagas' disease has been recognized since 1952. Until recently, no cases were reported outside of Latin America. However, emigration during the past 20 years expanded its transfusional geographic borders to North America. Trypanosoma cruzi-infected donors usually are asymptomatic, often for a lifetime. This situation complicates donor screening, particularly in regions where blood bank personnel are not familiar with the risk factors and natural history of this transfusion-transmitted infection. This review addresses the main aspects of epidemiology, risks of infection, clinical symptoms in donors and recipients, preventive measures, and blood donor screening to prevent transfusion-transmitted Chagas' disease.

  20. [Part V. Laboratory diagnosis of Chagas disease].

    PubMed

    Apt B, Werner; Heitmann G, Ingrid; Jercic L, M Isabel; Jofré M, Leonor; Muñoz C Del V, Patricia; Noemí H, Isabel; San Martín V, Ana M; Sapunar P, Jorge; Torres H, Marisa; Zulantay A, Inés

    2008-10-01

    In this fifth part of Guidelines for Chagas disease, diagnostic techniques for Trypanosoma cruzi infection in humans are reviewed, the interpretation of laboratory results and an algorithm for laboratory diagnosis in immunocompetent hosts are presented. Chagas disease may be diagnosed by three kinds of techniques: direct, which allow detect the presence of the parasite in different kind of samples; indirect, based on the search of immune specific response against T. cruzi antigens and molecular, which detect parasite genetic material. Direct techniques are utilized mainly in acute phase of disease, as the parasite is present in blood of infected host. These techniques do not require be confirmed by other methods. For chronic undetermined phase and for symptomatic phase it is recommended to use indirect techniques; generally, immunoassay techniques (ELISA) that detect IgG antibodies directed against T. cruzi antigens are performed. As false positive results are possible, a positive or undetermined result must be confirmed by at least another technique (indirect immunofluorescence or indirect hemmaglutination). In Chile, confirmation of infection is performed by the Instituto de Salud Pública National Reference Laboratory or at surrogate centers. Molecular methods may be used to make the diagnosis in acute or chronic phase of infection, with more accuracy in the acute phase, and it is mainly recommended to diagnose vertical transmission of T. cruzi as early diagnosis of congenital infection increases the possibility to cure the sibling and besides it is a good marker to evaluate the effectiveness of treatment.

  1. Global economic burden of Chagas disease: a computational simulation model

    PubMed Central

    Lee, Bruce Y; Bacon, Kristina M; Bottazzi, Maria Elena; Hotez, Peter J

    2013-01-01

    of Chagas disease is similar to or exceeds those of other prominent diseases globally (eg, rotavirus $2·0 billion, cervical cancer $4·7 billion) even in the USA (Lyme disease $2·5 billion), where Chagas disease has not been traditionally endemic, suggesting an economic argument for more attention and efforts towards control of Chagas disease. Funding Bill & Melinda Gates Foundation, the National Institute of General Medical Sciences Models of Infectious Disease Agent Study. PMID:23395248

  2. [Globalization, inequity and Chagas disease].

    PubMed

    Dias, João Carlos Pinto

    2007-01-01

    Chagas disease (American trypanosomiasis) bears a close relationship to multiple social and political aspects involving issues of globalization and inequity. Such relations concern the process of disease production and control in parallel with medical management. Despite the poverty in Latin America and various problems related to inequities and globalization, Chagas disease has been controlled in several areas, a fact that reinforces the countries' self-reliance. Several problems and challenges related to the disease can be expected in the future, mainly concerning medical care for already infected individuals and the sustainability of effective epidemiological surveillance. Both points depend heavily on improved performance by the national health systems, principally in terms of their efficiency and their capacity to overcome inequity. A particularly important role has been attributed to the Latin American scientific and academic community in the implementation and sustainability of efficient control policies. Control activities have now evolved towards internationally shared initiatives, a major new stride forward in the region's political context.

  3. Duodenogastric reflux in Chagas' disease

    SciTech Connect

    Troncon, L.E.; Rezende Filho, J.; Iazigi, N.

    1988-10-01

    Increased duodenogastric reflux has been recognized as a cause of gastric mucosa damage. The frequent finding of bile-stained gastric juice and a suggested higher frequency of lesions of the gastric mucosa in patients with Chagas' disease, which is characterized by a marked reduction of myenteric neurons, suggest that impairment of intrinsic innervation of the gut might be associated with increased duodenogastric reflux. Duodenogastric bile reflux was quantified after intravenous injection of 99mtechnetium-HIDA, in 18 patients with chronic Chagas' disease, 12 controls, and 7 patients with Billroth II gastrectomy. All but one of the chagasic patients were submitted to upper digestive tract endoscopy. High reflux values (greater than or equal to 10%) were detected both in chagasic patients and in the controls, but the values for both groups were significantly lower (P less than 0.01) than those obtained for Billroth II patients (median: 55.79%; range: 12.58-87.22%). Reflux values tended to be higher in the Chagas' disease group (median: 8.20%; range: 0.0-29.40%) than in the control group (median: 3.20%; range: 0.0-30.64%), with no statistical difference between the two groups (P greater than 0.10). Chronic gastritis was detected by endoscopy in 12 chagasic patients, benign gastric ulcer in 2 patients, and a pool of bile in the stomach in 11 patients. However, neither the occurrence of gastric lesions nor the finding of bile-stained gastric juice was associated with high reflux values after (99mTc)HIDA injection. This study suggests that lesions of the intramural nervous system of the gut in Chagas' disease do not appear to be associated with abnormally increased duodenogastric reflux.

  4. Heterologous Infection During Chagas' Disease

    NASA Astrophysics Data System (ADS)

    Sibona, G. J.; Condat, C. A.; Cossi Isasi, S.

    2007-05-01

    Human populations are often infected with more than one parasite strain. This is frequently the case with ChagasŠ disease, which is endemic to large regions of Latin America. In the present work we study the dynamics of the heterologous infection for this disease, using a model for the interaction between the trypanosoma cruzi parasite and the immune system. We find the dependence of the nature of the post-acute stage on the parameters characterizing the inoculated infectious strains.

  5. Cell therapies for Chagas disease.

    PubMed

    Carvalho, Adriana Bastos; Goldenberg, Regina Coeli Dos Santos; Campos de Carvalho, Antonio Carlos

    2017-09-05

    In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  6. [Clinical profile of Chagas and non-Chagas' disease patients with cardiac pacemaker].

    PubMed

    Rincon, Leonor Garcia; Rocha, Manoel Otávio da Costa; Pires, Marco Túlio Baccarini; Oliveira, Bruna Guimarães; Barros, Vladimir da Costa Val; Barros, Marcio Vinicius Lins; Ribeiro, Antônio Luiz Pinho

    2006-01-01

    The aim of this study was to compare Chagas and non-Chagas' disease patients using single or dual-chamber pacemaker in relation to the ejection fraction of the left ventricle, the ventricular stimulation threshold and the occurrence of ventricular arrhythmia. From January, 2001 to November, 2002, 45 Chagas' disease patients and 35 non-Chagas' disease patients, all pacemaker users, were evaluated considering clinical history, echocardiographic study, Holter monitoring and analysis of the pacemaker telemetry data. Chagas' disease patients were significantly younger, but both groups were similar when chest X-Ray variables and right ventricular stimulation threshold were analyzed. Chagas' disease patients had a lower left ventricular ejection fraction and more frequent ventricular arrhythmia during Holter monitoring. A positive correlation between the low ejection fraction of the left ventricle and the intensity of ventricular arrhythmia was observed. In conclusion, among pacemaker user patients, Chagas' disease is related to cardiac markers of worse prognosis.

  7. Chagas Disease Risk in Texas

    PubMed Central

    Sarkar, Sahotra; Strutz, Stavana E.; Frank, David M.; Rivaldi, Chissa–Louise; Sissel, Blake; Sánchez–Cordero, Victor

    2010-01-01

    Background Chagas disease, caused by Trypanosoma cruzi, remains a serious public health concern in many areas of Latin America, including México. It is also endemic in Texas with an autochthonous canine cycle, abundant vectors (Triatoma species) in many counties, and established domestic and peridomestic cycles which make competent reservoirs available throughout the state. Yet, Chagas disease is not reportable in Texas, blood donor screening is not mandatory, and the serological profiles of human and canine populations remain unknown. The purpose of this analysis was to provide a formal risk assessment, including risk maps, which recommends the removal of these lacunae. Methods and Findings The spatial relative risk of the establishment of autochthonous Chagas disease cycles in Texas was assessed using a five–stage analysis. 1. Ecological risk for Chagas disease was established at a fine spatial resolution using a maximum entropy algorithm that takes as input occurrence points of vectors and environmental layers. The analysis was restricted to triatomine vector species for which new data were generated through field collection and through collation of post–1960 museum records in both México and the United States with sufficiently low georeferenced error to be admissible given the spatial resolution of the analysis (1 arc–minute). The new data extended the distribution of vector species to 10 new Texas counties. The models predicted that Triatoma gerstaeckeri has a large region of contiguous suitable habitat in the southern United States and México, T. lecticularia has a diffuse suitable habitat distribution along both coasts of the same region, and T. sanguisuga has a disjoint suitable habitat distribution along the coasts of the United States. The ecological risk is highest in south Texas. 2. Incidence–based relative risk was computed at the county level using the Bayesian Besag–York–Mollié model and post–1960 T. cruzi incidence data. This risk

  8. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors—autoimmunity—has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. PMID:25857229

  9. Association of uterine leiomyoma and Chagas' disease.

    PubMed

    Murta, Eddie Fernando Candido; Oliveira, Gustavo Paludetto; Prado, Fernando De Oliveira; De Souza, Maria Azniv Hazarabedian; Tavares Murta, Beatriz Martins; Adad, Sheila Jorge

    2002-03-01

    With the aim of studying the frequency of Chagas' disease among sufferers of uterine leiomyoma, we analyzed women older than 35 years who underwent surgery and presented with leiomyoma on anatomicopathological examination. The diagnosis of Chagas infection was based on positivity to at least two of three serological tests: enzyme-linked immunosorbent assay, passive hemagglutination, and immunofluorescence. The study was case controlled, matching for age, skin color, and parity. The control group consisted of women undergoing surgery for other benign gynecological alterations. During this period, 118 women presented with uterine leiomyoma, 27.1% of whom were serologically positive for Chagas' disease versus 16.1% of the controls (P < 0.05). Matching by skin color and parity showed that 40% of the white multiparous women with uterine leiomyoma had Chagas' disease versus 10% of the controls (P < 0.05). We concluded that there appears to be an association between Chagas' disease and uterine leiomyoma.

  10. The Chronic Gastrointestinal Manifestations of Chagas Disease

    PubMed Central

    Matsuda, Nilce Mitiko; Miller, Steven M.; Evora, Paulo R. Barbosa

    2009-01-01

    Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi. The disease mainly affects the nervous system, digestive system and heart. The objective of this review is to revise the literature and summarize the main chronic gastrointestinal manifestations of Chagas disease. The chronic gastrointestinal manifestations of Chagas disease are mainly a result of enteric nervous system impairment caused by T. cruzi infection. The anatomical locations most commonly described to be affected by Chagas disease are salivary glands, esophagus, lower esophageal sphincter, stomach, small intestine, colon, gallbladder and biliary tree. Chagas disease has also been studied in association with Helicobacter pylori infection, interstitial cells of Cajal and the incidence of gastrointestinal cancer. PMID:20037711

  11. The Vasculature in Chagas Disease

    PubMed Central

    Prado, Cibele M.; Jelicks, Linda A.; Weiss, Louis M.; Factor, Stephen M.; Tanowitz, Herbert B.; Rossi, Marcos A.

    2013-01-01

    The cardiovascular manifestations of Chagas disease are well known. However, the contribution of the vasculature and specifically the microvasculature has received little attention. This chapter reviews the evidence supporting the notion that alterations in the microvasculature especially in the heart contribute to the pathogenesis of chagasic cardiomyopathy. These data may also be important in understanding the contributions of the microvasculature in the aetiologies of other cardiomyopathies. The role of endothelin-1 and of thromboxane A2 vascular spasm and platelet aggregation is also discussed. Further, these observations may provide target(s) for intervention. PMID:21884888

  12. [Oral transmission of Chagas' disease].

    PubMed

    Toso M, Alberto; Vial U, Felipe; Galanti, Norbel

    2011-02-01

    The traditional transmission pathways of Chagas' disease are vectorial, transfusional, transplacental and organ transplantation. However, oral transmission is gaining importance. The first evidence of oral transmission was reported in Brazil in 1965. Nowadays the oral route is the transmission mode in 50% of cases in the Amazon river zone. Oral infection is produced by the ingestion of infected triatomine bugs or their feces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials. Therefore travelers to those zones should be advised about care to be taken with ingested food. In Chile, this new mode of transmission should be considered in public health policies.

  13. Angiotensin-Converting Enzyme ID Polymorphism in Patients with Heart Failure Secondary to Chagas Disease.

    PubMed

    Silva, Silene Jacinto da; Rassi, Salvador; Pereira, Alexandre da Costa

    2017-09-28

    Changes in the angiotensin-converting enzyme (ACE) gene may contribute to the increase in blood pressure and consequently to the onset of heart failure (HF). The role of polymorphism is very controversial, and its identification in patients with HF secondary to Chagas disease in the Brazilian population is required. To determine ACE polymorphism in patients with HF secondary to Chagas disease and patients with Chagas disease without systolic dysfunction, and to evaluate the relationship of the ACE polymorphism with different clinical variables. This was a comparative clinical study with 193 participants, 103 of them with HF secondary to Chagas disease and 90 with Chagas disease without systolic dysfunction. All patients attended the outpatient department of the General Hospital of the Federal University of Goias general hospital. Alleles I and D of ACE polymorphism were identified by polymerase chain reaction of the respective intron 16 fragments in the ACE gene and visualized by electrophoresis. In the group of HF patients, 63% were male, whereas 53.6% of patients with Chagas disease without systolic dysfunction were female (p = 0,001). The time from diagnosis varied from 1 to 50 years. Distribution of DD, ID and II genotypes was similar between the two groups, without statistical significance (p = 0,692). There was no difference in clinical characteristics or I/D genotypes between the groups. Age was significantly different between the groups (p = 0,001), and mean age of patients with HF was 62.5 years. No differences were observed in the distribution of (Insertion/Deletion) genotype frequencies of ACE polymorphism between the studied groups. The use of this genetic biomarker was not useful in detecting a possible relationship between ACE polymorphism and clinical manifestations in HF secondary to Chagas disease.

  14. Economic evaluation of Chagas disease screening in Spain.

    PubMed

    Imaz-Iglesia, Iñaki; Miguel, Lucía García-San; Ayala-Morillas, L Eduardo; García-Pérez, Lidia; González-Enríquez, Jesús; Blasco-Hernández, Teresa; Martín-Águeda, María Belén; Sarría-Santamera, Antonio

    2015-08-01

    Although Spain is the European country with the highest Chagas disease burden, the country does not have a national control program of the disease. The purpose of this study is to evaluate the efficiency of several strategies for Chagas disease screening among Latin American residents living in Spain. The following screening strategies were evaluated: (1) non-screening; (2) screening of the Latin American pregnant women and their newborns; (3) screening also the relatives of the positive pregnant women; (4) screening also the relatives of the negative pregnant women. A cost-utility analysis was carried out to compare the four strategies from two perspectives, the societal and the Spanish National Health System (SNHS). A decision tree representing the clinical evolution of Chagas disease throughout patient's life was built. The strategies were compared through the incremental cost-utility ratio, using euros as cost measurement and quality-adjusted life years as utility measurement. A sensitivity analysis was performed to test the model parameters and their influence on the results. We found the "Non-screening" as the most expensive and less effective of the evaluated strategies, from both the societal and the SNHS perspectives. Among the screening evaluated strategies the most efficient was, from both perspectives, to extent the antenatal screening of the Latin American pregnant women and their newborns up to the relatives of the positive women. Several parameters influenced significantly on the sensitivity analyses, particularly the chronic treatment efficacy or the prevalence of Chagas disease. In conclusion, for the general Latin American immigrants living in Spain the most efficient would be to screen the Latin American mothers, their newborns and the close relatives of the mothers with a positive serology. However for higher prevalence immigrant population the most efficient intervention would be to extend the program to the close relatives of the negative

  15. Chagas Heart Disease: Report on Recent Developments

    PubMed Central

    Machado, Fabiana S.; Jelicks, Linda A.; Kirchhoff, Louis V.; Shirani, Jamshid; Nagajyothi, Fnu; Mukherjee, Shankar; Nelson, Randin; Coyle, Christina M.; Spray, David C.; Campos de Carvalho, Antonio C.; Guan, Fangxia; Prado, Cibele M.; Lisanti, Michael P.; Weiss, Louis M.; Montgomery, Susan P.; Tanowitz, Herbert B.

    2011-01-01

    Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. It is now being diagnosed in non-endemic areas due to immigration. Typical cardiac manifestations of Chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism and stroke. Clinical and laboratory-based research to define the pathology resulting from T. cruzi infection has shed light on many of the cellular and molecular mechanisms leading to these manifestations. Antiparasitic treatment may not be appropriate for patients with advanced cardiac disease. Clinical management of Chagas heart disease is similar to that used for cardiomyopathies due to other processes. Cardiac transplantation has been successfully performed in a small number of patients with Chagas heart disease. PMID:22293860

  16. Chagas' disease as a foodborne illness.

    PubMed

    Pereira, Karen Signori; Schmidt, Flávio Luis; Guaraldo, Ana M A; Franco, Regina M B; Dias, Viviane L; Passos, Luiz A C

    2009-02-01

    Various researchers have studied the importance of the oral transmission of Chagas' disease since the mid-20th century. Only in recent years, due to an outbreak that occurred in the Brazilian State of Santa Catarina in 2005 and to various outbreaks occurring during the last 3 years in the Brazilian Amazon basin, mainly associated with the consumption of Amazonian palm berry or açaí (Euterpe oleracea Mart.) juice, has this transmission route aroused the attention of researchers. Nevertheless, reports published in the 1960s already indicated the possibility of Chagas' disease transmission via food in Brazil, mainly in the Amazonian region. Recently, in December 2007, an outbreak of Chagas' disease occurred in Caracas, Venezuela, related to ingestion of contaminated fruit juices. The objective of this article is to point out the importance of foodborne transmission in the etiology of Chagas' disease, on the basis of published research and Brazilian epidemiology data.

  17. Chaga mushroom-induced oxalate nephropathy.

    PubMed

    Kikuchi, Yuko; Seta, Koichi; Ogawa, Yayoi; Takayama, Tatsuya; Nagata, Masao; Taguchi, Takashi; Yahata, Kensei

    2014-06-01

    Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms.

  18. Chagas Disease Cardiomyopathy: Immunopathology and Genetics

    PubMed Central

    Chevillard, Christophe

    2014-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30% of infected patients develop CCC suggest there might be a genetic component to disease susceptibility. Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper, we will review the immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC. PMID:25210230

  19. Orally-transmitted Chagas disease.

    PubMed

    Filigheddu, Maria Teresa; Górgolas, Miguel; Ramos, José Manuel

    2017-02-09

    Chagas disease is a zoonosis caused by protozoan parasite Trypanosoma cruzi, which is most frequently associated with a vectorial transmission. However, in recent years we have observed a significant increase in the oral transmission of the disease, associated mainly with the consumption of drinks made from fruit or other vegetables contaminated with triatomine faeces or secretions from infected mammals. After a latency period of 3 to 22 days after ingestion, the oral infection is characterized by more severe manifestations than those associated with vectorial transmission: prolonged fever, acute myocarditis with heart failure and, in some cases, meningoencephalitis. Mortality can reach up to 33% of those infected. The aim of this paper is to review this matter and to promote prevention practices. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  20. Lymphocyte Transformation in Chagas Disease

    PubMed Central

    Tschudi, E. Irene; Anziano, Dante F.; Dalmasso, Agustin P.

    1972-01-01

    The in vitro response of human peripheral lymphocytes to Trypanosoma (Schizotrypanum) cruzi antigens and to phytohemagglutinin was used to study the role of cellular immunity in Chagas disease (American trypanosomiasis). Solubilized T. cruzi antigens elicited 5 to 30% transformed cells in 5-day cultures of lymphocytes from adults chronically infected with T. cruzi. No major difference was noted between the response of 22 asymptomatic individuals and of 3 patients with chagasic cardiopathy. No correlation was found between degree of lymphocytic transformation and serum antibody titer. Lymphocytes from 15 normal controls yielded no significant transformation. Intradermal tests provoked a local delayed hypersensitivity reaction in infected individuals only, as evaluated clinically and histologically. The response to phytohemagglutinin of lymphocytes from chronically infected individuals was identical with that of normal controls. Images PMID:4629392

  1. Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease.

    PubMed

    Najafzadeh, Mojgan; Reynolds, P Dominic; Baumgartner, Adolf; Jerwood, David; Anderson, Diana

    2007-01-01

    Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general.

  2. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease

    PubMed Central

    Bestetti, Reinaldo B.; Restini, Carolina Baraldi A.; Couto, Lucélio B.

    2016-01-01

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas. PMID:27223644

  3. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease.

    PubMed

    Bestetti, Reinaldo B; Restini, Carolina Baraldi A; Couto, Lucélio B

    2016-07-01

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

  4. American Trypanosomiasis (Also Known as Chagas Disease) Blood Screening FAQs

    MedlinePlus

    ... Tropical Diseases Laboratory Diagnostic Assistance [DPDx] Parasites Home Blood Screening FAQs Language: English Español (Spanish) Recommend on ... be concerned about getting Chagas disease? Why are blood banks now screening for Chagas disease? The transmission ...

  5. [Chagas disease with the acquired immunodeficiency syndrome. Clinical cases].

    PubMed

    Labarca, J; Acuña, G; Saavedra, H; Oddó, D; Sepúlveda, C; Ballesteros, J; Alvarez, M

    1992-02-01

    We report 2 patients with AIDS who developed Chagas infection, one with encephalitis, the other with acute myocarditis. The implications of immune depression for the manifestations and course of Chagas disease are discussed. Chagas disease should be considered in patients with AIDS who live in endemic zones and who develop cerebral or cardiac manifestations.

  6. Chagas Disease and Breast-feeding

    PubMed Central

    López-Vélez, Rogelio

    2013-01-01

    Chagas disease (infection by the protozoan Trypanosoma cruzi) is a major parasitic disease of the Americas and one of the main neglected tropical diseases. Although various routes of transmission sre recognized, the risk for transmission of the infection through breast-feeding has not clearly been established. We reviewed the literature on transmission of T. cruzi through breast-feeding to provide breast-feeding mothers with Chagas disease with medical guidance. Although data from animal studies and human studies are scarce, we do not recommend that mothers with Chagas disease discontinue breast-feeding, unless they are experiencing the acute phase of the disease, reactivated disease resulting from immunosuppression, or bleeding nipples. In these cases, thermal treatment of milk before feeding the infant may be considered. PMID:24050257

  7. [Part VI. Antiparasitic treatment for Chagas disease].

    PubMed

    B, Werner Apt; G, Ingrid Heitmann; L, M Isabel Jercic; M, Leonor Jofré; V, Patricia Muñoz C Del; H, Isabel Noemí; V, Ana M San Martín; P, Jorge Sapunar; H, Marisa Torres; A, Inés Zulantay

    2008-10-01

    As expert consensus has been arisen about universal antiparasitic treatment for all patients infected with Trypanosoma cruzi, most important drugs licensed for Chagas disease treatment are reviewed: nifurtimox and benznidazol, their mechanisms of action, doses, treatment schedules, adverse effects and contraindications. Two other drugs used for Chagas disease treatment, for which a Chilean experience may be exhibited, are allopurinol and itraconazole. Indications for treatment of Chagas disease in immunocompetent patients and immunocompromised hosts are detailed. This chapter refers besides to the evaluation and monitoring of antiparasitic therapy in immunocompromised patients, the availability of drugs and includes various forms facsimiles suggested to perform clinical and laboratory follow up of patients that undergo treatment, indicating the prescribed drug, adverse effects and time of follow up.

  8. Chagas disease and breast-feeding.

    PubMed

    Norman, Francesca F; López-Vélez, Rogelio

    2013-10-01

    Chagas disease (infection by the protozoan Trypanosoma cruzi) is a major parasitic disease of the Americas and one of the main neglected tropical diseases. Although various routes of transmission sre recognized, the risk for transmission of the infection through breast-feeding has not clearly been established. We reviewed the literature on transmission of T. cruzi through breast-feeding to provide breast-feeding mothers with Chagas disease with medical guidance. Although data from animal studies and human studies are scarce, we do not recommend that mothers with Chagas disease discontinue breast-feeding, unless they are experiencing the acute phase of the disease, reactivated disease resulting from immunosuppression, or bleeding nipples. In these cases, thermal treatment of milk before feeding the infant may be considered.

  9. Developments in the management of Chagas cardiomyopathy.

    PubMed

    Tanowitz, Herbert B; Machado, Fabiana S; Spray, David C; Friedman, Joel M; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi; Moraes, Diego N; Garg, Nisha Jain; Nunes, Maria Carmo P; Ribeiro, Antonio Luiz P

    2015-12-01

    Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising.

  10. Developments in the management of Chagas cardiomyopathy

    PubMed Central

    Tanowitz, Herbert B; Machado, Fabiana S; Spray, David C; Friedman, Joel M; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi; Moraes, Diego N; Garg, Nisha Jain; Nunes, Maria Carmo P; Ribeiro, Antonio Luiz P

    2016-01-01

    Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising. PMID:26496376

  11. [Chagas diseases seroepidemiology in schoolchildren of Jujuy].

    PubMed

    Tortora, C; Bejarano, I; Dipierri, J; Alfaro, E; García, T

    2000-01-01

    Chagas disease constitutes the main zoonosis in the province of Jujuy, Argentina, where it is one of the most important issues in public health. The purpose of this paper is to analyze the results of a serologic evaluation carried out for a seven-year period among schoolchildren in the Jujenean capital city. The population under study consisted of all seventh grade students of all schools in San Salvador de Jujuy. They were classified into three socioeconomic levels: High, Medium and Low levels. Indirect hemagglutination and immunofluorescence tests were performed. Percentages of seroprevalence were determined by sex, age group, and socioeconomic level. To analyze and check results, the following tests were applied: ANOVA, Tukey's and chi-square test. General prevalence was 1.95% with inter-annual statistically non-significant variations. Statistically significant variations were found among: 1) sex, where the feminine sex exhibited higher seroprevalence; 2) age groups, in which 12-year-olds showed higher seroprevalence; 3) socioeconomic levels, where seroprevalence increased as socioeconomic level decreased. Chagasic seroprevalence in children populations is an indicator that allows assessing both transmission risks in the community and the efficiency of preventive measures to control the vector. Data resulting from this study would indicate: 1) an adequate control both of non-vectorial transmission as well as of the vector, since no temporal variation was recorded in seroprevalence in the age-group analyzed; 2) higher seroprevalence in children belonging to a lower socioeconomic level, probably due to migrations of already-infected mothers coming from neighboring endemic, less epidemiologically controlled areas.

  12. Integrated control of Chagas disease for its elimination as public health problem--a review.

    PubMed

    Sosa-Estani, Sergio; Segura, Elsa Leonor

    2015-05-01

    Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease.

  13. Integrated control of Chagas disease for its elimination as public health problem - A Review

    PubMed Central

    Sosa-Estani, Sergio; Segura, Elsa Leonor

    2015-01-01

    Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease. PMID:25993503

  14. Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

    PubMed

    Bestetti, Reinaldo B; Cardinalli-Neto, Augusto; Restini, Carolina B A; Couto, Lucelio B

    2016-01-01

    In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute.

  15. Chagas disease prevalence in pregnant women: migration and risk of congenital transmission.

    PubMed

    Kolliker-Frers, Rodolfo A; Insua, Ivan; Razzitte, Gabriela; Capani, Francisco

    2016-09-30

    Argentina has been a preferential target for Bolivian immigrants for decades. The relatively recent migratory flux includes Germany, France, the United States, Australia, Japan, and some Latin American countries. The aim of this cross-sectional study was to describe the prevalence of Chagas disease in pregnant women, analyzing the Bolivian-specific Chagas prevalence as the main contributor of migratory populations from Chagas disease-endemic areas to Buenos Aires city, Argentina, and to evaluate the impact of these migrant influxes on the process of the "urbanization" of the disease in reference hospital José Maria Ramos Mejia (JMRM). Overall, 21,332 pregnant women (100%) between 15 and 49 years of age derived from the public maternity service of JMRMH were studied. Serology data was obtained from registered serological diagnosis data, consisting of three different serological tests performed at the Public Parasitology Unit. Although general prevalence decreased during the analyzed period, the specific prevalence of pregnant women from Bolivian origin showed a sustained growth during 1983-2013. Solely 5% of the total pregnant women population from Bolivia contributed to one third of the total Chagas prevalence. This study showed that a cohort of pregnant women from Bolivia who attended JMRMH during the period 1983-2007 constituted a population at risk for congenital transmission. Increased migration from endemic areas of Bolivia might potentially increase the prevalence of Chagas disease among pregnant women. In addition, this study highlights the importance to analyze specific prevalence according to endemic areas to determine the profiles of potential hidden prevalence.

  16. Flavonoids and Chagas' Disease: The Story So Far!

    PubMed

    Nabavi, Seyed Fazel; Sureda, Antoni; Daglia, Maria; Izadi, Morteza; Rastrelli, Luca; Nabavi, Seyed Mohammad

    2017-01-01

    Chagas disease is one of the major health problems in Central and South America, which is caused by the parasitic protozoa, Trypanosoma cruzi. It is commonly transmitted by members of blood-sucking subfamily Triatominae. Chagas disease is associated with cardiac and gastrointestinal manifestations. Up to now, there are no effective vaccines for treatment of Chagas disease and benznidazole and nifurtimox are the only effective anti-Chagas drugs that cause different adverse and side effects. Therefore, much attention has been paid to natural products as novel therapeutic strategies for Chagas disease and its manifestations. Nowadays, some flavonoids could be considered as effective and safe bioactive natural products with potential anti-Chagas activity. Despite the increasing evidence, there is lack of review papers regarding the beneficial effects of flavonoids against Chagas disease and its manifestations. The aim of this paper is to review the available scientific data on the beneficial effects of flavonoids on Chagas disease and its manifestations published over the past two decades. Moreover, we provide an overview on etiology, transmission, epidemiology, clinical manifestations, and current treatment protocols of Chagas disease.

  17. Immunosensor for the diagnosis of Chagas' disease.

    PubMed

    Ferreira, Antonio Aparecido Pupim; Colli, Walter; da Costa, Paulo Inácio; Yamanaka, Hideko

    2005-07-15

    Trypanosoma cruzi proteins from epimastigote membranes, herein referred as antigens, have been used for the construction of an amperometric immunosensor for serological diagnosis of Chagas' disease. The proteins used had a molecular mass ranging from 30 to 100 kDa. The gold electrode was treated with cysteamine and glutaraldehyde prior to antigen immobilization. Antibodies present in the serum of patients with Chagas' disease were captured by the immobilized antigens and the affinity interaction was monitored by chronoamperometry at a potential of -400 mV (versus Ag pseudo-reference electrode) using peroxidase-labeled IgG conjugate and hydrogen peroxide, iodide substrate. The incubation time to allow maximum antigen-antibody and antibody-peroxidase-labeled IgG interactions was 20 min with a reactivity threshold at -0.104 microA.

  18. The Southern Cone Initiative against Chagas disease.

    PubMed

    Schofield, C J; Dias, J C

    1999-01-01

    Chagas disease (also known as American trypanosomiasis) is now ranked as the most serious parasitic disease of the Americas, with an economic impact far outranking the combined effects of other parasitic diseases such as malaria, schistosomiasis and leishmaniasis. Although the chronic infection remains virtually incurable, transmission can be halted by eliminating the domestic insect vectors and screening blood donors to avoid transfusional transmission. In line with this strategy, governments of the six Southern Cone countries (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay) launched in 1991 an ambitious initiative to control Chagas disease through elimination of the main vector, Triatoma infestans, and large-scale screening of blood donors. Now at its mid-point, the programme has achieved remarkable success, with transmission halted over vast areas of the previously endemic regions. Well over 2 million rural houses have been sprayed to eliminate T. infestans, and the programme has already shown significant economic rates of return in addition to the medical and social benefits.

  19. Natural Chagas Disease in Four Baboons

    PubMed Central

    Williams, Jeff T.; Dick, Edward J.; VandeBerg, John L.; Hubbard, Gene B.

    2010-01-01

    Background Chagas disease is common in Central and South America and the southern United States. The causative agent is Trypanosoma cruzi (T cruzi, Order Kinetoplastida, Family Trypanosomatidae), a kinetoplastid protozoan parasite of humans and other vertebrates. It is a serious public health issue and the leading cause of heart disease and cardiovascular death in Central and South America. In 1984 a colony baboon was discovered to be infected with T cruzi. Methods Since the initial diagnosis was made by microscopic observation of the amastigote forms of T. cruzi in myocardial fibers, T. cruzi amastigotes have been identified in three additional baboons. Results The primary findings were similar in all four baboons and were congestive heart failure with edema of dependent areas, hydrothorax, hydropericardium, and multifocal to diffuse lymphoplasmacytic myocarditis. Conclusions A baboon animal model of Chagas disease could contribute significantly to the development of therapies for the disease in humans. PMID:18671766

  20. Palm trees and Chagas' disease in Panama.

    PubMed

    Whitlaw, J T; Chaniotis, B N

    1978-09-01

    An ecological survey of triatomines in the sylvan ecosystem of the Canal Zone and selected sites in Panama disclosed for the first time a close association of Rhodnius pullescens and Triatoma dimidiata, the two most important vector species of Chagas' disease in Panama, with a single species of a widely distributed palm tree, Scheelea zonensis. This association may explain why Chagas' disease is prevalent in certain rural communities in Central Panama and rare in others. An immense focus of zoonotic Trypanosoma cruzi infection exists in the forests of the Canal Zone with presence of large populations of triatomines, associated with scheelea zonensis and other yet undescribed microhabitats, and high (50--60%) trypanosome infections in all of the major triatomine species. Common opossums, anteaters, and spiny rats seem to be the principal animal reservoirs of T. cruzi in this complex and relatively undisturbed ecosystem.

  1. Ticks, ivermectin, and experimental Chagas disease.

    PubMed

    Dias, João Carlos Pinto; Schofield, Christopher J; Machado, Evandro Mm; Fernandes, Alexandre José

    2005-12-01

    Following an infestation of dogticks in kennels housing dogs used for long-term studies of the pathogenesis of Chagas disease, we examined the effect of ivermectin treatment on the dogs, ticks, trypanosome parasites, and also on triatomine vectors of Chagas disease. Ivermectin treatment was highly effective in eliminating the ticks, but showed no apparent effect on the dogs nor on their trypanosome infection. Triatominae fed on the dogs soon after ivermectin treatment showed high mortality, but this effect quickly declined for bugs fed at successive intervals after treatment. In conclusion, although ivermectin treatment may have a transient effect on peridomestic populations of Triatominae, it is not the treatment of choice for this situation. The study also showed that although the dogticks could become infected with Trypanosoma cruzi, this only occurred when feeding on dogs in the acute phase of infection, and there was no evidence of subsequent parasite development in the ticks.

  2. Apical aneurysm of Chagas's heart disease.

    PubMed Central

    Oliveira, J S; Mello De Oliveira, J A; Frederigue, U; Lima Filho, E C

    1981-01-01

    A retrospective study of Chagas's heart disease was carried out by a review of necropsy reports with special reference to the lesion known as the apical aneurysm. It was concluded that this lesion was more frequent in men, was unrelated to age, and was unrelated to heart weight. Patients dying of the cardiac consequences of Chagas's cardiomyopathy were more likely to have an apical aneurysm than those whose death was unrelated to the disease but the mode of death (sudden, or with heart failure) was unconnected with its presence. Transillumination from within the ventricle at necropsy was not only useful in demonstrating the aneurysm but also showed areas of myocardial thinning elsewhere. Thrombosis within the lesion was frequent. The aetiology of the apical aneurysm is discussed and it is concluded that while ischaemia, inflammation, thrombosis, and mechanical factors may produce and localise this lesion, the underlying cause is the basic pathogenetic process-parasympathetic nerve cell destruction. Images PMID:7295439

  3. Fatal acute Chagas Disease in a Chimpanzee

    DTIC Science & Technology

    2009-08-01

    Fatal Acute Chagas Disease in a Chimpanzee Yugendar R. Bommineni1, Edward J. Dick Jr.1, J. Scot Estep2, John L. Van de Berg1, and Gene B. Hubbard1...species and several insect vectors demonstrating a wide host distribution and low host specificity. Methods—A 23 year old male chimpanzee died acutely and... chimpanzee . Keywords Ape; nonhuman primate; protozoa; fatal case; Trypanosoma cruzi Introduction CD or American trypanosomiasis is caused by TC, a

  4. Chagas disease in the immunosuppressed host.

    PubMed

    Bern, Caryn

    2012-08-01

    This review examines recent literature on Chagas disease in the immunosuppressed host. Chagas disease in immunosuppressed patients may represent acute transmission in an organ recipient, or reactivation of chronic infection in an HIV-infected individual or patient receiving cardiac transplantation for Chagas cardiomyopathy. Transplantation of the kidney or liver from an infected donor resulted in transmission in 18-19 and 29%, respectively. Prospective monitoring usually detects acute infection before symptom onset; early treatment is highly effective. In heart transplant patients, reactivation symptoms include fever, myocarditis and skin lesions, and may mimic rejection. Approximately 20% of HIV- Trypanosoma cruzi infected patients experience reactivation; manifestations include meningoencephalitis and/or myocarditis. Transplantation of the heart from a T. cruzi-infected donor is contraindicated; use of other organs can be considered. Guidelines recommend prospective monitoring rather than prophylactic treatment in recipients. Posttransplant monitoring for acute infection or reactivation relies on PCR, culture and microscopy of blood specimens regularly for at least 6 months. Treatment employs standard courses of benznidazole or nifurtimox, and immune reconstitution for the HIV-coinfected patient. Case reports suggest some HIV-T. cruzi-infected patients may benefit from secondary prophylaxis, but more data are needed to determine efficacy and specific regimens.

  5. [Chagas disease (American trypanosomiasis) in France].

    PubMed

    Salamanca-Dejour, D; Blanchet, D; Aznar, C; La Ruche, G; Jeannel, D; Gastellu-Etchegorry, M

    2012-08-01

    Chagas disease is an anthropozoonotic infection caused by Trypanosoma cruzi, transmitted by a hematophagous triatomine insect vector belonging to the Reduviidae family, while taking a blood meal. There is a large reservoir of wild and domestic mammals. Human contamination may come via vectorial, transplacental, and digestive routes, blood transfusion, organ or tissue transplantation, and by accident. The disease has two phases. The acute phase, oligosymptomatic, is frequently undiagnosed. It is followed by a chronic phase. Most of the infected patients remain asymptomatic all life-long. But 10 or 25 years later, one third of infected patients present with cardiac or digestive complications. Chagas disease is endemic in Latin America, from Mexico to Argentina. In French Guyana, the prevalence of the infection was estimated at 0.25% and 0.5% (from 500 to 1000 infected patients) on blood samples collected from 1992 to 1998. In 2000 and 2009, 192 cases were diagnosed. In this district, there is no established domestic vector and the transmission risk is low. The vector is very easily found in forest habitats and even in the peridomestic persistent forest, with an infection rate of 46 to 86%. Vectorial eradication is impossible. Fighting against Chagas disease in French Guyana relies more on individual protection, control of blood transfusion, prevention of mother-to-child transmission, diagnosis, and treatment of infected patients than on vectorial control. Copyright © 2012. Published by Elsevier SAS.

  6. Paleoparasitology of Chagas disease--a review.

    PubMed

    Araújo, Adauto; Jansen, Ana Maria; Reinhard, Karl; Ferreira, Luiz Fernando

    2009-07-01

    One hundred years since the discovery of Chagas disease associated with Trypanosoma cruzi infection, growing attention has focused on understanding the evolution in parasite-human host interaction. This interest has featured studies and results from paleoparasitology, not only the description of lesions in mummified bodies, but also the recovery of genetic material from the parasite and the possibility of analyzing such material over time. The present study reviews the evidence of Chagas disease in organic remains excavated from archeological sites and discusses two findings in greater detail, both with lesions suggestive of chagasic megacolon and confirmed by molecular biology techniques. One of these sites is located in the United States, on the border between Texas and Mexico and the other in state of Minas Gerais, in the Brazilian cerrado (savannah). Dated prior to contact with Europeans, these results confirm that Chagas disease affected prehistoric human groups in other regions outside the Andean altiplanos and other transmission areas on the Pacific Coast, previously considered the origin of T. cruzi infection in the human host.

  7. Biomarkers and mortality in severe Chagas cardiomyopathy.

    PubMed

    Sherbuk, Jacqueline E; Okamoto, Emi E; Marks, Morgan A; Fortuny, Enzo; Clark, Eva H; Galdos-Cardenas, Gerson; Vasquez-Villar, Angel; Fernandez, Antonio B; Crawford, Thomas C; Do, Rose Q; Flores-Franco, Jorge Luis; Colanzi, Rony; Gilman, Robert H; Bern, Caryn

    2015-09-01

    Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival. This study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital. The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, electrocardiogram findings, medications, and serum cardiac biomarker levels (B-type natriuretic peptide [BNP], N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatine kinase-myocardial band [CK-MB], troponin I, matrix metalloproteinase [MMP]-2, MMP-9, tissue inhibitor of metalloproteinases [TIMP] 1 and 2, transforming growth factor [TGF] beta 1 and 2) were ascertained. Echocardiograms were performed on those with cardiac symptoms or electrocardiogram abnormalities at baseline. Participants were contacted approximately 1 year after initial evaluation; deaths were reported by family members. Receiver-operating characteristic curves (ROC) were used to optimize cutoff values for each marker. For markers with area under the curve (AUC) >0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality. The median follow-up time was 14.1 months (interquartile range 12.5, 16.7). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy at baseline, 20 (40%) had died. Higher baseline levels of BNP (HR: 3.1, 95% CI: 1.2 to 8.4), NT-proBNP (HR: 4.4, 95% CI: 1.8 to 11.0), CK-MB (HR: 3.3, 95% CI: 1.3 to 8.0), and MMP-2 (HR: 4.2, 95% CI: 1.5 to 11.8) were

  8. Molecular epidemiologic source tracking of orally transmitted Chagas disease, Venezuela.

    PubMed

    Segovia, Maikell; Carrasco, Hernán J; Martínez, Clara E; Messenger, Louisa A; Nessi, Anaibeth; Londoño, Juan C; Espinosa, Raul; Martínez, Cinda; Alfredo, Mijares; Bonfante-Cabarcas, Rafael; Lewis, Michael D; de Noya, Belkisyolé A; Miles, Michael A; Llewellyn, Martin S

    2013-07-01

    Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing.

  9. Molecular Epidemiologic Source Tracking of Orally Transmitted Chagas Disease, Venezuela

    PubMed Central

    Segovia, Maikell; Martínez, Clara E.; Messenger, Louisa A.; Nessi, Anaibeth; Londoño, Juan C.; Espinosa, Raul; Martínez, Cinda; Alfredo, Mijares; Bonfante-Cabarcas, Rafael; Lewis, Michael D.; de Noya, Belkisyolé A.; Miles, Michael A.; Llewellyn, Martin S.

    2013-01-01

    Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing. PMID:23768982

  10. Cardiac arrhythmias in Chagas' heart disease.

    PubMed

    Elizari, M V; Chiale, P A

    1993-10-01

    Chagas' disease is a chronic parasitosis affecting most Latin American countries. Its most important clinical manifestation is a late developing chronic myocarditis and, much less frequently, an early acute myocarditis. Chagasic myocardial damage is microfocal and disseminated throughout the heart. In most cases, the coexistence of areas of myocytic degeneration, inflammatory infiltration, and fibrosis suggests a permanent evolving process. Commonly, chronic chagasic myocarditis resembles a dilated cardiomyopathy, with characteristic ECG abnormalities (atrial and ventricular extrasystoles, intraventricular and/or AV conduction disturbances, and primary ST-T wave changes). Since myocardial damage is scattered throughout the heart, the ECG abnormalities (arrhythmias, conduction disturbances, and repolarization changes) are also representative of the widespread cardiac involvement. Thus, sick sinus syndrome, atrial extrasystoles, intraatrial conduction disturbances, and atrial fibrillation or flutter are common findings in different stages of the disease. At the ventricular level, both conduction disturbances and arrhythmias are conspicuous expressions of the myocardial damage. Right bundle branch block alone or in combination with left anterior hemiblock are the most common conduction defects. Further compromise of the conduction system can lead to different degrees of AV block. Chagas' disease is the main cause of bundle branch block and AV block in endemic areas. In advanced cases of Chagas' heart disease, ventricular premature contractions are extremely frequent, multiform, and repetitive (couplets and runs of ventricular tachycardia), and show R on T phenomenon. These arrhythmias are usually aggravated by increased sympathetic tone, implying an enhanced risk of cardiac sudden death among chagasic patients, which is sometimes the first manifestation of the illness. Chronic chagasic myocarditis is the leading cause of cardiovascular death, mostly as a consequence

  11. The controversy on the early history of Chagas disease.

    PubMed

    Löwy, I

    2005-12-01

    Recently historians of medicine have proposed three distinctive accounts of early history of Chagas disease (American trypasonomiasis). According to the first the disease, described by the Brazilian researcher Carlos Chagas in 1909, was "deconstructed" in the 1920s and disappeared for about twenty years, then was recovered in the 1940s, mainly through the epidemiological studies of Emmanuel Dias and his colleagues in Minas Gerais (Brazil). According to the second Chagas disease could not be "deconstructed" in the 1920s because it did not exist at that time. Chagas observations were inaccurate and unreliable and did not define a new human pathology. The entity called today "Chagas disease" appeared in the 1930, principally as the result of investigations of Cecilio Romaña in Argentina. Finally, a third view assumes that "Chagas disease" was constructed gradually between 1909 and the 1950s through the collective efforts of numerous Latino-American researchers. This paper juxtaposes different histories of Chagas disease, and argues that their divergences stems from allegiance to distinct, partly incommensurable epistemological "thought styles". The co-existence of divergent styles of historical investigation, this text proposes, should be perceived as potential source of enrichment of our understanding of the past.

  12. Chagas disease, a risk factor for high blood pressure.

    PubMed

    Vicco, Miguel Hernán; Rodeles, Luz; Yódice, Agustina; Marcipar, Iván

    2014-12-01

    Chagas disease is a parasite infection caused by the protozoan Trypanosoma cruzi. Its most common complications is chronic Chagas heart disease but impairments of the systemic vasculature also has been observed. Although the different mechanisms that regulate blood pressure are disrupted, to our knowledge data on the association of hypertension and chronic Chagas disease are scarce. In this regard we evaluate whether Chagas disease constitutes a high blood pressure risk factor. We recruited 200 individuals, half of them with positive serology for T. cruzi. They were subjected to a complete clinical examination. The mean age of sampled individuals was 46.7 ± 12.3, and the mean of systolic and diastolic blood pressure were 124 ± 12 mmHg and 82 ± 10 mmHg, respectively. There were no between-group differences regarding age, sex distribution or body mass index. Chagas disease contributed significantly to high blood pressure (OR = 4, 95% CI 1.8323-7.0864, p = 0.0002). Our results reveal an important association between Chagas disease and high blood pressure, which should be contemplated by physicians in order to promote preventive cardiovascular actions in patients with Chagas disease.

  13. A global systematic review of Chagas disease prevalence among migrants.

    PubMed

    Conners, Erin E; Vinetz, Joseph M; Weeks, John R; Brouwer, Kimberly C

    2016-04-01

    Human migration has been identified as a potential factor for increased Chagas disease risk and has transformed the disease from a Latin American problem to a global one. We conducted a systematic review of the scientific literature between 2004-2014 in order to: summarize recent seroprevalence estimates of Chagas disease among Latin American migrants, in both endemic and non-endemic settings; compare seroprevalence estimates in migrants to countrywide prevalence estimates; and identify risk factors for Chagas disease among migrants. A total of 320 studies were screened and 23 studies were included. We found evidence that the prevalence of Chagas disease is higher than expected in some migrant groups and that reliance on blood donor screening prevalence estimates underestimates the burden of disease. Overall there is a dearth of high quality epidemiologic studies on the prevalence of Chagas disease in migrants, especially among intra-regional migrants within Latin America. Given that this zoonotic disease cannot likely be eradicated, improved surveillance and reporting is vital to continuing control efforts. More accurate health surveillance of both Latin American migrants and the Chagas disease burden will help countries appropriately scale up their response to this chronic disease. Overall, improved estimates of Chagas disease among migrants would likely serve to highlight the real need for better screening, diagnostics, and treatment of individuals living with the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Dobutamine Stress Echocardiography Safety in Chagas Disease Patients

    PubMed Central

    Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Furtado, Rogerio Gomes; Turco, Fabio de Paula; Melato, Luciano Henrique; Hotta, Viviane Tiemi; Nunes, Colandy Godoy de Oliveira; Rassi Jr., Luiz; Rassi, Salvador

    2017-01-01

    Background A few decades ago, patients with Chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (CAD). As urbanization has increased, they became exposed to the same risk factors for CAD of uninfected individuals. Dobutamine stress echocardiography (DSE) has proven to be an important tool in CAD diagnosis. Despite being a potentially arrhythmogenic method, it is safe for coronary patients without Chagas disease. For Chagas disease patients, however, the indication of DSE in clinical practice is uncertain, because of the arrhythmogenic potential of that heart disease. Objectives To assess DSE safety in Chagas disease patients with clinical suspicion of CAD, as well as the incidence of arrhythmias and adverse events during the exam. Methods Retrospective analysis of a database of patients referred for DSE from May/2012 to February/2015. This study assessed 205 consecutive patients with Chagas disease suspected of having CAD. All of them had their serology for Chagas disease confirmed. Results Their mean age was 64±10 years and most patients were females (65.4%). No patient had significant adverse events, such as acute myocardial infarction, ventricular fibrillation, asystole, stroke, cardiac rupture and death. Regarding arrhythmias, ventricular extrasystoles occurred in 48% of patients, and non-sustained ventricular tachycardia in 7.3%. Conclusion DSE proved to be safe in this population of Chagas disease patients, in which no potentially life-threatening outcome was found. PMID:28099588

  15. Community resilience and Chagas disease in a rural region of Mexico.

    PubMed

    Rangel, José Antonio Santana; Monreal, Luz Arenas; Ramsey, Janine M

    2016-08-04

    To explore the pillars of community resilience in a region where Chagas disease is endemic, with the aim of promoting participatory processes to deal with this condition from the resilience of the population. Qualitative study using ethnographic record and six interviews of focus groups with young people, women and men. The research was carried out in a rural area of the state of Morelos, Mexico, between 2006 and 2007. We carried out educational sessions with the population in general, so that residents could identify the relationship between the vector Triatoma pallidipennis, the parasite (Trypanosoma cruzi), symptoms, and preventive actions for Chagas disease. The ethnographic record and groups were analyzed based on Taylor and Bogdan's modification, and the focus was to understand the socio-cultural meanings that guide the speeches and activities of residents in relation to the pillars of community resilience. The population felt proud of belonging to that location and three pillars of community resilience were clearly identified: collective self-esteem, cultural identity, and social honesty. Having these pillars as bases, we promoted the participation of the population concerning Chagas disease, and a Community Action Group was formed with young people, adult men and women, and social leaders. This Group initiated actions of epidemiological and entomological surveillance in the community to deal with this problem. It is necessary to create more experiences that deepen the understanding of the pillars of community resilience, and how they contribute to enhance participation in health to deal with Chagas disease. Explorar los pilares de la resiliencia comunitaria en una región en la que la enfermedad de Chagas es endémica, con la finalidad de partir de la resiliencia de la población para impulsar procesos participativos para enfrentar este padecimiento. Estudio cualitativo que utilizó registro etnográfico y seis entrevistas de grupos focales con j

  16. [Standardization of serological tests for Chagas disease: an immunoenzymatic test for blood donors triage].

    PubMed

    Ferreira, A W; Belem, Z R; Moura, M E; Camargo, M E

    1991-01-01

    In the serological diagnosis of Chagas disease large divergences may be found even between laboratories with experience, as a consequence of different criteria for the standardization of the tests. To standardize a immunoenzymatic test developed primarily for screening blood donors, serum panels were carefully chosen so as to best represent chagasic and non-chagasic populations. Produced for the highest sensibility and stability, the new reagent (bioELISA cruzi, Biolab Diagnóstica S/A, Brasil), was tested in serum from 1648 patients 219 with Chagas disease and 104 with other diseases, plus a comparison with well standardized immunofluorescence and hemagglutination tests in 1325 sera. In the immunoenzymatic assays, the cut off was indicated by the absorbance value of a chagasic serum showing a minimal reactivity. ELISA sensibility was 0.9954 and specificity 0.9969, as co-negativity. False positive results were absent with sera from syphilis, toxoplasmosis, mononucleosis and high titered sera for antistreptolysin 0 antibodies. However they were seen in 5 to 15 cases of tegumentar leishmaniasis, 1 of 12 Kala-azar 1 of 15 rheumatoid arthritis and 1 of 12 systemic lupus erythematosus. The high sensibility in chagasics and high specificity in the general population indicate the confiability of the immunoenzymatic assay for screening blood donors and even to confirm a clinical diagnosis of Chagas' disease.

  17. Chronic Chagas Disease Diagnosis: A Comparative Performance of Commercial Enzyme Immunoassay Tests

    PubMed Central

    Santos, Fred Luciano Neves; de Souza, Wayner Vieira; da Silva Barros, Michelle; Nakazawa, Mineo; Krieger, Marco Aurélio; de Miranda Gomes, Yara

    2016-01-01

    There is a significant heterogeneity in reported performance of serological assays for Chagas disease diagnosis. The conventional serology testing in laboratory diagnosis and in blood banks is unsatisfactory because of a high number of inconclusive and misclassified results. We aimed to assess the quality of four commercially available enzyme-linked immunosorbent assay tests for their ability to detect Trypanosoma cruzi antibodies in 685 sera samples. Cross-reactivity was assessed by using 748 sera from patients with unrelated diseases. Initially, we found that the reactivity index against T. cruzi antigen was statistically higher in sera from Chagas disease patients compared with those from non-chagasic patients, supporting the notion that all evaluated tests have a good discriminatory ability toward the diagnosis of T. cruzi infection in patients in the chronic phase of the disease. Although all tests were similarly sensitive for diagnosing T. cruzi infection, there were significant variations in terms of specificity and cross-reactivity among them. Indeed, we obtained divergent results when testing sera from patient with unrelated diseases, particularly leishmaniasis, with the levels of cross-reactivity being higher in tests using whole T. cruzi extracts compared with those using recombinant proteins. Our data suggest that all four tests may be used for the laboratory diagnosis and routine blood screening diagnose for Chagas disease. We also emphasize that, despite their general good performance, caution is needed when analyzing the results when these tests are performed in areas where other diseases, particularly leishmaniasis, are endemic. PMID:26976886

  18. Community resilience and Chagas disease in a rural region of Mexico

    PubMed Central

    Rangel, José Antonio Santana; Monreal, Luz Arenas; Ramsey, Janine M

    2016-01-01

    ABSTRACT OBJECTIVE To explore the pillars of community resilience in a region where Chagas disease is endemic, with the aim of promoting participatory processes to deal with this condition from the resilience of the population. METHODS Qualitative study using ethnographic record and six interviews of focus groups with young people, women and men. The research was carried out in a rural area of the state of Morelos, Mexico, between 2006 and 2007. We carried out educational sessions with the population in general, so that residents could identify the relationship between the vector Triatoma pallidipennis, the parasite (Trypanosoma cruzi), symptoms, and preventive actions for Chagas disease. The ethnographic record and groups were analyzed based on Taylor and Bogdan’s modification, and the focus was to understand the socio-cultural meanings that guide the speeches and activities of residents in relation to the pillars of community resilience. RESULTS The population felt proud of belonging to that location and three pillars of community resilience were clearly identified: collective self-esteem, cultural identity, and social honesty. Having these pillars as bases, we promoted the participation of the population concerning Chagas disease, and a Community Action Group was formed with young people, adult men and women, and social leaders. This Group initiated actions of epidemiological and entomological surveillance in the community to deal with this problem. CONCLUSIONS It is necessary to create more experiences that deepen the understanding of the pillars of community resilience, and how they contribute to enhance participation in health to deal with Chagas disease. PMID:27509012

  19. Lower richness of small wild mammal species and chagas disease risk.

    PubMed

    Xavier, Samanta Cristina das Chagas; Roque, André Luiz Rodrigues; Lima, Valdirene dos Santos; Monteiro, Kerla Joeline Lima; Otaviano, Joel Carlos Rodrigues; Ferreira da Silva, Luiz Felipe Coutinho; Jansen, Ana Maria

    2012-01-01

    A new epidemiological scenario involving the oral transmission of Chagas disease, mainly in the Amazon basin, requires innovative control measures. Geospatial analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have been scarce. We applied interpolation and map algebra methods to evaluate mammalian fauna variables related to small wild mammals and the T. cruzi infection pattern in dogs to identify hotspot areas of transmission. We also evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease. Dogs (n = 649) were examined by two parasitological and three distinct serological assays. kDNA amplification was performed in patent infections, although the infection was mainly sub-patent in dogs. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 11-89% in different localities. The interpolation method and map algebra were employed to test the associations between the lower richness in mammal species and the risk of exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the reduction of the mammal fauna (richness and abundance) was associated with higher parasitemia in small wild mammals and higher exposure of dogs to infection. A Generalized Linear Model (GLM) demonstrated that species richness and positive hemocultures in wild mammals were associated with T. cruzi infection in dogs. Domestic canine infection rates differed significantly between areas with and without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by interpolation and map algebra methods proved to be a powerful tool in the evaluation of areas of T. cruzi transmission. Dog infection was shown to not only be an efficient indicator of reduction of wild mammalian fauna richness but to also act as a signal for the presence of small wild mammals with high parasitemia. The lower richness of small mammal species is discussed as a risk factor for the re-emergence of Chagas disease.

  20. Placental alkaline phosphatase (PLAP) enzyme activity and binding to IgG in Chagas' disease.

    PubMed

    Lin, S; Sartori, M J; Mezzano, L; de Fabro, S P

    2005-11-01

    Placentas and plasma from women with and without Chagas' disease and cultures of human placental villi with Trypanosoma cruzi, neuraminidase, phospholipase A2 and phospholipase C were analyzed in order to verify if the alterations in placental alkaline phosphatase (PLAP) enzyme activity are caused by T. cruzi as observed in previous works. As IgG receptivity happens to be one of the proposed functions of PLAP, general IgG binding ability of the placentas treated with the mentioned enzymes, which are present on the parasite's surface, were also tested. The phospholipases caused an increase of PLAP's enzyme activity in the supernatant of infected placentas and a decrease of enzyme activity in the membrane of cultured placentas, therefore suggesting the cleavage of PLAP by parasitic enzymes. Desialylation could also partially inhibit PLAP's enzyme activity in supernatant and membrane of placenta culture. Placentas from healthy patients presented higher IgG receptivity than those from patients with Chagas' disease. In vitro infection of healthy placentas with T. cruzi caused no difference in IgG receptivity in placental sections with respect to controls but the phospholipases and neuraminidase increased the IgG receptivity of cultured placentas. The IgG transference index was higher for patients with Chagas' disease than for those without it. Although binding to IgG does not completely inhibit the enzyme activity of PLAP, it interferes with the enzyme activity of PLAP. We concluded that the enzymes on the surface of T. cruzi trypomastigotes can not only affect PLAP's enzyme activity but also increase the IgG binding ability of the placenta and this can be related to the actions of neuraminidase-transsialidase, phospholipase A2 and phospholipase C on the parasite surface. The modification of PLAP from women with Chagas' disease should be considered as a result of multiple factors.

  1. Immunoregulatory networks in human Chagas disease

    PubMed Central

    Dutra, Walderez O.; Menezes, Cristiane A.S.; Magalhães, Luisa M. D.; Gollob, Kenneth J.

    2014-01-01

    Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and, thus, influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies have led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks. PMID:24611805

  2. Chagas disease and globalization of the Amazon.

    PubMed

    Briceño-León, Roberto

    2007-01-01

    The increasing number of autochthonous cases of Chagas disease in the Amazon since the 1970s has led to fear that the disease may become a new public health problem in the region. This transformation in the disease's epidemiological pattern in the Amazon can be explained by environmental and social changes in the last 30 years. The current article draws on the sociological theory of perverse effects to explain these changes as the unwanted result of the shift from the "inward" development model prevailing until the 1970s to the "outward" model that we know as globalization, oriented by industrial forces and international trade. The current article highlights the implementation of five new patterns in agriculture, cattle-raising, mining, lumbering, and urban occupation that have generated changes in the environment and the traditional indigenous habitat and have led to migratory flows, deforestation, sedentary living, the presence of domestic animals, and changes in the habitat that facilitate colonization of human dwellings by vectors and the domestic and work-related transmission of the disease. The expansion of Chagas disease is thus a perverse effect of the globalization process in the Amazon.

  3. Chagas' Disease: Pregnancy and Congenital Transmission

    PubMed Central

    Hernández, Roberto

    2014-01-01

    Chagas disease is a chronic infection that kills approximately 12,000 people a year. Mass migration of chronically infected and asymptomatic persons has caused globalization of Chagas disease and has made nonvectorial infection, including vertical and blood-borne transmission, more of a threat to human communities than vectorial infection. To control transmission, it is essential to test all pregnant women living in endemic countries and all pregnant women having migrated from, or having lived in, endemic countries. All children born to seropositive mothers should be tested not only within the first month of life but also at ~6 months and ~12 months of age. The diagnosis is made by identification of the parasite in blood before the age of 6 months and by identification of the parasite in blood and/or positive serology after 10 months of age. Follow up for a year is essential as a significant proportion of cases are initially negative and are only detected at a later stage. If the condition is diagnosed and treated early, the clinical response is excellent and the majority of cases are cured. PMID:24949443

  4. Chagas disease: changes in knowledge and management.

    PubMed

    Lescure, François-Xavier; Le Loup, Guillaume; Freilij, Hector; Develoux, Michel; Paris, Luc; Brutus, Laurent; Pialoux, Gilles

    2010-08-01

    More than 100 years after the discovery of human American trypanosomiasis by Carlos Chagas, our knowledge and management of the disease are profoundly changing. Substantial progress made by disease control programmes in most endemic areas contrasts with persisting difficulties in the Gran Chaco region in South America and the recent emergence of the disease in non-endemic areas because of population movements. In terms of pathogenesis, major discoveries have been made about the life cycle and genomics of Trypanosoma cruzi, and the role of the parasite itself in the chronic phase of the disease. From a clinical perspective, a growing number of arguments have challenged the notion of an indeterminate phase, and suggest new approaches to manage patients. New methods such as standardised PCR will be necessary to ensure follow-up of this chronic infection. Although drugs for treatment of Chagas disease are limited, poorly tolerated, and not very effective, treatment indications are expanding. The results of the Benznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT) trial in 2012 will also help to inform treatment. Mobilisation of financial resources to fund research on diagnosis and randomised controlled trials of treatment are international health priorities.

  5. Melatonin in Chagas' disease. Possible therapeutic value.

    PubMed

    Cardinali, Daniel P; Alvarez, Carlos B

    2011-01-01

    Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO) production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1 /MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas' disease.

  6. Current and Future Chemotherapy for Chagas Disease.

    PubMed

    Gaspar, Luís; Moraes, Carolina B; Freitas-Junior, Lucio H; Ferrari, Stefania; Costantino, Luca; Costi, Maria Paola; Coron, Ross P; Smith, Terry K; Siqueira-Neto, Jair L; McKerrow, James H; Cordeiro-da-Silva, Anabela

    2015-01-01

    Human American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease - a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates; posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments. In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. We also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near future.

  7. [The third and new face of Chagas disease].

    PubMed

    Pays, J-F

    2016-08-01

    After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease".

  8. Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Medina, R.; Jugo, D.; Nunez, T. J.; Borrego, A.; Arellano, E.; Arenare, B.; DePalma, J. L.; Greco, E. C.; Starc, V.

    2007-01-01

    were not significantly different between groups. Patients with Chagas heart disease have increased cardiac repolarization abnormalities, especially by advanced ECG. Moreover, as a group, they have decreased uncorrected JT and QT interval durations and increased filtered QRS interval durations (versus age/gender-matched controls), all suggesting a potential loss of cardiac sodium channel function that might be mediated, in part, by cardiac autonomic damage. Overall findings support Brugada et al's recent hypothesis that the pathway leading to sudden death may often be similar in Chagas' disease and Brugada syndrome i.e., damage to the sodium channel (infectious/immunologic/autonomic in Chagas' genetic in Brugada) with consequent loss of sodium currents may facilitate a phase II-reentry based arrhythmic substrate for ventricular fibrillation in both conditions. In general, JT interval-related results have been underreported in the Chagas literature.

  9. American Trypanosomiasis (Also Known as Chagas Disease) Detailed FAQs

    MedlinePlus

    ... Trypanosoma cruzi , which is transmitted to animals and people by insect vectors that are found only in the Americas (mainly, in rural areas of Latin America where poverty is widespread). Chagas disease ( T. cruzi infection) is ...

  10. 2 nd Brazilian Consensus on Chagas Disease, 2015.

    PubMed

    Dias, João Carlos Pinto; Ramos, Alberto Novaes; Gontijo, Eliane Dias; Luquetti, Alejandro; Shikanai-Yasuda, Maria Aparecida; Coura, José Rodrigues; Torres, Rosália Morais; Melo, José Renan da Cunha; Almeida, Eros Antonio de; Oliveira, Wilson de; Silveira, Antônio Carlos; Rezende, Joffre Marcondes de; Pinto, Fabiane Scalabrini; Ferreira, Antonio Walter; Rassi, Anis; Fragata, Abílio Augusto; Sousa, Andréa Silvestre de; Correia, Dalmo; Jansen, Ana Maria; Andrade, Glaucia Manzan Queiroz; Britto, Constança Felícia De Paoli de Carvalho; Pinto, Ana Yecê das Neves; Rassi, Anis; Campos, Dayse Elisabeth; Abad-Franch, Fernando; Santos, Silvana Eloi; Chiari, Egler; Hasslocher-Moreno, Alejandro Marcel; Moreira, Eliane Furtado; Marques, Divina Seila de Oliveira; Silva, Eliane Lages; Marin-Neto, José Antonio; Galvão, Lúcia Maria da Cunha; Xavier, Sergio Salles; Valente, Sebastião Aldo da Silva; Carvalho, Noêmia Barbosa; Cardoso, Alessandra Viana; Silva, Rafaella Albuquerque E; Costa, Veruska Maia da; Vivaldini, Simone Monzani; Oliveira, Suelene Mamede; Valente, Vera da Costa; Lima, Mayara Maia; Alves, Renato Vieira

    2016-12-01

    Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research .

  11. Tc-99m pyrophosphate myocardial scanning in Chagas' disease

    SciTech Connect

    Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

    1981-04-01

    Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

  12. Tc-99m pyrophosphate myocardial scanning in Chagas' disease

    SciTech Connect

    da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

    1981-04-01

    Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

  13. Therapeutical approaches under investigation for treatment of Chagas disease.

    PubMed

    Bahia, Maria Terezinha; Diniz, Lívia de Figueiredo; Mosqueira, Vanessa Carla Furtado

    2014-09-01

    A century after its discovery, American trypanosomiasis or Chagas disease remains a serious health problem in Latin America, where it affects around 7 - 8 million people. The prevalence of Chagas disease in the poorer parts of the world has meant that it has largely been neglected with limited progress that made in identifying new drugs for the treatment. The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available for Chagas disease with limitations that include variable efficacy, long treatment courses and toxicity. This review focuses on different therapeutic strategies that have been used for the discovery of new treatments for Chagas disease. These include combination chemotherapy, drug repositioning, re-dosing regimens for current drugs and the identification of new drugs with specified target profiles. There are currently several reasons for a more optimistic view about chemotherapy with Chagas disease. However, despite some progress being made in preclinical studies, there is yet to be an ideal drug or formulation for human treatment. One major drawback in the evaluation of potential Chagas disease therapeutics is the lack of tools available to perform the said evaluation. Indeed, there is a great need to discover a better biomarker that could determine the efficacy of potential chemotherapeutics in treated patients.

  14. Altered Cardiomyocyte Function and Trypanosoma cruzi Persistence in Chagas Disease.

    PubMed

    Cruz, Jader Santos; Santos-Miranda, Artur; Sales-Junior, Policarpo Ademar; Monti-Rocha, Renata; Campos, Paula Peixoto; Machado, Fabiana Simão; Roman-Campos, Danilo

    2016-05-04

    Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase chain reaction, we detected parasites at 90 dpi in right and left ventricles. In addition, we observed action potential prolongation and reduced transient outward K(+) current and L-type Ca(2+) current at 30 and 90 dpi. Taking together, our results demonstrate that T. cruzi infection leads to important modifications in electrical properties associated with inflammatory infiltrate and parasite persistence in mice right ventricle, suggesting a causal role between inflammation, parasite persistence, and altered cardiomyocyte function in Chagas disease. Thus, arrhythmias observed in Chagas disease may be partially related to altered electrical function in right ventricle. © The American Society of Tropical Medicine and Hygiene.

  15. [Chagas disease in the Americas: an ecohealth perspective].

    PubMed

    Briceño-León, Roberto

    2009-01-01

    The historical processes involved in Chagas disease transmission relate to the patterns and conditions of human settlements, especially in rural areas, due to proximity to forest areas, where both vectors and Trypanosoma cruzi can occur, combined with precarious housing conditions and underlying poverty. However, seasonal and permanent rural-urban migration has played a major role in re-mobilizing vectors, T. cruzi, and Chagas-infected individuals. A new agricultural frontier in the Amazon has led to a new transmission pattern, especially with palm trees located close to houses. Improved blood bank surveillance has decreased transmission by blood transfusions. International migration also plays a role in Chagas disease epidemiology. The United States and Spain, where specific health services for Chagas disease diagnosis and treatment are largely absent, harbor an unknown number of individuals with Chagas, probably infected decades ago. The article discusses major strides in Chagas disease knowledge and control, besides identifying persistent gaps, such as the need for housing improvements, especially in poor rural areas in the Americas.

  16. Serological screening of Chagas disease in an immigrant population in Asturias, Spain proceeding from Chagas-endemic areas.

    PubMed

    Rodríguez-Guardado, Azucena; Rodríguez, Mercedes; Alonso, Paula; Seco, Carolina; Flores-Chavez, Maria; Mejuto, Patricia; Cartón, Jose A

    2009-01-01

    Population movements from Chagas disease-endemic areas to non-endemic countries due to immigration make the occurrence of this disease in these latter areas possible. We describe the results of a screening programme conducted in an immigrant population from endemic areas, attending the Tropical Medicine Unit of the Hospital Central de Asturias between June 2006 and June 2008. The ID-Chagas antibody test (particle gel immunoassay (PaGIA); DiaMed-ID) was used as a screening assay. We analysed 64 patients, 9 of whom (14%) tested positive for Chagas disease antibodies, a diagnosis that was confirmed in all cases. Six patients came from Bolivia, 2 from Paraguay and 1 from Brazil. Chagas disease is of increasing importance, even in areas with low migratory flows; hence screening programmes for this population group are especially important.

  17. Acquired non-Chagas megacolon associated with the use of psychiatric medication: case report and differential diagnosis with Chagas megacolon.

    PubMed

    Adad, Sheila Jorge; Souza, Moisés Amâncio; Silva, Gisele Barbosa E; Carmo Junior, José do; Godoy, Charles Antônio Pires de; Micheletti, Adilha Misson Rua

    2008-01-01

    A case of acquired megacolon in a 62-year-old man with acute abdomen due to sigmoid volvulus is reported. The case was associated with the use of psychiatric medications. The aim in this report was to emphasize the differential diagnosis with Chagas megacolon. Anatomopathological examination did not show any evidence of denervation, ganglionitis and/or myositis, and the serological test for Chagas disease was negative.

  18. Inhibitory effect of chaga mushroom extract on compound 48/80-induced anaphylactic shock and IgE production in mice.

    PubMed

    Yoon, Taek Joon; Lee, Sue Jung; Kim, Eun Young; Cho, Eun Hee; Kang, Tae Bong; Yu, Kwang-Won; Suh, Hyung Joo

    2013-04-01

    Chaga mushrooms (Inonotus obliquus) are hypothesised to exhibit general immune-potentiating, anti-inflammatory, and antitumor properties, but their anti-allergic activities are not fully understood. Therefore, this study investigated whether a chaga mushroom extract (C-HE) might have anti-allergic activity. This activity was assessed through the levels of the IgE Ab produced in response to an allergen (OVA). The administration of C-HE prophylactically inhibited the systemic anaphylactic shock induced by compound 48/80 in mice. The oral administration of C-HE significantly reduced the total IgE levels in mice and slightly affected the production of IgG1. Furthermore, spleen cell cultures harvested from OVA-sensitised mice that had received C-HE orally showed a significant increase in Th1-derived responses (IFN-γ production). Therefore, our results suggest that the chaga mushroom extract may be used as an anti-allergic functional food.

  19. Chagas disease (American trypanosomiasis) in Mexico: an update.

    PubMed

    Carabarin-Lima, Alejandro; González-Vázquez, María Cristina; Rodríguez-Morales, Olivia; Baylón-Pacheco, Lidia; Rosales-Encina, José Luis; Reyes-López, Pedro Antonio; Arce-Fonseca, Minerva

    2013-08-01

    Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, a flagellated organism that is transmitted mainly to humans through the infected feces of triatomine kissing bugs (vector transmission in endemic areas) or by transfusion of infected blood, donations of infected organ, or transmission from an infected mother to her child at birth. Chagas disease was first described in 1909 by the Brazilian physician Carlos Chagas, and due to the parasite's distribution throughout North, Central and South America, the disease is commonly known as American trypanosomiasis. However, this disease is now present in non-endemic countries such as Canada, the United States of America, and several countries in Europe (principally Spain). Moreover, Chagas disease was recently designated by the World Health Organization as one of the main neglected tropical diseases. The aim of this review is to summarize the research efforts recently described in studies conducted in Mexico on Chagas disease. In this country, there are no existing vector control programs. In addition, there is no consensus on the diagnostic methods for acute and chronic Chagas disease in maternity wards and blood banks, and trypanocidal therapy is not administered to chronic patients. The actual prevalence of the disease is unknown because no official reporting of cases is performed. Therefore, the number of people infected by different routes of transmission (vector, congenital, blood transfusion, organ transplantation, or oral) is unknown. We believe that by promoting education about Chagas disease in schools starting at the basic elementary level and including reinforcement at higher education levels will ensure that the Mexican population would be aware of this health problem and that the control measures adopted will have more acceptance and success. We hope that this review sensitizes the relevant authorities and that the appropriate measures to reduce the risk of infection by T. cruzi

  20. [Guidelines for chagas disease: Part IV. Chagas disease in immune compromised patients].

    PubMed

    Apt B, Werner; Heitmann G, Ingrid; Jercic L, M Isabel; Jotré M, Leonor; Muñoz C Del V, Patricia; Noemí H, Isabel; San Martin V, Ana M; Sapunar P, Jorge; Torres H, Marisa; Zulantay A, Inés

    2008-08-01

    A summary of different kind of immune suppressed hosts and the importance of Trypanosoma cruzi infection in this group of patients is presented. Then, most relevant aspects of immune compromised host-parasite interaction are analyzed such as the moment of acquiring the infection, immune compromise level, mechanisms of acquisition the infection and geographic region. Clinical features of primary infection and reactivation of infection in chronic Chagasic patients are described making special emphasis in solid organ transplant and BMT. Chagas disease in AIDS patients is discussed including its treatment, follow up, monitoring the immune compromise level and prophylaxis.

  1. Acute Chagas disease in El Salvador 2000-2012 - Need for surveillance and control

    PubMed Central

    Sasagawa, Emi; de Aguilar, Ana Vilma Guevara; de Ramírez, Marta Alicia Hernández; Chévez, José Eduardo Romero; Nakagawa, Jun; Cedillos, Rafael Antonio; Kita, Kiyoshi

    2014-01-01

    Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole. PMID:24676660

  2. Acute Chagas disease in El Salvador 2000-2012 - need for surveillance and control.

    PubMed

    Sasagawa, Emi; Aguilar, Ana Vilma Guevara de; Ramírez, Marta Alicia Hernández de; Chévez, José Eduardo Romero; Nakagawa, Jun; Cedillos, Rafael Antonio; Kita, Kiyoshi

    2014-04-01

    Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole.

  3. [Seroepidemiology of Chagas disease in the Province of Jujuy].

    PubMed

    Tortora, C C; Quincoces, V; Dipierri, J E

    1996-01-01

    Chagas disease is the principal zoonosis of the Province of Jujuy where it represents a major public health problem. In this paper the results of a serological screening of T. cruzi infection carried out in the Province of Jujuy are analyzed to determine the general prevalence, age and geographic distribution, sex ratio, prevalence in foreign population and their relation with migratory process. In every individual (N = 16482) indirect hemagglutination (IHA) and immunofluorescence (TIF) tests have been carried out. In 5879 of them the birth place in the territory of the Province and the number of foreign individuals (313, all Bolivians) were confirmed. Based on these data the individuals were grouped according to: a) the four geographical regions of the Province located at different altitude levels, Puna, Quebrada, Valle and Ramal; b) towns placed on or away from the main routes of communication of the Province. For the statistical analysis the X2 and Z tests were employed. The results show that: 1) the general prevalence was of 11.50%; 2) no differences existed between the sexes: 3) the region with the highest prevalence was the Valley (12.84%) followed by Ramal (10.43%), Quebrada (8.53%) and Puna (2.98%); 4) differences of the serum prevalence can be observed between the residents on and away from the main routes of communication denoting the existence of a migratory effect in the distribution of chagasic infection; 5) prevalence differences exist between naturalized foreigns (39.30%) and Argentines (10.25%), data which strengthen the previous remark. Except for the general prevalence, there are no similar serological surveys which might allow us to establish relationships with our results of which the outstanding one is the influence of the migratory aspect upon the prevalence and distribution of T. cruzi in the Province of Jujuy.

  4. Antioxidant small phenolic ingredients in Inonotus obliquus (persoon) Pilat (Chaga).

    PubMed

    Nakajima, Yuki; Sato, Yuzo; Konishi, Tetsuya

    2007-08-01

    Inonotus obliquus (persoon) Pilat (Chaga, in Russia, kabanoanatake in Japan) is a fungus having been used as a folk medicine in Russia and said to have many health beneficial functions such as immune modulating and anti-cancer activities. In the present study, the antioxidant activity of hot water extract (decoction) of Chaga was precisely compared with those of other medicinal fungi (Agaricus blazei Mycelia, Ganoderma lucidum and Phellinus linteus) showing Chaga had the strongest antioxidant activity among fungi examined in terms of both superoxide and hydroxyl radicals scavenging activities. Further determination of the antioxidant potential of isolated fruiting body (brown part) and Sclerotium (black part) revealed the 80% MeOH extract of fruiting body had the highest potential as high as that of Chaga decoction. Finally, seven antioxidant components were isolated and purified from the 80% MeOH extract of Chaga fruiting body, and their chemical structures were determined as small phenolics as follows: 4-hydroxy-3,5-dimethoxy benzoic acid 2-hydroxy-1-hydroxymethyl ethyl ester (BAEE), protocatechic acid (PCA), caffeic acid (CA), 3,4-dihybenzaladehyde (DB), 2,5-dihydroxyterephtalic acid (DTA), syringic acid (SA) and 3,4-dihydroxybenzalacetone (DBL). Notably, BAEE was assigned as the new compound firstly identified from the natural source in the present study.

  5. Perspectives on Trypanosoma cruzi-induced heart disease (Chagas disease)

    PubMed Central

    Tanowitz, Herbert B.; Machado, Fabiana S.; Jelicks, Linda A.; Shirani, Jamshid; Campos de Carvalho, Antonio C.; Spray, David C.; Factor, Stephen M.; Kirchhoff, Louis V.; Weiss, Louis M.

    2009-01-01

    Chagas disease is caused by the parasite Trypanosoma cruzi it is the most common cause of heart disease in endemic areas of Latin America. The year 2009 marks the 100th anniversary of the discovery of T. cruzi infection and Chagas disease by the Brazilian physician Carlos Chagas. Chagasic cardiomyopathy develops in from 10 to 30 percent of persons who are chronically infected with this parasite. Echocardiography and magnetic resonance imaging are important modalities in the evaluation and prognosis of individuals with chagasic heart disease. The etiology of chagasic heart disease likely is multifactorial. Parasite persistence, autoimmunity, and microvascular abnormalities have been studied extensively as possible pathogenic mechanisms. Experimental studies suggest that alterations in cardiac gap junctions may be etiologic in the pathogenesis of conduction abnormalities. The diagnosis of chronic Chagas disease is made by serology. The treatment of this infection has shortcomings that need to be addressed. Cardiac transplantation and bone marrow stem cell therapy for persons with Chagas disease have received increasing research attention in recent years. PMID:19410685

  6. Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease.

    PubMed

    Nogueira, Luciana Gabriel; Frade, Amanda Farage; Ianni, Barbara Maria; Laugier, Laurie; Pissetti, Cristina Wide; Cabantous, Sandrine; Baron, Monique; Peixoto, Gisele de Lima; Borges, Ariana de Melo; Donadi, Eduardo; Marin-Neto, José A; Schmidt, André; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Martinelli, Martino; Lensi, Mariana; Siqueira, Sergio Freitas; Pereira, Alexandre Costa; Rodrigues, Virmondes; Kalil, Jorge; Chevillard, Christophe; Cunha-Neto, Edecio

    2015-05-01

    Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Cholinesterase inhibition reduces arrhythmias in asymptomatic Chagas disease.

    PubMed

    Castro, Renata R T; Porphirio, Graciema; Xavier, Sergio S; Moraes, Ruy S; Ferlin, Elton L; Ribeiro, Jorge P; da Nóbrega, Antonio C L

    2017-10-01

    Parasympathetic dysfunction may play a role in the genesis of arrhythmias in Chagas disease. This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinesterase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. Following a double-blind, randomized, placebo-controlled, cross-over protocol, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24-hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA). Pyridostigmine reduced the 24-hours incidence (median [25%-75%]) of premature ventricular beats-PLA: 2998 (1920-4870), PYR: 2359 (940-3253), P=.044; ventricular couplets-PLA: 84 (15-159), PYR: 33 (6-94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0-8]) and PYR (0 [0-4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). Acute administration of pyridostigmine reduced the incidence of nonsustained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow-up are warranted. © 2017 John Wiley & Sons Ltd.

  8. Chagas' disease and ageing: the coexistence of other chronic diseases with Chagas' disease in elderly patients.

    PubMed

    Alves, Rosalía Matera de Angelis; Thomaz, Raquel Prado; Almeida, Eros Antônio de; Wanderley, Jamiro da Silva; Guariento, Maria Elena

    2009-01-01

    This study aimed to identify the main comorbidities in elderly chagasic patients treated in a reference service and identify possible associations between the clinical form of Chagas' disease and chronic diseases. Ninety patients aged 60 years-old or over were interviewed and their clinical diagnoses recorded. The study population profile was: women (55.6%); median age (67 years); married (51.1%); retired (73.3%); up to four years' education (64.4%); and earning less than two minimum wages (67.8%). The predominant forms of Chagas' disease were the cardiac (46.7%) and mixed forms (30%). There was a greater proportion of mild cardiac dysfunction (84.1%), frequently in association with megaesophagus. The mean number of concurrent diseases was 2.856 +/- 1.845, and 33% of the patients had four or more comorbidities. The most frequent were systemic arterial hypertension (56.7%), osteoporosis (23.3%), osteoarthritis (21.2%) and dyslipidemia (20%). Positive correlations were verified between sex and comorbidities and between age group and comorbidities.

  9. Epidemiology of American trypanosomiasis (Chagas disease).

    PubMed

    Kirchhoff, Louis V

    2011-01-01

    Trypanosoma cruzi, the cause of American trypanosomiasis, or Chagas disease, is a protozoan parasite that is enzootic and endemic in much of the Americas, where it infects a wide variety of wild and domestic mammals as well as many species of triatomine vectors, in addition to humans. Historically, vector-borne transmission of T. cruzi has been the most important mechanism through which humans have become infected with the parasite, but transmission by blood transfusion and congenital transmission also have been important. In many of the endemic countries transmission of T. cruzi has improved markedly in recent years as vector control and donor screening programs have been implemented on a widespread basis. In the United States autochthonous transmission of T. cruzi appears to be extremely rare. Five persons are known to have become infected with T. cruzi through organ transplants here, and prior to the implementation of blood donor screening in 2007 five instances of transmission by transfusion had been reported. Current estimates put the total number of T. cruzi-infected persons living in the United States at 300,000, essentially all of whom are immigrants from the endemic countries. The obstacles that stand in the way of the total elimination of T. cruzi transmission throughout the endemic range are economic and political, and no major technological advances are needed to accomplish this goal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Highly Effective Serodiagnosis for Chagas' Disease ▿

    PubMed Central

    Hernández, Pilar; Heimann, Michael; Riera, Cristina; Solano, Marco; Santalla, José; Luquetti, Alejandro O.; Beck, Ewald

    2010-01-01

    Many proteins of Trypanosoma cruzi, the causative agent of Chagas' disease, contain characteristic arrays of highly repetitive immunogenic amino acid motifs. Diagnostic tests using these motifs in monomeric or dimeric form have proven to provide markedly improved specificity compared to conventional tests based on crude parasite extracts. However, in many cases the available tests still suffer from limited sensitivity. In this study we produced stable synthetic genes with maximal codon variability for the four diagnostic antigens, B13, CRA, TcD, and TcE, each containing between three and nine identical amino acid repeats. These genes were combined by linker sequences encoding short proline-rich peptides, giving rise to a 24-kDa fusion protein which was used as a novel diagnostic antigen in an enzyme-linked immunosorbent assay setup. Validation of the assay with a large number of well-characterized patient sera from Bolivia and Brazil revealed excellent diagnostic performance. The high sensitivity of the new test may allow future studies to use blood collected by finger prick and dried on filter paper, thus dramatically reducing the costs and effort for the detection of T. cruzi infection. PMID:20668136

  11. Behavioural biology of Chagas disease vectors

    PubMed Central

    Lazzari, Claudio Ricardo; Pereira, Marcos Horácio; Lorenzo, Marcelo Gustavo

    2013-01-01

    Many arthropod species have adopted vertebrate blood as their main food source. Blood is rich in nutrients and, except for the presence of parasites, sterile. However, this food source is not freely available, nor is obtaining it devoid of risk. It circulates inside vessels hidden underneath the skin of mobile hosts that are able to defend themselves and even predate the insects that try to feed on them. Thus, the haematophagous lifestyle is associated with major morphological, physiological and behavioural adaptations that have accumulated throughout the evolutionary history of the various lineages of blood-sucking arthropods. These adaptations have significant consequences for the evolution of parasites as well as for the epidemiology of vector-transmitted diseases. In this review article, we analyse various aspects of the behaviour of triatomine bugs to illustrate how each behavioural trait represents a particular adaptation to their close association with their hosts, which may easily turn into predators. Our aim is to offer to the reader an up-to-date integrative perspective on the behaviour of Chagas disease vectors and to propose new research avenues to encourage both young and experienced colleagues to explore this aspect of triatomine biology. PMID:24473801

  12. Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease.

    PubMed

    Sbaraglini, María L; Bellera, Carolina L; Fraccaroli, Laura; Larocca, Luciana; Carrillo, Carolina; Talevi, Alan; Alba Soto, Catalina D

    2016-07-01

    Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.

  13. Would selenium supplementation aid in therapy for Chagas Disease?

    PubMed Central

    Jelicks, Linda A.; de Souza, Andréa P.; Araújo-Jorge, Tania C; Tanowitz, Herbert B.

    2010-01-01

    Chagas disease, a neglected tropical disease discovered over 100 years ago, is caused by the intracellular parasite Trypanosoma cruzi and is most frequently associated with chronic cardiomyopathy and digestive disorders. Initial invasion of cells is followed by progressive inflammatory destruction of heart, muscles, nerves, and gastrointestinal (GI) tract tissue. About 30% of patients progress to a chronic cardiomyopathy associated with increased morbidity and mortality. Seven to 10% of patients develop megasyndromes involving the GI tract, in particular, the esophagus and the colon. Results from several studies suggest that selenium (Se) deficiency may be an important factor in the pathogenesis of Chagas disease. In this opinion article, Se supplementation is proposed as an adjuvant therapy for treatment of chronic Chagas disease. PMID:21212020

  14. Biologic and Genetics Aspects of Chagas Disease at Endemic Areas

    PubMed Central

    Bellini, Marilanda Ferreira; Silistino-Souza, Rosana; Varella-Garcia, Marileila; de Azeredo-Oliveira, Maria Tercília Vilela; Silva, Ana Elizabete

    2012-01-01

    The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease. PMID:22529863

  15. VNI Cures Acute and Chronic Experimental Chagas Disease

    PubMed Central

    Villalta, Fernando; Dobish, Mark C.; Nde, Pius N.; Kleshchenko, Yulia Y.; Hargrove, Tatiana Y.; Johnson, Candice A.; Waterman, Michael R.; Johnston, Jeffrey N.; Lepesheva, Galina I.

    2013-01-01

    Chagas disease is a deadly infection caused by the protozoan parasite Trypanosoma cruzi. Afflicting approximately 8 million people in Latin America, Chagas disease is now becoming a serious global health problem proliferating beyond the traditional geographical borders, mainly because of human and vector migration. Because the disease is endemic in low-resource areas, industrial drug development has been lethargic. The chronic form remains incurable, there are no vaccines, and 2 existing drugs for the acute form are toxic and have low efficacy. Here we report the efficacy of a small molecule, VNI, including evidence of its effectiveness against chronic Chagas disease. VNI is a potent experimental inhibitor of T. cruzi sterol 14α-demethylase. Nontoxic and highly selective, VNI displays promising pharmacokinetics and administered orally to mice at 25 mg/kg for 30 days cures, with 100% cure rate and 100% survival, the acute and chronic T. cruzi infection. PMID:23372180

  16. Chagas Heart Failure in Patients from Latin America

    PubMed Central

    2016-01-01

    Physicians working in Europe and the United States should suspect Chagas heart failure in every patient coming from Latin America with chronic heart failure. Diagnosis should be confirmed by positive serology. Right bundle branch block and left anterior fascicular block on 12-lead electrocardiogram, enlarged cardiac silhouette with no pulmonary congestion on chest X-ray and left ventricular apical aneurysm on echocardiography are the distinctive features of this condition. The clinical course is poorer than that of non-Chagas heart failure; however, medical treatment is similar. Implantable cardioverter-defibrillators are useful in the primary and secondary prevention of sudden cardiac death. Cardiac resynchronisation therapy can be given to patients on optimal medical therapy and with lengthened QRS complex. Heart transplantation is the treatment of choice for patients with end-stage Chagas heart failure. PMID:28785459

  17. Gallbladder neuron count in cholelithiasis patients with and without Chagas disease.

    PubMed

    Crema, Eduardo; Ribeiro, Lara Beatriz Prata; Adad, Sheila Jorge; Ectchebehere, Renata Margarida; Martins Júnior, Aiodair; Silva, Alex Augusto

    2007-01-01

    Various investigators agree that the incidence of cholelithiasis is greater in patients with Chagas disease. The most plausible explanation for this is based on the parasympathetic denervation that occurs over the whole digestive tract due to Chagas disease. In order to analyze the occurrence of this alteration, gallbladder neuron counts were performed on cholelithiasis patients with and without Chagas disease who were being treated at the Department of Digestive Surgery, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil. In the present study, a notable reduction in the number of neurons in the gallbladder wall was observed in Chagas patients, in comparison with non-Chagas subjects.

  18. The Costs of Preventing and Treating Chagas Disease in Colombia

    PubMed Central

    Castillo-Riquelme, Marianela; Guhl, Felipe; Turriago, Brenda; Pinto, Nestor; Rosas, Fernando; Martínez, Mónica Flórez; Fox-Rushby, Julia; Davies, Clive; Campbell-Lendrum, Diarmid

    2008-01-01

    Background The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare. PMID:19015725

  19. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  20. Chagas disease: role of parasite genetic variation in pathogenesis.

    PubMed

    Macedo, Andra M; Oliveira, Riva P; Pena, Srgio D J

    2002-03-05

    Chagas disease, caused by the parasite protozoan Trypanosoma cruzi, is characterised by a variable clinical course, from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. This variability has been attributed both to differences in the host response and to genomic heterogeneity of the parasite. This article reviews the evidence in favour of an important role of the genetic constitution of T. cruzi in determining the clinical characteristics of Chagas disease and discusses the basis of the 'Clonal-Histotropic Model' for the pathogenesis of this disease.

  1. Interrupting Chagas disease transmission in Venezuela.

    PubMed

    Aché, A; Matos, A J

    2001-01-01

    The interruption of vectorial transmission of Chagas disease in Venezuela is attributed to the combined effects of ongoing entomoepidemiological surveillance, ongoing house spraying with residual insecticides and the concurrent building and modification of rural houses in endemic areas during almost five decades. The original endemic areas which totaled 750,000 km(2), have been reduced to 365,000 km(2). During 1958-1968, initial entomological evaluations carried out showed that the house infestation index ranged between 60-80%, the house infection index at 8-11% and a house density index of 30-50 triatomine bugs per house. By 1990-98, these indexes were further reduced to 1.6-4.0%, 0.01-0.6% and 3-4 bugs per house respectively. The overall rural population seroprevalence has declined from 44.5% (95% C.I.: 43.4-45.3%) to 9.2% (95% C.I.: 9.0-9.4%) for successive grouped periods from 1958 to 1998. The annual blood donor prevalence is firmly established below 1%. The population at risk of infection has been estimated to be less than four million. Given that prevalence rates are stable and appropriate for public health programmes, consideration has been given to potential biases that may distort results such as: a) geographical differences in illness or longevity of patients; b) variations in levels of ascertainment; c) variations in diagnostic criteria; and d) variations in population structure, mainly due to appreciable population migration. The endemic areas with continuous transmission are now mainly confined to piedmonts, as well as patchy foci in higher mountainous ranges, where the exclusive vector is Rhodnius prolixus. There is also an unstable area, of which landscapes are made up of grasslands with scattered broad-leaved evergreen trees and costal plains, where transmission is very low and occasional outbreaks are reported.

  2. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients.

    PubMed

    Guedes, Paulo Marcos Matta; de Andrade, Cléber Mesquita; Nunes, Daniela Ferreira; de Sena Pereira, Nathalie; Queiroga, Tamyres Bernadete Dantas; Machado-Coelho, George Luiz Lins; Nascimento, Manuela Sales Lima; Do-Valle-Matta, Maria Adelaide; da Câmara, Antônia Cláudia Jácome; Chiari, Egler; Galvão, Lúcia Maria da Cunha

    2016-04-01

    Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease.

  3. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients

    PubMed Central

    Guedes, Paulo Marcos Matta; de Andrade, Cléber Mesquita; Nunes, Daniela Ferreira; de Sena Pereira, Nathalie; Queiroga, Tamyres Bernadete Dantas; Machado-Coelho, George Luiz Lins; Nascimento, Manuela Sales Lima; Do-Valle-Matta, Maria Adelaide; da Câmara, Antônia Cláudia Jácome; Chiari, Egler; Galvão, Lúcia Maria da Cunha

    2016-01-01

    Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease. PMID

  4. T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease

    PubMed Central

    Deborggraeve, Stijn; Coronado, Ximena; Solari, Aldo; Zulantay, Ines; Apt, Werner; Mertens, Pascal; Laurent, Thierry; Leclipteux, Thierry; Stessens, Tim; Dujardin, Jean-Claude; Herdewijn, Piet; Büscher, Philippe

    2009-01-01

    Background PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization. Methodology We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile. Principal Findings The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively. Conclusions The T. cruzi OligoC-TesT showed high sensitivity and specificity on a diverse panel of biological samples. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease. PMID:19503815

  5. Development of chagas cardiac manifestations among Texas blood donors.

    PubMed

    Garcia, Melissa N; Murray, Kristy O; Hotez, Peter J; Rossmann, Susan N; Gorchakov, Rodion; Ontiveros, Alejandra; Woc-Colburn, Laila; Bottazzi, Maria Elena; Rhodes, Charles E; Ballantyne, Christie M; Aguilar, David

    2015-01-01

    Chagas disease, infection with the parasite Trypanosoma cruzi, has recently been identified as an important emerging parasitic disease in the United States. To describe the cardiac abnormalities in T. cruzi-positive blood donors in southeastern Texas, a pilot study of donors who had screened positive from 2007 to 2012 was performed. This one-time assessment included (1) a questionnaire to evaluate the source of infection, cardiac symptoms, and health co-morbidities; (2) electrocardiography; (3) echocardiography if electrocardiographic findings were abnormal; and (4) measurement of a high-sensitivity troponin T biomarker. Of those with confirmed infection, 41% (7 of 17) had electrocardiographic abnormalities consistent with Chagas cardiomyopathy. In addition, 36% (6 of 17) were suspected to be locally acquired cases. High-sensitivity troponin T serum levels increased with cardiac severity. In conclusion, cardiologists should consider Chagas disease in their differential diagnoses for patients who may have clinically compatible electrocardiographic changes or nonischemic cardiomyopathy, even if the patients have no histories of residing in Chagas-endemic countries. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. American Trypanosomiasis (Also Known as Chagas Disease) Treatment

    MedlinePlus

    ... Laboratory Diagnostic Assistance [DPDx] Parasites Home Treatment Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Treatment for Chagas disease is recommended for people diagnosed early in the course of infection (acute phase), congenital infection, and for ...

  7. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    PubMed Central

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  8. Chagas disease transmission in periurban communities of Arequipa, Peru.

    PubMed

    Bowman, Natalie M; Kawai, Vivian; Levy, Michael Z; Cornejo del Carpio, Juan Geny; Cabrera, Lilia; Delgado, F; Malaga, Francisco; Cordova Benzaquen, Eleazar; Pinedo, Viviana V; Steurer, Francis; Seitz, Amy E; Gilman, Robert H; Bern, Caryn

    2008-06-15

    Chagas disease, caused by Trypanosoma cruzi infection, is an urban problem in Arequipa, Peru, and the epidemiology of Chagas disease is likely to be quite different in this area, compared with in rural zones. We conducted a serosurvey of 1615 children <18 years old in periurban districts that included hillside shantytowns and slightly more affluent low-lying communities. In addition, 639 adult residents of 1 shantytown were surveyed to provide data across the age spectrum for this community. Of 1615 children, 75 (4.7%) were infected with Trypanosoma cruzi. Infection risk increased by 12% per year of age, and children living in hillside shantytowns were 2.5 times as likely to be infected as were those living in lower-lying communities. However, age-prevalence data from 1 shantytown demonstrated that adults were no more likely to be seropositive than were teenagers; the results of maximum likelihood modeling suggest that T. cruzi transmission began in this community <20 years ago. The problem of Chagas disease in periurban settings, such as those around Arequipa, must be addressed to achieve elimination of vector-borne T. cruzi transmission. Identification of infected children, vector-control efforts, and education to avoid modifiable risk factors are necessary to decrease the burden of Chagas disease.

  9. Experimental Vaccines against Chagas Disease: A Journey through History

    PubMed Central

    Rodríguez-Morales, Olivia; Monteón-Padilla, Víctor; Carrillo-Sánchez, Silvia C.; Rios-Castro, Martha; Martínez-Cruz, Mariana; Carabarin-Lima, Alejandro; Arce-Fonseca, Minerva

    2015-01-01

    Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms “Chagas disease” and “American trypanosomiasis” together with “vaccines” or “immunization”. In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed. PMID:26090490

  10. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    PubMed

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease. © 2016 John Wiley & Sons Ltd.

  11. Chagas Parasite Detection in Blood Images Using AdaBoost

    PubMed Central

    Uc-Cetina, Víctor; Brito-Loeza, Carlos; Ruiz-Piña, Hugo

    2015-01-01

    The Chagas disease is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi. Visual detection of such parasite through microscopic inspection is a tedious and time-consuming task. In this paper, we provide an AdaBoost learning solution to the task of Chagas parasite detection in blood images. We give details of the algorithm and our experimental setup. With this method, we get 100% and 93.25% of sensitivity and specificity, respectively. A ROC comparison with the method most commonly used for the detection of malaria parasites based on support vector machines (SVM) is also provided. Our experimental work shows mainly two things: (1) Chagas parasites can be detected automatically using machine learning methods with high accuracy and (2) AdaBoost + SVM provides better overall detection performance than AdaBoost or SVMs alone. Such results are the best ones known so far for the problem of automatic detection of Chagas parasites through the use of machine learning, computer vision, and image processing methods. PMID:25861375

  12. Estimating the Burden of Chagas Disease in the United States

    PubMed Central

    Manne-Goehler, Jennifer; Umeh, Chukwuemeka A.; Montgomery, Susan P.; Wirtz, Veronika J.

    2016-01-01

    Background In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. Methods In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). Findings The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. Conclusions This study demonstrates a substantial burden of Chagas disease in the US, with state

  13. Chagas disease: control, elimination and eradication. Is it possible?

    PubMed

    Coura, José Rodrigues

    2013-12-01

    From an epidemiological point of view, Chagas disease and its reservoirs and vectors can present the following characteristics: (i) enzooty, maintained by wild animals and vectors, with broad occurrence from southern United States of America (USA) to southern Argentina and Chile (42ºN 49ºS), (ii) anthropozoonosis, when man invades the wild ecotope and becomes infected with Trypanosoma cruzi from wild animals or vectors or when the vectors and wild animals, especially marsupials, invade the human domicile and infect man, (iii) zoonosis-amphixenosis and exchanged infection between animals and humans by domestic vectors in endemic areas and (iv) zooanthroponosis, infection that is transmitted from man to animals, by means of domestic vectors, which is the rarest situation in areas endemic for Chagas disease. The characteristics of Chagas disease as an enzooty of wild animals and as an anthropozoonosis are seen most frequently in the Brazilian Amazon and in the Pan-Amazon region as a whole, where there are 33 species of six genera of wild animals: Marsupialia, Chiroptera, Rodentia, Edentata (Xenarthra), Carnivora and Primata and 27 species of triatomines, most of which infected with T. cruzi . These conditions place the resident populations of this area or its visitors - tourists, hunters, fishermen and especially the people whose livelihood involves plant extraction - at risk of being affected by Chagas disease. On the other hand, there has been an exponential increase in the acute cases of Chagas disease in that region through oral transmission of T. cruzi , causing outbreaks of the disease. In four seroepidemiological surveys that were carried out in areas of the microregion of the Negro River, state of Amazonas, in 1991, 1993, 1997 and 2010, we found large numbers of people who were serologically positive for T. cruzi infection. The majority of them and/or their relatives worked in piassava extraction and had come into contact with and were stung by wild

  14. Chagas disease: control, elimination and eradication. Is it possible?

    PubMed Central

    Coura, José Rodrigues

    2013-01-01

    From an epidemiological point of view, Chagas disease and its reservoirs and vectors can present the following characteristics: (i) enzooty, maintained by wild animals and vectors, with broad occurrence from southern United States of America (USA) to southern Argentina and Chile (42ºN 49ºS), (ii) anthropozoonosis, when man invades the wild ecotope and becomes infected with Trypanosoma cruzi from wild animals or vectors or when the vectors and wild animals, especially marsupials, invade the human domicile and infect man, (iii) zoonosis-amphixenosis and exchanged infection between animals and humans by domestic vectors in endemic areas and (iv) zooanthroponosis, infection that is transmitted from man to animals, by means of domestic vectors, which is the rarest situation in areas endemic for Chagas disease. The characteristics of Chagas disease as an enzooty of wild animals and as an anthropozoonosis are seen most frequently in the Brazilian Amazon and in the Pan-Amazon region as a whole, where there are 33 species of six genera of wild animals: Marsupialia, Chiroptera, Rodentia, Edentata (Xenarthra), Carnivora and Primata and 27 species of triatomines, most of which infected with T. cruzi . These conditions place the resident populations of this area or its visitors - tourists, hunters, fishermen and especially the people whose livelihood involves plant extraction - at risk of being affected by Chagas disease. On the other hand, there has been an exponential increase in the acute cases of Chagas disease in that region through oral transmission of T. cruzi , causing outbreaks of the disease. In four seroepidemiological surveys that were carried out in areas of the microregion of the Negro River, state of Amazonas, in 1991, 1993, 1997 and 2010, we found large numbers of people who were serologically positive for T. cruzi infection. The majority of them and/or their relatives worked in piassava extraction and had come into contact with and were stung by wild

  15. Estimating the Burden of Chagas Disease in the United States.

    PubMed

    Manne-Goehler, Jennifer; Umeh, Chukwuemeka A; Montgomery, Susan P; Wirtz, Veronika J

    2016-11-01

    In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. This study demonstrates a substantial burden of Chagas disease in the US, with state variation that reflects the distribution of

  16. Rational spatio-temporal strategies for controlling a Chagas disease vector in urban environments

    PubMed Central

    Levy, Michael Z.; Malaga Chavez, Fernando S.; Cornejo del Carpio, Juan G.; Vilhena, Daril A.; McKenzie, F. Ellis; Plotkin, Joshua B.

    2010-01-01

    The rational design of interventions is critical to controlling communicable diseases, especially in urban environments. In the case of the Chagas disease vector Triatoma infestans, successful control is stymied by the return of the insect after the effectiveness of the insecticide wanes. Here, we adapt a genetic algorithm, originally developed for the travelling salesman problem, to improve the spatio-temporal design of insecticide campaigns against T. infestans, in a complex urban environment. We find a strategy that reduces the expected instances of vector return 34-fold compared with the current strategy of sequential insecticide application to spatially contiguous communities. The relative success of alternative control strategies depends upon the duration of the effectiveness of the insecticide, and it shows chaotic fluctuations in response to unforeseen delays in a control campaign. We use simplified models to analyse the outcomes of qualitatively different spatio-temporal strategies. Our results provide a detailed procedure to improve control efforts for an urban Chagas disease vector, as well as general guidelines for improving the design of interventions against other disease agents in complex environments. PMID:20061346

  17. Current drug therapy and pharmaceutical challenges for Chagas disease.

    PubMed

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection.

  18. The burden of Chagas disease: estimates and challenges.

    PubMed

    Stanaway, Jeffrey D; Roth, Gregory

    2015-09-01

    Chagas disease, caused by infection with the protozoa Trypanosoma cruzi is transmitted most often by Triatominae insect vectors, but also through blood transfusion, organ transplant, and congenital transmission. Between 5 and 18 million people are currently infected and the infection is estimated to cause more than 10,000 deaths annually. The disease has 3 phases: acute, indeterminate, and chronic. The acute phase immediately follows infection. It is typically asymptomatic but produces fever and malaise in up to 5% of people. The indeterminate phase is asymptomatic. More than one-half of those infected will remain in this phase for life and never experience long-term sequelae. After a decade or more, 20% to 30% of people will experience chronic cardiovascular Chagas disease with sequelae including heart failure, arrhythmias, and thromboembolism. Another 15% to 20% will experience chronic digestive sequela including megaesophagus and megacolon. A complete accounting of the burden of Chagas disease requires estimating the prevalence of the infection, the prevalence of each of its sequelae among those with the infection, and the number of deaths attributable to the infection. Attempts to estimate Chagas disease prevalence are complicated by several challenges imposed by the disease's extreme spatial heterogeneity, quickly evolving temporal trends, the decades-long lag between infection and symptomatic disease, biased prevalence data, incomplete recognition of Chagas-attributable deaths, limited data on sequela, and a near total absence of data outside of endemic countries. Even though researchers have found methodological approaches to dealing with these challenges, there is a need for better data. Copyright © 2015 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

  19. Chagas disease in a Texan horse with neurologic deficits.

    PubMed

    Bryan, Laura K; Hamer, Sarah A; Shaw, Sarah; Curtis-Robles, Rachel; Auckland, Lisa D; Hodo, Carolyn L; Chaffin, Keith; Rech, Raquel R

    2016-01-30

    A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Justice where justice is due: A posthumous Nobel Prize to Carlos Chagas (1879-1934), the discoverer of American Trypanosomiasis (Chagas' disease).

    PubMed

    Bestetti, Reinaldo B; Martins, Cláudia A; Cardinalli-Neto, Augusto

    2009-05-01

    Working in the Brazilian backland, Chagas described a new disease. He discovered the etiologic agent, the vector, the reservoir, the acute stage, the several clinical aspects of the chronic stage (particularly the heart disease), role of autoimmunity in its pathogenesis, and anticipated the social impact of the disease. Chagas was nominated to Nobel Prize twice: in 1913, and in 1921. In 1913, Richet won the prize because his work on anaphylaxis. In 1921, no one received the Nobel Prize. It is believed that detraction of Chagas' work at the National Academy of Medicine, made by jealousy, mediocrity, and political rivalries can be maculated the image of the scientist. Furthermore, misperception of Chagas' work may also have led the Nobel Committee not to award him. One-hundred years after the discovery, we can appreciate the greatness of the discovery of Carlos Chagas, never seem in the realm of biological research. Time to make justice, therefore, has finally come.

  1. Dobutamine Stress Echocardiography Safety in Chagas Disease Patients.

    PubMed

    Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Furtado, Rogerio Gomes; Turco, Fabio de Paula; Melato, Luciano Henrique; Hotta, Viviane Tiemi; Nunes, Colandy Godoy de Oliveira; Rassi, Luiz; Rassi, Salvador

    2017-02-01

    A few decades ago, patients with Chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (CAD). As urbanization has increased, they became exposed to the same risk factors for CAD of uninfected individuals. Dobutamine stress echocardiography (DSE) has proven to be an important tool in CAD diagnosis. Despite being a potentially arrhythmogenic method, it is safe for coronary patients without Chagas disease. For Chagas disease patients, however, the indication of DSE in clinical practice is uncertain, because of the arrhythmogenic potential of that heart disease. To assess DSE safety in Chagas disease patients with clinical suspicion of CAD, as well as the incidence of arrhythmias and adverse events during the exam. Retrospective analysis of a database of patients referred for DSE from May/2012 to February/2015. This study assessed 205 consecutive patients with Chagas disease suspected of having CAD. All of them had their serology for Chagas disease confirmed. Their mean age was 64±10 years and most patients were females (65.4%). No patient had significant adverse events, such as acute myocardial infarction, ventricular fibrillation, asystole, stroke, cardiac rupture and death. Regarding arrhythmias, ventricular extrasystoles occurred in 48% of patients, and non-sustained ventricular tachycardia in 7.3%. DSE proved to be safe in this population of Chagas disease patients, in which no potentially life-threatening outcome was found. Até poucas décadas atrás, os pacientes chagásicos eram predominantemente trabalhadores rurais, com baixo perfil de risco para doença obstrutiva coronária. Com a crescente urbanização, passaram a ter os mesmos fatores de risco para doença aterosclerótica que indivíduos não infectados. O ecocardiograma sob estresse com dobutamina (EED) é uma importante ferramenta no diagnóstico de coronariopatia. É referido, porém, como um método potencialmente arritmogênico, mas

  2. Chagas Disease, Migration and Community Settlement Patterns in Arequipa, Peru

    PubMed Central

    Gilman, Robert H.; Cornejo del Carpio, Juan G.; Naquira, Cesar; Bern, Caryn; Levy, Michael Z.

    2009-01-01

    Background Chagas disease is one of the most important neglected tropical diseases in the Americas. Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission. Methodology/Principal Findings This was a qualitative study that employed focus group discussions and in-depth interviews. Five focus groups and 50 in-depth interviews were carried out with 94 community members from three shantytowns and two traditional towns near Arequipa, Peru. Focus groups utilized participatory methodologies to explore the community's mobility patterns and the historical and current presence of triatomine vectors. In-depth interviews based on event history calendars explored participants' migration patterns and experience with Chagas disease and vectors. Focus group data were analyzed using participatory analysis methodologies, and interview data were coded and analyzed using a grounded theory approach. Entomologic data were provided by an ongoing vector control campaign. We found that migrants to shantytowns in Arequipa were unlikely to have brought triatomines to the city upon arrival. Frequent seasonal moves, however, took shantytown residents to valleys surrounding Arequipa where vectors are prevalent. In addition, the pattern of settlement of shantytowns and the practice of raising domestic animals by residents creates a favorable environment for vector proliferation and dispersal. Finally, we uncovered a phenomenon of population loss and replacement by low-income migrants in one traditional town, which created the human settlement pattern of a new shantytown within this traditional community. Conclusions/Significance The pattern of human migration is therefore an important underlying determinant of

  3. Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries

    PubMed Central

    Coura, José Rodrigues; Viñas, Pedro Albajar; Junqueira, Angela CV

    2014-01-01

    Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries. PMID:25410988

  4. Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries.

    PubMed

    Coura, José Rodrigues; Viñas, Pedro Albajar; Junqueira, Angela Cv

    2014-11-01

    Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries.

  5. Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries.

    PubMed

    Coura, José Rodrigues; Viñas, Pedro Albajar; Junqueira, Angela Cv

    2014-10-21

    Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries.

  6. Dissecting slander and crying for justice: Carlos Chagas and the Nobel Prize of 1921.

    PubMed

    Bestetti, Reinaldo B; Cardinalli-Neto, Augusto

    2013-10-03

    Chagas disease was discovered by Carlos Chagas in 1909. Chagas worked at Oswaldo Cruz Institute, where the bases of experimental medicine were settled in Brazil, and that had no connection with the Faculty of Medicine of Rio de Janeiro. Chagas had several enemies at Oswaldo Cruz Institute mainly because of his election to Head of Service in 1910, and for the position of Oswaldo Cruz Directorship in 1917. Furthermore, Chagas gained enemies at Faculty of Medicine of Rio de Janeiro, which did not like to see the economical political autonomy of Oswaldo Cruz Institute. This allowed the Institute not only to perform top experimental research, but also to take the leadership of research in the country. Chagas was nominated to the Nobel Prize of 1921 in December, 1920. None was awarded the Nobel Prize in that year. He seems to have been evaluated by the Noble Committee of Karolinska Institute from March to May of 1921. At that time, his enemies were denying his discovery of Trypanosoma cruzi, a key point in Chagas' nomination by Karolinska Institute, and giving no epidemiological importance for the disease. By the same way, the obligation of small pox vaccination was tarnishing his public image. Having taken into account the epidemiologic importance of Chagas disease, the strong historical mistake in the process of Chagas evaluation, and the inequity behind all these facts, we insist on a posthumous Nobel Prize for the man who made the most complete medical-scientist discovery of all time.

  7. Physician Knowledge of Chagas Disease in Hispanic Immigrants Living in Appalachian Ohio.

    PubMed

    Amstutz-Szalay, Shelley

    2017-06-01

    Studies have indicated that US physicians may not consider Chagas disease when diagnosing immigrant patients from Chagas-endemic areas. The purpose of this study was to evaluate physician knowledge of Chagas disease in six Appalachian Ohio counties. Physician knowledge was assessed by self-administrated survey (n = 105). Over 80 % of physicians reported that their current knowledge of Chagas disease was limited or very limited, and 50 % reported never considering Chagas disease diagnosis for their at-risk patients. Nearly 70 % of physicians were unaware of the percentage of chronic Chagas patients that develop clinical disease, and 36 % could not correctly identify the disease course. In addition, over 30 % of physicians reported that no services were available within their practice to assist Spanish-speaking patients with limited English proficiency. A lack of physician awareness of Chagas disease, coupled with a lack of translation services, may create a barrier to care by decreasing the likelihood of identification of patients at risk for Chagas disease. The results of this study support the need for interventions to ensure proper diagnosis and treatment of Chagas disease in Hispanic immigrants in rural Appalachian Ohio.

  8. Motor unit involvement in human acute Chagas' disease.

    PubMed

    Benavente, O R; Patiño, O L; Peña, L B; Lugònes, H; Kalala, E; Meneclier, C R; Genovese, O; Sica, R E

    1989-09-01

    Thirty five patients with acute Chagas' disease who demonstrated parasitaemia at the time of the investigation were submitted to a detailed electromyographical study. With their muscles at rest, 12 patients showed fibrillation potentials and/or positive sharp waves. On volitional contraction, 7 had short duration motor unit potentials (MUPs) and low polyphasic MUPs. On motor and sensory nerve fibers conduction studies, 20 disclosed values below the lower control limit within one or more nerves. Finally, 12 patients produced a muscle decremental response on nerve supramaximal repetitive stimulation. The findings signal that primary muscle involvement, neuropathy and impairement of the neuromuscular transmission, either isolated or combined, may be found in the acute stage of human Chagas' disease.

  9. Neglected Parasitic Infections in the United States: Chagas Disease

    PubMed Central

    Montgomery, Susan P.; Starr, Michelle C.; Cantey, Paul T.; Edwards, Morven S.; Meymandi, Sheba K.

    2014-01-01

    Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi, can lead to severe cardiac and gastrointestinal disease. Most persons acquire this infection through contact with vector bugs carrying T. cruzi in endemic areas of Latin America. Infection can also be acquired by congenital, transfusion, transplantation, and foodborne transmission. Although an estimated 300,000 persons with Chagas disease live in the United States, little is known about the burden of chagasic heart disease. It is not known how often congenital or vector-borne transmission of T. cruzi occurs in the United States, although it is known that infected mothers and infected vector bugs are found in this country. Better diagnostic tests and treatment drugs are needed to improve patient care, and research is needed to define transmission risks and develop strategies to prevent new infections and reduce the burden of disease. PMID:24808250

  10. Therapy of Chagas Disease: Implications for Levels of Prevention

    PubMed Central

    Sosa-Estani, Sergio; Colantonio, Lisandro; Segura, Elsa Leonor

    2012-01-01

    This paper reviews the evidence supporting the use of etiological treatment for Chagas disease that has changed the standard of care for patients with Trypanosoma cruzi infection in the last decades. Implications of this evidence on different levels of prevention as well as gaps in current knowledge are also discussed. In this regard, etiological treatment has shown to be beneficial as an intervention for secondary prevention to successfully cure the infection or to delay, reduce, or prevent the progression to disease, and as primary disease prevention by breaking the chain of transmission. Timely diagnosis during initial stages would allow for the prescription of appropriate therapies mainly in the primary health care system thus improving chances for a better quality of life. Based on current evidence, etiological treatment has to be considered as an essential public health strategy useful to reduce disease burden and to eliminate Chagas disease altogether. PMID:22523499

  11. Multicenter epidemiological and clinical study on imported Chagas diseases in Alicante, Spain

    PubMed Central

    Ramos, José M; Torrús, Diego; Amador, Concepción; Jover, Francisco; Pérez-Chacón, Fabiola; Ponce, Yamileth; Arjona, Francisco J; Caro, Elena; Martínez-Peinado, Concepción; Gallegos, Ingrid; Cuadrado, José M; Tello, Antonio; Gutiérrez, Felix

    2012-01-01

    Recently, there has been an increase in the number of patients with Chagas disease outside of areas that are generally considered endemic. The aim of this investigation is to describe the clinical profile of a series of patients with Chagas disease in Alicante, Spain, which is a province located on the coast of the Mediterranean Sea. This study was performed at four general hospitals in Alicante between January 2002 and May 2011. A total of 128 patients from seven countries were diagnosed with Trypanosoma cruzi. The main country of origin of these patients was Bolivia (n = 101; 78.9%), and the median of age of these patients was 35 years (range: 0–72 years). Four (3.3%) patients were children under 14 years of age, and 81 (63.3%) were female. Polymerase chain reaction (PCR) was used to analyze 106 patients, 66.0% of whom demonstrated positive PCR results. Visceral involvement was diagnosed in 26.8%: 24.1% demonstrated cardiac involvement, 0.9% demonstrated gastrointestinal involvement, 0.9% demonstrated cardiac and gastrointestinal involvement, and 0.9% demonstrated involvement of the central nervous system. Syncope was found to be associated with cardiomyopathy (28.0% versus 5.2%) (odds ratio: 6.5; 95% confidence interval: 1.5–27.1). Seventy-six patients received treatment with benznidazole, of whom 57 (75.0%) completed the treatment course without significant adverse events and 17.1% discontinued benznidazole due to adverse events. In total, 50% of patients experienced documented adverse reactions. Among patients with positive PCR results before treatment, all demonstrated negative PCR results following treatment. In conclusion, majority of our patients were female Bolivians immigrants, one of four of our patients demonstrated cardiac involvement, and treatment tolerance was poor. It is important to improve the clinical and epidemiological knowledge of Chagas disease in nonendemic with additional multicenter studies in order to determine the magnitude of

  12. Challenges and perspectives of Chagas disease: a review

    PubMed Central

    2013-01-01

    Chagas disease (CD), also known as American trypanosomiasis, is caused by the flagellated protozoan Trypanosoma cruzi, and affects an estimated 8 to 10 million people worldwide. In Latin America, 25 million people live in risk areas, while in 2008 alone, 10,000 CD-related deaths were reported. This review aimed to evaluate the challenges of CD control, future perspectives, and actions performed worldwide to control expansion of the disease and its impact on public health in Latin America. PMID:24354455

  13. [Chagas' disease in Mexico. Report of 5 proven cases].

    PubMed

    Marcuchamer Miller, J; Reyes López, P A

    1978-01-01

    Seroepidemiologic studies demonstrated that American Trypanosomiasis is highly prevalent among rural communities in Mexico. However, Chagas' disease seems to be a rarity. That could be a wrong concept. In just a few months 5 patients with epidemiological, clinical and immunologic evidence for Chagasic miocardiopathy or miocarditis were identified in our Institution. Their cardiologic findings have been discussed, as well as diagnostic approaches in different stages of the disease.

  14. Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

    PubMed Central

    Hidron, Alicia I.; Gilman, Robert H.; Justiniano, Juan; Blackstock, Anna J.; LaFuente, Carlos; Selum, Walter; Calderon, Martiza; Verastegui, Manuela; Ferrufino, Lisbeth; Valencia, Eduardo; Tornheim, Jeffrey A.; O'Neal, Seth; Comer, Robert; Galdos-Cardenas, Gerson; Bern, Caryn

    2010-01-01

    Background Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common. Methodology/Principal Findings The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz, Bolivia. Data included risk factors for T. cruzi infection, medical history, physical examination, electrocardiogram, echocardiogram, and contact 9 months after initial data collection to ascertain mortality. Serology and PCR for Trypanosoma cruzi were performed. Of 394 participants, 251 (64%) had confirmed T. cruzi infection by serology. Among seropositive participants, 109 (43%) had positive results by conventional PCR; of these, 89 (82%) also had positive results by real time PCR. There was a high prevalence of hypertension (64%) and overweight (body mass index [BMI] >25; 67%), with no difference by T. cruzi infection status. Nearly 60% of symptomatic congestive heart failure was attributed to Chagas cardiomyopathy; mortality was also higher for seropositive than seronegative patients (p = 0.05). In multivariable models, longer residence in an endemic province, residence in a rural area and poor housing conditions were associated with T. cruzi infection. Male sex, increasing age and poor housing were independent predictors of Chagas cardiomyopathy severity. Males and participants with BMI ≤25 had significantly higher likelihood of positive PCR results compared to females or overweight participants. Conclusions Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease. PMID:20502520

  15. Potential Distribution of Chagas Disease Vectors (Hemiptera, Reduviidae, Triatominae) in Colombia, Based on Ecological Niche Modeling.

    PubMed

    Parra-Henao, Gabriel; Suárez-Escudero, Laura C; González-Caro, Sebastián

    2016-01-01

    Ecological niche modeling of Triatominae bugs allow us to establish the local risk of transmission of the parasite Trypanosoma cruzi, which causes Chagas disease. This information could help to guide health authority recommendations on infection monitoring, prevention, and control. In this study, we estimated the geographic distribution of triatomine species in Colombia and identified the relationship between landscape structure and climatic factors influencing their occurrence. A total of 2451 records of 4 triatomine species (Panstrongylus geniculatus, Rhodnius pallescens, R. prolixus, and Triatoma maculata) were analyzed. The variables that provided more information to explain the ecologic niche of these vectors were related to precipitation, altitude, and temperature. We found that the species with the broadest potential geographic distribution were P. geniculatus, R. pallescens, and R. prolixus. In general, the models predicted the highest occurrence probability of these vectors in the eastern slope of the Eastern Cordillera, the southern region of the Magdalena valley, and the Sierra Nevada of Santa Marta.

  16. Potential Distribution of Chagas Disease Vectors (Hemiptera, Reduviidae, Triatominae) in Colombia, Based on Ecological Niche Modeling

    PubMed Central

    Suárez-Escudero, Laura C.; González-Caro, Sebastián

    2016-01-01

    Ecological niche modeling of Triatominae bugs allow us to establish the local risk of transmission of the parasite Trypanosoma cruzi, which causes Chagas disease. This information could help to guide health authority recommendations on infection monitoring, prevention, and control. In this study, we estimated the geographic distribution of triatomine species in Colombia and identified the relationship between landscape structure and climatic factors influencing their occurrence. A total of 2451 records of 4 triatomine species (Panstrongylus geniculatus, Rhodnius pallescens, R. prolixus, and Triatoma maculata) were analyzed. The variables that provided more information to explain the ecologic niche of these vectors were related to precipitation, altitude, and temperature. We found that the species with the broadest potential geographic distribution were P. geniculatus, R. pallescens, and R. prolixus. In general, the models predicted the highest occurrence probability of these vectors in the eastern slope of the Eastern Cordillera, the southern region of the Magdalena valley, and the Sierra Nevada of Santa Marta. PMID:28115946

  17. Opportunity cost for early treatment of Chagas disease in Mexico.

    PubMed

    Ramsey, Janine M; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

    2014-04-01

    Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life.

  18. Trypanosoma cruzi and Chagas' Disease in the United States.

    PubMed

    Bern, Caryn; Kjos, Sonia; Yabsley, Michael J; Montgomery, Susan P

    2011-10-01

    Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century.

  19. Prophylactic and therapeutic DNA vaccines against Chagas disease.

    PubMed

    Arce-Fonseca, Minerva; Rios-Castro, Martha; Carrillo-Sánchez, Silvia del Carmen; Martínez-Cruz, Mariana; Rodríguez-Morales, Olivia

    2015-02-24

    Chagas disease is a zoonosis caused by Trypanosoma cruzi in which the most affected organ is the heart. Conventional chemotherapy has a very low effectiveness; despite recent efforts, there is currently no better or more effective treatment available. DNA vaccines provide a new alternative for both prevention and treatment of a variety of infectious disorders, including Chagas disease. Recombinant DNA technology has allowed some vaccines to be developed using recombinant proteins or virus-like particles capable of inducing both a humoral and cellular specific immune response. This type of immunization has been successfully used in preclinical studies and there are diverse models for viral, bacterial and/or parasitic diseases, allergies, tumors and other diseases. Therefore, several research groups have been given the task of designing a DNA vaccine against experimental infection with T. cruzi. In this review we explain what DNA vaccines are and the most recent studies that have been done to develop them with prophylactic or therapeutic purposes against Chagas disease.

  20. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

    PubMed Central

    Pinho, Rosa T.; Waghabi, Mariana C.; Cardillo, Fabíola; Mengel, José; Antas, Paulo R. Z.

    2016-01-01

    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials. PMID:27563302

  1. Trypanosoma cruzi and Chagas' Disease in the United States

    PubMed Central

    Bern, Caryn; Kjos, Sonia; Yabsley, Michael J.; Montgomery, Susan P.

    2011-01-01

    Summary: Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century. PMID:21976603

  2. Ecologic Niche Modeling and Potential Reservoirs for Chagas Disease, Mexico.

    PubMed Central

    Sánchez-Cordero, Victor; Ben Beard, C.; Ramsey, Janine M.

    2002-01-01

    Ecologic niche modeling may improve our understanding of epidemiologically relevant vector and parasite-reservoir distributions. We used this tool to identify host relationships of Triatoma species implicated in transmission of Chagas disease. Associations have been documented between the protracta complex (Triatoma: Triatominae: Reduviidae) with packrat species (Neotoma spp.), providing an excellent case study for the broader challenge of developing hypotheses of association. Species pairs that were identified coincided exactly with those in previous studies, suggesting that local interactions between Triatoma and Neotoma species and subspecies have implications at a geographic level. Nothing is known about sylvatic associates of T. barberi, which are considered the primary Chagas vector in Mexico; its geographic distribution coincided closely with that of N. mexicana, suggesting interaction. The presence of the species was confirmed in two regions where it had been predicted but not previously collected. This approach may help in identifying Chagas disease risk areas, planning vector-control strategies, and exploring parasite-reservoir associations for other emerging diseases. PMID:12095431

  3. The Role of Haptoglobin Genotypes in Chagas Disease

    PubMed Central

    Mundaray Fernández, Ninomar; Fernández-Mestre, Mercedes

    2014-01-01

    Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection. PMID:25147423

  4. Opportunity Cost for Early Treatment of Chagas Disease in Mexico

    PubMed Central

    Ramsey, Janine M.; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

    2014-01-01

    Background Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. Methodology/Principal Findings A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. Conclusions/Significance In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life. PMID:24743112

  5. Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States

    PubMed Central

    Gilner, Jennifer B.; Hernandez, Jose; Kurtzberg, Joanne; Heine, R. Phillips

    2016-01-01

    To assess patterns of Chagas disease, we reviewed results of screening umbilical cord blood from a US public cord blood bank during 2007–2014. Nineteen maternal donors tested positive for Trypanosoma cruzi parasites (0.04%). Because perinatal transmission of Chagas disease is associated with substantial illness, targeted prenatal programs should screen for this disease. PMID:27433974

  6. Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study.

    PubMed

    Álvarez, María G; Vigliano, Carlos; Lococo, Bruno; Bertocchi, Graciela; Viotti, Rodolfo

    2017-10-01

    Since the decline in new cases of infection by insect/vector, congenital Chagas disease has become more relevant in the transmission of Chagas disease. Treatment with benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. The objective of this study was to evaluate whether treatment with benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital Chagas disease. An historical cohort study that included all women in reproductive age (15-45 years) assisted in our center was designed. We included 67 mothers with chronic Chagas disease; 35 women had not been treated prior to pregnancy, 15 had been treated prior to pregnancy and 17 gave birth prior and after treatment with benznidazole. Eight mothers gave birth to 16 children with congenital Chagas disease (8/67, 12%). The prevalence of congenital Chagas was 16/114 (14%) children born to untreated mothers and 0/42 (0%) children born to benznidazole- treated mothers, p=0.01. No significant differences were observed in clinical, serologic, epidemiological or socioeconomic baseline variables between mothers with and without children born with congenital Chagas. A 32% conversion rate to negative serology was observed in benznidazole-treated women after long-term follow up. Antiparasitic treatment administered to women in reproductive age can prevent the occurrence of congenital Chagas disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Evaluation of Right Ventricular Systolic Function in Chagas Disease Using Cardiac Magnetic Resonance Imaging.

    PubMed

    Moreira, Henrique T; Volpe, Gustavo J; Marin-Neto, José A; Ambale-Venkatesh, Bharath; Nwabuo, Chike C; Trad, Henrique S; Romano, Minna M D; Pazin-Filho, Antonio; Maciel, Benedito C; Lima, João A C; Schmidt, André

    2017-03-01

    Right ventricular (RV) impairment is postulated to be responsible for prominent systemic congestion in Chagas disease. However, occurrence of primary RV dysfunction in Chagas disease remains controversial. We aimed to study RV systolic function in patients with Chagas disease using cardiac magnetic resonance. This cross-sectional study included 158 individuals with chronic Chagas disease who underwent cardiac magnetic resonance. RV systolic dysfunction was defined as reduced RV ejection fraction based on predefined cutoffs accounting for age and sex. Multivariable logistic regression was used to verify the relationship of RV systolic dysfunction with age, sex, functional class, use of medications for heart failure, atrial fibrillation, and left ventricular systolic dysfunction. Mean age was 54±13 years, 51.2% men. RV systolic dysfunction was identified in 58 (37%) individuals. Although usually associated with reduced left ventricular ejection fraction, isolated RV systolic dysfunction was found in 7 (4.4%) patients, 2 of them in early stages of Chagas disease. Presence of RV dysfunction was not significantly different in patients with indeterminate/digestive form of Chagas disease (35.7%) compared with those with Chagas cardiomyopathy (36.8%) (P=1.000). In chronic Chagas disease, RV systolic dysfunction is more commonly associated with left ventricular systolic dysfunction, although isolated and early RV dysfunction can also be identified. © 2017 American Heart Association, Inc.

  8. Fatal congenital Chagas' disease in a non-endemic area: a case report

    PubMed Central

    Flores-Chávez, María; Faez, Yamile; Olalla, José M; Cruz, Israel; Gárate, Teresa; Rodríguez, Mercedes; Blanc, Pilar; Cañavate, Carmen

    2008-01-01

    The early diagnosis of congenital Chagas' disease is very important if infected newborns, whether symptomatic or not, are to receive adequate treatment. This paper describes the complications arising in the diagnosis of a newborn with fatal congenital Chagas' disease in Spain, a non-endemic area where visceral leishmaniasis is present. PMID:18992159

  9. Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

    PubMed Central

    Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

    2014-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

  10. From Lemongrass to Ivermectin: Ethnomedical Management of Chagas Disease in Tropical Bolivia.

    PubMed

    Forsyth, Colin

    2017-07-31

    Chagas disease is a neglected tropical disease; the only viable drugs are outdated and produce frequent side effects, and the overwhelming majority of cases are undiagnosed and untreated. Globally, people encounter numerous impediments to accessing biomedical treatment for Chagas disease. However, little is known about how people with Chagas disease manage their health outside the biomedical system. In this article, I discuss knowledge of ethnomedical treatments among marginalized patients in an endemic area of Bolivia. I interviewed 68 patients, 63 (93 percent) of whom had positive diagnoses for Chagas disease. Participants free listed 66 ethnomedical remedies either for Chagas disease (n = 39) or its cardiac symptoms. Participants stressed the accessibility of ethnomedical remedies in contrast to the multiple barriers to accessing biomedical treatment. Far from eroding in the face of globalization and sociopolitical marginalization, ethnomedical knowledge in the study area is dynamic and flexible, communicated through various channels.

  11. Challenges in the management of Chagas disease in Latin-American migrants in Europe.

    PubMed

    Monge-Maillo, B; López-Vélez, R

    2017-05-01

    Chagas disease is endemic in Latin America. Due to migration the infection has crossed borders and it is estimated that 68,000-120,000 people with Chagas disease are currently living in Europe and 30% of them may develop visceral involvement. However, up to 90% of Chagas disease cases in Europe remain undiagnosed. The challenges which have to be overcome in Chagas disease in non-endemic countries are focused on related downing barriers to health care access, and related to screening, diagnostic tools and therapeutic management. The aim of this review is to highlight how healthcare management for Latin American migrants with Chagas disease in Europe may be improved. Medical literature was searched using PubMed. No limits were placed with respect to the language or date of publication although most of the articles selected were articles published in the last five years. Chosen search terms were "Chagas disease" AND ("migrants" OR "screening" OR "transmission" OR "treatment"; OR "knowledge" OR "non-endemic countries"); migrants AND ("Public health" OR "Health Service Accessibility" OR "Delivery of Health care"); and "Congenital Chagas disease". Healthcare management of migrant populations with Chagas disease in Europe has to be improved: -Surveillance programmes are needed to measure the burden of the disease; -screening programmes are needed; -administrative and cultural barriers in the access to health care for migrants should be reduced; -education programmes on Chagas disease should be performed -research on new diagnostic tools and therapeutic options are required. This review highlights the needs of profound changes in the health care of Latin American migrants with Chagas disease in Europe. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Accuracy of a Rapid Diagnostic Test (Cypress Chagas Quick Test(®)) for the Diagnosis of Chronic Chagas Disease in a Nonendemic Area: A Retrospective Longitudinal Study.

    PubMed

    Angheben, Andrea; Staffolani, Silvia; Anselmi, Mariella; Tais, Stefano; Degani, Monica; Gobbi, Federico; Buonfrate, Dora; Gobbo, Maria; Bisoffi, Zeno

    2017-08-14

    We analyzed the accuracy of Chagas Quick Test(®), a rapid diagnostic test, for the diagnosis of chronic Chagas disease through a retrospective study on a cohort of 669 patients consecutively examined at a single reference center in Italy, during a 7-year period. We observed high concordance with serological reference standard but low accuracy for screening purposes (sensitivity/specificity: 82.8%/98.7%) at least in our nonendemic context.

  13. Ecological Connectivity of Trypanosoma cruzi Reservoirs and Triatoma pallidipennis Hosts in an Anthropogenic Landscape with Endemic Chagas Disease

    PubMed Central

    Ramsey, Janine M.; Gutiérrez-Cabrera, Ana E.; Salgado-Ramírez, Liliana; Peterson, A. Townsend; Sánchez-Cordero, Victor; Ibarra-Cerdeña, Carlos N.

    2012-01-01

    Traditional methods for Chagas disease prevention are targeted at domestic vector reduction, as well as control of transfusion and maternal-fetal transmission. Population connectivity of Trypanosoma cruzi-infected vectors and hosts, among sylvatic, ecotone and domestic habitats could jeopardize targeted efforts to reduce human exposure. This connectivity was evaluated in a Mexican community with reports of high vector infestation, human infection, and Chagas disease, surrounded by agricultural and natural areas. We surveyed bats, rodents, and triatomines in dry and rainy seasons in three adjacent habitats (domestic, ecotone, sylvatic), and measured T. cruzi prevalence, and host feeding sources of triatomines. Of 12 bat and 7 rodent species, no bat tested positive for T. cruzi, but all rodent species tested positive in at least one season or habitat. Highest T. cruzi infection prevalence was found in the rodents, Baiomys musculus and Neotoma mexicana. In general, parasite prevalence was not related to habitat or season, although the sylvatic habitat had higher infection prevalence than by chance, during the dry season. Wild and domestic mammals were identified as bloodmeals of T. pallidipennis, with 9% of individuals having mixed human (4.8% single human) and other mammal species in bloodmeals, especially in the dry season; these vectors tested >50% positive for T. cruzi. Overall, ecological connectivity is broad across this matrix, based on high rodent community similarity, vector and T. cruzi presence. Cost-effective T. cruzi, vector control strategies and Chagas disease transmission prevention will need to consider continuous potential for parasite movement over the entire landscape. This study provides clear evidence that these strategies will need to include reservoir/host species in at least ecotones, in addition to domestic habitats. PMID:23049923

  14. Immunoblot assay using excreted-secreted antigens of Trypanosoma cruzi in serodiagnosis of congenital, acute, and chronic Chagas' disease.

    PubMed Central

    Umezawa, E S; Nascimento, M S; Kesper, N; Coura, J R; Borges-Pereira, J; Junqueira, A C; Camargo, M E

    1996-01-01

    Immunoblotting with trypomastigote excreted-secreted antigens (TESA blot) of Trypanosoma cruzi was evaluated as a method for diagnosis of chronic and acute phases as well as congenital (in newborn children) Chagas' disease. Serum samples from acute-phase and congenital infections were considered to be positive when they reacted with ladder-like bands of 130- to 200-kDa antigens, recognized by immunoglobulin M (IgM) and IgG antibodies, while IgG from chronic-phase sera recognized a broad band antigen of 150 to 160 kDa. Nonchagasic sera were not reactive to these antigens. The study was carried out on 512 patients, 111 of whom were nonchagasic but included cases of leishmaniasis or other pathologies, and 401 chagasic patients. The latter group comprised 361 chronic cases, 36 acute cases, and 4 congenital cases in newborn children. Among the chronic cases, 256 were from areas in which T. cruzi is endemic but which differed widely in the pathogenic expression of T. cruzi infection and in parasitemia levels. These patients at the same time showed a broad range of low, medium, and high reactivity to conventional enzyme-linked immunosorbent assays and indirect immunofluorescence serotests for Chagas' disease. For these reasons they may better represent the universe of chagasic patients than would a sample of highly reactive sera obtained from chagasic patients in a single area endemic for T. cruzi. All acute and congenital cases showed positivity in the IgM and IgG TESA blots, while chronic cases were 100% positive for IgG antibodies. In nonchagasic sera, including 30 cases of visceral and muco-cutaneous leishmaniasis, the specificity index was 1.000, and no cross-reactions were observed. The TESA blot thus seems to be useful as a sensitive and specific diagnostic assay in cases of suspected acute or congenital T. cruzi infection and as a general confirmatory test for conventional Chagas' disease serology. PMID:8862574

  15. Information on Vinchucas and Chagas disease.

    NASA Astrophysics Data System (ADS)

    Schenone, H.

    1981-12-01

    Following a significant increase in the number of vinchucas observed at La Silla during the last summer, the Director-General of ESO asked Prof. Hugo Schenone, Director of the Department of Microbiology and Parasitology of the University of Chile to pay a visit to La Silla to investigate the situation. The following gives a summary of the resulting report.

  16. IL18 Gene Variants Influence the Susceptibility to Chagas Disease.

    PubMed

    Leon Rodriguez, Daniel A; Carmona, F David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-03-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

  17. Retracing Micro-Epidemics of Chagas Disease Using Epicenter Regression

    PubMed Central

    Levy, Michael Z.; Small, Dylan S.; Vilhena, Daril A.; Bowman, Natalie M.; Kawai, Vivian; Cornejo del Carpio, Juan G.; Cordova-Benzaquen, Eleazar; Gilman, Robert H.; Bern, Caryn; Plotkin, Joshua B.

    2011-01-01

    Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1 PMID:21935346

  18. Ergosterol biosynthesis and drug development for Chagas disease.

    PubMed

    Urbina, Julio A

    2009-07-01

    This article presents an overview of the currently available drugs nifurtimox (NFX) and benznidazole (BZN) used against Trypanosoma cruzi, the aetiological agent of Chagas disease; herein we discuss their limitations along with potential alternatives with a focus on ergosterol biosynthesis inhibitors (EBI). These compounds are currently the most advanced candidates for new anti-T. cruzi agents given that they block de novo production of 24-alkyl-sterols, which are essential for parasite survival and cannot be replaced by a host's own cholesterol. Among these compounds, new triazole derivatives that inhibit the parasite's C14alpha sterol demethylase are the most promising, as they have been shown to have curative activity in murine models of acute and chronic Chagas disease and are active against NFX and BZN-resistant T. cruzi strains; among this class of compounds, posaconazole (Schering-Plough Research Institute) and ravuconazole (Eisai Company) are poised for clinical trials in Chagas disease patients in the short term. Other T. cruzi-specific EBI, with in vitro and in vivo potency, include squalene synthase, lanosterol synthase and squalene epoxidase-inhibitors as well as compounds with dual mechanisms of action (ergosterol biosynthesis inhibition and free radical generation), but they are less advanced in their development process. The main putative advantages of EBI over currently available therapies include their higher potency and selectivity in both acute and chronic infections, activity against NFX and BZN-resistant T. cruzi strains, and much better tolerability and safety profiles. Limitations may include complexity and cost of manufacture of the new compounds. As for any new drug, such compounds will require extensive clinical testing before being introduced for clinical use, and the complexity of such studies, particularly in chronic patients, will be compounded by the current limitations in the verification of true parasitological cures for T. cruzi

  19. Resveratrol Reverses Functional Chagas Heart Disease in Mice.

    PubMed

    Vilar-Pereira, Glaucia; Carneiro, Vitor C; Mata-Santos, Hilton; Vicentino, Amanda R R; Ramos, Isalira P; Giarola, Naira L L; Feijó, Daniel F; Meyer-Fernandes, José R; Paula-Neto, Heitor A; Medei, Emiliano; Bozza, Marcelo T; Lannes-Vieira, Joseli; Paiva, Claudia N

    2016-10-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol's actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.

  20. Chagas disease diagnostic applications: present knowledge and future steps

    PubMed Central

    Balouz, Virginia; Agüero, Fernán; Buscaglia, Carlos A.

    2017-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery. PMID:28325368

  1. Resveratrol Reverses Functional Chagas Heart Disease in Mice

    PubMed Central

    Mata-Santos, Hilton; Vicentino, Amanda R. R.; Feijó, Daniel F.; Meyer-Fernandes, José R.; Paula-Neto, Heitor A.; Medei, Emiliano; Bozza, Marcelo T.; Lannes-Vieira, Joseli; Paiva, Claudia N.

    2016-01-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC. PMID:27788262

  2. Retracing micro-epidemics of Chagas disease using epicenter regression.

    PubMed

    Levy, Michael Z; Small, Dylan S; Vilhena, Daril A; Bowman, Natalie M; Kawai, Vivian; Cornejo del Carpio, Juan G; Cordova-Benzaquen, Eleazar; Gilman, Robert H; Bern, Caryn; Plotkin, Joshua B

    2011-09-01

    Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.

  3. Chagas' achalasia treated by a jejunal interposed segment.

    PubMed

    Dantas, A N; Carvalho, J L; Coelho, F K; Teixeira, A M; Lyra, L G; Rebouças, G; Didier, F V

    1975-01-01

    Resection of the achalasic area and replacement by a segment of jejunal loop, associated with vagotomy and pyloroplasty, has been performed in 21 patients. The majority of these patients had Chagas' disease, with a dilated esophagus wider than 7 cm. This surgical procedure offered symptomatic relief in 20 of our 21 cases. One patient died, but the death was not necessarily related to the operation. Although disphagia and regurgitation did not disappear entirely in all cases the decrease in severity of these symptoms was such to allow the few symptomatic patients to lead an entirely normal life after the operation.

  4. Diagnosis of Chagas' cardiomyopathy. Non-invasive techniques.

    PubMed Central

    Puigbó, J. J.; Valecillos, R.; Hirschhaut, E.; Giordano, H.; Boccalandro, I.; Suárez, C.; Aparicio, J. M.

    1977-01-01

    The natural history of Chagas' disease and its manifestations when the heart is involved are detailed clinically and pathologically. Three phases are recognized: the acute phase, lasting from 1-3 months, the latent phase, which may last from 10-20 years, and the chronic phase, which has the most serious manifestations. This phase is subdivided into three clinical stages. An analysis of the varied cardiac manifestations on 235 patients is included. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:412174

  5. Sylvatic focus of Chagas' disease in Oaxaca, Mexico.

    PubMed

    Rojas, J C; Malo, E A; Espinoza-Medinilla, E; Ondarza, R N

    1989-04-01

    During three field trips to the community of 'La Humedad', municipality of Santiago Jamiltepec, Oaxaca (a State in the southern part of the Mexican Republic), live specimens of Triatoma mazzottii Usinger (Hemiptera: Reduviidae) were found infected with Trypanosoma cruzi. The insects were captured in only one of the dwellings inspected in the locality, and in four small caves where bats and other mammals live. These findings suggest the need for further studies on the existence of a sylvatic cycle of Chagas' disease in Mexico, which has not yet been established.

  6. Tropical diseases encountered in Canada: 1. Chagas' disease.

    PubMed Central

    Schipper, H.; McClarty, B. M.; McRuer, K. E.; Nash, R. A.; Penney, C. J.

    1980-01-01

    Chagas' disease, or South American trypanosomiasis, is an endemic South American disease now being seen in Canada in both acute and chronic forms. It is characterized by an initial parasitemia that elicits a brisk immune response. Evidence is mounting that the debilitating chronic form, which is characterized by cardiac and visceral organ failure, results from antigenic cross-reactivity between the parasite and the human host, which generates an aberrant, destructive, cell-mediated immune response. Diagnosis, treatment and potential areas for investigation are discussed. PMID:6767543

  7. Electrocardiographic and echocardiographic abnormalities in Chagas disease: findings in residents of rural Bolivian communities hyperendemic for Chagas disease.

    PubMed

    Fernandez, Antonio B; Nunes, Maria Carmo P; Clark, Eva H; Samuels, Aaron; Menacho, Silvio; Gomez, Jesus; Bozo Gutierrez, Ricardo W; Crawford, Thomas C; Gilman, Robert H; Bern, Caryn

    2015-09-01

    Chagas disease is a neglected and preventable tropical disease that causes significant cardiac morbidity and mortality in Latin America. This study sought to describe cardiac findings among inhabitants of rural communities of the Bolivian Chaco. The cardiac study drew participants from an epidemiologic study in 7 indigenous Guarani communities. All infected participants 10 years or older were asked to undergo a brief physical examination and 12-lead electrocardiogram (ECG). A subset had echocardiograms. ECG and echocardiograms were read by 1 or more cardiologists. Of 1,137 residents 10 years or older, 753 (66.2%) had Trypanosoma cruzi infection. Cardiac evaluations were performed for 398 infected participants 10 years or older. Fifty-five participants (13.8%) had 1 or more ECG abnormalities suggestive of Chagas cardiomyopathy. The most frequent abnormalities were bundle branch blocks in 42 (11.3%), followed by rhythm disturbances or ventricular ectopy in 13 (3.3%), and atrioventricular blocks (AVB) in 10 participants (2.6%). The prevalence of any abnormality rose from 1.1% among those 10 to 19 years old to 14.2%, 17.3%, and 26.4% among those 20 to 39, 40 to 59, and older than 60 years, respectively. First-degree AVB was seen most frequently in participants 60 years or older, but the 4 patients with third-degree AVB were all under 50 years old. Eighteen and 2 participants had a left ventricular ejection fraction of 40% to 54% and <40%, respectively. An increasing number of ECG abnormalities was associated with progressively larger left ventricular end-diastolic dimensions and lower left ventricular ejection fraction. We found a high prevalence of ECG abnormalities and substantial evidence of Chagas cardiomyopathy. Programs to improve access to basic cardiac care (annual ECG, antiarrhythmics, pacemakers) could have an immediate impact on morbidity and mortality in these highly endemic communities. Copyright © 2015 World Heart Federation (Geneva). All rights reserved.

  8. When a misperception favors a tragedy: Carlos Chagas and the Nobel Prize of 1921.

    PubMed

    Bestetti, Reinaldo B; Couto, Lucélio B; Cardinalli-Neto, Augusto

    2013-11-20

    Carlos Chagas, the discoverer of Chagas' disease was nominated to the Nobel Prize in 1921, but none did win the prize in that year. As a leader of a young scientist team, he discovered all aspects of the new disease from 1909 to 1920. It is still obscure why he did not win the Nobel Prize in 1921. Chagas was discarded by Gunnar Hedrèn on April 16, 1921. Hedrèn should have made a written report about the details of his evaluation to the Nobel Committee. However, such a document has not been found in the Nobel Committee Archives. No evidence of detractions made by Brazilian scientists on Chagas was found. Since Chagas nomination was consistent with the Nobel Committee requirements, as seen in the presentation letter by until now unknown Cypriano de Freitas, it become clear that Chagas did not win the Nobel Prize exclusively because the Nobel Committee did not perceive the importance of his discovery. Thus, it would be fair a posthumous Nobel Prize of 1921 to Carlos Chagas. A diploma of the Nobel Prize, as precedent with Dogmack in 1947, would recognize the merit of the scientist who made the most complete medical discovery of all times.

  9. Chagas disease awareness among Latin American immigrants living in Los Angeles, California.

    PubMed

    Sanchez, Daniel R; Traina, Mahmoud I; Hernandez, Salvador; Smer, Aiman M; Khamag, Haneen; Meymandi, Sheba K

    2014-11-01

    Approximately 300,000 persons have Chagas disease in the United States, although almost all persons acquired the disease in Latin America. We examined awareness of Chagas disease among Latin American immigrants living in Los Angeles, California. We surveyed 2,677 persons (age range = 18-60 years) in Los Angeles who resided in Latin America for at least six months. A total of 62% of the participants recalled seeing triatomines in Latin America, and 27% of the participants reported triatomine bites at least once per year while living abroad. A total of 86% of the participants had never heard of Chagas disease. Of persons who had heard of Chagas disease, 81% believed that it was not serious. More than 95% of those who had heard of Chagas disease would want to be tested and treated. Most Latin American immigrants living in Los Angeles recalled exposure to vectors of Chagas disease. However, they have little knowledge of this disease. Increasing awareness of Chagas disease is needed in this high-risk population.

  10. Chagas Disease Awareness among Latin American Immigrants Living in Los Angeles, California

    PubMed Central

    Sanchez, Daniel R.; Traina, Mahmoud I.; Hernandez, Salvador; Smer, Aiman M.; Khamag, Haneen; Meymandi, Sheba K.

    2014-01-01

    Approximately 300,000 persons have Chagas disease in the United States, although almost all persons acquired the disease in Latin America. We examined awareness of Chagas disease among Latin American immigrants living in Los Angeles, California. We surveyed 2,677 persons (age range = 18–60 years) in Los Angeles who resided in Latin America for at least six months. A total of 62% of the participants recalled seeing triatomines in Latin America, and 27% of the participants reported triatomine bites at least once per year while living abroad. A total of 86% of the participants had never heard of Chagas disease. Of persons who had heard of Chagas disease, 81% believed that it was not serious. More than 95% of those who had heard of Chagas disease would want to be tested and treated. Most Latin American immigrants living in Los Angeles recalled exposure to vectors of Chagas disease. However, they have little knowledge of this disease. Increasing awareness of Chagas disease is needed in this high-risk population. PMID:25200261

  11. Risks of endemicity, morbidity and perspectives regarding the control of Chagas disease in the Amazon Region.

    PubMed

    Coura, José Rodrigues; Junqueira, Angela Cv

    2012-03-01

    Chagas disease, in the Amazon Region as elsewhere, can be considered an enzootic disease of wild animals or an anthropozoonosis, an accidental disease of humans that is acquired when humans penetrate a wild ecosystem or when wild triatomines invade human dwellings attracted by light or searching for human blood. The risk of endemic Chagas disease in the Amazon Region is associated with the following phenomena: (i) extensive deforestation associated with the displacement of wild mammals, which are the normal sources of blood for triatomines, (ii) adaptation of wild triatomines to human dwellings due to the need for a new source of blood for feeding and (iii) uncontrolled migration of human populations and domestic animals that are already infected with Trypanosoma cruzi from areas endemic for Chagas disease to the Amazon Region. Several outbreaks of severe acute cases of Chagas disease, as well as chronic cases, have been described in the Amazon Region. Control measures targeted to avoiding endemic Chagas disease in the Amazon Region should be the following: improving health education in communities, training public health officials and communities for vector and Chagas disease surveillance and training local physicians to recognise and treat acute and chronic cases of Chagas diseases as soon as possible.

  12. Mortality Related to Chagas Disease and HIV/AIDS Coinfection in Brazil

    PubMed Central

    Martins-Melo, Francisco Rogerlândio; Ramos, Alberto Novaes; Alencar, Carlos Henrique; Heukelbach, Jorg

    2012-01-01

    Chagas disease in patients with HIV infection represents a potentially serious event with high case fatality rates. This study describes epidemiological and clinical aspects of deaths related to Chagas disease and HIV/AIDS coinfection in Brazil, 1999–2007. We performed a descriptive study based on mortality data from the nationwide Mortality Information System. Of a total of about 9 million deaths, Chagas disease and HIV/AIDS were mentioned in the same death certificate in 74 cases. AIDS was an underlying cause in 77.0% (57) and Chagas disease in 17.6% (13). Males (51.4%), white skin color (50%), age group 40–49 years (29.7%), and residents in the Southeast region (75.7%) were most common. Mean age at death was significantly lower in the coinfected (47.1 years [SD ± 14.6]), as compared to Chagas disease deaths (64.1 years [SD ± 14.7], P < 0.001). Considering the lack of data on morbidity related to Chagas disease and AIDS coinfection, the use of mortality data may be an appropriate sentinel approach to monitor the occurrence of this association. Due to the epidemiological transition in Brazil, chronic Chagas disease and HIV/AIDS coinfection will be further complicated and require the development of evidence-based preventive control measures. PMID:22969814

  13. SEROPREVALENCE OF T. cruzi INFECTION IN BLOOD DONORS AND CHAGAS CARDIOMYOPATHY IN PATIENTS FROM THE COAL MINING REGION OF COAHUILA, MEXICO

    PubMed Central

    Martínez-Tovar, José Gerardo; Rebollar-Téllez, Eduardo A.; Salas, Ildefonso Fernández

    2014-01-01

    Context and Objective: Chagas disease is considered a worldwide emerging disease; it is endemic in Mexico and the state of Coahuila and is considered of little relevance. The objective of this study was to determine the seroprevalence of T. cruzi infection in blood donors and Chagas cardiomyopathy in patients from the coal mining region of Coahuila, Mexico. Design and Setting: Epidemiological, exploratory and prospective study in a general hospital during the period January to June 2011. Methods: We performed laboratory tests ELISA and indirect hemagglutination in three groups of individuals: 1) asymptomatic voluntary blood donors, 2) patients hospitalized in the cardiology department and 3) patients with dilated cardiomyopathy. Results: There were three levels of seroprevalence: 0.31% in asymptomatic individuals, 1.25% in cardiac patients and in patients with dilated cardiomyopathy in 21.14%. Conclusions: In spite of having detected autochthonous cases of Chagas disease, its importance to local public health remains to be established as well as the details of the dynamics of transmission so that the study is still in progress. PMID:24626421

  14. Squalene Synthase As a Target for Chagas Disease Therapeutics

    PubMed Central

    Chan, Hsiu-Chien; Li, Jikun; Zheng, Yingying; Huang, Chun-Hsiang; Ren, Feifei; Chen, Chun-Chi; Zhu, Zhen; Galizzi, Melina; Li, Zhu-Hong; Rodrigues-Poveda, Carlos A.; Gonzalez-Pacanowska, Dolores; Veiga-Santos, Phercyles; de Carvalho, Tecia Maria Ulisses; de Souza, Wanderley; Urbina, Julio A.; Wang, Andrew H.-J.; Docampo, Roberto; Li, Kai; Liu, Yi-Liang; Oldfield, Eric; Guo, Rey-Ting

    2014-01-01

    Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS) from a trypanosomatid parasite, Trypanosoma cruzi, the causative agent of Chagas disease. We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. We also show that the lipophilic bisphosphonates have low nM activity against T. cruzi and inhibit endogenous sterol biosynthesis and that E5700 acts synergistically with the azole drug, posaconazole. The determination of the structures of trypanosomatid and human SQS enzymes with a diverse set of inhibitors active in cells provides insights into SQS inhibition, of interest in the context of the development of drugs against Chagas disease. PMID:24789335

  15. Advances in Chagas disease drug development: 2009-2010

    PubMed Central

    Buckner, Frederick S.; Navabi, Nazlee

    2013-01-01

    Purpose of Review The need for better drugs to treat patients with Chagas disease remains urgent. This review summarizes the advancements in drug development over the past two years. Recent Findings Drug development efforts are almost exclusively occurring as preclinical research. The exceptions being Phase I safety studies for the cruzain inhibitor, K-777, and potential Phase II studies for the antifungal drug, posaconazole, and a prodrug of ravuconazole. Several recent laboratory investigations demonstrate anti-T. cruzi activity of novel small molecules in animal models. These include nonpeptidic cruzain inhibitors, novel inhibitors of the sterol 14α-demethylase enzyme, new compounds (arylimidamides) related to pentamidine, derivatives of nifurtimox, compounds using ruthenium complexes, and several natural products. The recent implementation of a high-throughput screen of >300,000 compounds against intracellular T. cruzi amastigotes done at the Broad Institute is an important development, yielding ~300 selective inhibitors, many of which may serve as leads for medicinal chemistry efforts. Summary Progress is slow, but recent advancements in both drug development and advocacy for research on neglected diseases are encouraging. Efforts to define a target product profile and to harmonize methodologies for testing drugs for Chagas disease are described herein. PMID:20885320

  16. Biological factors that impinge on Chagas disease drug development.

    PubMed

    Francisco, Amanda F; Jayawardhana, Shiromani; Lewis, Michael D; Taylor, Martin C; Kelly, John M

    2017-08-23

    Chagas disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi, and is the most important parasitic infection in Latin America. The current drugs, benznidazole and nifurtimox, are characterized by limited efficacy and toxic side-effects, and treatment failures are frequently observed. The urgent need for new therapeutic approaches is being met by a combined effort from the academic and commercial sectors, together with major input from not-for-profit drug development consortia. With the disappointing outcomes of recent clinical trials against chronic Chagas disease, it has become clear that an incomplete understanding of parasite biology and disease pathogenesis is impacting negatively on the development of more effective drugs. In addition, technical issues, including difficulties in establishing parasitological cure in both human patients and animal models, have greatly complicated the assessment of drug efficacy. Here, we outline the major questions that need to be addressed and discuss technical innovations that can be exploited to accelerate the drug development pipeline.

  17. Right ventricular endomyocardial biopsy in chronic Chagas' disease.

    PubMed

    Pereira Barretto, A C; Mady, C; Arteaga-Fernandez, E; Stolf, N; Lopes, E A; Higuchi, M L; Bellotti, G; Pileggi, F

    1986-02-01

    Right ventricular endomyocardial biopsy was used to study myocardial involvement in 42 patients with chronic Chagas' disease. Patients were divided into three groups: group A included 16 patients with normal ECGs, normal chest x-rays, and no symptoms; group B included 15 patients with abnormal ECGs and no cardiomegaly; and group C included 11 patients with abnormal ECGs and cardiomegaly. Biopsy fragments were analyzed for hypertrophy, degeneration of myocardial fibers, and interstitial changes such as edema, fibrosis, and inflammatory infiltrate. In group A, 5 of 16 biopsies exhibited none of the previously mentioned alterations. The frequencies pathologic alterations in groups A, B, and C, respectively, were: hypertrophy 31%, 66%, and 100%; degeneration 50%, 86%, and 81%; edema 43%, 46%, and 36%; fibrosis 12%, 33%, and 54%; and inflammatory infiltrate 37%, 66%, and 65%. These data suggest that myocardial lesions of Chagas' disease represent a continuous progression from fiber destruction to substitution by fibrosis, with compensatory hypertrophy; these data also suggest that cardiac dilatation occurs when the extent of fibrosis no longer allows for efficient compensatory hypertrophy.

  18. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis.

    PubMed

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html.

  19. Antigenuria in infants with acute and congenital Chagas' disease.

    PubMed Central

    Freilij, H L; Corral, R S; Katzin, A M; Grinstein, S

    1987-01-01

    Detection and partial characterization of Trypanosoma cruzi soluble antigens (SAg) in urine, as well as demonstration of parasite circulating antigens (CAg) in serum from pediatric patients with acute (10 patients) and congenital (10 patients) Chagas' disease, are reported. Classical techniques for parasite detection and antibody serology were also conducted in both groups. Samples collected before the onset of parasiticidal drug treatment were tested by an enzyme-linked immunosorbent assay for SAg and CAg demonstration. The control population consisted of 6 children with acute toxoplasmosis, 6 with cutaneous leishmaniasis, and 20 healthy individuals. Patients with acute cases were 100% positive for both SAg and CAg, whereas patients with congenital disease were 80% CAg positive and 100% SAg positive. Controls yielded negative results in all cases. Partial characterization of SAg from two patients with acute disease was performed by iodination, affinity chromatography, immunoprecipitation, and two-dimensional gel electrophoresis. Two different antigenic glycoproteins (80 kilodaltons, pI 6 to 6.5 and 55 kilodaltons, pI 6.5 to 7) were identified by these methods. Traditional serology and classical parasitologic tests failed, each in a different way, to provide an accurate diagnosis in the total of our patients. The enzyme-linked immunosorbent assay for SAg detection proved to be the most effective procedure for achieving early and precise proof of infection in acute and congenital cases of Chagas' disease. Images PMID:3098778

  20. [Composition and biological activity of triterpenes and steroids from Inonotus obliquus (chaga)].

    PubMed

    Nikitina, S A; Khabibrakhmanova, V R; Sysoeva, M A

    2016-05-01

    Data on the chemical composition of triterpenic and steroid compounds, isolated from the chaga mushroom grown in natural environment or in a synthetic culture have been summarized. Special attention has been paid to the biological activity of chaga mushroom extracts and these particular compounds against various cancer cell lines in vitro and in vivo. This analysis has demonstrated some common features in inhibition of growth of various cell lines by chaga mushroom components. In this context, the most active are triterpene compounds containing OH group at C-22 and a side chain unsaturated bond.

  1. High Interleukin 17 Expression Is Correlated With Better Cardiac Function in Human Chagas Disease

    PubMed Central

    Magalhães, Luisa M. D.; Villani, Fernanda N. A.; Nunes, Maria do Carmo P.; Gollob, Kenneth J.; Rocha, Manoel O. C.; Dutra, Walderez O.

    2013-01-01

    This study was designed to investigate whether the expression of interleukin 17 (IL-17) is associated with the indeterminate or cardiac clinical forms of Chagas disease and whether IL-17 expression can be correlated with patients' cardiac function. Our results demonstrated that cardiac Chagas patients have a lower intensity of expression of IL-17 by total lymphocytes and lower frequency of circulating T helper 17 cells. Correlative analysis showed that high IL-17 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Therefore, IL-17 expression can be a protective factor to prevent myocardial damage in human Chagas disease. PMID:23204182

  2. [Human American trypanosomiasis 90 years after its discovery by Carlos Chagas. II--Clinical aspects, physiopathology, diagnosis and treatment].

    PubMed

    Pays, J F

    1999-01-01

    Cardiac, neurologic, and gastrointestinal manifestations of Chagas Disease have been well documented, but underlying pathophysiologic mechanisms, especially of chronic myocarditis, remain unclear. In the last decades, vectorial and transfusional transmission has been diminished. However congenital forms, which were long unknown and are still poorly understood, and reactive forms, which occur in patients with acquired or induced immunodeficiency, have confounded conventional wisdom concerning the evolution of this disease. Several new diagnostic tools have been developed without replacing the traditional methods, e.g. the xenodiagnostic technique proposed by Brumpt. With regard to indirect diagnosis, further progress is needed to improve specificity and sensitivity as well as the discriminating ability of the numerous techniques now available. Recently several double-blind randomized trials showed that benznidazole may be useful for early stage disease in children under 12 years of age. Further study with long-term follow-up will be necessary to determine the value of generalizing treatment to all patients with Chagas disease regardless of age and disease stage. However the ideal trypanocidal agent has yet to be found. Although attempts to immunize animals have not been complete failures, current results are not adequate to hold forth hope of a vaccine for use in man within the foreseeable future.

  3. Gene-deleted live-attenuated Trypanosoma cruzi parasites as vaccines to protect against Chagas disease.

    PubMed

    Sánchez-Valdéz, Fernando J; Pérez Brandán, Cecilia; Ferreira, Arturo; Basombrío, Miguel Ángel

    2015-05-01

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. This illness is now becoming global, mainly due to congenital transmission, and so far, there are no prophylactic or therapeutic vaccines available to either prevent or treat Chagas disease. Therefore, different approaches aimed at identifying new protective immunogens are urgently needed. Live vaccines are likely to be more efficient in inducing protection, but safety issues linked with their use have been raised. The development of improved protozoan genetic manipulation tools and genomic and biological information has helped to increase the safety of live vaccines. These advances have generated a renewed interest in the use of genetically attenuated parasites as vaccines against Chagas disease. This review discusses the protective capacity of genetically attenuated parasite vaccines and the challenges and perspectives for the development of an effective whole-parasite Chagas disease vaccine.

  4. Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy.

    PubMed

    Morillo, Carlos A; Marin-Neto, Jose Antonio; Avezum, Alvaro; Sosa-Estani, Sergio; Rassi, Anis; Rosas, Fernando; Villena, Erick; Quiroz, Roberto; Bonilla, Rina; Britto, Constança; Guhl, Felipe; Velazquez, Elsa; Bonilla, Laura; Meeks, Brandi; Rao-Melacini, Purnima; Pogue, Janice; Mattos, Antonio; Lazdins, Janis; Rassi, Anis; Connolly, Stuart J; Yusuf, Salim

    2015-10-01

    The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven. We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event. The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction). Trypanocidal therapy with benznidazole in patients with

  5. IL18 Gene Variants Influence the Susceptibility to Chagas Disease

    PubMed Central

    Leon Rodriguez, Daniel A; Carmona, F. David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-01-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control. PMID:27027876

  6. On palms, bugs, and Chagas disease in the Americas.

    PubMed

    Abad-Franch, Fernando; Lima, Marli M; Sarquis, Otília; Gurgel-Gonçalves, Rodrigo; Sánchez-Martín, María; Calzada, José; Saldaña, Azael; Monteiro, Fernando A; Palomeque, Francisco S; Santos, Walter S; Angulo, Victor M; Esteban, Lyda; Dias, Fernando B S; Diotaiuti, Liléia; Bar, María Esther; Gottdenker, Nicole L

    2015-11-01

    Palms are ubiquitous across Neotropical landscapes, from pristine forests or savannahs to large cities. Although palms provide useful ecosystem services, they also offer suitable habitat for triatomines and for Trypanosoma cruzi mammalian hosts. Wild triatomines often invade houses by flying from nearby palms, potentially leading to new cases of human Chagas disease. Understanding and predicting triatomine-palm associations and palm infestation probabilities is important for enhancing Chagas disease prevention in areas where palm-associated vectors transmit T. cruzi. We present a comprehensive overview of palm infestation by triatomines in the Americas, combining a thorough reanalysis of our published and unpublished records with an in-depth review of the literature. We use site-occupancy modeling (SOM) to examine infestation in 3590 palms sampled with non-destructive methods, and standard statistics to describe and compare infestation in 2940 palms sampled by felling-and-dissection. Thirty-eight palm species (18 genera) have been reported to be infested by ∼39 triatomine species (10 genera) from the USA to Argentina. Overall infestation varied from 49.1-55.3% (SOM) to 62.6-66.1% (dissection), with important heterogeneities among sub-regions and particularly among palm species. Large palms with complex crowns (e.g., Attalea butyracea, Acrocomia aculeata) and some medium-crowned palms (e.g., Copernicia, Butia) are often infested; in slender, small-crowned palms (e.g., Euterpe) triatomines associate with vertebrate nests. Palm infestation tends to be higher in rural settings, but urban palms can also be infested. Most Rhodnius species are probably true palm specialists, whereas Psammolestes, Eratyrus, Cavernicola, Panstrongylus, Triatoma, Alberprosenia, and some Bolboderini seem to use palms opportunistically. Palms provide extensive habitat for enzootic T. cruzi cycles and a critical link between wild cycles and transmission to humans. Unless effective means to

  7. Acute Chagas' cardiopathy in a polar bear (Ursus maritimus) in Guadalajara, Mexico.

    PubMed

    Jaime-Andrade, J; Avila-Figueroa, D; Lozano-Kasten, F J; Hernández-Gutiérrez, R J; Magallón-Gastélum, E; Kasten-Monges, M J; Lopes, E R

    1997-01-01

    We report a 24-year-old female polar bear (Ursus maritimus) who contracted Chagas' infection at the Guadalajara Zoo, in Jalisco, México, and died of acute Chagas' carditis 15 days later. The histopathological findings are described, as well as the presence of triatomids (Triatoma longipennis Usinger) infected with Trypanosoma cruzi collected within 5 meters from the place where the animal lived in the city of Guadalajara.

  8. Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

    PubMed Central

    Abras, Alba; Gállego, Montserrat; Llovet, Teresa; Tebar, Silvia; Herrero, Mercedes; Berenguer, Pere; Ballart, Cristina; Martí, Carmen

    2016-01-01

    Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity with Leishmania spp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity with Leishmania species. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease. PMID:27053668

  9. Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

    PubMed

    Abras, Alba; Gállego, Montserrat; Llovet, Teresa; Tebar, Silvia; Herrero, Mercedes; Berenguer, Pere; Ballart, Cristina; Martí, Carmen; Muñoz, Carmen

    2016-06-01

    Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity with Leishmania spp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity with Leishmania species. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. [Current status of knowledge on Chagas' disease in the Mexican Republic].

    PubMed

    Tay, J; Schenone, H; Sánchez, J T; Robert, L

    1992-01-01

    A thorough review of the medical literature is made regarding Chagas' disease in Mexico and elsewhere since 1939, when Trypanosoma cruzi was first reported in this country, until 1991. The location where human cases, non human reservoirs and vectors have been found and are pointed out by means of tables and charts. Comments are made regarding the results reported. The importance of increasing the studies of Chagas' disease in Mexican Republic is stressed.

  11. Historical Perspectives on the Epidemiology of Human Chagas Disease in Texas and Recommendations for Enhanced Understanding of Clinical Chagas Disease in the Southern United States.

    PubMed

    Garcia, Melissa N; Woc-Colburn, Laila; Aguilar, David; Hotez, Peter J; Murray, Kristy O

    2015-11-01

    Chagas disease (Trypanosoma cruzi infection) has recently been identified as an important neglected tropical disease in the United States. Anecdotally referred to as a "silent killer," it leads to the development of potentially fatal cardiac disease in approximately 30% of those infected. In an attempt to better understand the potential of Chagas disease as a significant underlying cause of morbidity in Texas, we performed a historical literature review to assess disease burden. Human reports of triatomine bites and disease exposure were found to be prevalent in Texas. Despite current beliefs that Chagas disease is a recently emerging disease, we report historical references dating as far back as 1935. Both imported cases and autochthonous transmission contribute to the historical disease burden in Texas. We end by discussing the current knowledge gaps, and recommend priorities for advancing further epidemiologic studies and their policy implications.

  12. Historical Perspectives on the Epidemiology of Human Chagas Disease in Texas and Recommendations for Enhanced Understanding of Clinical Chagas Disease in the Southern United States

    PubMed Central

    Garcia, Melissa N.; Woc-Colburn, Laila; Aguilar, David; Hotez, Peter J.; Murray, Kristy O.

    2015-01-01

    Chagas disease (Trypanosoma cruzi infection) has recently been identified as an important neglected tropical disease in the United States. Anecdotally referred to as a “silent killer,” it leads to the development of potentially fatal cardiac disease in approximately 30% of those infected. In an attempt to better understand the potential of Chagas disease as a significant underlying cause of morbidity in Texas, we performed a historical literature review to assess disease burden. Human reports of triatomine bites and disease exposure were found to be prevalent in Texas. Despite current beliefs that Chagas disease is a recently emerging disease, we report historical references dating as far back as 1935. Both imported cases and autochthonous transmission contribute to the historical disease burden in Texas. We end by discussing the current knowledge gaps, and recommend priorities for advancing further epidemiologic studies and their policy implications. PMID:26540273

  13. Chagas disease and transfusion medicine: a perspective from non-endemic countries

    PubMed Central

    Angheben, Andrea; Boix, Lucia; Buonfrate, Dora; Gobbi, Federico; Bisoffi, Zeno; Pupella, Simonetta; Gandini, Giorgio; Aprili, Giuseppe

    2015-01-01

    In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their “historical” boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas. PMID:26513769

  14. Assessment of Rectocolonic Morphology and Function in Patients with Chagas Disease in Barcelona (Spain)

    PubMed Central

    Salvador, Fernando; Mego, Marianela; Sánchez-Montalvá, Adrián; Morís, María; Ramírez, Kathleen; Accarino, Ana; Malagelada, Juan-Ramon; Azpiroz, Fernando; Molina, Israel

    2015-01-01

    The aim of this study was to determine the relationship between colonic symptoms, radiological abnormalities, and anorectal dysfunction in patients with Chagas disease. We performed a cross-sectional study of untreated patients diagnosed with Chagas disease. All patients were evaluated clinically (by a questionnaire for colonic symptoms based on Rome III criteria) and underwent a barium enema and anorectal manometry. A control group of patients with functional constipation and without Chagas disease was included in the study. Overall, 69 patients were included in the study: 42 patients were asymptomatic and 27 patients had abdominal symptoms according to Rome III criteria. Anorectal manometry showed a higher proportion of abnormalities in symptomatic patients than in asymptomatic ones (73% versus 21%, respectively; P < 0.0001). Megarectum was detected in a similar proportion in the different subgroups regardless of the presence of symptoms or abnormalities in anorectal functions. Among non-Chagas disease patients with functional constipation, 90% had an abnormal anorectal manometry study. Patients with Chagas disease present a high proportion of constipation with dyssynergic defecation in anorectal manometry but a low prevalence of impaired rectoanal inhibitory reflex, although these abnormalities may be nonspecific for Chagas disease. The presence of megarectum is a nonspecific finding. PMID:25778503

  15. Chagas disease and transfusion medicine: a perspective from non-endemic countries.

    PubMed

    Angheben, Andrea; Boix, Lucia; Buonfrate, Dora; Gobbi, Federico; Bisoffi, Zeno; Pupella, Simonetta; Gandini, Giorgio; Aprili, Giuseppe

    2015-10-01

    In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their "historical" boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas.

  16. Molecular mechanisms of cardiac electromechanical remodeling during Chagas disease: Role of TNF and TGF-β.

    PubMed

    Cruz, Jader Santos; Machado, Fabiana Simão; Ropert, Catherine; Roman-Campos, Danilo

    2017-02-01

    Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-β) although other cytokines may be involved in the chagasic cardiomyopathy.

  17. Does my patient have chronic Chagas disease? Development and temporal validation of a diagnostic risk score.

    PubMed

    Brasil, Pedro Emmanuel Alvarenga Americano do; Xavier, Sergio Salles; Holanda, Marcelo Teixeira; Hasslocher-Moreno, Alejandro Marcel; Braga, José Ueleres

    2016-01-01

    With the globalization of Chagas disease, unexperienced health care providers may have difficulties in identifying which patients should be examined for this condition. This study aimed to develop and validate a diagnostic clinical prediction model for chronic Chagas disease. This diagnostic cohort study included consecutive volunteers suspected to have chronic Chagas disease. The clinical information was blindly compared to serological tests results, and a logistic regression model was fit and validated. The development cohort included 602 patients, and the validation cohort included 138 patients. The Chagas disease prevalence was 19.9%. Sex, age, referral from blood bank, history of living in a rural area, recognizing the kissing bug, systemic hypertension, number of siblings with Chagas disease, number of relatives with a history of stroke, ECG with low voltage, anterosuperior divisional block, pathologic Q wave, right bundle branch block, and any kind of extrasystole were included in the final model. Calibration and discrimination in the development and validation cohorts (ROC AUC 0.904 and 0.912, respectively) were good. Sensitivity and specificity analyses showed that specificity reaches at least 95% above the predicted 43% risk, while sensitivity is at least 95% below the predicted 7% risk. Net benefit decision curves favor the model across all thresholds. A nomogram and an online calculator (available at http://shiny.ipec.fiocruz.br:3838/pedrobrasil/chronic_chagas_disease_prediction/) were developed to aid in individual risk estimation.

  18. Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction.

    PubMed

    Ferreira, Ludmila Rodrigues Pinto; Ferreira, Frederico Moraes; Nakaya, Helder Imoto; Deng, Xutao; Cândido, Darlan da Silva; de Oliveira, Lea Campos; Billaud, Jean-Noel; Lanteri, Marion C; Rigaud, Vagner Oliveira-Carvalho; Seielstad, Mark; Kalil, Jorge; Fernandes, Fabio; Ribeiro, Antonio Luiz P; Sabino, Ester Cerdeira; Cunha-Neto, Edecio

    2017-02-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina.

    PubMed

    Moscatelli, Guillermo; Berenstein, Ada; Tarlovsky, Ana; Siniawski, Susana; Biancardi, Miguel; Ballering, Griselda; Moroni, Samanta; Schwarcz, Marta; Hernández, Susana; García-Bournissen, Facundo; Cozzi, Andrés Espejo; Freilij, Héctor; Altcheh, Jaime

    2015-08-01

    The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate.

  20. Chronic Chagas disease with advanced cardiac complications in Japan: Case report and literature review.

    PubMed

    Imai, Kazuo; Maeda, Takuya; Sayama, Yusuke; Osa, Morichika; Mikita, Kei; Kurane, Ichiro; Miyahira, Yasushi; Kawana, Akihiko; Miura, Sachio

    2015-10-01

    Due to the unprecedented recent increases in global migration, Chagas disease has become a global health threat and its epidemiology has drastically changed. Here we describe the first case in Japan of benznidazole treatment for chronic Chagas disease characterized by advanced cardiac complications. A 55-year-old Japanese-Brazilian woman who had previously presented with chronic heart failure was diagnosed as having Chagas disease and treated with benznidazole to prevent aggravation of her cardiac complications. However, benznidazole administration was stopped on day 56 due to severe drug-induced peripheral neuritis. Sixteen months later, her serologic test for Trypanosoma cruzi is still positive and she is being followed regularly by cardiology. Despite an estimated prevalence of over 4000 cases in Japan, only a few cases of Chagas disease have been reported. A Medline search revealed only 7 cases identified between 1995 and 2014 in Japan: in 6 cases, complications of chronic Chagas disease were apparent at the time of presentation, and sudden death occurred in 2 of these cases due to cardiac complications. This clinical case and literature review re-emphasize the urgent need to establish a surveillance network and improve the diagnostic methods and treatment framework for Chagas disease in Japan. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Chagas disease in the United States: a cause for concern in Louisiana?

    PubMed

    Diaz, James H

    2007-01-01

    Chagas disease, or American trypanosomiasis, is an arthropod-borne protozoan infectious disease, hyperendemic throughout Latin America, caused by Trypanosoma cruzi, and transmitted to man by reduviid or kissing bugs. Throughout the Americas, Chagas disease shares many life cycle features with malaria, including transmission of infectious stages by local arthropods, exacerbation or reactivation of subclinical infections by immunosuppression (particularly HIV/AIDS) and pregnancy, and both transplacental and transfusion-related transmission. Although most cases of Chagas disease in the United States (US) are imported, significant numbers of Latin American immigrants contribute to the US blood supply and donate cadaveric tissues and organs for human transplantation, thus increasing the risks of both transfusion and transplantation-transmitted Chagas disease from unscreened blood products and transplantable tissues and organs. In addition, the risks of local reduviid bug-transmitted autochthonous or indigenous Chagas disease are also increasing as more immigrant workers enter the displaced populations of the Gulf South, including Louisiana, to assist in rebuilding efforts after Hurricanes Katrina and Rita. Although screening donated blood products for malaria remains impractical, consideration should now be given to serologically screening all donated blood and organs for Chagas disease in the US, as in most countries of Latin America, especially in high risk areas of California and the southern US, including Louisiana.

  2. Risk factors for Chagas disease among pregnant women in El Salvador.

    PubMed

    Sasagawa, Emi; Aiga, Hirotsugu; Corado, Edith Y; Cuyuch, Blanca L; Hernández, Marta A; Guevara, Ana V; Romero, José E; Ramos, Hector M; Cedillos, Rafael A; Misago, Chizuru; Kita, Kiyoshi

    2015-03-01

    To determine the seroprevalence of Chagas disease among pregnant women and estimate the risk factors for Chagas disease during pregnancies. Community-based serological tests on Trypanosoma cruzi and structured interviews on socio-demographic and socio-economic status were conducted with pregnant women registered at three health centres in Sonsonate province, El Salvador. Of 797 pregnant women participating in the study, 29 (3.6%) were infected with Chagas disease. None had clinical symptoms. The results of bivariate analyses showed the significant association between seropositivity and maternal age ≥35 years, anaemia, illiteracy, having no formal school education and having knowledge on Chagas disease (P < 0.05). The results of multivariate analysis indicate that age ≥35 years and anaemia were significantly associated with being infected with Chagas disease among pregnant women (OR = 3.541 and 5.197, respectively). We recommend that the national Chagas disease control programme be better coordinated with the national maternal and child health programme to introduce blood screening for T. cruzi during antenatal visits. If financial constraint allows systematic blood screening to be only partially implemented, resources should be focused on pregnant women ≥35 years and women who have anaemia. © 2014 John Wiley & Sons Ltd.

  3. Chagas disease. What is known and what should be improved: a systemic review.

    PubMed

    Coura, José Rodrigues; Borges-Pereira, José

    2012-06-01

    This study consists of a broad review on what is known and what should be improved regarding knowledge of Chagas disease, not only through analysis on the main studies published on the topics discussed, but to a large extent based on experience of this subject, acquired over the past 50 years (1961-2011). Among the subjects covered, we highlight the pathogenesis and evolution of infection by Trypanosoma cruzi, drugs in use and new strategies for treating Chagas disease; the serological tests for the diagnosis and the controls of cure the infection; the regional variations in prevalence, morbidity and response to treatment of the disease; the importance of metacyclogenesis of T. cruzi in different species of triatomines and its capacity to transmit Chagas infection; the risks of adaptation of wild triatomines to human dwellings; the morbidity and need for a surveillance and control program for Chagas disease in the Amazon region and the need to prioritize initiatives for controlling Chagas disease in Latin America and Mexico and in non-endemic countries, which is today a major international dilemma. Finally, we raise the need for to create a new initiative for controlling Chagas disease in the Gran Chaco, which involves parts of Argentina, Bolivia and Paraguay.

  4. Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina

    PubMed Central

    Moscatelli, Guillermo; Berenstein, Ada; Tarlovsky, Ana; Siniawski, Susana; Biancardi, Miguel; Ballering, Griselda; Moroni, Samanta; Schwarcz, Marta; Hernández, Susana; García-Bournissen, Facundo; Cozzi, Andrés Espejo; Freilij, Héctor; Altcheh, Jaime

    2015-01-01

    The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate. PMID:26222020

  5. [Science as a profession: an interview with Carlos Chagas Filho].

    PubMed

    Chagas Filho, Carlos

    2012-06-01

    The editing of this interview focuses on aspects of the extensive professional career of Carlos Chagas Filho, who was the founder of the Instituto de Biofísica of the Universidade do Brasil, currently the Universidade Federal do Rio de Janeiro. It highlights the scientific and political role he played in Brazilian science and on the international scene. His memoirs include his experience at the Instituto Oswaldo Cruz, where he began his scientific training; the efforts to create the Laboratório de Física Biológica, succeeded by the Instituto de Biofísica; his work on the Conselho Nacional de Pesquisas and the Academia Brasileira de Ciências; the part he played at the United Nations Educational, Scientific and Cultural Organization; his time as president of the Pontifical Academy of Sciences of the Vatican, which led him to ponder questions about the relationship between science and religion.

  6. Agrochemicals against Malaria, Sleeping Sickness, Leishmaniasis and Chagas Disease

    PubMed Central

    Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

    2012-01-01

    In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively. PMID:23145187

  7. The Evolutionary Origin of Diversity in Chagas Disease Vectors.

    PubMed

    Justi, Silvia A; Galvão, Cleber

    2017-01-01

    Chagas disease is amongst the ten most important neglected tropical diseases but knowledge on the diversification of its vectors, Triatominae (Hemiptera: Reduviidae), is very scarce. Most Triatominae species occur in the Americas, and are all considered potential vectors. Despite its amazing ecological vignette, there are remarkably few evolutionary studies of the whole subfamily, and only one genome sequence has been published. The young age of the subfamily, coupled with the high number of independent lineages, are intriguing, yet the lack of genome-wide data makes it a challenge to infer the phylogenetic relationships within Triatominae. Here we synthesize what is known, and suggest the next steps towards a better understanding of how this important group of disease vectors came to be.

  8. Putting Infection Dynamics at the Heart of Chagas Disease.

    PubMed

    Lewis, Michael D; Kelly, John M

    2016-11-01

    In chronic Trypanosoma cruzi infections, parasite burden is controlled by effective, but nonsterilising immune responses. Infected cells are difficult to detect because they are scarce and focally distributed in multiple sites. However, advances in detection technologies have established a link between parasite persistence and the pathogenesis of Chagas heart disease. Long-term persistence likely involves episodic reinvasion as well as continuous infection, to an extent that varies between tissues. The primary reservoir sites in humans are not definitively known, but analysis of murine models has identified the gastrointestinal tract. Here, we highlight that quantitative, spatial, and temporal aspects of T. cruzi infection are central to a fuller understanding of the association between persistence, pathogenesis, and immunity, and for optimising treatment.

  9. Chagas Disease: Increased Parasitemia during Pregnancy Detected by Hemoculture

    PubMed Central

    da Rocha Siriano, Liliane; Luquetti, Alejandro Ostermayer; Avelar, Juliana Boaventura; Marra, Neusa Leal; de Castro, Ana Maria

    2011-01-01

    One hundred fifty-two Trypanosoma cruzi seropositive women were submitted to a single hemoculture; 101 were pregnant, and 51 were not pregnant. Seven tubes from each individual were harvested with liver infusion tryptose (LIT) medium and observed monthly until the fifth month. Hemocultures were positive in 50% (76 of 152) of the women. Results showed that the positivity was 29.4% (15 of 51) among non-pregnant women and 60.4% (61 of 101) in pregnant women (P < 0.05). In relation to gestational age, there were significant differences in positivity, with a higher proportion of women with positive hemocultures (20 of 25) before 21 weeks and lower after 30 weeks (10 of 21; P = 0.02). We conclude that pregnancy enhances the parasitemia in Chagas disease, with a higher effect early in pregnancy. PMID:21460012

  10. Membranous nephropathy PLA2R+ associated with Chagas disease

    PubMed Central

    Silva, Vanessa dos Santos; Viero, Rosa Marlene

    2015-01-01

    Chagas disease (CD) — a tropical parasitic disease caused by the protozoan Trypanosoma cruzi — is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure. PMID:26558244

  11. Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas disease.

    PubMed

    Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

    2012-01-01

    In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.

  12. Autochthonous Chagas disease in the southern United States: A case report of suspected residential and military exposures.

    PubMed

    Harris, N; Woc-Colburn, L; Gunter, S M; Gorchakov, R; Murray, K O; Rossmann, S; Garcia, M N

    2017-09-01

    Chagas disease is a parasitic infection that can result in a progressive dilated cardiomyopathy. Here, we present the epidemiologic details of a suspected locally acquired transmission case originating from the southern United States. This is the first published report of Chagas disease in a young, healthy United States veteran with repeat triatomine exposures in Arizona. Military personnel and Arizona residents should be aware of their Chagas disease transmission risks. © 2017 Blackwell Verlag GmbH.

  13. Epicuticular lipids induce aggregation in Chagas disease vectors.

    PubMed

    Figueiras, Alicia N Lorenzo; Girotti, Juan R; Mijailovsky, Sergio J; Juárez, M Patricia

    2009-01-27

    The triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Aggregation behavior plays an important role in their survival by facilitating the location of refuges and cohesion of aggregates, helping to keep them safely assembled into shelters during daylight time, when they are vulnerable to predators. There are evidences that aggregation is mediated by thigmotaxis, by volatile cues from their faeces, and by hexane-extractable contact chemoreceptive signals from their cuticle surface. The epicuticular lipids of Triatoma infestans include a complex mixture of hydrocarbons, free and esterified fatty acids, alcohols, and sterols. We analyzed the response of T. infestans fifth instar nymphs after exposure to different amounts either of total epicuticular lipid extracts or individual lipid fractions. Assays were performed in a circular arena, employing a binary choice test with filter papers acting as aggregation attractive sites; papers were either impregnated with a hexane-extract of the total lipids, or lipid fraction; or with the solvent. Insects were significantly aggregated around papers impregnated with the epicuticular lipid extracts. Among the lipid fractions separately tested, only the free fatty acid fraction promoted significant bug aggregation. We also investigated the response to different amounts of selected fatty acid components of this fraction; receptiveness varied with the fatty acid chain length. No response was elicited by hexadecanoic acid (C16:0), the major fatty acid component. Octadecanoic acid (C18:0) showed a significant assembling effect in the concentration range tested (0.1 to 2 insect equivalents). The very long chain hexacosanoic acid (C26:0) was significantly attractant at low doses (Chagas disease vector control. These data may be

  14. Epicuticular lipids induce aggregation in Chagas disease vectors

    PubMed Central

    Figueiras, Alicia N Lorenzo; Girotti, Juan R; Mijailovsky, Sergio J; Juárez, M Patricia

    2009-01-01

    Background The triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Aggregation behavior plays an important role in their survival by facilitating the location of refuges and cohesion of aggregates, helping to keep them safely assembled into shelters during daylight time, when they are vulnerable to predators. There are evidences that aggregation is mediated by thigmotaxis, by volatile cues from their faeces, and by hexane-extractable contact chemoreceptive signals from their cuticle surface. The epicuticular lipids of Triatoma infestans include a complex mixture of hydrocarbons, free and esterified fatty acids, alcohols, and sterols. Results We analyzed the response of T. infestans fifth instar nymphs after exposure to different amounts either of total epicuticular lipid extracts or individual lipid fractions. Assays were performed in a circular arena, employing a binary choice test with filter papers acting as aggregation attractive sites; papers were either impregnated with a hexane-extract of the total lipids, or lipid fraction; or with the solvent. Insects were significantly aggregated around papers impregnated with the epicuticular lipid extracts. Among the lipid fractions separately tested, only the free fatty acid fraction promoted significant bug aggregation. We also investigated the response to different amounts of selected fatty acid components of this fraction; receptiveness varied with the fatty acid chain length. No response was elicited by hexadecanoic acid (C16:0), the major fatty acid component. Octadecanoic acid (C18:0) showed a significant assembling effect in the concentration range tested (0.1 to 2 insect equivalents). The very long chain hexacosanoic acid (C26:0) was significantly attractant at low doses (≤ 1 equivalent), although a repellent effect was observed at higher doses. Conclusion The detection of contact aggregation pheromones has practical application in Chagas disease

  15. Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil.

    PubMed

    Carranza, Julio César; Valadares, Helder M S; D'Avila, Daniella A; Baptista, Rodrigo P; Moreno, Margoth; Galvão, Lúcia M C; Chiari, Egler; Sturm, Nancy R; Gontijo, Eliane D; Macedo, Andrea M; Zingales, Bianca

    2009-07-15

    The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, approximately 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex I) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T. cruzi II (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T. cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T. cruzi II cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite.

  16. Under-Expression of Chemosensory Genes in Domiciliary Bugs of the Chagas Disease Vector Triatoma brasiliensis

    PubMed Central

    Marchant, Axelle; Mougel, Florence; Jacquin-Joly, Emmanuelle; Costa, Jane; Almeida, Carlos Eduardo; Harry, Myriam

    2016-01-01

    Background In Latin America, the bloodsucking bugs Triatominae are vectors of Trypanosoma cruzi, the parasite that causes Chagas disease. Chemical elimination programs have been launched to control Chagas disease vectors. However, the disease persists because native vectors from sylvatic habitats are able to (re)colonize houses—a process called domiciliation. Triatoma brasiliensis is one example. Because the chemosensory system allows insects to interact with their environment and plays a key role in insect adaption, we conducted a descriptive and comparative study of the chemosensory transcriptome of T. brasiliensis samples from different ecotopes. Methodology/Principal Finding In a reference transcriptome built using de novo assembly, we found transcripts encoding 27 odorant-binding proteins (OBPs), 17 chemosensory proteins (CSPs), 3 odorant receptors (ORs), 5 transient receptor potential channel (TRPs), 1 sensory neuron membrane protein (SNMPs), 25 takeout proteins, 72 cytochrome P450s, 5 gluthatione S-transferases, and 49 cuticular proteins. Using protein phylogenies, we showed that most of the OBPs and CSPs for T. brasiliensis had well supported orthologs in the kissing bug Rhodnius prolixus. We also showed a higher number of these genes within the bloodsucking bugs and more generally within all Hemipterans compared to the other species in the super-order Paraneoptera. Using both DESeq2 and EdgeR software, we performed differential expression analyses between samples of T. brasiliensis, taking into account their environment (sylvatic, peridomiciliary and domiciliary) and sex. We also searched clusters of co-expressed contigs using HTSCluster. Among differentially expressed (DE) contigs, most were under-expressed in the chemosensory organs of the domiciliary bugs compared to the other samples and in females compared to males. We clearly identified DE genes that play a role in the chemosensory system. Conclusion/Significance Chemosensory genes could be good

  17. Under-Expression of Chemosensory Genes in Domiciliary Bugs of the Chagas Disease Vector Triatoma brasiliensis.

    PubMed

    Marchant, Axelle; Mougel, Florence; Jacquin-Joly, Emmanuelle; Costa, Jane; Almeida, Carlos Eduardo; Harry, Myriam

    2016-10-01

    In Latin America, the bloodsucking bugs Triatominae are vectors of Trypanosoma cruzi, the parasite that causes Chagas disease. Chemical elimination programs have been launched to control Chagas disease vectors. However, the disease persists because native vectors from sylvatic habitats are able to (re)colonize houses-a process called domiciliation. Triatoma brasiliensis is one example. Because the chemosensory system allows insects to interact with their environment and plays a key role in insect adaption, we conducted a descriptive and comparative study of the chemosensory transcriptome of T. brasiliensis samples from different ecotopes. In a reference transcriptome built using de novo assembly, we found transcripts encoding 27 odorant-binding proteins (OBPs), 17 chemosensory proteins (CSPs), 3 odorant receptors (ORs), 5 transient receptor potential channel (TRPs), 1 sensory neuron membrane protein (SNMPs), 25 takeout proteins, 72 cytochrome P450s, 5 gluthatione S-transferases, and 49 cuticular proteins. Using protein phylogenies, we showed that most of the OBPs and CSPs for T. brasiliensis had well supported orthologs in the kissing bug Rhodnius prolixus. We also showed a higher number of these genes within the bloodsucking bugs and more generally within all Hemipterans compared to the other species in the super-order Paraneoptera. Using both DESeq2 and EdgeR software, we performed differential expression analyses between samples of T. brasiliensis, taking into account their environment (sylvatic, peridomiciliary and domiciliary) and sex. We also searched clusters of co-expressed contigs using HTSCluster. Among differentially expressed (DE) contigs, most were under-expressed in the chemosensory organs of the domiciliary bugs compared to the other samples and in females compared to males. We clearly identified DE genes that play a role in the chemosensory system. Chemosensory genes could be good candidates for genes that contribute to adaptation or plastic

  18. "I Cannot Be Worried": Living with Chagas Disease in Tropical Bolivia

    PubMed Central

    2017-01-01

    Background Chagas disease (CD) profoundly affects the social and emotional dimensions of patients’ lives, and disproportionately impacts poor, marginalized populations in Latin America. Biomedical treatment for CD fails to reach up to 99% of the people affected, and in any case seldom addresses the emotional health or socioeconomic conditions of patients. This study examines patient strategies for coping with CD in the department of Santa Cruz, Bolivia. Methodology In this ethnographic study, semistructured interviews took place from March-June 2013 with 63 patients who had previously tested positive for CD. During the fieldwork period, participant observation was conducted and patient family members, providers, community members, and public health officials were consulted. Principal Findings Patients often experienced emotional distress when diagnosed with CD, yet were generally unable to find biomedical treatment. Respondents stressed the need to avoid powerful emotions which would worsen the impact of CD symptoms. To manage CD, patients embraced a calm state of mind, described in Spanish as tranquilidad, which partially empowered them to return to a normal existence. Conclusions In the perceived absence of biomedical treatment options, patients seek their own means of coping with CD diagnosis. Rather than fatalism or resignation, patients’ emphasis on maintaining calm and not worrying about CD represents a pragmatic strategy for restoring a sense of normalcy and control to their lives. Programs focused on treatment of CD should remain mindful of the emotional and social impact of the disease on patients. PMID:28099488

  19. A role for extracellular amastigotes in the immunopathology of Chagas disease.

    PubMed

    Scharfstein, J; Morrot, A

    1999-01-01

    In spite of the growing knowledge obtained about immune control of Trypanosoma cruzi infection, the mechanisms responsible for the variable clinico-pathological expression of Chagas disease remain unknown. In a twist from previous concepts, recent studies indicated that tissue parasitism is a pre-requisite for the development of chronic myocarditis. This fundamental concept, together with the realization that T. cruzi organisms consist of genetically heterogeneous clones, offers a new framework for studies of molecular pathogenesis. In the present article, we will discuss in general terms the possible implications of genetic variability of T. cruzi antigens and proteases to immunopathology. Peptide epitopes from a highly polymorphic subfamily of trans-sialidase (TS) antigens were recently identified as targets of killer T cell (CTL) responses, both in mice and humans. While some class I MHC restricted CTL recognize epitopes derived from amastigote-specific TS-related antigens (TSRA), others are targeted to peptide epitopes originating from trypomastigote-specific TSRA. A mechanistic hypothesis is proposed to explain how the functional activity and specificity of class I MHC restricted killer T cells may control the extent to which tissue are exposed to prematurely released amastigotes. Chronic immunopathology may be exacerbated due the progressive accumulation of amastigote-derived antigens and pro-inflammatory molecules (eg. GPI-mucins and kinin-releasing proteases) in dead macrophage bodies.

  20. "I Cannot Be Worried": Living with Chagas Disease in Tropical Bolivia.

    PubMed

    Forsyth, Colin J

    2017-01-01

    Chagas disease (CD) profoundly affects the social and emotional dimensions of patients' lives, and disproportionately impacts poor, marginalized populations in Latin America. Biomedical treatment for CD fails to reach up to 99% of the people affected, and in any case seldom addresses the emotional health or socioeconomic conditions of patients. This study examines patient strategies for coping with CD in the department of Santa Cruz, Bolivia. In this ethnographic study, semistructured interviews took place from March-June 2013 with 63 patients who had previously tested positive for CD. During the fieldwork period, participant observation was conducted and patient family members, providers, community members, and public health officials were consulted. Patients often experienced emotional distress when diagnosed with CD, yet were generally unable to find biomedical treatment. Respondents stressed the need to avoid powerful emotions which would worsen the impact of CD symptoms. To manage CD, patients embraced a calm state of mind, described in Spanish as tranquilidad, which partially empowered them to return to a normal existence. In the perceived absence of biomedical treatment options, patients seek their own means of coping with CD diagnosis. Rather than fatalism or resignation, patients' emphasis on maintaining calm and not worrying about CD represents a pragmatic strategy for restoring a sense of normalcy and control to their lives. Programs focused on treatment of CD should remain mindful of the emotional and social impact of the disease on patients.

  1. A Critical Assessment of Officially Reported Chagas Disease Surveillance Data in Mexico

    PubMed Central

    Shelly, Ellen M.; Acuna-Soto, Rodolfo; Ernst, Kacey C.; Sterling, Charles R.

    2016-01-01

    Objective Chagas disease, a disease caused by Trypanosoma cruzi, disproportionately affects poor people throughout Latin America. In Mexico, assessments of officially reported burden have not been previously reported. To evaluate discontinuity between surveillance data and data from other sources, we used data from the Mexican Ministry of Health to describe the distribution of reported Chagas disease over time in Mexico and compare it with estimates from the literature. Methods We summarized age and sex differences for Chagas cases and mortality for 1995–2013 and 1982–2010, respectively. We examined the spatial distribution of Chagas disease over time with respect to disease burden. We further compared officially reported figures with estimates from the literature. Results Among 6,494 officially reported cases, rates of Chagas disease were highest in adults aged 25–44 years (47.3%). Mortality was highest in adults aged ≥45 years (423/495, 85.5%). The data indicated increasing temporal trends for incidence and mortality. The greatest burden occurred in southern states, with increasing spatial distribution over time. Fewer than 900 cases and 40 deaths were officially reported annually, in contrast to estimates from the literature of approximately 69,000 new cases and 25,000 deaths annually. Conclusion While increasing trends in officially reported data have been observed, large discrepancies in case estimates compromise our understanding of Chagas disease epidemiology. Reported cases based on current practices are not enough to correctly assess the Chagas disease burden and spatial distribution in Mexico. Understanding the true epidemiology of this disease will lead to more focused and successful control and prevention strategies to decrease disease burden. PMID:26843671

  2. A Critical Assessment of Officially Reported Chagas Disease Surveillance Data in Mexico.

    PubMed

    Shelly, Ellen M; Acuna-Soto, Rodolfo; Ernst, Kacey C; Sterling, Charles R; Brown, Heidi E

    2016-01-01

    Chagas disease, a disease caused by Trypanosoma cruzi, disproportionately affects poor people throughout Latin America. In Mexico, assessments of officially reported burden have not been previously reported. To evaluate discontinuity between surveillance data and data from other sources, we used data from the Mexican Ministry of Health to describe the distribution of reported Chagas disease over time in Mexico and compare it with estimates from the literature. We summarized age and sex differences for Chagas cases and mortality for 1995-2013 and 1982-2010, respectively. We examined the spatial distribution of Chagas disease over time with respect to disease burden. We further compared officially reported figures with estimates from the literature. Among 6,494 officially reported cases, rates of Chagas disease were highest in adults aged 25-44 years (47.3%). Mortality was highest in adults aged ≥45 years (423/495, 85.5%). The data indicated increasing temporal trends for incidence and mortality. The greatest burden occurred in southern states, with increasing spatial distribution over time. Fewer than 900 cases and 40 deaths were officially reported annually, in contrast to estimates from the literature of approximately 69,000 new cases and 25,000 deaths annually. While increasing trends in officially reported data have been observed, large discrepancies in case estimates compromise our understanding of Chagas disease epidemiology. Reported cases based on current practices are not enough to correctly assess the Chagas disease burden and spatial distribution in Mexico. Understanding the true epidemiology of this disease will lead to more focused and successful control and prevention strategies to decrease disease burden.

  3. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis.

    PubMed

    Egüez, Karina E; Alonso-Padilla, Julio; Terán, Carolina; Chipana, Zenobia; García, Wilson; Torrico, Faustino; Gascon, Joaquim; Lozano-Beltran, Daniel-Franz; Pinazo, María-Jesús

    2017-04-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.). Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia). Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.

  4. A strategy for scaling up access to comprehensive care in adults with Chagas disease in endemic countries: The Bolivian Chagas Platform.

    PubMed

    Pinazo, Maria-Jesus; Pinto, Jimy; Ortiz, Lourdes; Sánchez, Jareth; García, Wilson; Saravia, Ruth; Cortez, Mirko-R; Moriana, Silvia; Grau, Enric; Lozano, Daniel; Gascon, Joaquim; Torrico, Faustino

    2017-08-01

    Bolivia has the highest prevalence of Chagas disease (CD) in the world (6.1%), with more than 607,186 people with Trypanosoma cruzi infection, most of them adults. In Bolivia CD has been declared a national priority. In 2009, the Chagas National Program (ChNP) had neither a protocol nor a clear directive for diagnosis and treatment of adults. Although programs had been implemented for congenital transmission and for acute cases, adults remained uncovered. Moreover, health professionals were not aware of treatment recommendations aimed at this population, and research on CD was limited; it was difficult to increase awareness of the disease, understand the challenges it presented, and adapt strategies to cope with it. Simultaneously, migratory flows that led Bolivian patients with CD to Spain and other European countries forced medical staff to look for solutions to an emerging problem. In this context, thanks to a Spanish international cooperation collaboration, the Bolivian platform for the comprehensive care of adults with CD was created in 2009. Based on the establishment of a vertical care system under the umbrella of ChNP general guidelines, six centres specialized in CD management were established in different epidemiological contexts. A common database, standardized clinical forms, a and a protocolized attention to adults patients, together with training activities for health professionals were essential for the model success. With the collaboration and knowledge transfer activities between endemic and non-endemic countries, the platform aims to provide care, train health professionals, and create the basis for a future expansion to the National Health System of a proven model of care for adults with CD. From 2010 to 2015, a total of 26,227 patients were attended by the Platform, 69% (18,316) were diagnosed with T. cruzi, 8,567 initiated anti-parasitic treatment, more than 1,616 health professionals were trained, and more than ten research projects developed

  5. A strategy for scaling up access to comprehensive care in adults with Chagas disease in endemic countries: The Bolivian Chagas Platform

    PubMed Central

    Pinto, Jimy; Ortiz, Lourdes; Sánchez, Jareth; García, Wilson; Saravia, Ruth; Cortez, Mirko-R; Moriana, Silvia; Grau, Enric; Lozano, Daniel; Gascon, Joaquim; Torrico, Faustino

    2017-01-01

    Background Bolivia has the highest prevalence of Chagas disease (CD) in the world (6.1%), with more than 607,186 people with Trypanosoma cruzi infection, most of them adults. In Bolivia CD has been declared a national priority. In 2009, the Chagas National Program (ChNP) had neither a protocol nor a clear directive for diagnosis and treatment of adults. Although programs had been implemented for congenital transmission and for acute cases, adults remained uncovered. Moreover, health professionals were not aware of treatment recommendations aimed at this population, and research on CD was limited; it was difficult to increase awareness of the disease, understand the challenges it presented, and adapt strategies to cope with it. Simultaneously, migratory flows that led Bolivian patients with CD to Spain and other European countries forced medical staff to look for solutions to an emerging problem. Intervention In this context, thanks to a Spanish international cooperation collaboration, the Bolivian platform for the comprehensive care of adults with CD was created in 2009. Based on the establishment of a vertical care system under the umbrella of ChNP general guidelines, six centres specialized in CD management were established in different epidemiological contexts. A common database, standardized clinical forms, a and a protocolized attention to adults patients, together with training activities for health professionals were essential for the model success. With the collaboration and knowledge transfer activities between endemic and non-endemic countries, the platform aims to provide care, train health professionals, and create the basis for a future expansion to the National Health System of a proven model of care for adults with CD. Results From 2010 to 2015, a total of 26,227 patients were attended by the Platform, 69% (18,316) were diagnosed with T. cruzi, 8,567 initiated anti-parasitic treatment, more than 1,616 health professionals were trained, and more than

  6. SQ109, a new drug lead for Chagas disease.

    PubMed

    Veiga-Santos, Phercyles; Li, Kai; Lameira, Lilianne; de Carvalho, Tecia Maria Ulisses; Huang, Guozhong; Galizzi, Melina; Shang, Na; Li, Qian; Gonzalez-Pacanowska, Dolores; Hernandez-Rodriguez, Vanessa; Benaim, Gustavo; Guo, Rey-Ting; Urbina, Julio A; Docampo, Roberto; de Souza, Wanderley; Oldfield, Eric

    2015-04-01

    We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug

  7. Population Pharmacokinetics of Benznidazole in Adult Patients with Chagas Disease

    PubMed Central

    Aldasoro, E.; Guerrero, L.; Posada, E.; Serret, N.; Mejía, T.; Urbina, J. A.; Gascón, J.

    2015-01-01

    The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h; V/F, 89.6 liters; and Ka, 1.15 h−1). No covariates were found to be significant for CL/F and V/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011

  8. Esophageal body motility in achalasia and Chagas' disease.

    PubMed

    Abrahão, L J; de Oliveira Lemme, E M

    2011-07-01

    Previous studies have correlated esophageal body motility findings in idiopathic (IdAc) achalasia and achalasia secondary to Chagas' disease (ChAc) with degree of megaesophagus. The aim of this study was to compare esophageal body manometric data in patients with IdAc and achalasia secondary to Chagas' disease and correlate it with the degree of megaesophagus and symptom duration. One hundred nontreated patients with achalasia, 79% IdAc and 21% secondary to ChAc were compared with regards to age of presentation, duration of symptoms, amplitude and duration of simultaneous contractions, frequency of failed contractions, and degree of megaesophagus. Seventy-one percent of patients were classified as nonadvanced megaesophagus (60 [76%] with IdAc and 11 [52%] with ChAc) and 29% as advanced megaesophagus (19 [24%] with IdAc and 10 [48%] with ChAc, P= 0.04). In IdAc but not in ChAc, the symptom duration was significantly longer in advanced megaesophagus (A) compared with nonadvanced megaesophagus (NA) (34.8 ± 6.3 months vs. 95.4 ± 22.2 months, P= 0.001). There was no difference in amplitude and duration of simultaneous contractions in both achalasia groups (P > 0.05). Duration of contractions were longer in IdAc compared with ChAc in (NA) (P < 0.05), but not in (A). In IdAc but not in ChAc the amplitude of simultaneous contractions decreased with increased esophageal dilatation (P < 0.05). In ChAc but not in IdAC, the duration of contractions increased with esophageal dilatation (P < 0.05). Failed contractions were more frequent in ChAc group (28.6%) than in IdAc (10% -P= 0.03). Patients with ChAc have a higher prevalence of advanced megaesophagus compared with IdAc at diagnosis. In IdAc there was a strong correlation between advanced megaesophagus and longer symptom duration, suggesting disease progression over time, not observed in ChAc in which a more extensive denervation occurs earlier in the disease process.

  9. SQ109, a New Drug Lead for Chagas Disease

    PubMed Central

    Veiga-Santos, Phercyles; Li, Kai; Lameira, Lilianne; de Carvalho, Tecia Maria Ulisses; Huang, Guozhong; Galizzi, Melina; Shang, Na; Li, Qian; Gonzalez-Pacanowska, Dolores; Hernandez-Rodriguez, Vanessa; Benaim, Gustavo; Guo, Rey-Ting; Urbina, Julio A.; Docampo, Roberto; de Souza, Wanderley

    2015-01-01

    We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug

  10. Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease

    PubMed Central

    Alarcón de Noya, B.; Araujo-Jorge, T.; Grijalva, M. J.; Guhl, F.; López, M. C.; Ramsey, J. M.; Ribeiro, I.; Schijman, A. G.; Sosa-Estani, S.; Torrico, F.; Gascon, J.

    2014-01-01

    Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients. PMID:24247135

  11. Controlled but not cured: Structural processes and explanatory models of Chagas disease in tropical Bolivia.

    PubMed

    Forsyth, Colin

    2015-11-01

    Dressler (2001:456) characterizes medical anthropology as divided between two poles: the constructivist, which focuses on the "meaning and significance that events have for people," and the structuralist, which emphasizes socioeconomic processes and relationships. This study synthesizes structuralist and constructivist perspectives by investigating how structural processes impact explanatory models of Chagas disease in a highly endemic area. The research took place from March-June 2013 through the Centro Medico Humberto Parra, a non-profit clinic servicing low income populations in Palacios, Bolivia and surrounding communities. Semistructured interviews (n = 68) and consensus analysis questionnaires (n = 48) were administered to people dealing with Chagas disease. In the interview narratives, respondents link Chagas disease with experiences of marginalization and rural poverty, and describe multilayered impediments to accessing treatment. They often view the disease as incurable, but this reflects inconsistent messages from the biomedical system. The consensus analysis results show strong agreement on knowledge of the vector, ethnomedical treatment, and structural factors related to Chagas disease. In interpreting Chagas disease, respondents account for the structural factors which place them at risk and impede access to care.

  12. Socio-cultural aspects of Chagas disease: a systematic review of qualitative research.

    PubMed

    Ventura-Garcia, Laia; Roura, Maria; Pell, Christopher; Posada, Elisabeth; Gascón, Joaquim; Aldasoro, Edelweis; Muñoz, Jose; Pool, Robert

    2013-01-01

    Globally, more than 10 million people are infected with Trypanosoma cruzi, which causes about 20 000 annual deaths. Although Chagas disease is endemic to certain regions of Latin America, migratory flows have enabled its expansion into areas where it was previously unknown. Economic, social and cultural factors play a significant role in its presence and perpetuation. This systematic review aims to provide a comprehensive overview of qualitative research on Chagas disease, both in endemic and non-endemic countries. Searches were carried out in ten databases, and the bibliographies of retrieved studies were examined. Data from thirty-three identified studies were extracted, and findings were analyzed and synthesized along key themes. Themes identified for endemic countries included: socio-structural determinants of Chagas disease; health practices; biomedical conceptions of Chagas disease; patient's experience; and institutional strategies adopted. Concerning non-endemic countries, identified issues related to access to health services and health seeking. The emergence and perpetuation of Chagas disease depends largely on socio-cultural aspects influencing health. As most interventions do not address the clinical, environmental, social and cultural aspects jointly, an explicitly multidimensional approach, incorporating the experiences of those affected is a potential tool for the development of long-term successful programs. Further research is needed to evaluate this approach.

  13. Socio-Cultural Aspects of Chagas Disease: A Systematic Review of Qualitative Research

    PubMed Central

    Ventura-Garcia, Laia; Roura, Maria; Pell, Christopher; Posada, Elisabeth; Gascón, Joaquim; Aldasoro, Edelweis; Muñoz, Jose; Pool, Robert

    2013-01-01

    Background Globally, more than 10 million people are infected with Trypanosoma cruzi, which causes about 20 000 annual deaths. Although Chagas disease is endemic to certain regions of Latin America, migratory flows have enabled its expansion into areas where it was previously unknown. Economic, social and cultural factors play a significant role in its presence and perpetuation. This systematic review aims to provide a comprehensive overview of qualitative research on Chagas disease, both in endemic and non-endemic countries. Methodology/Principal Findings Searches were carried out in ten databases, and the bibliographies of retrieved studies were examined. Data from thirty-three identified studies were extracted, and findings were analyzed and synthesized along key themes. Themes identified for endemic countries included: socio-structural determinants of Chagas disease; health practices; biomedical conceptions of Chagas disease; patient's experience; and institutional strategies adopted. Concerning non-endemic countries, identified issues related to access to health services and health seeking. Conclusions The emergence and perpetuation of Chagas disease depends largely on socio-cultural aspects influencing health. As most interventions do not address the clinical, environmental, social and cultural aspects jointly, an explicitly multidimensional approach, incorporating the experiences of those affected is a potential tool for the development of long-term successful programs. Further research is needed to evaluate this approach. PMID:24069473

  14. Translational challenges of animal models in Chagas disease drug development: a review

    PubMed Central

    Chatelain, Eric; Konar, Nandini

    2015-01-01

    Chagas disease, or American trypanosomiasis, caused by Trypanosoma cruzi parasite infection is endemic in Latin America and presents an increasing clinical challenge due to migrating populations. Despite being first identified over a century ago, only two drugs are available for its treatment, and recent outcomes from the first clinical trials in 40 years were lackluster. There is a critical need to develop new drugs to treat Chagas disease. This requires a better understanding of the progression of parasite infection, and standardization of animal models designed for Chagas disease drug discovery. Such measures would improve comparison of generated data and the predictability of test hypotheses and models designed for translation to human disease. Existing animal models address both disease pathology and treatment efficacy. Available models have limited predictive value for the preclinical evaluation of novel therapies and need to more confidently predict the efficacy of new drug candidates in clinical trials. This review highlights the overall lack of standardized methodology and assessment tools, which has hampered the development of efficacious compounds to treat Chagas disease. We provide an overview of animal models for Chagas disease, and propose steps that could be undertaken to reduce variability and improve predictability of drug candidate efficacy. New technological developments and tools may contribute to a much needed boost in the drug discovery process. PMID:26316715

  15. Four TDR diseases can be "eliminated". 3. Chagas success in Brazil and Colombia.

    PubMed

    1996-03-01

    Recent figures published by Brazil's Chagas disease control program indicate that the disease will soon be eradicated in Brazil. For example, in 1982, 711 Brazilian municipalities reported infestation with Triatoma infestans, the most important domiciliary vector of Chagas disease. However, in 1993, only 83 municipalities reported any infestation. Disease transmission through blood transfusion in the country has also been dramatically reduced. In 1982, 6.5% of blood donations in Brazil were infected with Trypanosoma cruzi, but by 1992 the level of infection had fallen to only 1%. 4.2% of infected individuals aged 7-14 years converted serologically in 1980, compared to only 0.15% in 1994, indicating a 95% decline in the incidence of newly infected cases in that age group. Furthermore, 84,000 infected triatomine insects were captured in households in endemic areas in 1983, far more than the 2500 collected throughout the entire country in 1993. The complete interruption of Chagas disease transmission in Brazil is expected in 1998. Work is also progressing with a control plan by countries in which the disease is transmitted by insects with an extradomiciliary life cycle. Colombia is the 15th of the 21 Chagas-endemic countries in Latin America where, due to blood bank screening, the transfusional transmission of Chagas disease has been interrupted.

  16. Purified Excreted-Secreted Antigens from Trypanosoma cruzi Trypomastigotes as Tools for Diagnosis of Chagas' Disease

    PubMed Central

    Berrizbeitia, Mariolga; Ndao, Momar; Bubis, José; Gottschalk, Marcelo; Aché, Alberto; Lacouture, Sonia; Medina, Mehudy; Ward, Brian J.

    2006-01-01

    There is currently no “gold standard” test for the diagnosis of late-stage Chagas' disease. As a result, protection of the blood supply in areas where Chagas' disease is endemic remains problematic. A panel of 709 serum samples from subjects with confirmed Chagas' disease (n = 195), healthy controls (n = 400), and patients with other parasitic diseases (n = 114) was used to assess enzyme-linked immunosorbent assays (ELISAs) based on a concentrated extract of excretory-secretory antigens from either Brazil or Tulahuen strain Trypanosoma cruzi trypomastigotes (total trypomastigote excretory-secretory antigens [TESAs]). The total TESA-based assays had excellent overall sensitivity (100%) and specificity (>94%), except for cross-reactivity with Leishmania-infected sera. In an attempt to increase the specificity of the assay, immunoaffinity chromatography was used to purify the TESA proteins (TESAIA proteins). By Western blotting, a series of polypeptide bands with molecular masses ranging from 60 to 220 kDa were recognized by pooled sera positive for Chagas' disease. An ELISA based on TESAIA proteins had a slightly lower sensitivity (98.6%) but an improved specificity (100%) compared to the sensitivity and specificity of the total TESA protein-based ELISAs. A 60-kDa polypeptide was identified as a major contributor to the cross-reactivity with Leishmania. These data suggest the need for field validation studies of TESA- and TESAIA-based assays in regions where Chagas' disease is endemic. PMID:16455872

  17. What Do We Know About Chagas Disease in the United States?

    PubMed

    Montgomery, Susan P; Parise, Monica E; Dotson, Ellen M; Bialek, Stephanie R

    2016-12-07

    Chagas disease, caused by the parasite Trypanosoma cruzi, affects more than 5 million people worldwide leading to serious heart and gastrointestinal disease in a proportion of chronically infected patients. Important modes of transmission include vector-borne, congenital, and via blood transfusion or organ transplant from an infected donor. Vector-borne transmission of Chagas disease occurs in the Americas, including the southern half of North America, where the specific vector insects (triatomines), T. cruzi, and infected reservoir mammalian hosts are found. In the United States, there are estimated to be at least 300,000 cases of chronic Chagas disease among people originally from countries of Latin America where Chagas disease is endemic. Fewer than 30 cases of locally acquired infection have been documented in the United States, although a sylvatic transmission cycle has been known to exist in this country for at least a century. Studies defining risks for locally acquired infection and effective prevention strategies are needed to help prevent domestic transmission of T. cruzi To help address Chagas disease in the United States, improved health-care provider awareness and knowledge, better tools for screening and diagnosing patients, and wider availability of treatment drugs are needed. © The American Society of Tropical Medicine and Hygiene.

  18. Chagas Disease Knowledge and Risk Behaviors of the Homeless Population in Houston, TX.

    PubMed

    Ingber, Alexandra; Garcia, Melissa N; Leon, Juan; Murray, Kristy O

    2017-05-31

    Chagas disease is a parasitic infection, caused by Trypanosoma cruzi, endemic in Latin America. Sylvatic T. cruzi-infected triatomine vectors are present in rural and urban areas in the southern USA and may transmit T. cruzi infection to at-risk populations, such as homeless individuals. Our study aimed to evaluate Chagas disease knowledge and behaviors potentially associated with transmission risk of Chagas disease among Houston, Texas' homeless population by performing interviews with 212 homeless individuals. The majority of the 212 surveyed homeless individuals were male (79%), African-American (43%), American-born individuals (96%). About 30% of the individuals reported having seen triatomines in Houston, and 25% had evidence of blood-borne transmission risk (IV drug use and/or unregulated tattoos). The median total time homeless was significantly associated with recognition of the triatomine vector. Our survey responses indicate that the homeless populations may exhibit potential risks for Chagas disease, due to increased vector exposure, and participation in blood-borne pathogen risk behaviors. Our findings warrant additional research to quantify the prevalence of Chagas disease among homeless populations.

  19. Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

    PubMed

    Halperin, Anthony; Pajuelo, Monica; Tornheim, Jeffrey A; Vu, Nancy; Carnero, Andrés M; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Camacho, Marilyn; Justiniano, Juan; Colanzi, Rony; Bowman, Natalie M; Morris, Tiffany; MacDougall, Hamish; Bern, Caryn; Moore, Steven T; Gilman, Robert H

    2016-06-01

    Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients. © The American Society of Tropical Medicine and Hygiene.

  20. [Study of the factors determining an unexpected occurrecne of Chagas cardiomyopathy in Sucre, Bolivia].

    PubMed

    De Muynck, A; Muñoz, R; Manirankunda, L; Pizzaro, J C; Gutierrez, J

    1998-01-01

    The purpose of this case-control study carried out between February 1, 1994 and December 22, 1994 at the "Instituto de Gastroenterologia Boliviano-Japonés" in Sucre, Bolivia was to determine risk factors for chronic Chagas cardiomyopathy in adult patients with positive serological tests for Trypanosoma cruzi. A total of 196 subjects were included. Inclusion criteria were positive serological tests for Trypanosoma cruzi, residence in the city of Sucre, Bolivia for at least 3 months, and age over 14 years. There were 62 cases presenting electrocardiographic findings consistent with Chagas cardiomyopathy and 134 controls presenting normal electrocardiographic findings. Both cases and controls underwent a standardized protocol including physical examination and laboratory tests. Interviews were set up to evaluate personal and familial history of Chagas disease, socioeconomic status, and presence of Triatoma infestans in the home. Bivariate analysis of data indicated that Chagas cardiomyopathy was associated with the following risk factors: heart rate (p < 0.05), fecaloma (p < 0.05), occupation requiring strenuous physical exertion (p < 0.001), proximity with domestic animals (p < 0.005), especially pigs (p < 0.005), dwelling features including outbuildings, more than 2 bedrooms, and inside ceilings (p < 0.001). Multivariate analysis revealed the following risk factors: occupation requiring strenuous physical exertion (p < 0.005), a yard around the house (p < 0.05), and inside ceilings (p < 0.05). The results of this study show that prevention of chronic Chagas cardiomyopathy in Sucre, Bolivia will depend on improvement of living conditions.

  1. Towards a paradigm shift in the treatment of chronic Chagas disease.

    PubMed

    Viotti, R; Alarcón de Noya, B; Araujo-Jorge, T; Grijalva, M J; Guhl, F; López, M C; Ramsey, J M; Ribeiro, I; Schijman, A G; Sosa-Estani, S; Torrico, F; Gascon, J

    2014-01-01

    Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.

  2. Chagas disease in Australia and New Zealand: risks and needs for public health interventions.

    PubMed

    Jackson, Yves; Pinto, Angie; Pett, Sarah

    2014-02-01

    International migration has changed the global distribution of Chagas disease, with the emerging importance of non-endemic regions. We aimed at better documenting the Australia and New Zealand risk of Chagas disease and needs for interventions. We reviewed Chagas disease-related evidences, policies and practices in Australia and New Zealand and calculated the estimated prevalence. Australia hosts a rapidly growing population at risk and had 1928 infected residents in 2011; New Zealand had 98 in 2006. These figures underestimate the real situation, as they do not consider non-permanent residents. The only existing policy in both countries is the identification of blood donors with a history of or a risk of infection via questionnaire. There is no programme of detection and care of patients. The lifetime economic burden of disease for society is potentially very high. Chagas disease is an emerging health risk with potential high human and economic costs in Australia and New Zealand in the absence of public health attention. Implementing strategies to screen high-risk groups and prevent transmission should be considered. Moreover, migration between the Western Pacific and Chagas endemic regions and the presence of vectors means this risk applies in the whole region. © 2013 John Wiley & Sons Ltd.

  3. [Seroprevalence of Chagas disease in Aguarico canton in the Ecuadorian Amazon].

    PubMed

    Amunárriz, Manuel; Quito, Segundo; Tandazo, Víctor; López, Mayra

    2010-07-01

    Determine the current seroprevalence of Chagas disease in the population of Aguarico canton, and compare the findings with data from other epidemiological studies. From September 2008 to October 2009, 2 033 serum samples were collected from 36.6% of the total population in Aguarico canton. The Chagatest recombinant ELISA v.3.0 was used to determine positivity to Chagas disease. Cases that tested positive were confirmed by indirect hemagglutination and ELISA. Of the 2 033 serum samples obtained, 73 tested positive for Chagas disease (3.6%). Seroprevalence in communities with positive cases ranged from 1.4% to 13.3%, with 60.3% of the positive cases found in females. These findings are similar to the 1990 comparison studies. The data obtained confirm the existence of an indigenous focus of Chagas disease in the Ecuadorian Amazon, with a percentage higher that the average for the Amazon region. No acute clinical cases or chronic pathologies were detected. Implementation of a culturally appropriate Chagas control program for the region is urgently needed.

  4. Triatominae Biochemistry Goes to School: Evaluation of a Novel Tool for Teaching Basic Biochemical Concepts of Chagas Disease Vectors

    ERIC Educational Resources Information Center

    Cunha, Leonardo Rodrigues; de Oliveria Cudischevitch, Cecília; Carneiro, Alan Brito; Macedo, Gustavo Bartholomeu; Lannes, Denise; da Silva-Neto, Mário Alberto Cardoso

    2014-01-01

    We evaluate a new approach to teaching the basic biochemistry mechanisms that regulate the biology of Triatominae, major vectors of "Trypanosoma cruzi," the causative agent of Chagas disease. We have designed and used a comic book, "Carlos Chagas: 100 years after a hero's discovery" containing scientific information obtained by…

  5. Triatominae Biochemistry Goes to School: Evaluation of a Novel Tool for Teaching Basic Biochemical Concepts of Chagas Disease Vectors

    ERIC Educational Resources Information Center

    Cunha, Leonardo Rodrigues; de Oliveria Cudischevitch, Cecília; Carneiro, Alan Brito; Macedo, Gustavo Bartholomeu; Lannes, Denise; da Silva-Neto, Mário Alberto Cardoso

    2014-01-01

    We evaluate a new approach to teaching the basic biochemistry mechanisms that regulate the biology of Triatominae, major vectors of "Trypanosoma cruzi," the causative agent of Chagas disease. We have designed and used a comic book, "Carlos Chagas: 100 years after a hero's discovery" containing scientific information obtained by…

  6. Circulating serum markers and QRS scar score in Chagas cardiomyopathy.

    PubMed

    Clark, Eva H; Marks, Morgan A; Gilman, Robert H; Fernandez, Antonio B; Crawford, Thomas C; Samuels, Aaron M; Hidron, Alicia I; Galdos-Cardenas, Gerson; Menacho-Mendez, Gilberto Silvio; Bozo-Gutierrez, Ricardo W; Martin, Diana L; Bern, Caryn

    2015-01-01

    Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies. © The American Society of Tropical Medicine and Hygiene.

  7. Direct micromethod for diagnosis of acute and congenital Chagas' disease.

    PubMed Central

    Feilij, H; Muller, L; Gonzalez Cappa, S M

    1983-01-01

    A microhematocrit concentration method (MH) for immediate diagnosis of Chagas' disease during the acute stage or in congenital cases was standardized. Parasitemia as low as 1,000 parasites per ml was detected, after centrifugation of six 50-microliters capillary tubes, by 10-min microscopic observation of each buffy coat spread between slide and cover glass. Operator's time was reduced by at least one-third when compared with a fresh blood observation (FB). In 12 of the 15 patients studied, diagnosis was performed in 4.9 +/- 3.08 min with MH, whereas 27.0 +/- 12.1 min were necessary when FB was used. In the three remaining patients whose FB results were negative, MH became positive after 13, 16, and 40 min. In our experience, FB proved to be more sensitive than previously reported. Suckling mouse inoculation also proved to be sensitive but, as in xenodiagnosis and in hemoculture, the delay in getting the final result was a limiting factor. PMID:6413530

  8. Genomic Changes of Chagas Disease Vector, South America

    PubMed Central

    Dujardin, Jean Pierre; Nicolini, Paula; Caraccio, María Noel; Rose, Virginia; Tellez, Tatiana; Bermúdez, Hernán; Bargues, María Dolores; Mas-Coma, Santiago; O’Connor, José Enrique; Pérez, Ruben

    2004-01-01

    We analyzed the main karyologic changes that have occurred during the dispersion of Triatoma infestans, the main vector of Chagas disease. We identified two allopatric groups, named Andean and non-Andean. The Andean specimens present C-heterochromatic blocks in most of their 22 chromosomes, whereas non-Andean specimens have only 4–7 autosomes with C-banding. These heterochromatin differences are the likely cause of a striking DNA content variation (approximately 30%) between Andean and non-Andean insects. Our study, together with previous historical and genetic data, suggests that T. infestans was originally a sylvatic species, with large quantities of DNA and heterochromatin, inhabiting the Andean region of Bolivia. However, the spread of domestic T. infestans throughout the non-Andean regions only involved insects with an important reduction of heterochromatin and DNA amounts. We propose that heterochromatin and DNA variation mainly reflected adaptive genomic changes that contribute to the ability of T. infestans to survive, reproduce, and disperse in different environments. PMID:15109410

  9. A Model for Chagas Disease with Oral and Congenital Transmission

    PubMed Central

    Coffield, Daniel J.; Spagnuolo, Anna Maria; Shillor, Meir; Mema, Ensela; Pell, Bruce; Pruzinsky, Amanda; Zetye, Alexandra

    2013-01-01

    This work presents a new mathematical model for the domestic transmission of Chagas disease, a parasitic disease affecting humans and other mammals throughout Central and South America. The model takes into account congenital transmission in both humans and domestic mammals as well as oral transmission in domestic mammals. The model has time-dependent coefficients to account for seasonality and consists of four nonlinear differential equations, one of which has a delay, for the populations of vectors, infected vectors, infected humans, and infected mammals in the domestic setting. Computer simulations show that congenital transmission has a modest effect on infection while oral transmission in domestic mammals substantially contributes to the spread of the disease. In particular, oral transmission provides an alternative to vector biting as an infection route for the domestic mammals, who are key to the infection cycle. This may lead to high infection rates in domestic mammals even when the vectors have a low preference for biting them, and ultimately results in high infection levels in humans. PMID:23840647

  10. Chagas disease vector control in Tupiza, southern Bolivia.

    PubMed

    Guillen, G; Diaz, R; Jemio, A; Cassab, J A; Pinto, C T; Schofield, C J

    1997-01-01

    Heavy domestic and peridomestic infestations of Triatoma infestans were controlled in two villages in southern Bolivia by the application of deltamethrin SC25 (2.5% suspension concentrate) at a target dose of 25 mg a.i./m2. Actual applied dose was monitored by HPLC analysis of filter papers placed at various heights on the house walls, and was shown to range from 0 to 59.6 about a mean of 28.5 mg a.i./m2. Wall bioassays showed high mortality of T. infestans during the first month after the application of deltamethrin. Mortality declined to zero as summer temperatures increased, but reappeared with the onset of the following winter. In contrast, knockdown was apparent throughout the trial, showing no discernible temperature dependence. House infestation rates, measured by manual sampling and use of paper sheets to collect bug faeces, declined from 79% at the beginning of the trial to zero at the 6 month evaluation. All but one of the houses were still free of T. infestans at the final evaluation 12 months after spraying, although a small number of bugs were found at this time in 5 of 355 peridomestic dependencies. Comparative cost studies endorse the recommendation of large-scale application of deltamethrin, or pyrethroid of similar cost-effectiveness, as a means to eliminate domestic T. infestans populations in order to interrupt transmission of Chagas disease.

  11. Archaeosomes display immunoadjuvant potential for a vaccine against Chagas disease

    PubMed Central

    Higa, Leticia H.; Corral, Ricardo S.; Morilla, María José; Romero, Eder L.; Petray, Patricia B.

    2013-01-01

    Archaeosomes (ARC), vesicles made from lipids extracted from Archaea, display strong adjuvant properties. In this study, we evaluated the ability of the highly stable ARC formulated from total polar lipids of a new Halorubrum tebenquichense strain found in Argentinean Patagonia, to act as adjuvant for soluble parasite antigens in developing prophylactic vaccine against the intracellular protozoan T. cruzi, the etiologic agent of Chagas disease. We demonstrated for the first time that C3H/HeN mice subcutaneously immunized with trypanosomal antigens entrapped in these ARC (ARC-TcAg) rapidly developed higher levels of circulating T. cruzi antibodies than those measured in the sera from animals receiving the antigen alone. Enhanced humoral responses elicited by ARC-TcAg presented a dominant IgG2a antibody isotype, usually associated with Th1-type immunity and resistance against T. cruzi. More importantly, ARC-TcAg-vaccinated mice displayed reduced parasitemia during early infection and were protected against an otherwise lethal challenge with the virulent Tulahuén strain of the parasite. Our findings suggest that, as an adjuvant, H. tebenquichense-derived ARC may hold great potential to develop a safe and helpful vaccine against this relevant human pathogen. PMID:23291939

  12. Urbanization, land tenure security and vector-borne Chagas disease

    PubMed Central

    Levy, Michael Z.; Barbu, Corentin M.; Castillo-Neyra, Ricardo; Quispe-Machaca, Victor R.; Ancca-Juarez, Jenny; Escalante-Mejia, Patricia; Borrini-Mayori, Katty; Niemierko, Malwina; Mabud, Tarub S.; Behrman, Jere R.; Naquira-Velarde, Cesar

    2014-01-01

    Modern cities represent one of the fastest growing ecosystems on the planet. Urbanization occurs in stages; each stage characterized by a distinct habitat that may be more or less susceptible to the establishment of disease vector populations and the transmission of vector-borne pathogens. We performed longitudinal entomological and epidemiological surveys in households along a 1900 × 125 m transect of Arequipa, Peru, a major city of nearly one million inhabitants, in which the transmission of Trypanosoma cruzi, the aetiological agent of Chagas disease, by the insect vector Triatoma infestans, is an ongoing problem. The transect spans a cline of urban development from established communities to land invasions. We find that the vector is tracking the development of the city, and the parasite, in turn, is tracking the dispersal of the vector. New urbanizations are free of vector infestation for decades. T. cruzi transmission is very recent and concentrated in more established communities. The increase in land tenure security during the course of urbanization, if not accompanied by reasonable and enforceable zoning codes, initiates an influx of construction materials, people and animals that creates fertile conditions for epidemics of some vector-borne diseases. PMID:24990681

  13. Lack of Segregation between Two Species of Chagas Disease Vectors

    PubMed Central

    Mota, Theo; Lorenzo, Marcelo Gustavo

    2012-01-01

    Triatoma infestans and Panstrongylus megistus are relevant Chagas disease vectors. An apparent segregation among these triatomine species inside human households was suggested to rely on mutual repellence between them. However, P. megistus and T. infestans show aggregation responses to chemical signals emitted by the other species. These findings do not rule out the possibility that stimuli other than chemical signals could mediate repellence when these species exploit shelters simultaneously. In the present study, we investigated how P. megistus and T. infestans exploit shelters in controlled laboratory conditions and how insect density and environmental illumination modulate this behavior. We evaluated whether these species aggregate inside shelters or mutually repel each other. Panstrongylus megistus and T. infestans show specific patterns of shelter exploitation, which are differentially affected by insect density and environment illumination. In particular, P. megistus is more sensitive to insect density than T. infestans, whereas T. infestans shows higher sensitivity to illumination than P. megistus. Nevertheless, these species exploit shelters randomly without any apparent repellence. PMID:22764300

  14. Chagas Cardiomyopathy in New Orleans and the Southeastern United States

    PubMed Central

    Hsu, Robert C.; Burak, Joshua; Tiwari, Sumit; Chakraborti, Chayan; Sander, Gary E.

    2016-01-01

    Background: Chagas disease (CD), caused by Trypanosoma cruzi, affects 6-7 million people worldwide annually, primarily in Central and South America, and >300,000 people in the United States. CD consists of acute and chronic stages. Hallmarks of acute CD include fever, myalgia, diaphoresis, hepatosplenomegaly, and myocarditis. Symptoms of chronic CD include pathologic involvement of the heart, esophagus, and colon. Myocardial involvement is identifiable by electrocardiogram and cardiac magnetic resonance imaging showing inflammation and left ventricular wall functional abnormalities. Case Reports: We present two cases of CD identified in a single hospital in the Southeastern United States. Case 1 presents a patient with symptoms of anginal chest pain and associated shortness of breath with myocardial involvement suggestive of ischemic infarction but normal coronary arteries. Case 2 describes a patient with no physical symptoms and echocardiogram with ejection fraction of 50% with posterolateral and anterolateral wall hypokinesis but normal coronary arteries. Conclusion: With a growing number of immigrants from Central and South America in the United States, it is imperative for clinicians to include CD as part of the differential diagnosis for patients presenting with heart disease who have a history of exposure to T. cruzi endemic areas. PMID:27660581

  15. Urbanization, land tenure security and vector-borne Chagas disease.

    PubMed

    Levy, Michael Z; Barbu, Corentin M; Castillo-Neyra, Ricardo; Quispe-Machaca, Victor R; Ancca-Juarez, Jenny; Escalante-Mejia, Patricia; Borrini-Mayori, Katty; Niemierko, Malwina; Mabud, Tarub S; Behrman, Jere R; Naquira-Velarde, Cesar

    2014-08-22

    Modern cities represent one of the fastest growing ecosystems on the planet. Urbanization occurs in stages; each stage characterized by a distinct habitat that may be more or less susceptible to the establishment of disease vector populations and the transmission of vector-borne pathogens. We performed longitudinal entomological and epidemiological surveys in households along a 1900 × 125 m transect of Arequipa, Peru, a major city of nearly one million inhabitants, in which the transmission of Trypanosoma cruzi, the aetiological agent of Chagas disease, by the insect vector Triatoma infestans, is an ongoing problem. The transect spans a cline of urban development from established communities to land invasions. We find that the vector is tracking the development of the city, and the parasite, in turn, is tracking the dispersal of the vector. New urbanizations are free of vector infestation for decades. T. cruzi transmission is very recent and concentrated in more established communities. The increase in land tenure security during the course of urbanization, if not accompanied by reasonable and enforceable zoning codes, initiates an influx of construction materials, people and animals that creates fertile conditions for epidemics of some vector-borne diseases.

  16. Trypanosoma cruzi Antioxidant Enzymes As Virulence Factors in Chagas Disease

    PubMed Central

    Piacenza, Lucía; Peluffo, Gonzalo; Alvarez, María Noel; Martínez, Alejandra

    2013-01-01

    Abstract Significance: Chagas disease (CD) affects several million people in Latin America and is spreading beyond its classical boundaries due to the migration of infected host and insect vectors, HIV co-infection, and blood transfusion. The current therapy is not adequate for treatment of the chronic phase of CD, and new drugs are warranted. Recent Advances: Trypanosoma cruzi is equipped with a specialized and complex network of antioxidant enzymes that are located at different subcellular compartments which defend the parasite against host oxidative assaults. Recently, strong evidence has emerged which indicates that enzyme components of the T. cruzi antioxidant network (cytosolic and mitochondrial peroxiredoxins and trypanothione synthetase) in naturally occurring strains act as a virulence factor for CD. This precept is recapitulated with the observed increased resistance of T. cruzi peroxirredoxins overexpressers to in vivo or in vitro nitroxidative stress conditions. In addition, the modulation of mitochondrial superoxide radical levels by iron superoxide dismutase (FeSODA) influences parasite programmed cell death, underscoring the role of this enzyme in parasite survival. Critical Issues: The unraveling of the biological significance of FeSODs in T. cruzi programmed cell death in the context of chronic infection in CD is still under examination. Future Directions: The role of the antioxidant enzymes in the pathogenesis of CD, including parasite virulence and persistence, and their feasibility as pharmacological targets justifies further investigation. Antioxid. Redox Signal. 19, 723–734. PMID:22458250

  17. Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

    PubMed

    Riarte, A; Luna, C; Sabatiello, R; Sinagra, A; Schiavelli, R; De Rissio, A; Maiolo, E; Garcìa, M M; Jacob, N; Pattin, M; Lauricella, M; Segura, E L; Vázquez, M

    1999-09-01

    Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.

  18. [What is not searched, it is difficult to find: Chagas' disease].

    PubMed

    Briceno, Luis; Mosca, Walter

    2016-05-01

    A conservative estimation indicates that more than 400 000 Latin American immigrants are living in Italy. Several studies have shown that among these, the prevalence of Chagas disease is between 3.9% and 17%, so it is not unlikely to find a patient with this disease during a cardiology visit. How many patients from Latin America are diagnosed with heart failure in Italy and no one has ever thought about a possible Chagas disease? This brief review describes the situation of the disease in Italy, its characteristics, the etiology of this disease and its treatment. The latter aspect will be discussed considering the recent published results of the BENEFIT study, where it was found that treatment with benznidazole in patients with Chagas' cardiomyopathy is able to reduce significantly the detection of parasites in the blood, but it is not able to prevent clinical deterioration during 5 years of follow-up. The possible implications of these results will be discussed.

  19. The Sphingolipid Biosynthetic Pathway Is a Potential Target for Chemotherapy against Chagas Disease

    PubMed Central

    Koeller, Carolina Macedo; Heise, Norton

    2011-01-01

    The protozoan parasite Trypanosoma cruzi is the causative agent of human Chagas disease, for which there currently is no cure. The life cycle of T. cruzi is complex, including an extracellular phase in the triatomine insect vector and an obligatory intracellular stage inside the vertebrate host. These phases depend on a variety of surface glycosylphosphatidylinositol-(GPI-) anchored glycoconjugates that are synthesized by the parasite. Therefore, the surface expression of GPI-anchored components and the biosynthetic pathways of GPI anchors are attractive targets for new therapies for Chagas disease. We identified new drug targets for chemotherapy by taking the available genome sequence information and searching for differences in the sphingolipid biosynthetic pathways (SBPs) of mammals and T. cruzi. In this paper, we discuss the major steps of the SBP in mammals, yeast and T. cruzi, focusing on the IPC synthase and ceramide remodeling of T. cruzi as potential therapeutic targets for Chagas disease. PMID:21603271

  20. Karyotype and spermatogenesis in Triatoma lenti (Hemiptera: Triatominae), a potential Chagas vector.

    PubMed

    Alevi, K C C; Mendonça, P P; Succi, M; Pereira, N P; Rosa, J A; Azeredo-Oliveira, M T V

    2012-12-17

    All species of Triatominae are susceptible to infection by Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) and consequently, potential insect vectors of Chagas disease. Currently, there are 140 known species of triatomine bugs, which can be grouped into specific species complexes. The species Triatoma lenti (Hemiptera: Triatominae) is found only in Brazil and is considered a potential vector of Chagas disease. We karyotyped male T. lenti and examined its spermatogenesis in detail. The karyotype was found to be 2n = 20A + XY, demonstrating that this organism has the modal chromosome set found in triatomines. This new information concerning males of this species contributed to biological data that will be useful for understanding this potentially important Chagas disease vector.

  1. Nonpeptidic Tetrafluorophenoxymethyl Ketone Cruzain Inhibitors as Promising New Leads for Chagas Disease Chemotherapy†

    PubMed Central

    Brak, Katrien; Kerr, Iain D.; Barrett, Kimberly T.; Fuchi, Nobuhiro; Debnath, Moumita; Engel, Juan C.; McKerrow, James H.; Doyle, Patricia S.; Brinen, Linda S.; Ellman, Jonathan A.

    2010-01-01

    A century after discovering that the Trypanosoma cruzi parasite is the etiological agent of Chagas disease, treatment is still plagued by limited efficacy, toxicity, and the emergence of drug resistance. The development of inhibitors of the major T. cruzi cysteine protease, cruzain, has been demonstrated to be a promising drug discovery avenue for this neglected disease. Here we establish that a nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitor substantially ameliorates symptoms of acute Chagas disease in a mouse model with no apparent toxicity. A high-resolution crystal structure confirmed the mode of inhibition and revealed key binding interactions of this novel inhibitor class. Subsequent structure-guided optimization then resulted in inhibitor analogs with improvements in potency despite minimal or no additions in molecular weight. Evaluation of the analogs in cell culture showed enhanced activity. These results suggest that nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors have the potential to fulfill the urgent need for improved Chagas disease chemotherapy. PMID:20088534

  2. [Knowledge, attitudes, and practices concerning Chagas disease in schoolchildren from an endemic area in Peru].

    PubMed

    Cabrera, Rufino; Mayo, Carlos; Suárez, Nicolás; Infante, César; Náquira, César; García-Zapata, Marco Tulio A

    2003-01-01

    This study analyzes knowledge, attitudes, and practices concerning Chagas disease among 241 primary schoolchildren in "La Tinguiña", Ica, Peru (December 2000 - January 2001). Less than 1% of those interviewed knew that triatomines transmit Chagas disease, while nearly a quarter recognized the illness based on the appearance of "lumps" on the skin; 35.27% knew that vector infestation is controlled using insecticides; 26.56% recognized the adult stage of the vector, and 21.16% the nymphal instar; 14.11% knew triatomines or "kissing bugs" by the name "chirimacha"; 82.57% would accept an entomological survey, 66.80% would submit to a serological study, and 63.90% would participate in a triatomine search. The study shows that the population, despite having very limited knowledge on the disease and its vectors, shows interest in collaborating. Therefore, it is recommended that Chagas disease surveillance and control include educational programs and community participation.

  3. A three-dimensional multi-agent-based model for the evolution of Chagas' disease.

    PubMed

    Galvão, Viviane; Miranda, José Garcia Vivas

    2010-06-01

    A better understanding of Chagas' disease is important because the knowledge about the progression and the participation of the different types of cells in this disease are still lacking. To clarify this system, the kinetics of inflammatory cells and parasite nests was shown in an experiment. Using this experimental data, we have developed a three-dimensional multi-agent-based computational model for the evolution of Chagas' disease. Our model includes five different types of agents: inflammatory cell, fibrosis, cardiomyocyte, fibroblast, and Trypanosoma cruzi. Fibrosis is fixed and the other types of agents can move through the empty space. They move randomly by using the Moore neighborhood. This model reproduces the acute and chronic phases of Chagas' disease and the volume occupied by all different types of cells in the cardiac tissue.

  4. [Control of Chagas disease in pregnant Latin-American women and her children].

    PubMed

    Merino, Francisco J; Martínez-Ruiz, Rocío; Olabarrieta, Iciar; Merino, Paloma; García-Bujalance, Silvia; Gastañaga, Teresa; Flores-Chavez, María

    2013-09-01

    Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area.

  5. Trypanosoma cruzi trans-sialidase as a drug target against Chagas disease (American trypanosomiasis).

    PubMed

    Miller, Bill R; Roitberg, Adrian E

    2013-10-01

    Chagas disease (or American trypanosomiasis) is a deadly tropical disease that affects millions of people worldwide, primarily in rural regions of South America. Trypanosoma cruzi, the parasitic cause of Chagas disease, possesses a membrane-anchored trans-sialidase enzyme that transfers sialic acids from the host cell surface to the parasitic cell surface, allowing T. cruzi to effectively evade the host's immune system. This enzyme has no analogous human counterpart and thus has become an interesting drug target to combat the parasite. Recent computational efforts have improved our knowledge about the enzyme's structure, dynamics and catalyzed reaction. Many compounds have been tested against trans-sialidase activity, but no strong inhibitors have been identified yet. The current lack of drugs for Chagas disease necessitates more R&D into the design and discovery of strong inhibitors of T. cruzi trans-sialidase.

  6. Chagas disease (Trypanosoma cruzi) and HIV co-infection in Colombia.

    PubMed

    Hernández, Carolina; Cucunubá, Zulma; Parra, Edgar; Toro, German; Zambrano, Pilar; Ramírez, Juan David

    2014-09-01

    Chagas disease is a complex zoonotic pathology caused by the kinetoplastid Trypanosoma cruzi. This parasite presents remarkable genetic variability and has been grouped into six discrete typing units (DTUs). The association between the DTUs and clinical outcome remains unknown. Chagas disease and co-infection with HIV/AIDS has been reported widely in Brazil and Argentina. Herein, we present the molecular analyses from a Chagas disease patient with HIV/AIDS co-infection in Colombia who presented severe cardiomyopathy, pleural effusion, and central nervous system involvement. A mixed infection by T. cruzi genotypes was detected. We suggest including T. cruzi in the list of opportunistic pathogens for the management of HIV patients in Colombia. The epidemiological implications of this finding are discussed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Oesophageal manometric studies in patients with chronic Chagas disease and megacolon

    PubMed Central

    Heitmann, Peter; Espinoza, Julio

    1969-01-01

    Intraluminal manometric studies performed on 12 patients with chronic Chagas disease and megacolon without clinical or radiological abnormalities of the oesophagus showed no alteration in oesophageal physiology under basal conditions when compared with a control group of 30 healthy subjects. Oesophageal peristalsis was unimpaired. Patients with chronic Chagas disease and megacolon differed from normals in their reaction to a small dose of a cholinergic drug. This agent induced an isolated but significant increase in resting pressure at the level of the oesophagogastric sphincter, accompanied in most cases by an increase in spontaneous activity but not by a change in resting pressure in the body of the oesophagus. This is interpreted as a subclinical expression of oesophageal pathology related to Chagas disease. PMID:4981710

  8. Genetic transformation of a Corynebacterial symbiont from the Chagas disease vector Triatoma infestans.

    PubMed

    Durvasula, Ravi V; Sundaram, Ranjini K; Kirsch, Philipp; Hurwitz, Ivy; Crawford, Carl V; Dotson, Ellen; Beard, Charles B

    2008-05-01

    Insect-borne diseases have experienced a troubling resurgence in recent years. Emergence of resistance to pesticides greatly hampers control efforts. Paratransgenesis, or the genetic transformation of bacterial symbionts of disease vectors, is an alternative to traditional approaches. Previously, we developed paratransgenic lines of Rhodnius prolixus, a vector of Chagas disease in Central America. Here, we report identification of a Corynebacterial species as a symbiont of Triatoma infestans, a leading vector of Chagas disease in South America. We have modified this bacterium to produce an immunologically active single chain antibody fragment, termed rDB3. This study establishes the basis for generating paratransgenic T. infestans as a strategy for control of Chagas disease.

  9. High specificity of Trypanosoma cruzi epimastigote ribonucleoprotein as antigen in serodiagnosis of Chagas' disease.

    PubMed Central

    Solana, M E; Katzin, A M; Umezawa, E S; Miatello, C S

    1995-01-01

    We assessed the performance of an enzyme-linked immunosorbent assay (ELISA) with the Trypanosoma cruzi epimastigote ribosomal fraction (Tulahuen and Y strains) in order to improve the diagnostic specificity of the test. A total of 100 serum samples from patients with chronic Chagas' disease from Brazil and Argentina were studied. Sera from 116 patients, without Chagas' disease, including 10 with active mucocutaneous leishmaniasis and 20 with visceral leishmaniasis, were used as controls. Immunoglobulin G (IgG) antibodies against the ribosomal fraction (ribonucleoproteins [RNPs]) in the ELISA were found in 97% of samples from patients with Chagas' disease. A total of 99% of the sera from patients without the disease were negative, including sera from patients with mucocutaneous and visceral leishmaniases. The distribution of IgG isotypes in randomly chosen serum samples was determined by ELISA; IgG1 and IgG3 were predominant (100% exhibited IgG1 and 85% exhibited IgG3, and 50% also presented the IgG2 isotype. The distribution of the IgG subclasses was confirmed by the Western blot (immunoblot) technique. When total IgG was assayed by Western blot assay, no correlation was found between the pattern of serum reactivity and the clinical features of the patients with Chagas' disease. Therefore, no typical profile of polypeptide recognition could be associated with any clinical form of Chagas' disease (cardiomyopathy or megaviscera). Our results showed that sera from patients with Chagas' disease react with ribosomal antigens and display a typical profile of IgG isotypes (IgG1 plus IgG3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7650167

  10. Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers

    PubMed Central

    Salvador, F.; Sánchez-Montalvá, A.; Treviño, B.; Serre, N.; Sao Avilés, A.; Almirante, B.

    2015-01-01

    Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals. PMID:26195525

  11. Field Evaluation of the InBios Chagas Detect Plus Rapid Test in Serum and Whole-Blood Specimens in Bolivia

    PubMed Central

    Shah, Vishal; Ferrufino, Lisbeth; Gilman, Robert H.; Ramirez, Margot; Saenza, Eliana; Malaga, Edith; Sanchez, Gerardo; Okamoto, Emi E.; Sherbuck, Jacqueline E.; Clark, Eva H.; Galdos-Cardenas, Gerson; Bozo, Ricardo; Flores-Franco, Jorge Luis; Colanzi, Rony; Verastegui, Manuela

    2014-01-01

    Trypanosoma cruzi causes Chagas disease, which affects an estimated 7 million to 8 million people. Chagas disease is endemic throughout Latin America, with the highest prevalence in Bolivia. Conventional diagnosis requires a well-equipped laboratory with experienced personnel. We evaluated the Chagas Detect Plus (CDP) (InBios, Seattle, WA), a rapid immunochromatographic assay for IgG antibodies to T. cruzi. CDP performance was compared to infection status based on results obtained by indirect hemagglutination assay, immunofluorescent-antibody test, and enzyme-linked immunosorbent assay. Confirmed infection required positive results by at least 2 conventional assays. We used specimens from adults of both sexes in a general hospital in the city of Santa Cruz and from pregnant women in a hospital and children in villages in the Bolivian Chaco, an area of hyperendemicity. CDP was performed in paired whole-blood and serum specimens from 385 individuals in the two hospital studies and in 200 serum specimens from the community study. CDP showed sensitivities/specificities of 96.2% (95% confidence interval, 92.7 to 98.4)/98.8% (95.9 to 99.9) in whole blood and 99.3% (97.5 to 99.9)/96.9% (94.2 to 98.6) in serum, with no differences by sex, age group, or study site. CDP showed excellent sensitivity and specificity in our study population, comparable to those of conventional serology. The test is reliable for field surveys, requires no laboratory equipment, and performed well in serum and whole blood. The CDP could also be used for accurate maternal screening to identify neonates at risk of congenital transmission. CDP performance data in diverse geographic areas are needed to strengthen the evidence base for its use. PMID:25274804

  12. Field evaluation of the InBios Chagas detect plus rapid test in serum and whole-blood specimens in Bolivia.

    PubMed

    Shah, Vishal; Ferrufino, Lisbeth; Gilman, Robert H; Ramirez, Margot; Saenza, Eliana; Malaga, Edith; Sanchez, Gerardo; Okamoto, Emi E; Sherbuck, Jacqueline E; Clark, Eva H; Galdos-Cardenas, Gerson; Bozo, Ricardo; Flores-Franco, Jorge Luis; Colanzi, Rony; Verastegui, Manuela; Bern, Caryn

    2014-12-01

    Trypanosoma cruzi causes Chagas disease, which affects an estimated 7 million to 8 million people. Chagas disease is endemic throughout Latin America, with the highest prevalence in Bolivia. Conventional diagnosis requires a well-equipped laboratory with experienced personnel. We evaluated the Chagas Detect Plus (CDP) (InBios, Seattle, WA), a rapid immunochromatographic assay for IgG antibodies to T. cruzi. CDP performance was compared to infection status based on results obtained by indirect hemagglutination assay, immunofluorescent-antibody test, and enzyme-linked immunosorbent assay. Confirmed infection required positive results by at least 2 conventional assays. We used specimens from adults of both sexes in a general hospital in the city of Santa Cruz and from pregnant women in a hospital and children in villages in the Bolivian Chaco, an area of hyperendemicity. CDP was performed in paired whole-blood and serum specimens from 385 individuals in the two hospital studies and in 200 serum specimens from the community study. CDP showed sensitivities/specificities of 96.2% (95% confidence interval, 92.7 to 98.4)/98.8% (95.9 to 99.9) in whole blood and 99.3% (97.5 to 99.9)/96.9% (94.2 to 98.6) in serum, with no differences by sex, age group, or study site. CDP showed excellent sensitivity and specificity in our study population, comparable to those of conventional serology. The test is reliable for field surveys, requires no laboratory equipment, and performed well in serum and whole blood. The CDP could also be used for accurate maternal screening to identify neonates at risk of congenital transmission. CDP performance data in diverse geographic areas are needed to strengthen the evidence base for its use. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

    PubMed Central

    Zingales, Bianca; Miles, Michael A; Moraes, Carolina B; Luquetti, Alejandro; Guhl, Felipe; Schijman, Alejandro G; Ribeiro, Isabela

    2014-01-01

    This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape. PMID:25317712

  14. Should trypanocidal therapy be used to treat patients in the chronic phase of Chagas disease?

    PubMed

    Popoff, Federico; Izcovich, Ariel

    2015-10-26

    Antiparasitic treatment of patients with Chagas’ disease in chronic stage could prevent the complications related to the disease. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials and 11 observational studies. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether antiparasitic treatment improves survival or reduces complications related to chronic Chagas’ disease because the certainty of the evidence is very low.

  15. [Chagas's disease and deep ecology: the anti-vectorial fight in question].

    PubMed

    Siqueira-Batista, Rodrigo; Gomes, Andréia Patrícia; Rôças, Giselle; Cotta, Rosângela Minardi Mitre; Rubião, Eduardo Cárdenas Nogueira; Pissinatti, Alcides

    2011-02-01

    The inter-relations between man and the environment are among the main themes currently debated by the Brazilian public health. On such horizon, the questions concerning Chagas's disease are found to remain specially in the scope of the directed actions of control to the triatomine, the anti-vectorial fight , though already a century since its first description by Carlos Chagas, a major epidemiological problem in Latin America. Based on these considerations the present article will seek to discuss the main ecological aspects related to the American trypanosomiasis, emphasizing the control of the vectorial transmission in the context of the deep ecology.

  16. Impaired coronary flow reserve in patients with indeterminate form of Chagas' disease.

    PubMed

    Rabelo, Daniel R; Rocha, Manoel Otávio da Costa; de Barros, Márcio V L; Silva, José Luiz Padilha da; Tan, Timothy C; Nunes, Maria C P

    2014-01-01

    Previous studies suggest that microvascular abnormalities may contribute to the pathogenesis of Chagas' heart disease. Coronary flow reserve (CFR) expressed by the maximum achievable flow relative to baseline flow in the coronary microcirculation, may be useful in identifying patients who may be developing cardiac manifestations of the disease. This study aims to assess the CFR in patients with indeterminate form of Chagas' disease, and also to identify the determinants of CFR. Sixty-four asymptomatic patients (37% male; age 49.9 ± 11.5 years) with normal cardiovascular exams classified as in indeterminate form of Chagas' disease underwent transthoracic dipyridamole (0.84 mg/kg in 6 min) stress echocardiography, and were compared with a control group of healthy patients. Coronary flow reserve was assessed on left anterior descending artery using pulsed Doppler as the ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. A treadmill exercise test was performed to rule out ischemia. All patients had good functional capacity assessed by exercise testing with peak oxygen consumption (VO2 ) of 28 ± 11 mL/kg per minute, similar to the controls. There were no differences in the echocardiographic parameters of diastolic and systolic left ventricular function and right ventricular function between the patients and controls. Coronary flow reserve was significantly lower in Chagas' disease patients than those in healthy individuals (1.9 ± 0.4 vs. 2.6 ± 0.5; P < 0.001). Several factors were correlated with the CFR, including age, ejection fraction, left ventricular diastolic function, heart rate recovery, and the presence of Chagas' disease. In a multivariate analysis, age and positive serology for Chagas' disease were independent factors associated with the CFR. Coronary flow reserve was impaired in Chagas' disease patients in the indeterminate form compared with healthy individuals with similar clinical features. Among all

  17. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.

    PubMed

    Zingales, Bianca; Miles, Michael A; Moraes, Carolina B; Luquetti, Alejandro; Guhl, Felipe; Schijman, Alejandro G; Ribeiro, Isabela

    2014-09-01

    This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.

  18. Community Participation in Chagas Disease Vector Surveillance: Systematic Review

    PubMed Central

    Abad-Franch, Fernando; Vega, M. Celeste; Rolón, Miriam S.; Santos, Walter S.; Rojas de Arias, Antonieta

    2011-01-01

    Background Vector control has substantially reduced Chagas disease (ChD) incidence. However, transmission by household-reinfesting triatomines persists, suggesting that entomological surveillance should play a crucial role in the long-term interruption of transmission. Yet, infestation foci become smaller and harder to detect as vector control proceeds, and highly sensitive surveillance methods are needed. Community participation (CP) and vector-detection devices (VDDs) are both thought to enhance surveillance, but this remains to be thoroughly assessed. Methodology/Principal Findings We searched Medline, Web of Knowledge, Scopus, LILACS, SciELO, the bibliographies of retrieved studies, and our own records. Data from studies describing vector control and/or surveillance interventions were extracted by two reviewers. Outcomes of primary interest included changes in infestation rates and the detection of infestation/reinfestation foci. Most results likely depended on study- and site-specific conditions, precluding meta-analysis, but we re-analysed data from studies comparing vector control and detection methods whenever possible. Results confirm that professional, insecticide-based vector control is highly effective, but also show that reinfestation by native triatomines is common and widespread across Latin America. Bug notification by householders (the simplest CP-based strategy) significantly boosts vector detection probabilities; in comparison, both active searches and VDDs perform poorly, although they might in some cases complement each other. Conclusions/Significance CP should become a strategic component of ChD surveillance, but only professional insecticide spraying seems consistently effective at eliminating infestation foci. Involvement of stakeholders at all process stages, from planning to evaluation, would probably enhance such CP-based strategies. PMID:21713022

  19. Barriers to treatment access for Chagas disease in Mexico.

    PubMed

    Manne, Jennifer M; Snively, Callae S; Ramsey, Janine M; Salgado, Marco Ocampo; Bärnighausen, Till; Reich, Michael R

    2013-01-01

    According to World Health Organization (WHO) prevalence estimates, 1.1 million people in Mexico are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease (CD). However, limited information is available about access to antitrypanosomal treatment. This study assesses the extent of access in Mexico, analyzes the barriers to access, and suggests strategies to overcome them. Semi-structured in-depth interviews were conducted with 18 key informants and policymakers at the national level in Mexico. Data on CD cases, relevant policy documents and interview data were analyzed using the Flagship Framework for Pharmaceutical Policy Reform policy interventions: regulation, financing, payment, organization, and persuasion. Data showed that 3,013 cases were registered nationally from 2007-2011, representing 0.41% of total expected cases based on Mexico's national prevalence estimate. In four of five years, new registered cases were below national targets by 11-36%. Of 1,329 cases registered nationally in 2010-2011, 834 received treatment, 120 were pending treatment as of January 2012, and the treatment status of 375 was unknown. The analysis revealed that the national program mainly coordinated donation of nifurtimox and that important obstacles to access include the exclusion of antitrypanosomal medicines from the national formulary (regulation), historical exclusion of CD from the social insurance package (organization), absence of national clinical guidelines (organization), and limited provider awareness (persuasion). Efforts to treat CD in Mexico indicate an increased commitment to addressing this disease. Access to treatment could be advanced by improving the importation process for antitrypanosomal medicines and adding them to the national formulary, increasing education for healthcare providers, and strengthening clinical guidelines. These recommendations have important implications for other countries in the region with similar problems in access to

  20. Antimutagenic effects of subfractions of Chaga mushroom (Inonotus obliquus) extract.

    PubMed

    Ham, Seung-Shi; Kim, Soo-Hyun; Moon, Sun-Young; Chung, Mi Ja; Cui, Cheng-Bi; Han, Eun-Kyung; Chung, Cha-Kwon; Choe, Myeon

    2009-01-01

    Inonotus obliquus is a mushroom commonly known as Chaga that is widely used in folk medicine in Siberia, North America, and North Europe. Here, we evaluated the antimutagenic and antioxidant capacities of subfractions of Inonotus obliquus extract. The ethyl acetate extract was separated by vacuum chromatography into three fractions, and the fraction bearing the highest antimutagenic activity was subsequently separated into four fractions by reversed phase (ODS-C18) column chromatography. The most antimutagenic fraction was then separated into two subfractions (subfractions 1 and 2) by normal phase silica gel column chromatography. Ames test analysis revealed that the subfractions were not mutagenic. At 50 μg/plate, subfractions 1 and 2 strongly inhibited the mutagenesis induced in Salmonella typhimurium strain TA100 by the directly acting mutagen MNNG (0.4 μg/plate) by 80.0% and 77.3%, respectively. They also inhibited 0.15 μg/plate 4NQO-induced mutagenesis in TA98 and TA100 by 52.6-62.0%. The mutagenesis in TA98 induced by the indirectly acting mutagens Trp-P-1 (0.15 μg/plate) and B(α)P (10 μg/plate) was reduced by 47.0-68.2% by the subfractions, while the mutagenesis in TA100 by Trp-P-1 and B(α)P was reduced by 70.5-87.2%. Subfraction 1 was more inhibitory than subfraction 2 with regard to the mutagenic effects of 4NQO, Trp-P-1, and B(α)P. Subfractions 1 and 2 also had a strong antioxidant activity against DPPH radicals and were identified by MS, 1H NMR and 13C NMR analyses as 3β-hydroxy-lanosta-8, 24-dien-21-al and inotodiol, respectively. Thus, we show that the 3beta-hydroxy-lanosta-8, 24-dien-21-al and inotodiol components of Inonotus obliquus bear antimutagenic and antioxidative activities.

  1. Barriers to Treatment Access for Chagas Disease in Mexico

    PubMed Central

    Manne, Jennifer M.; Snively, Callae S.; Ramsey, Janine M.; Salgado, Marco Ocampo; Bärnighausen, Till; Reich, Michael R.

    2013-01-01

    Background According to World Health Organization (WHO) prevalence estimates, 1.1 million people in Mexico are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease (CD). However, limited information is available about access to antitrypanosomal treatment. This study assesses the extent of access in Mexico, analyzes the barriers to access, and suggests strategies to overcome them. Methods and Findings Semi-structured in-depth interviews were conducted with 18 key informants and policymakers at the national level in Mexico. Data on CD cases, relevant policy documents and interview data were analyzed using the Flagship Framework for Pharmaceutical Policy Reform policy interventions: regulation, financing, payment, organization, and persuasion. Data showed that 3,013 cases were registered nationally from 2007–2011, representing 0.41% of total expected cases based on Mexico's national prevalence estimate. In four of five years, new registered cases were below national targets by 11–36%. Of 1,329 cases registered nationally in 2010–2011, 834 received treatment, 120 were pending treatment as of January 2012, and the treatment status of 375 was unknown. The analysis revealed that the national program mainly coordinated donation of nifurtimox and that important obstacles to access include the exclusion of antitrypanosomal medicines from the national formulary (regulation), historical exclusion of CD from the social insurance package (organization), absence of national clinical guidelines (organization), and limited provider awareness (persuasion). Conclusions Efforts to treat CD in Mexico indicate an increased commitment to addressing this disease. Access to treatment could be advanced by improving the importation process for antitrypanosomal medicines and adding them to the national formulary, increasing education for healthcare providers, and strengthening clinical guidelines. These recommendations have important implications for other countries in

  2. Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

    PubMed Central

    Ramírez, Juan David; Montilla, Marleny; Cucunubá, Zulma M.; Floréz, Astrid Carolina; Zambrano, Pilar; Guhl, Felipe

    2013-01-01

    Background Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. Methodology and Principal Findings High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. Conclusions These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed. PMID:23437405

  3. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  4. Environmental Changes Can Produce Shifts in Chagas Disease Infection Risk

    PubMed Central

    Cordovez, Juan M; Sanabria, Camilo

    2014-01-01

    An epidemiological network contains all the organisms involved (types) in the transmission of a parasite. The nodes of the network represent reservoirs, hosts, and vectors, while the links between the nodes represent the strength and direction of parasite movement. Networks that contain humans are of special interest because they are of concern to public health authorities. Under these circumstances, it is possible, in principle, to identify cycles (closed paths in the network) that include humans and select the ones that carry the maximum probability of human infection. The basic reproduction number R0 in such a network gives the average number of new infections of any type after the introduction of one individual infected by any type. To obtain R0 for complex networks, one can use the next-generation matrix (NGM) approach. Every entry in NGM will average the contribution of each link that connects two types. To tease the contribution of every cycle apart, we define the virulence as the geometric mean of the NGM entries corresponding to the links therein. This approach allows for the quantification of specific cycles of interest while it also makes the computation of the sensitivity and elasticity of the parameters easier. In this work, we compute the virulence for the transmission dynamics of Chagas disease for a typical rural area in Colombia incorporating the effect of environmental changes on the vector population size. We concluded that the highest contribution to human infection comes from humans themselves, which is a surprising and interesting result. In addition, sensitivity analysis revealed that increasing vector population size increases the risk of human infection. PMID:25574142

  5. Environmental changes can produce shifts in chagas disease infection risk.

    PubMed

    Cordovez, Juan M; Sanabria, Camilo

    2014-01-01

    An epidemiological network contains all the organisms involved (types) in the transmission of a parasite. The nodes of the network represent reservoirs, hosts, and vectors, while the links between the nodes represent the strength and direction of parasite movement. Networks that contain humans are of special interest because they are of concern to public health authorities. Under these circumstances, it is possible, in principle, to identify cycles (closed paths in the network) that include humans and select the ones that carry the maximum probability of human infection. The basic reproduction number R 0 in such a network gives the average number of new infections of any type after the introduction of one individual infected by any type. To obtain R 0 for complex networks, one can use the next-generation matrix (NGM) approach. Every entry in NGM will average the contribution of each link that connects two types. To tease the contribution of every cycle apart, we define the virulence as the geometric mean of the NGM entries corresponding to the links therein. This approach allows for the quantification of specific cycles of interest while it also makes the computation of the sensitivity and elasticity of the parameters easier. In this work, we compute the virulence for the transmission dynamics of Chagas disease for a typical rural area in Colombia incorporating the effect of environmental changes on the vector population size. We concluded that the highest contribution to human infection comes from humans themselves, which is a surprising and interesting result. In addition, sensitivity analysis revealed that increasing vector population size increases the risk of human infection.

  6. Modulation of immune response in experimental Chagas disease.

    PubMed

    Basso, Beatriz

    2013-02-20

    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

  7. Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

    PubMed Central

    Fares, Rafaelle Christine Gomes; Gomes, Juliana de Assis Silva; Garzoni, Luciana Ribeiro; Waghabi, Mariana Caldas; Saraiva, Roberto Magalhães; Medeiros, Nayara Ingrid; Oliveira-Prado, Roberta; Sangenis, Luiz Henrique Conde; Chambela, Mayara da Costa; de Araújo, Fernanda Fortes; Teixeira-Carvalho, Andréa; Damásio, Marcos Paulo; Valente, Vanessa Azevedo; Ferreira, Karine Silvestre; Sousa, Giovane Rodrigo; Rocha, Manoel Otávio da Costa

    2013-01-01

    Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8+ T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules. PMID:23856618

  8. San Ignacio (La Tembladera) geothermal site, Departamento de Francisco Morazan, Honduras, Central America: Geological field report

    SciTech Connect

    Aldrich, M.J.; Eppler, D.; Heiken, G.; Flores, W.; Ramos, N.; Ritchie, A.

    1987-06-01

    The San Ignacio (La Tembladera) geothermal site is located on the north side of the Siria Valley, Departamento de Francisco Morazan, near the village of Barrosa. Hot springs are located along a northwest-trending fault scarp at the edge of the valley and along north-trending faults that cross the scarp. The rocks in the area are primarily Paleozoic metamorphic rocks, overlain by patches of Tertiary Padre Miguel Group tuffs and alluvial deposits. Movement probably occurred along several faults during latest Tertiary and possibly early Quaternary times. Four spring areas were mapped. Area 1, the largest, is associated with a sinter mound and consists of 40 spring groups. About half of the springs, aligned along a north-south trend, are boiling. Area 2 is a small sinter mound with several seeps. Area 3 consists of a group of hot and boiling springs aligned along a north-trending fault. The springs rise through fractured schists and a thin cover of alluvium. Area 4 is located at the intersection of several faults and includes one of the largest boiling springs in the area.

  9. FC-TRIPLEX Chagas/Leish IgG1: A Multiplexed Flow Cytometry Method for Differential Serological Diagnosis of Chagas Disease and Leishmaniasis

    PubMed Central

    Teixeira-Carvalho, Andréa; Campos, Fernanda Magalhães Freire; Geiger, Stefan Michael; Rocha, Roberta Dias Rodrigues; de Araújo, Fernanda Fortes; Vitelli-Avelar, Danielle Marquete; Andrade, Mariléia Chaves; Araújo, Márcio Sobreira Silva; Lemos, Elenice Moreira; de Freitas Carneiro Proietti, Anna Bárbara; Sabino, Ester Cerdeira; Caldas, Rafaella Gaiotti; Freitas, Carolina Renata Camargos; Campi-Azevedo, Ana Carolina; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis

    2015-01-01

    Differential serological diagnosis of Chagas disease and leishmaniasis is difficult owing to cross-reactivity resulting from the fact that the parasites that cause these pathologies share antigenic epitopes. Even with optimized serological assays that use parasite-specific recombinant antigens, inconclusive test results continue to be a problem. Therefore, new serological tests with high sensitivity and specificity are needed. In the present work, we developed and evaluated the performance of a new flow cytometric serological method, referred to as FC-TRIPLEX Chagas/Leish IgG1, for the all-in-one classification of inconclusive tests. The method uses antigens for the detection of visceral leishmaniasis, localized cutaneous leishmaniasis, and Chagas disease and is based on an inverted detuned algorithm for analysis of anti-Trypanosomatidae IgG1 reactivity. First, parasites were label with fluorescein isothiocyanate or Alexa Fluor 647 at various concentrations. Then serum samples were serially diluted, the dilutions were incubated with suspensions of mixed labeled parasites, and flow cytometric measurements were performed to determine percentages of positive fluorescent parasites. Using the new method, we obtained correct results for 76 of 80 analyzed serum samples (95% overall performance), underscoring the outstanding performance of the method. Moreover, we found that the fluorescently labeled parasite suspensions were stable during storage at room temperature, 4°C, and –20°C for 1 year. In addition, two different lots of parasite suspensions showed equivalent antigen recognition; that is, the two lots showed equivalent categorical segregation of anti-Trypanosomatidae IgG1 reactivity at selected serum dilutions. In conclusion, we have developed a sensitive and selective method for differential diagnosis of Chagas disease, visceral leishmaniasis, and localized cutaneous leishmaniasis. PMID:25875961

  10. FC-TRIPLEX Chagas/Leish IgG1: a multiplexed flow cytometry method for differential serological diagnosis of chagas disease and leishmaniasis.

    PubMed

    Teixeira-Carvalho, Andréa; Campos, Fernanda Magalhães Freire; Geiger, Stefan Michael; Rocha, Roberta Dias Rodrigues; de Araújo, Fernanda Fortes; Vitelli-Avelar, Danielle Marquete; Andrade, Mariléia Chaves; Araújo, Márcio Sobreira Silva; Lemos, Elenice Moreira; de Freitas Carneiro Proietti, Anna Bárbara; Sabino, Ester Cerdeira; Caldas, Rafaella Gaiotti; Freitas, Carolina Renata Camargos; Campi-Azevedo, Ana Carolina; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis

    2015-01-01

    Differential serological diagnosis of Chagas disease and leishmaniasis is difficult owing to cross-reactivity resulting from the fact that the parasites that cause these pathologies share antigenic epitopes. Even with optimized serological assays that use parasite-specific recombinant antigens, inconclusive test results continue to be a problem. Therefore, new serological tests with high sensitivity and specificity are needed. In the present work, we developed and evaluated the performance of a new flow cytometric serological method, referred to as FC-TRIPLEX Chagas/Leish IgG1, for the all-in-one classification of inconclusive tests. The method uses antigens for the detection of visceral leishmaniasis, localized cutaneous leishmaniasis, and Chagas disease and is based on an inverted detuned algorithm for analysis of anti-Trypanosomatidae IgG1 reactivity. First, parasites were label with fluorescein isothiocyanate or Alexa Fluor 647 at various concentrations. Then serum samples were serially diluted, the dilutions were incubated with suspensions of mixed labeled parasites, and flow cytometric measurements were performed to determine percentages of positive fluorescent parasites. Using the new method, we obtained correct results for 76 of 80 analyzed serum samples (95% overall performance), underscoring the outstanding performance of the method. Moreover, we found that the fluorescently labeled parasite suspensions were stable during storage at room temperature, 4 °C, and -20 °C for 1 year. In addition, two different lots of parasite suspensions showed equivalent antigen recognition; that is, the two lots showed equivalent categorical segregation of anti-Trypanosomatidae IgG1 reactivity at selected serum dilutions. In conclusion, we have developed a sensitive and selective method for differential diagnosis of Chagas disease, visceral leishmaniasis, and localized cutaneous leishmaniasis.

  11. Further genetic characterization of the two Trypanosoma cruzi Berenice strains (Be-62 and Be-78) isolated from the first human case of Chagas disease (Chagas, 1909).

    PubMed

    Cruz, R E; Macedo, A M; Barnabé, C; Freitas, J M; Chiari, E; Veloso, V M; Carneiro, C M; Bahia, M T; Tafuri, Washington L; Lana, M

    2006-03-01

    We describe here an extension of a previous genetic characterization of Trypanosoma cruzi strains (Be-62 and Be-78) isolated from the patient Berenice, the first human case of Chagas disease [Chagas, C., 1909. Nova Tripanomíase humana. Estudos sobre morfologia e o ciclo evolutivo do Schizotrypanum cruzi, n. gen., n. sp., agente etiolójico da nova entidade morbida do homem. Mem. Inst. Oswaldo Cruz 1, 159-218]. We wanted to verify the composition of T. cruzi populations originated from these two isolates. In the present work, 22 enzymatic loci (MLEE), nine RAPD primers and 7 microsatellite loci were analyzed. Clones from both strains were also characterized to verify whether these strains are mono or polyclonal. Be-62 and Be-78 strains were different in 3 out of 22 enzymatic systems, in 3 out of 9 RAPD primers tested and in all microsatellite loci investigated. However, our data suggests that both strains are phylogenetically closely related, belonging to genetic group 32 from Tibayrenc and Ayala [Tibayrenc, M., Ayala, F.J., 1988. Isoenzime variability in Trypanosoma cruzi, the agent of Chagas' disease: genetical, taxonomical, and epidemiological significance. Evolution 42, 277-292], equivalent to zymodeme 2 and T. cruzi II major lineage which, in Brazil, comprises parasites from the domestic cycle of the disease. Microsatellite analyses showed differences between the parental strains but suggested that both populations are monoclonal since each strain and their respective clones showed the same amplification products.

  12. Mode of Death on Chagas Heart Disease: Comparison with Other Etiologies. A Subanalysis of the REMADHE Prospective Trial

    PubMed Central

    Ayub-Ferreira, Silvia M.; Mangini, Sandrigo; Issa, Victor S.; Cruz, Fátima D.; Bacal, Fernando; Guimarães, Guilherme V.; Chizzola, Paulo R.; Conceição-Souza, Germano E.; Marcondes-Braga, Fabiana G.; Bocchi, Edimar A.

    2013-01-01

    Background Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy. Methods and results We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34–5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04–1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97–0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47–6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01–1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34–0.94; p = 0.014) were independently associated with sudden death mortality. Conclusions In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death. Trial Registration ClinicalTrails.gov NCT00505050 (REMADHE) PMID:23638197

  13. Spatial Patterns in Discordant Diagnostic Test Results for Chagas Disease: Links to Transmission Hotspots

    PubMed Central

    Levy, Michael Z.; Bowman, Natalie M.; Kawai, Vivian; Plotkin, Joshua B.; Waller, Lance A.; Cabrera, Lilia; Steurer, Frank; Seitz, Amy E.; Pinedo-Cancino, Viviana V.; Carpio, Juan Geny Cornejo del; Benzaquen, Eleazar Cordova; McKenzie, F. Ellis; Maguire, James H.; Gilman, Robert H.; Bern, Caryn

    2009-01-01

    Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting. PMID:19278335

  14. Modeling Chagas Disease at Population Level to Explain Venezuela's Real Data

    PubMed Central

    González-Parra, Gilberto; Chen-Charpentier, Benito M.; Bermúdez, Moises

    2015-01-01

    Objectives In this paper we present an age-structured epidemiological model for Chagas disease. This model includes the interactions between human and vector populations that transmit Chagas disease. Methods The human population is divided into age groups since the proportion of infected individuals in this population changes with age as shown by real prevalence data. Moreover, the age-structured model allows more accurate information regarding the prevalence, which can help to design more specific control programs. We apply this proposed model to data from the country of Venezuela for two periods, 1961–1971, and 1961–1991 taking into account real demographic data for these periods. Results Numerical computer simulations are presented to show the suitability of the age-structured model to explain the real data regarding prevalence of Chagas disease in each of the age groups. In addition, a numerical simulation varying the death rate of the vector is done to illustrate prevention and control strategies against Chagas disease. Conclusion The proposed model can be used to determine the effect of control strategies in different age groups. PMID:26929912

  15. PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL.

    PubMed

    Lopes, Patrícia da Silva; Ramos, Eliezer Lucas Pires; Gómez-Hernández, César; Ferreira, Gabriela Lícia Santos; Rezende-Oliveira, Karine

    2015-12-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results.

  16. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches

    PubMed Central

    de Noya, Belkisyolé Alarcón; Díaz-Bello, Zoraida; Colmenares, Cecilia; Ruiz-Guevara, Raiza; Mauriello, Luciano; Muñoz-Calderón, Arturo; Noya, Oscar

    2015-01-01

    Orally transmitted Chagas disease has become a matter of concern due to outbreaks reported in four Latin American countries. Although several mechanisms for orally transmitted Chagas disease transmission have been proposed, food and beverages contaminated with whole infected triatomines or their faeces, which contain metacyclic trypomastigotes of Trypanosoma cruzi, seems to be the primary vehicle. In 2007, the first recognised outbreak of orally transmitted Chagas disease occurred in Venezuela and largest recorded outbreak at that time. Since then, 10 outbreaks (four in Caracas) with 249 cases (73.5% children) and 4% mortality have occurred. The absence of contact with the vector and of traditional cutaneous and Romana’s signs, together with a florid spectrum of clinical manifestations during the acute phase, confuse the diagnosis of orally transmitted Chagas disease with other infectious diseases. The simultaneous detection of IgG and IgM by ELISA and the search for parasites in all individuals at risk have been valuable diagnostic tools for detecting acute cases. Follow-up studies regarding the microepidemics primarily affecting children has resulted in 70% infection persistence six years after anti-parasitic treatment. Panstrongylus geniculatus has been the incriminating vector in most cases. As a food-borne disease, this entity requires epidemiological, clinical, diagnostic and therapeutic approaches that differ from those approaches used for traditional direct or cutaneous vector transmission. PMID:25946155

  17. On the possibility of autochthonous Chagas disease in Roraima, Amazon region, Brazil, 2000-2001.

    PubMed

    Luitgards-Moura, José Francisco; Borges-Pereira, José; Costa, Jane; Zauza, Patrícia Lago; Rosa-Freitas, Maria Goreti

    2005-01-01

    Chagas disease has been almost entirely eradicated from the arid zones in Central and Northeastern Brazil where rare or no autochthonous cases have been reported. However, in the last 10 years the disease has increasingly been registered in the Amazon Region. Aiming to investigate the possibility of the occurrence of autochthonous cycle of Chagas disease in Roraima, triatomine collections, vectorial susceptibility studies (this one to be shown elsewhere), parasitological and serological analyses were conducted in three agricultural settlement areas (Rorainópolis, Passarão Project and Ilha Community). Blood-donor candidates were also investigated. This is the first epidemiological survey on Chagas disease conducted in agricultural settlements in Roraima. Triatomine species found were Triatoma maculata, Rhodnius pictipes, Rhodnius robustus and Panstrongylus geniculatus. Trypanosoma cruzi detection analyses included xenodiagnosis, indirect immunofluorescence, indirect hemaglutination, ELISA and kinetoplast PCR amplification. Natural triatomine infection was not found in intestinal contents. Twenty-five adult settlers (1.4% out of 1821, all > 15 year-old, 20 migrants) presented anti-T. cruzi antibodies. Two migrant settlers (from Minas Gerais and Maranhão) tested positive for more than two serological tests, besides either being positive for xenodiagnosis or PCR. Results show that Chagas disease is not endemic in the areas studied. However, all elements of the transmission cycle are present, demanding for an adequate and continuous vigilance.

  18. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

    PubMed Central

    Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

    2015-01-01

    The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario. PMID:26676323

  19. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches.

    PubMed

    Noya, Belkisyolé Alarcón de; Díaz-Bello, Zoraida; Colmenares, Cecilia; Ruiz-Guevara, Raiza; Mauriello, Luciano; Muñoz-Calderón, Arturo; Noya, Oscar

    2015-05-01

    Orally transmitted Chagas disease has become a matter of concern due to outbreaks reported in four Latin American countries. Although several mechanisms for orally transmitted Chagas disease transmission have been proposed, food and beverages contaminated with whole infected triatomines or their faeces, which contain metacyclic trypomastigotes of Trypanosoma cruzi, seems to be the primary vehicle. In 2007, the first recognised outbreak of orally transmitted Chagas disease occurred in Venezuela and largest recorded outbreak at that time. Since then, 10 outbreaks (four in Caracas) with 249 cases (73.5% children) and 4% mortality have occurred. The absence of contact with the vector and of traditional cutaneous and Romana's signs, together with a florid spectrum of clinical manifestations during the acute phase, confuse the diagnosis of orally transmitted Chagas disease with other infectious diseases. The simultaneous detection of IgG and IgM by ELISA and the search for parasites in all individuals at risk have been valuable diagnostic tools for detecting acute cases. Follow-up studies regarding the microepidemics primarily affecting children has resulted in 70% infection persistence six years after anti-parasitic treatment. Panstrongylus geniculatus has been the incriminating vector in most cases. As a food-borne disease, this entity requires epidemiological, clinical, diagnostic and therapeutic approaches that differ from those approaches used for traditional direct or cutaneous vector transmission.

  20. Increasing Access to Treatment for Chagas Disease: The Case of Morelos, Mexico

    PubMed Central

    Manne-Goehler, Jennifer; Ramsey, Janine M.; Salgado, Marco Ocampo; Wirtz, Veronika J.; Reich, Michael R.

    2014-01-01

    Chagas disease is a neglected vector-borne disease with an estimated prevalence of 1.1 million cases in Mexico. Recent research showed that access to treatment of Chagas disease is limited in Mexico, with < 0.5% of infected cases treated. This brief report used quantitative data from the Morelos Program on Chagas disease and qualitative analysis of key informant interviews to examine strategies to increase treatment access for infected patients in Morelos, Mexico. From 2007 to 2011, 263 (9.2%) of the registered cases of Chagas disease in Mexico occurred in Morelos. Among these, 152 (57.8%) were treated and 97.3% of those treated received benznidazole. The assessment finds that state officials decided to directly purchase benznidazole from the distributor to increase access and improve clinical quality of treatment of patients in their state. They also faced significant barriers, especially in regulation and health system organization, which limited efforts to make high quality treatment available. PMID:25266353

  1. A 4-year follow-up study of a rural community with endemic Chagas' disease*

    PubMed Central

    Puigbó, J. J.; Rhode, J. R. Nava; Barrios, H. García; Yépez, C. Gil

    1968-01-01

    The paper reports on a 4-year follow-up study that represents the continuation of a previous cross-sectional study on Chagas' disease carried out in a rural community (Belén) in Venezuela. The earlier study included 1210 persons all over 5 years of age out of a total of 1656 inhabitants and demonstrated a high prevalence of Chagas' infection (47.3%) and a high rate of Chagas' disease seropositivity among those with chronic myocardial heart disease (84.8%); heart disease was found in 17.3% of persons studied. The follow-up study was based on 812 persons and established that in the sample the frequency of Chagas' infection was 16.3% and that of heart disease 2.2%. Clinical, electrocardiographic and radiological analyses were made on patients with previous heart disease as well as on new patients. Different evolutive electrocardiographic patterns have been found, including variations ranging from normal to definitively abnormal. ImagesFIG. 1FIG. 2 PMID:4974002

  2. Towards Chagas disease elimination: Neonatal screening for congenital transmission in rural communities.

    PubMed

    Pennington, Pamela Marie; Juárez, José Guillermo; Arrivillaga, Margarita Rivera; De Urioste-Stone, Sandra María; Doktor, Katherine; Bryan, Joe P; Escobar, Clara Yaseli; Cordón-Rosales, Celia

    2017-09-11

    Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities. From December 2015 to April 2016, we jointly developed a strategy to illustratively advertise newborn screening at the Health Center. The strategy included socioculturally appropriate promotional and educational material, in collaboration with midwives, nurses and nongovernmental organizations. By March 2016, eight of 228 (3.9%) pregnant women had been diagnosed with T. cruzi at the Health Center. Up to this date, no neonatal screening had been performed. By August 2016, seven of eight newborns born to Chagas seropositive women had been parasitologically screened at the Health Center, according to international standards. Thus, we implemented a successful community-based neonatal screening strategy to promote congenital Chagas disease healthcare in a rural setting. The success of the health promotion strategies developed will depend on local access to maternal-infant services, integration with detection of other congenital diseases and reliance on community participation in problem and solution definition.

  3. Modeling Chagas Disease at Population Level to Explain Venezuela's Real Data.

    PubMed

    González-Parra, Gilberto; Chen-Charpentier, Benito M; Bermúdez, Moises

    2015-10-01

    In this paper we present an age-structured epidemiological model for Chagas disease. This model includes the interactions between human and vector populations that transmit Chagas disease. The human population is divided into age groups since the proportion of infected individuals in this population changes with age as shown by real prevalence data. Moreover, the age-structured model allows more accurate information regarding the prevalence, which can help to design more specific control programs. We apply this proposed model to data from the country of Venezuela for two periods, 1961-1971, and 1961-1991 taking into account real demographic data for these periods. Numerical computer simulations are presented to show the suitability of the age-structured model to explain the real data regarding prevalence of Chagas disease in each of the age groups. In addition, a numerical simulation varying the death rate of the vector is done to illustrate prevention and control strategies against Chagas disease. The proposed model can be used to determine the effect of control strategies in different age groups.

  4. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    PubMed Central

    Gonzalez-Mejia, Martha Elba; Torres-Rasgado, Enrique; Porchia, Leonardo M; Salgado, Hilda Rosas; Totolhua, José-Luis; Ortega, Arturo; Hernández-Kelly, Luisa Clara Regina; Ruiz-Vivanco, Guadalupe; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels. PMID:24676665

  5. Mother-child transmission of Chagas disease: could coinfection with human immunodeficiency virus increase the risk?

    PubMed

    Scapellato, Pablo Gustavo; Bottaro, Edgardo Gabriel; Rodríguez-Brieschke, María Teresa

    2009-01-01

    A study was conducted on all newborns from mothers with Chagas disease who were attended at Hospital Donación F. Santojanni between January 1, 2001, and August 31, 2007. Each child was investigated for the presence of Trypanosoma cruzi parasitemia through direct examination of blood under the microscope using the buffy coat method on three occasions during the first six months of life. Serological tests were then performed. Ninety-four children born to mothers infected with Trypanosoma cruzi were attended over the study period. Three of these children were born to mothers coinfected with the human immunodeficiency virus. Vertical transmission of Chagas disease was diagnosed in 13 children, in all cases by identifying parasitemia. The overall Chagas disease transmission rate was 13.8% (13/94). It was 100% (3/3) among the children born to mothers with HIV infection and 10.9% (10/91) among children born to mothers without HIV [Difference = 0.89; CI95 = 0.82-0.95; p = 0.0021]. We concluded that coinfection with HIV could increase the risk of vertical transmission of Chagas disease.

  6. [The first case of congenital Chagas' disease analyzed by AP-PCR in Colombia].

    PubMed

    Pavia, Paula Ximena; Montilla, Marleny; Flórez, Carolina; Herrera, Giomar; Ospina, Juan Manuel; Manrique, Fred; Nicholls, Rubén Santiago; Puerta, Concepción

    2009-12-01

    The main route of Chagas disease transmission is through vectors of the insect family Reduviidae. However, the parasite can also be transmitted from infected mothers to their fetus in utero. Until now, no cases of congenital Chagas disease have been reported in Colombia. A congenital Chagas disease case occurred in Moniquirá County, Boyacá, Colombia. It was confirmed by comparing strains isolated from the mother and her baby using polymerase chain reaction (PCR) with arbitrary primers. The parasite DNA was extracted from positive blood cultures of the afflicted mother and her son. The species confirmation and group detection were performed by PCR. The strain genotypes were determined by AP-PCR with two oligonucleotides based on the genes for the b-globin (5'-CCTCACCTTCTTTCATGGAG-3') and 16S RrNA (5'-ACGGGCAGTGTGTACAAGACC-3'), in different reactions. The T. cruzi strains isolated from the blood cultures of the mother and her son showed the same amplification profile by the two AP-PCR tests; this corresponded with profiles of the T. cruzi I strains used as controls. However, T. cruzi II was also found in the blood culture from the newborn. This is the first case of Chagas disease transmission reported in Moniquirá, demonstrating that this form of transmission occurs in Colombia. The presence of both groups of T. cruzi in the newborn sample suggests mixed infection in the mother as well, with a higher prevalence of T. cruzi I, at least in the mother's blood culture.

  7. Chaga mushroom extract inhibits oxidative DNA damage in human lymphocytes as assessed by comet assay.

    PubMed

    Park, Yoo Kyoung; Lee, Hyang Burm; Jeon, Eun-Jae; Jung, Hack Sung; Kang, Myung-Hee

    2004-01-01

    The Chaga mushroom (Inonotus obliquus) is claimed to have beneficial properties for human health, such as anti-bacterial, anti-allergic, anti-inflammatory and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protection of cell components against free radicals. We evaluated the effect of aqueous Chaga mushroom extracts for their potential for protecting against oxidative damage to DNA in human lymphocytes. Cells were pretreated with various concentrations (10, 50, 100 and 500 microg/mL) of the extract for 1 h at 37 degrees C. Cells were then treated with 100 microM of H2O2 for 5 min as an oxidative stress. Evaluation of oxidative damage was performed using single-cell gel electrophoresis for DNA fragmentation (Comet assay). Using image analysis, the degree of DNA damage was evaluated as the DNA tail moment. Cells pretreated with Chaga extract showed over 40% reduction in DNA fragmentation compared with the positive control (100 micromol H2O2 treatment). Thus, Chaga mushroom treatment affords cellular protection against endogenous DNA damage produced by H2O2.

  8. Oral transmission of Chagas disease by consumption of açaí palm fruit, Brazil.

    PubMed

    Nóbrega, Aglaêr A; Garcia, Marcio H; Tatto, Erica; Obara, Marcos T; Costa, Elenild; Sobel, Jeremy; Araujo, Wildo N

    2009-04-01

    In 2006, a total of 178 cases of acute Chagas disease were reported from the Amazonian state of Pará, Brazil. Eleven occurred in Barcarena and were confirmed by visualization of parasites on blood smears. Using cohort and case-control studies, we implicated oral transmission by consumption of açaí palm fruit.

  9. Oral Transmission of Chagas Disease by Consumption of Açaí Palm Fruit, Brazil

    PubMed Central

    Garcia, Marcio H.; Tatto, Erica; Obara, Marcos T.; Costa, Elenild; Sobel, Jeremy; Araujo, Wildo N.

    2009-01-01

    In 2006, a total of 178 cases of acute Chagas disease were reported from the Amazonian state of Pará, Brazil. Eleven occurred in Barcarena and were confirmed by visualization of parasites on blood smears. Using cohort and case–control studies, we implicated oral transmission by consumption of açaí palm fruit. PMID:19331764

  10. Trypanosoma cruzi strain TcI is associated with chronic Chagas disease in the Brazilian Amazon

    PubMed Central

    2014-01-01

    Background Chagas disease in the Amazon region is considered an emerging anthropozoonosis with a predominance of the discrete typing units (DTUs) TcI and TcIV. These DTUs are responsible for cases of acute disease associated with oral transmission. Chronic disease cases have been detected through serological surveys. However, the mode of transmission could not be determined, or any association of chronic disease with a specific T. cruzi DTU’s. The aim of this study was to characterize Trypanosoma cruzi in patients with chronic Chagas disease in the State of Amazonas, Brazil. Methods Blood culture and xenodiagnosis were performed in 36 patients with positive serology for Chagas disease who participated in a serological survey performed in urban and rural areas of Manaus, Amazonas. DNA samples were extracted from the feces of triatomines used for xenodiagnosis, and the nontranscribed spacer of the mini-exon gene and the mitochondrial gene cytochrome oxidase subunit II (COII) were amplified by PCR and sequenced. Results Blood culture and xenodiagnosis were negative in 100% of samples; however, molecular techniques revealed that in 13 out of 36 (36%) fecal samples from xenodiagnosis, T. cruzi was characterized as the DTU TcI, and different haplotypes were identified within the same DTU. Conclusion The DTU TcI, which is mainly associated with acute cases of Chagas disease in the Amazon region, is also responsible for chronic infection in patients from a region in the State of Amazonas. PMID:24916362

  11. Certifying achievement in the control of Chagas disease native vectors: what is a viable scenario?

    PubMed Central

    Hashimoto, Ken; Yoshioka, Kota

    2014-01-01

    As an evaluation scheme, we propose certifying for “control”, as alternative to “interruption”, of Chagas disease transmission by native vectors, to project a more achievable and measurable goal and sharing good practices through an “open online platform” rather than “formal certification” to make the key knowledge more accumulable and accessible. PMID:25317713

  12. PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL

    PubMed Central

    LOPES, Patrícia da Silva; RAMOS, Eliezer Lucas Pires; GÓMEZ-HERNÁNDEZ, César; FERREIRA, Gabriela Lícia Santos; REZENDE-OLIVEIRA, Karine

    2015-01-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results. PMID:27049698

  13. Chagas Disease in Mexico: Report of 14 Cases of Chagasic Cardiomyopathy in Children.

    PubMed

    Salazar-Schettino, Paz María; Cabrera-Bravo, Margarita; Vazquez-Antona, Clara; Zenteno, Edgar; Alba-Alvarado, Mariana De; Gutierrez, Elia Torres; Gomez, Yolanda Guevara; Perera-Salazar, María Gabriela; Torre, Guadalupe Garcia de la; Bucio-Torres, Martha Irene

    2016-01-01

    Chagas disease is a parasitic infection mainly found in Latin America; it is transmitted by a triatomine, also known as assassin bug or kissing bug. In humans, the parasite causes mostly cardiac disorders. Two-thirds of the Mexican territory are regarded as risk areas for vector transmission of Trypanosoma cruzi, the causal agent. The parasite can be found as a blood-borne trypomastigote or as an intracellular amastigote. The progression and severity of lesions could be due to frequent reinfections or to infection by highly virulent strains. A total of 3,327 individuals younger than 18 years old, living in risk areas for this disease in the rural setting of the States of Queretaro, San Luis Potosi, and Veracruz, underwent a seroepidemiological study. Among them, 37 subjects were seropositive for T. cruzi, and were studied to look for signs of cardiac pathology, which has only been reported in adults. A clinical record was prepared for all included individuals, and electrocardiography (ECG) and echocardiography (ECHO) studies were performed; 25 cases showed lesions compatible with the onset of Chagas cardiomyopathy. The other 12 patients showed either normal ECG and ECHO data or showed abnormal parameters that were not regarded as significant. Lesions found in the onset of Chagas cardiomyopathy in children are herein reported, along with 14 cases of cardiac pathology compatible with Chagas disease. Our results indicate that patients younger than 18 years can show a cardiac pathology similar to that observed in adults.

  14. Chagas Disease in 2 Geriatric Rhesus Macaques (Macaca mulatta) Housed in the Pacific Northwest

    PubMed Central

    Dickerson, Mary F; Astorga, Nestor Gerardo; Astorga, Nestor Rodrigo; Lewis, Anne D

    2014-01-01

    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission. PMID:25296019

  15. Chagas Disease in a Domestic Transmission Cycle in Southern Texas, USA

    PubMed Central

    Pye, Greg; Steurer, Frank J.; Rodriguez, Ray; Campman, Richard; Peterson, A. Townsend; Ramsey, Janine; Wirtz, Robert A.; Robinson, Laura E.

    2003-01-01

    After three dogs died from acute Chagas cardiomyopathy at one location, an investigation was conducted of the home, garage, and grounds of the owner. A serologic study was conducted on stray dogs, and an ecologic niche model was developed to predict areas where the vector Tryiatoma gerstaeckeri might be expected. PMID:12533289

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

    PubMed

    de Carvalho, Katherine Athayde Teixeira; Abdelwahid, Eltyeb; Ferreira, Reginaldo Justino; Irioda, Ana Carolina; Guarita-Souza, Luiz Cesar

    2013-12-24

    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.

  17. Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

    PubMed

    Vasconcelos, R H T; Azevedo, E de A N; Diniz, G T N; Cavalcanti, M da G A de M; de Oliveira, W; de Morais, C N L; Gomes, Y de M

    2015-07-01

    In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease. © 2015 John Wiley & Sons Ltd.

  18. Applicability of a novel immunoassay based on surface plasmon resonance for the diagnosis of Chagas disease.

    PubMed

    Luz, João G G; Souto, Dênio E P; Machado-Assis, Girley F; de Lana, Marta; Luz, Rita C S; Martins-Filho, Olindo A; Damos, Flávio S; Martins, Helen R

    2016-02-15

    We defined the methodological criteria for the interpretation of the results provided by a novel immunoassay based on surface plasmon resonance (SPR) to detect antibodies anti-Trypanosoma cruzi in human sera (SPRCruzi). Then, we evaluated its applicability as a diagnostic tool for Chagas disease. To define the cut-off point and serum dilution factor, 57 samples were analyzed at SPRCruzi and the obtained values of SPR angle displacement (ΔθSPR) were submitted to statistical analysis. Adopting the indicated criteria, its performance was evaluated into a wide panel of samples, being 99 Chagas disease patients, 30 non-infected subjects and 42 with other parasitic/infectious diseases. In parallel, these samples were also analyzed by ELISA. Our data demonstrated that 1:320 dilution and cut-off point at ∆θSPR=17.2 m° provided the best results. Global performance analysis demonstrated satisfactory sensitivity (100%), specificity (97.2%), positive predictive value (98%), negative predictive value (100%) and global accuracy (99.6%). ELISA and SPRCruzi showed almost perfect agreement, mainly between chagasic and non-infected individuals. However, the new immunoassay was better in discriminate Chagas disease from other diseases. This work demonstrated the applicability of SPRCruzi as a feasible, real time, label free, sensible and specific methodology for the diagnosis of Chagas disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Chagas' disease and the use of implantable cardioverter-defibrillators in Brazil.

    PubMed

    Rosa, Ronaldo F; Neto, Argemiro S; Franken, Roberto A

    2006-01-01

    The authors discuss the epidemiology and pathogenesis of Chagas' disease in Brazil, including the use of treatment with a cardioverter-defibrillator in patients with low ejection fraction. Select patients may benefit from resynchronization therapy associated with cardioverter-defibrillator treatment. Electrophysiologic study is indicated in the assessment of the potential utility of an implantable cardioverter-defibrillator.

  20. The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease.

    PubMed

    Junqueira, Caroline; Caetano, Braulia; Bartholomeu, Daniella C; Melo, Mariane B; Ropert, Catherine; Rodrigues, Maurício M; Gazzinelli, Ricardo T

    2010-09-15

    Infection with the protozoan parasite Trypanosoma cruzi, the agent of Chagas disease, is characterised by a variable clinical course - from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. The variability in disease outcome has been attributed to host responses as well as parasite heterogeneity. In this article, we review studies indicating the importance of immune responses as key determinants of host resistance to T. cruzi infection and the pathogenesis of Chagas disease. Particular attention is given to recent studies defining the role of cognate innate immune receptors and immunodominant CD8+ T cells that recognise parasite components - both crucial for host-parasite interaction and disease outcome. In light of these studies we speculate about parasite strategies that induce a strong and long-lasting T-cell-mediated immunity but at the same time allow persistence of the parasite in the vertebrate host. We also discuss what we have learned from these studies for increasing our understanding of Chagas pathogenesis and for the design of new strategies to prevent the development of Chagas disease. Finally, we highlight recent studies employing a genetically engineered attenuated T. cruzi strain as a vaccine shuttle that elicits potent T cell responses specific to a tumour antigen and protective immunity against a syngeneic melanoma cell line.

  1. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

    PubMed Central

    BRAVO-TOBAR, Iván Darío; NELLO-PÉREZ, Carlota; FERNÁNDEZ, Alí; MOGOLLÓN, Nora; PÉREZ, Mary Carmen; VERDE, Juan; CONCEPCIÓN, Juan Luis; RODRIGUEZ-BONFANTE, Claudina; BONFANTE-CABARCAS, Rafael

    2015-01-01

    SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease. PMID:26603224

  2. [Serologic study of the diagnosis of Chagas disease in Nicaraguan students in the Juventud island].

    PubMed

    Montes de Oca, N V; Cabrera Alonso, C; Martínez, R; Cantelar de Francisco, N; Pérez Insueta, O

    1989-01-01

    The results obtained during the serologic study for the diagnosis of Chagas' disease in 868 Nicaraguan students in the Isle of Youth are reported. Qualitative hemagglutination and indirect immunofluorescence were used. It was found that 8.5% of these students showed antibodies specific to Trypanosoma cruzi by means of this diagnostic test.

  3. Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

    PubMed

    Dumonteil, Eric; Bottazzi, Maria Elena; Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, B T; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto; Hotez, Peter J

    2012-09-01

    Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.

  4. Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects

    PubMed Central

    Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, BT; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto

    2013-01-01

    Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children’s Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA. PMID:23151163

  5. Dynamics of the antibody-T.cruzi competition during Chagas infection: Prognostic relevance of intracellular replication

    NASA Astrophysics Data System (ADS)

    Sibona, G. J.; Condat, C. A.; Isasi, S. Cossy

    2005-02-01

    A recently proposed model for the competitive parasite-antibody interactions in Chagas disease is extended by separately describing the parasitic intracellular and extracellular phases. The model solutions faithfully reproduce available population data and yield predictions for parasite-induced cardiac cell damage.

  6. Short report: Increasing access to treatment for Chagas disease: the case of Morelos, Mexico.

    PubMed

    Manne-Goehler, Jennifer; Ramsey, Janine M; Salgado, Marco Ocampo; Wirtz, Veronika J; Reich, Michael R

    2014-12-01

    Chagas disease is a neglected vector-borne disease with an estimated prevalence of 1.1 million cases in Mexico. Recent research showed that access to treatment of Chagas disease is limited in Mexico, with < 0.5% of infected cases treated. This brief report used quantitative data from the Morelos Program on Chagas disease and qualitative analysis of key informant interviews to examine strategies to increase treatment access for infected patients in Morelos, Mexico. From 2007 to 2011, 263 (9.2%) of the registered cases of Chagas disease in Mexico occurred in Morelos. Among these, 152 (57.8%) were treated and 97.3% of those treated received benznidazole. The assessment finds that state officials decided to directly purchase benznidazole from the distributor to increase access and improve clinical quality of treatment of patients in their state. They also faced significant barriers, especially in regulation and health system organization, which limited efforts to make high quality treatment available. © The American Society of Tropical Medicine and Hygiene.

  7. Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

    PubMed

    Chiale, P A; Przybylski, J; Laiño, R A; Halpern, M S; Sánchez, R A; Gabrieli, A; Elizari, M V; Rosenbaum, M B

    1982-01-01

    Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

  8. Role of PPARs in Trypanosoma cruzi Infection: Implications for Chagas Disease Therapy

    PubMed Central

    Hovsepian, Eugenia; Penas, Federico; Mirkin, Gerardo A.; Goren, Nora B.

    2012-01-01

    Chagas disease, which is caused by Trypanosoma cruzi (T. cruzi), remains a substantial public health concern and an important cause of morbidity and mortality in Latin America. T. cruzi infection causes an intense inflammatory response in diverse tissues by triggering local expression of inflammatory mediators, which results in the upregulation of the levels of cytokines and chemokines, and important cardiac alterations in the host, being one of the most characteristic damages of Chagas disease. Therefore, controlling the inflammatory reaction becomes critical for the control of the proliferation of the parasite and of the evolution of Chagas disease. The nuclear receptors known as peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of lipid metabolism and inflammation. The precise role of PPAR ligands in T. cruzi infection or in Chagas disease is poorly understood. This review summarizes our knowledge about T. cruzi infection as well as about the activation of PPARs and the potential role of their ligands in the resolution of inflammation, with the aim to address a new pharmacological approach to improve the host health. PMID:22448167

  9. Spatial patterns in discordant diagnostic test results for Chagas disease: links to transmission hotspots.

    PubMed

    Levy, Michael Z; Bowman, Natalie M; Kawai, Vivian; Plotkin, Joshua B; Waller, Lance A; Cabrera, Lilia; Steurer, Frank; Seitz, Amy E; Pinedo-Cancino, Viviana V; Cornejo del Carpio, Juan Geny; Cordova Benzaquen, Eleazar; McKenzie, F Ellis; Maguire, James H; Gilman, Robert H; Bern, Caryn

    2009-04-15

    Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting.

  10. Increased mortality attributed to Chagas disease: a systematic review and meta-analysis.

    PubMed

    Cucunubá, Zulma M; Okuwoga, Omolade; Basáñez, María-Gloria; Nouvellet, Pierre

    2016-01-27

    The clinical outcomes associated with Chagas disease remain poorly understood. In addition to the burden of morbidity, the burden of mortality due to Trypanosoma cruzi infection can be substantial, yet its quantification has eluded rigorous scrutiny. This is partly due to considerable heterogeneity between studies, which can influence the resulting estimates. There is a pressing need for accurate estimates of mortality due to Chagas disease that can be used to improve mathematical modelling, burden of disease evaluations, and cost-effectiveness studies. A systematic literature review was conducted to select observational studies comparing mortality in populations with and without a diagnosis of Chagas disease using the PubMed, MEDLINE, EMBASE, Web of Science and LILACS databases, without restrictions on language or date of publication. The primary outcome of interest was mortality (as all-cause mortality, sudden cardiac death, heart transplant or cardiovascular deaths). Data were analysed using a random-effects model to obtain the relative risk (RR) of mortality, the attributable risk percent (ARP), and the annual mortality rates (AMR). The statistic I(2) (proportion of variance in the meta-analysis due to study heterogeneity) was calculated. Sensitivity analyses and publication bias test were also conducted. Twenty five studies were selected for quantitative analysis, providing data on 10,638 patients, 53,346 patient-years of follow-up, and 2739 events. Pooled estimates revealed that Chagas disease patients have significantly higher AMR compared with non-Chagas disease patients (0.18 versus 0.10; RR = 1.74, 95% CI 1.49-2.03). Substantial heterogeneity was found among studies (I(2) = 67.3%). The ARP above background mortality was 42.5%. Through a sub-analysis patients were classified by clinical group (severe, moderate, asymptomatic). While RR did not differ significantly between clinical groups, important differences in AMR were found: AMR = 0.43 in

  11. Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.

    PubMed

    Pérez-Fuentes, Ricardo; Guégan, Jean-François; Barnabé, Christian; López-Colombo, Aurelio; Salgado-Rosas, Hilda; Torres-Rasgado, Enrique; Briones, Bernardo; Romero-Díaz, Mónica; Ramos-Jiménez, Judith; Sánchez-Guillén, María del Carmen

    2003-03-01

    Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease.

  12. High resolution of Trypanosoma cruzi amastigote antigen in serodiagnosis of different clinical forms of Chagas' disease.

    PubMed Central

    Matsumoto, T K; Hoshino-Shimizu, S; Nakamura, P M; Andrade, H F; Umezawa, E S

    1993-01-01

    The serodiagnosis of Chagas' disease, a highly prevalent disorder in South American countries, is usually made by the detection of antibodies to Trypanosoma cruzi epimastigote antigen. In this study, we assess the diagnostic performance of the immunofluorescence test with T. cruzi (Y strain) amastigote antigen from an LLC-MK2-infected cell supernatant in comparison with a test with the conventional epimastigote antigen. A total of 238 serum samples from patients in the acute and chronic phases of the disease, with the chronic indeterminate, cardiac, and digestive forms, and from nonchagasic individuals were tested for the presence of immunoglobulin G (IgG), IgM, and IgA antibodies. The reactivity of the amastigote antigen in terms of geometric mean titers was 2 to 4 times higher than that of the epimastigote antigen. Clear-cut results were obtained with the amastigote antigen, with no overlapping of true and false positives. IgG antibodies to amastigotes were found in all patients with Chagas' disease, whereas all sera from nonchagasic patients were negative, except for those from patients with visceral leishmaniasis, in which 63% cross-reactivity was observed. IgM antibodies to amastigotes were detected in 100% of sera from patients with acute Chagas' disease and in 7.5% of sera from patients with chronic Chagas' disease, whereas IgA antibodies were found in 60% of sera from patients in the acute phase and in 33% of sera from patients in the chronic phase. Despite the cross-reactivity observed with sera from visceral leishmaniasis patients, the IgG immunofluorescence test with the amastigote antigen had the highest sensitivity, specificity, and efficiency. No relationship was observed between the class-specific antibodies or their titers and the clinical forms of patients in the chronic phase. Amastigotes from the cell culture supernatant proved to be useful as an alternative antigen to epimastigotes because of their high resolution in the serodiagnosis of Chagas

  13. Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas' disease evolution.

    PubMed

    Rivarola, H W; Paglini-Oliva, P A

    2002-06-01

    Chagas' disease affects about 18 million people and 25% of the population of Latin America is at risk of acquiring Chagas' disease. The chemotherapy of Chagas' disease is still an open field and remains as an unsolved problem. Nifurtimox and benznidazole are currently used to treat this disease, however, both drugs have high toxicity and are mutagenic with the result that the patients frequently fail to follow treatment. T. cruzi enzimes such as trypanothione reductase, represent potential drug targets because they play an essential role in the life of this organism. This enzyme has been isolated, purified and studied by X ray crystallography. Phenothiazines and related compounds inhibit trypanothione reductase and a specially favoured fit is a phenothiazine with a 2- substitued with 2- chloro and 2- trifluoromethyl with a remote hydrophobic patch. The essential phenothiazine nucleus can adopt more than one inhibitory orientation in its binding site. Phenothiazines and related compounds are drugs used in psychiatric treatments. These anti-depressants inhibit trypanothione reductase through the peroxidase/ H2O2/ system, and also exert other trypanocidal effects upon epimastigotes and tripomastigotes forms: clomipramine through an anticalmodulin action; trifluopherazine and thioridazine induced disruption of mitochondria and prometazine provoked serious cell membrane disorganization. Clomipramine and thioridazine were also effective in treatment of mice with experimental Chagas' disease, significantly modifying the natural evolution of the infection; cardiac function and survival of infected and treated animals were not different from non infected animals. Phenothiazines and related compounds are promising trypanocidal agents for treatment of Chagas' disease. Other trypanocidal agents as nifurtimox, benznidazol,Allopurinol, cystein protease inhibitors and others, are also discussed.

  14. Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.

    PubMed

    Cruz, Gabriela da Silva; Angelo, Ana Luiza Dias; Larocca, Ticiana Ferreira; Macedo, Carolina Thé; Noya-Rabelo, Márcia; Correia, Luís Claudio Lemos; Torreão, Jorge Andion; Souza, Bruno Solano de Freitas; Santos, Ricardo Ribeiro Dos; Soares, Milena Botelho Pereira

    2015-11-01

    Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated. The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease. Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene. For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease. Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease.

  15. Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

    PubMed Central

    Cruz, Gabriela da Silva; Angelo, Ana Luiza Dias; Larocca, Ticiana Ferreira; Macedo, Carolina Thé; Noya- Rabelo, Márcia; Correia, Luís Claudio Lemos; Torreão, Jorge Andion; Souza, Bruno Solano de Freitas; dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira

    2015-01-01

    Background Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated. Objective The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease. Methods Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene. Results For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease. Conclusion Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. PMID:26312551

  16. Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

    PubMed

    Silva, Paula Simplício da; Mediano, Mauro Felippe Felix; Silva, Gilberto Marcelo Sperandio da; Brito, Patricia Dias de; Cardoso, Claudia Santos de Aguiar; Almeida, Cristiane Fonseca de; Sangenis, Luiz Henrique Conde; Pinheiro, Roberta Olmo; Hasslocher-Moreno, Alejandro Marcel; Brasil, Pedro Emmanuel Alvarenga Americano do; Sousa, Andrea Silvestre de

    2017-06-09

    Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. NCT01863576.

  17. Immunosuppression and Chagas disease; experience from a non-endemic country.

    PubMed

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Early polymerase chain reaction detection of Chagas disease reactivation in heart transplant patients.

    PubMed

    da Costa, Priscilla Almeida; Segatto, Marcela; Durso, Danielle Fernandes; de Carvalho Moreira, Wagson José; Junqueira, Lucas Lodi; de Castilho, Fábio Morato; de Andrade, Silvio Amadeu; Gelape, Cláudio Léo; Chiari, Egler; Teixeira-Carvalho, Andréa; Junho Pena, Sergio Danilo; Machado, Carlos Renato; Franco, Gloria Regina; Filho, Geraldo Brasileiro; Vieira Moreira, Maria da Consolação; Mara Macedo, Andréa

    2017-07-01

    Heart transplantation is a valuable therapeutic option for Chagas disease patients with severe cardiomyopathy. During patient follow-up, the differential diagnosis between cardiac transplant rejection and Chagas disease infection reactivation remains a challenging task, which hinders rapid implementation of the appropriate treatment. Herein we investigate whether polymerase chain reaction (PCR) strategies could facilitate early detection of Trypanosoma cruzi (T cruzi) in transplanted endomyocardial biopsies (EMBs). In this study we analyzed 500 EMB specimens obtained from 58 chagasic cardiac transplant patients, using PCR approaches targeted to nuclear (rDNA 24Sα) and kinetoplastid (kDNA) markers, and compared the efficiency of these approaches with that of other tests routinely used. T cruzi DNA was detected in 112 EMB specimens derived from 39 patients (67.2%). The first positive result occurred at a median 1.0 month post-transplant. Conventional histopathologic, blood smear and hemoculture analyses showed lower sensitivity and higher median time to the first positive result. Patient follow-up revealed that 31 of 39 PCR-positive cases presented clinical reactivation of Chagas disease at different time-points after transplantation. PCR techniques showed considerable sensitivity (0.82) and specificity (0.60), with area under the receiver operating characteristic (ROC) curves of 0.708 (p = 0.001). Moreover, PCR techniques anticipated the clinical signs of Chagas disease reactivation by up to 36 months, with a median time of 6 months and an average of 9.1 months. We found a good association between the PCR diagnosis and the clinical signs of the disease, indicating that the PCR approaches used herein are suitable for early diagnosis of Chagas disease reactivation, with high potential to assist physicians in treatment decisions. For this purpose, an algorithm is proposed for surveillance based on the molecular tests. Copyright © 2017 International Society for the

  19. [Investigation of vectors and reservoirs in an acute Chagas outbreak due to possible oral transmission in Aguachica, Cesar, Colombia].

    PubMed

    Soto, Hugo; Tibaduiza, Tania; Montilla, Marleny; Triana, Omar; Suárez, Diana Carolina; Torres Torres, Mariela; Arias, María Teresa; Lugo, Ligia

    2014-04-01

    Colombia recorded 11 cases of acute Chagas disease and 80 cases of oral contamination with Trypanosoma cruzi. The current study analyzes the entomological and parasitological characteristics of the outbreak in Aguachica, Cesar Department, in 2010. An interdisciplinary group of health professionals and regional university personnel conducted the laboratory tests in the patients and the investigation of the transmission focus. Eleven cases of acute Chagas diseases were detected in a single family in a dwelling with domiciliated triatomines and Rhodnius pallescens, Pantrongylus geniculatus, Eratyrus cuspidatus, and two Didelphis marsupialis opossums infected with T. cruzi in Attalea butyracea and Elaeis oleifera palm trees in the urban area of Aguachica. The study analyzes the role of R. pallescens and palm trees in the wild cycle of T. cruzi and in oral transmission of Chagas disease. Sporadic incursions by wild R. pallescens, P. geniculatus, and E. cuspidatus from the nearby palm trees into human dwellings may cause increasingly frequent outbreaks of oral Chagas disease.

  20. Antibodies to beta-adrenergic receptors disclosing agonist-like properties in idiopathic dilated cardiomyopathy and Chagas' heart disease.

    PubMed

    Rosenbaum, M B; Chiale, P A; Schejtman, D; Levin, M; Elizari, M V

    1994-04-01

    Recent studies confirm the existence of antibodies (Abs) to beta-adrenoceptors in patients with idiopathic dilated cardiomyopathy and Chagas' heart disease. These Abs can be shown to exert both stimulatory and inhibitory effects, which may play a role in the development of the cardiac abnormalities known to occur in these diseases, including advanced heart failure. The hypothesis is advanced that Chagas' heart disease and some forms of idiopathic dilated cardiomyopathy may represent, at least partially, a form of "adrenergic cardiomyopathy."

  1. Transmission of Donor-Derived Trypanosoma cruzi and Subsequent Development of Chagas Disease in a Lung Transplant Recipient

    PubMed Central

    Sonetti, D.; Maloney, J. D.; Montgomery, S. P.; Rademacher, B. L.; Taylor, L. J.; Smith, J. A.; Striker, R.

    2017-01-01

    Donor infection status should be considered when accepting an organ for transplant. Here we present a case of Chagas disease developing after a lung transplant where the donor was known to be Trypanosoma cruzi antibody positive. The recipient developed acute Trypanosoma cruzi infection with reactivation after treatment. Chagas disease-positive donors are likely to be encountered in the United States; donor targeted screening is needed to guide decisions regarding organ transplant and posttransplant monitoring.

  2. Pacemaker Implants in Children and Adolescents with Chagas Disease in Brazil: 18-Year Incidence.

    PubMed

    Mizzaci, Carolina Christianini; Souza, Thiago Gonçalves Schroder E; Targueta, Gabriel Pelegrineti; Tótora, Ana Paula Frederico; Mateos, Juan Carlos Pachón; Mateos, José Carlos Pachon

    2017-06-01

    Chagas disease continues to be a serious public health problem, and accounts for 25-30% of the indications for cardiac stimulation in Brazil. To assess clinical and epidemiological characteristics of patients with Chagas disease, younger than 18 years, who had undergone pacemaker implantation in Brazil between 1994 and 2011, and its temporal trend. This was a cross-sectional analysis of data from the Brazilian Pacemaker Registry database. The following variables were analyzed: year when pacemaker was implanted, location, age, sex, ethnic group, functional class and the main electrocardiographic findings at baseline. In a total of 183,123 implants performed between 1994 and 2011, 214 implants of cardiac stimulation device in Chagas disease patients aged younger than 18 years were identified. Mean age at implantation was 5.6 ± 6.2 years. Second- and third-degree atrioventricular blocks corresponded to 71% of indications for pacemaker implantation. Fifty-six percent of the procedures were performed in the southeast region. Regarding the total number of pacemaker implants per year, there was a remarkable increase in the implants for all causes. However, time series analysis of the implants in Chagas disease patients younger than 18 years revealed a significant reduction in the annual number of implants. There has been an important reduction in the number of pacemaker implantations among children and adolescents with Chagas disease, suggesting a reduction in the vertical transmission of the parasite. A doença de Chagas mantém-se como sério problema de saúde pública e tem sido responsável por aproximadamente 25% a 30% das indicações de estimulação cardíaca no Brasil. Estudar as características clínicas e epidemiológicas dos pacientes menores de 18 anos portadores de doença de Chagas submetidos a implante de marca-passo no território brasileiro entre 1994 e 2011, e sua tendência temporal. Trata-se de um estudo retrospectivo que utilizou informa

  3. The Role of Gender in Chagas Disease Prevention and Control in Honduras: An Analysis of Communication and Collaboration Networks.

    PubMed

    Triana, Diana Rocío Rodríguez; Mertens, Frédéric; Zúniga, Concepción Valeriano; Mendoza, Yolanda; Nakano, Eduardo Yoshio; Monroy, Maria Carlota

    2016-09-01

    In Honduras, where Chagas disease is a serious health and environmental concern, prevention measures face the challenge of achieving widespread and long-term sustainable adoption by communities. The article integrates social network analysis and a gender-sensitive approach to understand the role of men and women in the implementation of a community-level intervention, based on the adoption of housing improvements to reduce the presence of the insect vector. A total of 108 people in the community of El Salitre were interviewed. Data were collected on socio-demographic characteristics, participation in project activities, communication and collaboration networks related to Chagas disease prevention, knowledge of Chagas disease, and adoption of housing improvements techniques. Communication mostly occurred between the same gender individuals and was associated with knowledge of Chagas disease. Socioeconomic status, Chagas disease knowledge, and collaboration with men were associated with women adopting housing improvements. For men, however, participation in project activities, formal education, and collaboration with women were associated with adoption. These findings suggest that men and women were driven by distinct concerns, interests, and motivations when adopting new Chagas disease prevention strategies. Participatory community interventions that seek to generate health knowledge and foster collaborations to reduce health risk should address gender differences.

  4. Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells

    PubMed Central

    Youn, Myung-Ja; Kim, Jin-Kyung; Park, Seong-Yeol; Kim, Yunha; Kim, Se-Jin; Lee, Jin Seok; Chai, Kyu Yun; Kim, Hye-Jung; Cui, Ming-Xun; So, Hong Seob; Kim, Ki-Young; Park, Raekil

    2008-01-01

    AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines, HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, flow cytometry analysis, Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells, as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner, which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition, G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53, pRb, p27, cyclins D1, D2, E, cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option, as a potential anticancer agent, in the treatment of hepatoma. PMID:18203281

  5. Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease.

    PubMed

    Olivera, Mario J; Cucunubá, Zulma M; Valencia-Hernández, Carlos A; Herazo, Rafael; Agreda-Rudenko, Diana; Flórez, Carolina; Duque, Sofía; Nicholls, Rubén S

    2017-01-01

    Etiological treatment of Chagas disease in chronic asymptomatic patients is still in debate and the adverse effects of traditional drugs are one of the main concerns in clinical practice. This study evaluated retrospectively the safety profile of benznidazole (BZN) and identified predictive factors for definite treatment interruption and development of severe reactions in adult patients treated with BZN in Colombia. Retrospective follow-up study conducted by review of medical records of adults with chronic Chagas disease treated with BZN in Colombia. A parametric survival analysis based on a generalized gamma distribution was used for assessing risk factors for treatment interruption. A multinomial logistic regression model was used to estimate the probability of severe adverse drug reactions (ADRs). Statistical associations were expressed as time ratios (TR) and adjusted odds ratios (aOR) respectively. In total 224 adults patients treated with BZN were included; 172 (76.8%) completed the standard therapy (60 days of treatment), 205 (91.5%) presented ADRs and 52 cases (23.2%) required treatment interruption. The predominant symptoms were: rash (37.9%), itching (33.7%), epigastric pain (26.4%), abdominal bloating (24.2%) and nausea (22.1%). ADRs were mild (57.4%), moderate (35.5%) and severe (7.3%). Time to treatment interruption was significantly shorter when using doses of BZN ≥ 6 mg/kg/day (TR 0.55; 95% CI 0.39-0.76), presenting severe ADRs (TR 0.12; 95% CI: 0.07-0.19) and eosinophilia (TR 0.68; 95% CI: 0.49-0.94). Female sex (aOR 3.98; 95% CI 1.56-10.16), dose of BZN ≥ 6 mg/kg/day (aOR 1.41; 95% CI 1.17-1.70) and presence of > 3 ADRs (aOR 6.47; 95% CI 1.24-34.34) were considered as risk factors for developing severe ADRs. Dose, severity of ADRs, eosinophilia and female sex were the main predictors for treatment interruption or severe ADRs. The potential implications of these findings are discussed.

  6. Chagas Disease Vector Control in a Hyperendemic Setting: The First 11 Years of Intervention in Cochabamba, Bolivia

    PubMed Central

    Espinoza, Natalisisy; Borrás, Rafael; Abad-Franch, Fernando

    2014-01-01

    Background Chagas disease has historically been hyperendemic in the Bolivian Department of Cochabamba. In the early 2000s, an extensive vector control program was implemented; 1.34 million dwelling inspections were conducted to ascertain infestation (2000–2001/2003–2011), with blanket insecticide spraying in 2003–2005 and subsequent survey-spraying cycles targeting residual infestation foci. Here, we assess the effects of this program on dwelling infestation rates (DIRs). Methodology/Principal Findings Program records were used to calculate annual, municipality-level aggregate DIRs (39 municipalities); very high values in 2000–2001 (median: 0.77–0.69) dropped to ∼0.03 from 2004 on. A linear mixed model (with municipality as a random factor) suggested that infestation odds decreased, on average, by ∼28% (95% confidence interval [CI95] 6–44%) with each 10-fold increase in control effort. A second, better-fitting mixed model including year as an ordinal predictor disclosed large DIR reductions in 2001–2003 (odds ratio [OR] 0.11, CI95 0.06–0.19) and 2003–2004 (OR 0.22, CI95 0.14–0.34). Except for a moderate decrease in 2005–2006, no significant changes were detected afterwards. In both models, municipality-level DIRs correlated positively with previous-year DIRs and with the extent of municipal territory originally covered by montane dry forests. Conclusions/Significance Insecticide-spraying campaigns had very strong, long-lasting effects on DIRs in Cochabamba. However, post-intervention surveys consistently detected infestation in ∼3% of dwellings, underscoring the need for continuous surveillance; higher DIRs were recorded in the capital city and, more generally, in municipalities dominated by montane dry forest – an eco-region where wild Triatoma infestans are widespread. Traditional strategies combining insecticide spraying and longitudinal surveillance are thus confirmed as very effective means for area-wide Chagas disease vector

  7. The Catalonian Expert Patient Programme for Chagas Disease: An Approach to Comprehensive Care Involving Affected Individuals.

    PubMed

    Claveria Guiu, Isabel; Caro Mendivelso, Johanna; Ouaarab Essadek, Hakima; González Mestre, Maria Asunción; Albajar-Viñas, Pedro; Gómez I Prat, Jordi

    2017-02-01

    The Catalonian Expert Patient Programme on Chagas disease is a initiative, which is part of the Chronic Disease Programme. It aims to boost responsibility of patients for their own health and to promote self-care. The programme is based on nine sessions conducted by an expert patient. Evaluation was focusing in: habits and lifestyle/self-care, knowledge of disease, perception of health, self-esteem, participant satisfaction, and compliance with medical follow-up visits. Eighteen participants initiated the programme and 15 completed it. The participants were Bolivians. The 66.7 % of them had been diagnosed with chagas disease in Spain. The 100 % mentioned that they would participate in this activity again and would recommend it to family and friends. The knowledge about disease improve after sessions. The method used in the programme could serve as a key strategy in the field of comprehensive care for individuals with this disease.

  8. Circadian entrainment by light and host in the Chagas disease vector, Triatoma infestans.

    PubMed

    Valentinuzzi, Verónica Sandra; Amelotti, Ivana; Gorla, David Eladio; Catalá, Silvia Susana; Ralph, Martin Roland

    2014-03-01

    Triatoma infestans (Reduviidae: Triatominae, "kissing bug") is the main insect vector of Trypanosoma cruzi, the causative agent of Chagas disease, a chronic trypanosomiasis infecting 10 million people world-wide. This hematophagous bug feeds on diurnal and nocturnal species during each host's quiescent time. As the hosts are also its major predators, kissing bugs are subjected to dual selective pressures from a single source. Therefore, synchronization of feeding with the host's behavior is critical to the insects' survival. We show that nonphotic signals linked to the host eclipse the role of light and dark as the primary circadian zeitgeber for these bugs, although light still strongly inhibits locomotor behavior directly. In nature, this combination provides the insect with great flexibility in organizing physiology and behavior: anticipating a quiescent host or avoiding its potential predation while remaining directly responsive to immediate environmental conditions. Manipulation of nonphotic entrainment could be a useful chronobiotic tool in the control of Chagas disease.

  9. Sperm Morphological Features Associated with Chronic Chagas Disease in the Semen of Experimentally Infected Dogs

    PubMed Central

    Rodríguez-Morales, Olivia; Pedro-Martínez, Elvia; Hernández-Pichardo, José Ernesto; Alejandre-Aguilar, Ricardo; Aranda-Fraustro, Alberto; Graullera-Rivera, Verónica; Arce-Fonseca, Minerva

    2014-01-01

    The presence of trypanosomatids in the reproductive systems of different mammals (causing genital lesions in the acute stage of the disease) may predispose the animals to low semen quality. However, there are no studies examining the alterations in the sperm morphological features in the chronic stage of Trypanosoma cruzi infection. Knowledge of these aspects is important to understand the other ways of transmission of the Chagas disease. Progressive motility, mass motility, concentration, and sperm morphology of 84 ejaculates of dogs that were chronically infected with T. cruzi were evaluated. Most of the findings were consistent with the reference values and with those obtained from healthy control dogs. The scrotal circumference was not correlated with spermatozoa concentration in the infected animals. In conclusion, the T. cruzi Ninoa (MHOM/MX/1994/Ninoa) strain does not cause significant alterations in the semen quality of dogs experiencing chronic Chagas disease (at concentrations of 5 × 104 to 1 × 106 parasites per animal). PMID:25114010

  10. [Cecílio Romaña, Romaña's sign and Chagas' disease].

    PubMed

    Dias, J C

    1997-01-01

    Cecílio Romaña was an important Argentinean researcher dedicated to tropical diseases in the period 1930-1960, recently died in Barcelona. Working mainly on the epidemiological, clinical and pathological aspects of American trypanosomiasis, Romaña became very famous in 1935 when he accurately described the most typical portal recognized in all the endemic area with the cognomen of "Romaña sign". This description caused an enormous polemic with Romaña's then director, the great Salvador Mazza, who never accepted the specificity of the sign and, much less, its popular name (which was proposed by the Brazilian researchers Emmanuel Dias and Evandro Chagas). This history is briefly summarized in the present article, as well as the great impact of Romaña's discovery in the recognition of the acute Chagas' disease in all the endemic area.

  11. Rational Modification of a Candidate Cancer Drug for Use Against Chagas Disease

    PubMed Central

    Kraus, James M; Verlinde, Christophe LMJ; Karimi, Mandana; Lepesheva, Galina I.; Gelb, Michael H; Buckner, Frederick S.

    2009-01-01

    Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anti-cancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14α-demethylase (14DM). We rationally developed tipifarnib analogs that display reduced affinity for human PFT to reduce toxicity, while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease. PMID:19239254

  12. [Carlos Chagas Filho: an articulator of the history of sciences in Brazil].

    PubMed

    Domingues, Heloisa Maria Bertol

    2012-06-01

    A letter sent in 1982 by a group of scientists to the president of Conselho Nacional de Desenvolvimento Científico e Tecnológico appealed for a policy of preservation of Brazilian scientific culture. The name of Carlos Chagas Filho topped the list of signatures thereby proving his commitment to that proposal, the ideological structure of which was part of his experience in scientific policy in Brazil and abroad. This document harks back to the practice of the history of the sciences in Brazil and the creation of places for the safeguard and organization of scientific memory, such as the Museu de Astronomia e Ciências Afins, Casa de Oswaldo Cruz and the Sociedade Brasileira de História da Ciência, of which Carlos Chagas Filho was an inaugural member of the board of directors.

  13. Rational modification of a candidate cancer drug for use against Chagas disease.

    PubMed

    Kraus, James M; Verlinde, Christophe L M J; Karimi, Mandana; Lepesheva, Galina I; Gelb, Michael H; Buckner, Frederick S

    2009-03-26

    Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14 alpha-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.

  14. Epidemiology of Mortality Related to Chagas' Disease in Brazil, 1999–2007

    PubMed Central

    Martins-Melo, Francisco Rogerlândio; Alencar, Carlos Henrique; Ramos, Alberto Novaes; Heukelbach, Jorg

    2012-01-01

    Background Chagas' disease is an important neglected public health problem in many Latin American countries, but population-based epidemiological data are scarce. Here we present a nationwide analysis on Chagas-associated mortality, and risk factors for death from this disease. Methodology/Principal Findings We analyzed all death certificates of individuals who died between 1999 and 2007 in Brazil, based on the nationwide Mortality Information System (a total of 243 data sets with about 9 million entries). Chagas' disease was mentioned in 53,930 (0.6%) of death certificates, with 44,537 (82.6%) as an underlying cause and 9,387 (17.4%) as an associated cause of death. Acute Chagas' disease was responsible for 2.8% of deaths. The mean standardized mortality rate was 3.36/100.000 inhabitants/year. Nationwide standardized mortality rates reduced gradually, from 3.78 (1999) to 2.78 (2007) deaths/year per 100,000 inhabitants (−26.4%). Standardized mortality rates were highest in the Central-West region, ranging from 15.23 in 1999 to 9.46 in 2007 (−37.9%), with a significant negative linear trend (p = 0.001; R2 = 82%). Proportional mortality considering multiple causes of death was 0.60%. The Central-West showed highest proportional mortality among regions (2.17%), with a significant linear negative trend, from 2.28% to 1.90% (−19.5%; p = 0.001; R2 = 84%). There was a significant increase in the Northeast of 38.5% (p = 0.006; R2 = 82%). Bivariable analysis on risk factors for death from Chagas' disease showed highest relative risks (RR) in older age groups (RR: 10.03; 95% CI: 9.40–10.70; p<0.001) and those residing in the Central-West region (RR: 15.01; 95% CI: 3.90–16.22; p<0.001). In logistic regression analysis, age ≥30 years (adjusted OR: 10.81; 95% CI: 10.03–10.65; p<0.001) and residence in one of the three high risk states Minas Gerais, Goiás or the Federal District (adjusted OR: 5.12; 95% CI: 5.03–5.22, p<0.001) maintained

  15. [The contribution of Carlos Chagas Filho to the institutionalization of scientific research in Brazilian universities].

    PubMed

    Almeida, Darcy Fontoura de

    2012-06-01

    This paper studies the period considered the 'prehistory' of the Instituto de Biofísica, namely between November 1937 and October 1945, during which Carlos Chagas Filho championed the inclusion of scientific research at Universidade do Brasil (UB), despite facing multiple and complex obstacles. The lack of successful precedents at UB isolated him to one inexpressive chair. The equipment available was inadequate for his purposes; there were no official sources and forms of access to funding for science or trained personnel for research activities. On the other hand, Chagas Filho won over allies due both to the political and social clout of his name and his marriage, and to his scientific influence ensuing from his success in attaining the goals he fought for.

  16. Heart Failure Secondary to Chagas Disease: an Emerging Problem in Non-endemic Areas.

    PubMed

    Traina, Mahmoud; Meymandi, Sheba; Bradfield, Jason S

    2016-12-01

    Chagas disease affects millions of people worldwide. Though the majority of infected individuals remain asymptomatic, approximately 30 % of patients progress to develop cardiac manifestations and eventual heart failure. While vectorial transmission occurs predominantly in South America, Central America, and Mexico, millions of people originally from these endemic regions immigrate to non-endemic countries in North America, Europe, and Asia. Outside of rare specialized centers, health-care providers lack experience diagnosing and treating this disease. This lack of experience likely leads to far fewer Chagas disease patients being diagnosed than what actually exist in non-endemic countries, with subsequent adverse effect on patient outcomes and health-care expenses. Underdiagnosis increases the risk of developing cardiomyopathy, associated heart failure, and life-threatening ventricular arrhythmias as the disease progresses.

  17. [Progress towards the interruption of transmission of Chagas disease in the southern countries].

    PubMed

    Moncayo, A

    1999-01-01

    The epidemiological and entomological data and the trends observed in the decreasing of the incidence of infection in young age groups indicate that only ninety years after the discovery of Chagas disease, the control of vectorial and transfusional transmission has reduced the incidence by 70% in the Southern Cone countries (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay). This has been accomplished thanks to the political and financial engagement of the concerned governments who have invested US$340 millions since 1991 to the present. The initiatives to interrupt transmission of Chagas in the Andean countries and the Central American countries have begun their activities in 1997 and the evolution of the control operations allows to forecast the complete interruption in these areas before the year 2010 to comply with the mandate of Resolution WHA. 52.14 of the World Health Assembly in May 1998.

  18. Population genetic structure of Meccus longipennis (Hemiptera, Reduviidae, Triatominae), vector of Chagas disease in West Mexico.

    PubMed

    Brenière, Simone Frédérique; Waleckx, Etienne; Magallón-Gastélum, Ezequiel; Bosseno, Marie-France; Hardy, Xavier; Ndo, Cyrille; Lozano-Kasten, Felipe; Barnabé, Christian; Kengne, Pierre

    2012-03-01

    The originally wild species of the Meccus complex are important vectors of Chagas disease in Mexico. In West Mexico, Meccus longipennis plays an important epidemiological role. To understand the genetic structure of the domestic and wild populations of this species, a preliminary study with five polymorphic microsatellite loci was conducted. The population genetics analysis showed high structuring between peridomestic biotopes, with breeding subunits detected in a single peridomestic structure. In the wild environment, two genetic patterns were observed according to the biotope, possible breeding subunits in large rocky formations and a larger panmictic unit in agropastoral areas, suggesting considerable dispersal of bugs in this biotope. Moreover, the discovery of two foci of wild populations at the edge of Guadalajara city raises the question of new urban areas where the phenomenon of bug incursions into households could constitute a risk of transmission of Chagas disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Population differentiation of the Chagas disease vector Triatoma maculata (Erichson, 1848) from Colombia and Venezuela.

    PubMed

    Monsalve, Yoman; Panzera, Francisco; Herrera, Leidi; Triana-Chávez, Omar; Gómez-Palacio, Andrés

    2016-06-01

    The emerging vector of Chagas disease, Triatoma maculata (Hemiptera, Reduviidae), is one of the most widely distributed Triatoma species in northern South America. Despite its increasing relevance as a vector, no consistent picture of the magnitude of genetic and phenetic diversity has yet been developed. Here, several populations of T. maculata from eleven Colombia and Venezuela localities were analyzed based on the morphometry of wings and the mitochondrial NADH dehydrogenase subunit 4 (ND4) gene sequences. Our results showed clear morphometric and genetic differences among Colombian and Venezuelan populations, indicating high intraspecific diversity. Inter-population divergence is suggested related to East Cordillera in Colombia. Analyses of other populations from Colombia, Venezuela, and Brazil from distinct eco-geographic regions are still needed to understand its systematics and phylogeography as well as its actual role as a vector of Chagas disease.

  20. [Epidemiologic knowledge and current situation of Chagas disease in the state of Jalisco, Mexico].

    PubMed

    Lozano-Kasten, Felipe; Magallón-Gastélum, Ezequiel; Soto-Gutiérrez, Margarita; Kasten-Monges, Marina; Bosseno, Marie-France; Brenière, Simone Frédérique

    2008-01-01

    Chagas disease in the state of Jalisco, Mexico was described for the first time in 1967; however, knowledge on the disease remains in a slow process. Between 1967 and 2006, the disease was described in its acute and chronic forms. The vector species have been identified, and the parasite Trypanosoma cruzi has been isolated and genetically characterized. Also, the magnitude of the infection in humans has been determined through serological studies of different populations as well as of blood donors. The up-to-dateness of knowledge of the disease in the state of Jalisco, unveils a necessity of increased research on the epidemiology of Chagas disease as well as on clinical studies to assess the health of individuals and the populations.

  1. [Urbanization of Chagas disease in Peru: experiences in prevention and control].

    PubMed

    Náquira, César

    2014-04-01

    In Peru, Chagas disease has an epidemiological significance in three macro-regions, one of them is the southern macro-region formed by the departments of Arequipa, Moquegua and Tacna. In 1965 a successful control was performed by house spraying insecticides, however, the persistence of the vector made it necessary for a second control plan that was implemented in 2000 and followed the guidelines of CONAL Plan, based on the elimination of Triatoma infestans and screening in blood banks.This plan was successful in Tacna and Moquegua, therefore these departments were considered free of vectorial transmission by the Pan American Health Organization. A ssimilar situation has not been achieved in the department of Arequipa because of the presence, among other factors, of rural migration to the city, in this way the urbanization of Chagas disease is a new epidemiological scenario of which we need to know more.

  2. Radionuclide evaluation of left-ventricular function in chronic Chagas' cardiomyopathy

    SciTech Connect

    Arreaza, N.; Puigbo, J.J.; Acquatella, H. Casal, H.; Giordano, H.; Valecillos, R.; Mendoza, I.; Perez, J.F.; Hirschhaut, E.; Combellas, I.

    1983-07-01

    Left-ventricular ejection fraction (LVEF) and abnormalities of regional wall motion (WMA) were studied by means of radionuclide ventriculography in 41 patients prospectively diagnosed as having chronic Chagas' disease. Thirteen patients were asymptomatic (ASY), 16 were arrhythmic (ARR), and 12 had congestive heart failure (CHF). Mean LVEF was normal in ASY but markedly depressed in CHF. Regional WMAs were minimal in ASY and their severity increased in ARR. Most CHFs (75%) had diffuse hypokinesia of the left ventricle. Seven patients had a distinct apical aneurysm. Correlation between radionuclide and contrast ventriculography data was good in 17 patients. Selective coronary arteriography showed normal arteries in all patients. Therefore, chronic Chagas' heart disease joins ischemic heart disease as a cause of regional WMA.

  3. Massive right-sided cardiac thrombosis in Chagas' heart disease without left ventricular dysfunction.

    PubMed

    Bestetti, Reinaldo B; Corbucci, Hélio A R; Cardinalli-Neto, Augusto

    2011-02-01

    A 63-year-old woman with the diagnosis of mega-oesophagus secondary to chronic Chagas' disease and no past cardiac history was referred for cardiac evaluation. The resting ECG showed right bundle-branch block, whereas a 2-D echocardiogram revealed marked right ventricular dilatation with hypokinesia, right atrial dilatation, normal pulmonary artery pressure, and normal left ventricular ejection fraction. A large, irregularly shaped mass, arising from the right atrium and protruding into the right ventricle through the tricuspid valve, with several different bizarre forms inside the right atrium during systole and/or diastole was seen on 2-D echocardiogram. Therefore, massive right-sided thrombosis can be detected in Chagas' disease patients with no overt right- and left-sided ventricular failure.

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

    PubMed

    Sartori, A M C; Ibrahim, K Y; Nunes Westphalen, E V; Braz, L M A; Oliveira, O C; Gakiya, E; Lopes, M H; Shikanai-Yasuda, M A

    2007-01-01

    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.

  5. [Chagas' disease in patients in chronic hemodialysis. Prevalence and risk of transmission by blood transfusion].

    PubMed

    Lorca, M; Lorca, E; Atías, A; Plubins, L

    1989-06-01

    A serologic study of Chagas disease was performed in 110 patients submitted to chronic hemodialisis and blood transfusions. Immunofluorescence antibody testing (IgG and IgM) was positive in 6 out of 62 patients receiving multiple blood transfusions (9.7%), but negative in all 48 subjects without transfusions. Thus, repeated blood transfusion is a significant risk for T cruzi infection in chronic hemodialized patients.

  6. High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross-Sectional Evaluation

    PubMed Central

    Sánchez-Montalvá, Adrián; Moris, María; Mego, Marianela; Salvador, Fernando; Accarino, Anna; Ramírez, Kathleen; Azpiroz, Fernando; Ruiz-de-Leon, Antonio; Molina, Israel

    2016-01-01

    Introduction Gastrointestinal involvement affects 30–40% of the patients with chronic Chagas disease. Esophageal symptoms appear once the structural damage is established. Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement. Method We performed a cross-sectional study at the Vall d’Hebron University Hospital (Barcelona, Spain) between May 2011 and April 2012. Consecutive patients diagnosed with Chagas disease in the chronic phase were offered to participate. All patients underwent a structured questionnaire about digestive symptoms, a barium esophagogram (Rezende classification) and an esophageal high resolution manometry (HRM). A control group of patients with heartburn who underwent an esophageal HRM in our hospital was selected. Results 62 out of 73 patients that were included in the study fulfilled the study protocol. The median age of the Chagas disease group (CG) was 37 (IQR 32–45) years, and 42 (67.7%) patients were female. Twenty-seven (43.5%) patients had esophageal symptoms, heartburn being the most frequent. Esophagogram was abnormal in 5 (8.77%). The esophageal HRM in the CG showed a pathological motility pattern in 14 patients (22.6%). All of them had minor disorders of the peristalsis (13 with ineffective esophageal motility and 1 with fragmented peristalsis). Hypotonic lower esophageal sphincter was found more frequently in the CG than in the control group (21% vs 3.3%; p<0.01). Upper esophageal sphincter was hypertonic in 22 (35.5%) and hypotonic in 1 patient. When comparing specific manometric parameters or patterns in the CG according to the presence of symptoms or esophagogram no statistically significant association were seen, except for distal latency. Conclusion The esophageal involvement measured by HRM in patients with chronic Chagas disease in our cohort is 22.6%. All the patients with esophageal alterations had minor disorders of the peristalsis. Symptoms and

  7. Chagas disease in the State of Pernambuco, Brazil: analysis of admissions and mortality time series.

    PubMed

    Braz, Suellen Carvalho de Moura; Melo, Myllena de Fátima Alheiros Dias; Lorena, Virginia Maria Barros de; Souza, Wayner Vieira de; Gomes, Yara de Miranda

    2011-01-01

    A time series study of admissions, deaths and acute cases was conducted in order to evaluate the context of Chagas disease in Pernambuco. Data reported to the Information Technology Department of the Brazilian National Health Service between 1980 and 2008 was collected for regions and Federal Units of Brazil; and microregions and municipalities of Pernambuco. Rates (per 100,000 inhabitants) of hospitalization, mortality and acute cases were calculated using a national hospital database (SIH), a national mortality database (SIM) and the national Information System for Notifiable Diseases (SINAN), respectively. The national average for Chagas disease admissions was 0.99 from 1995 to 2008. Pernambuco obtained a mean of 0.39 in the same period, with the highest rates being concentrated in the interior of the state. The state obtained a mean mortality rate of 1.56 between 1980 and 2007, which was lower than the national average (3.66). The mortality rate has tended to decline nationally, while it has remained relatively unchanged in Pernambuco. Interpolating national rates of admissions and deaths, mortality rates were higher than hospitalization rates between 1995 and 2007. The same occurred in Pernambuco, except for 2003. Between 2001 and 2006, rates for acute cases were 0.56 and 0.21 for Brazil and Pernambuco, respectively. Although a decrease in Chagas mortality has occurred in Brazil, the disease remains a serious public health problem, especially in the Northeast region. It is thus essential that medical care, prevention and control regarding Chagas disease be maintained and improved.

  8. Human Chagas Disease and Migration in the Context of Globalization: Some Particular Aspects

    PubMed Central

    Pinto Dias, João Carlos

    2013-01-01

    Human Chagas disease originated in Latin America, being spread around the world in relation with multiple bioecological, sociocultural, and political factors. The process of the disease production and dispersion is discussed, emphasizing the human migration and correlated aspects, in the context of globalization. Positive and negative consequences concern the future of this trypanosomiasis, mainly in terms of the ecologic and sociopolitical characteristics of the endemic and nonendemic countries. PMID:23606862

  9. Accurate Real-Time PCR Strategy for Monitoring Bloodstream Parasitic Loads in Chagas Disease Patients

    PubMed Central

    Duffy, Tomas; Bisio, Margarita; Altcheh, Jaime; Burgos, Juan Miguel; Diez, Mirta; Levin, Mariano Jorge; Favaloro, Roberto Rene; Freilij, Hector; Schijman, Alejandro Gabriel

    2009-01-01

    Background This report describes a real-time PCR (Q-PCR) strategy to quantify Trypanosoma cruzi (T. cruzi) DNA in peripheral blood samples from Chagas disease patients targeted to conserved motifs within the repetitive satellite sequence. Methodology/Principal Findings The Q-PCR has a detection limit of 0.1 and 0.01 parasites/mL, with a dynamic range of 106 and 107 for Silvio X10 cl1 (T. cruzi I) and Cl Brener stocks (T. cruzi IIe), respectively, an efficiency of 99%, and a coefficient of determination (R2) of 0.998. In order to express accurately the parasitic loads: (1) we adapted a commercial kit based on silica-membrane technology to enable efficient processing of Guanidine Hydrochloride-EDTA treated blood samples and minimize PCR inhibition; (2) results were normalized incorporating a linearized plasmid as an internal standard of the whole procedure; and (3) a correction factor according to the representativity of satellite sequences in each parasite lineage group was determined using a modified real-time PCR protocol (Lg-PCR). The Q-PCR strategy was applied (1) to estimate basal parasite loads in 43 pediatric Chagas disease patients, (2) to follow-up 38 of them receiving treatment with benznidazole, and (3) to monitor three chronic Chagas heart disease patients who underwent heart-transplantation and displayed events of clinical reactivation due to immunosupression. Conclusion/Significance All together, the high analytical sensitivity of the Q-PCR strategy, the low levels of intra- and inter-assay variations, as well as the accuracy provided by the Lg-PCR based correction factor support this methodology as a key laboratory tool for monitoring clinical reactivation and etiological treatment outcome in Chagas disease patients. PMID:19381287

  10. Ischemic stroke classification and risk of embolism in patients with Chagas disease.

    PubMed

    Montanaro, Vinícius Viana Abreu; da Silva, Creuza Maria; de Viana Santos, Carla Verônica; Lima, Maria Inacia Ruas; Negrão, Edson Marcio; de Freitas, Gabriel R

    2016-12-01

    Ischemic stroke (IS) and Chagas disease are strongly related. Nevertheless, little attention has been paid to this association and its natural history. The current guidelines concerning the management and secondary prevention of IS are largely based on the incomplete information or extrapolation of knowledge from other stroke etiologies. We performed a retrospective study which compared stroke etiologies among a cohort of hospitalized patients with IS and Chagas disease. The Instituto de Pesquisa Evandro Chagas/Fundação Oswaldo Cruz (IPEC/FIOCRUZ) embolic score was also used to identify and evaluate the risk of embolism in this population. A total of 86 patients were included in the analysis. The mean age of the study population was 58 years, and 60 % were men. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification, 45 % of the strokes were of undetermined etiology and 45 % of cardioembolic origin, while the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST indicated that 34 % were undetermined and 50 % cardioembolic (p < 0.01); 44 % of these patients were classified as having a high embolic risk according to the IPEC/FIOCRUZ score. Among the undetermined causes, 83.3 % fulfilled the criteria for embolic stroke of undetermined source (ESUS). The SSS/CCS TOAST etiological classification system was superior to the classical TOAST criteria in identifying a cardioembolic etiology in patients with ischemic stroke and Chagas disease. The IPEC/FIOCRUZ score did not correlate with the number of patients who were determined to have cardioembolic stroke etiologies. The current guidelines for stroke prevention should be reviewed in this population.

  11. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

    PubMed

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Sexual transmission of American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites.

    PubMed

    Araujo, Perla F; Almeida, Adriana B; Pimentel, Carlos F; Silva, Adriano R; Sousa, Alessandro; Valente, Sebastião A; Valente, Vera C; Britto, Manuela M; Rosa, Ana C; Alves, Rozeneide M; Hagström, Luciana; Teixeira, Antonio Rl

    2017-06-01

    The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. A short-term longitudinal study was conducted to evaluate this hypothesis. The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the

  13. Chagas disease: a Latin American health problem becoming a world health problem.

    PubMed

    Schmunis, Gabriel A; Yadon, Zaida E

    2010-01-01

    Political repression and/or economic stagnation stimulated the flow of migration from the 17 Latin American countries endemic for Chagas disease to developed countries. Because of this migration, Chagas disease, an autochthonous disease of the Continental Western Hemisphere is becoming a global health problem. In 2006, 3.8% of the 80,522 immigrants from those 17 countries to Australia were likely infected with Trypanosoma cruzi. In Canada in 2006, 3.5% of the 156,960 immigrants from Latin America whose country of origin was identified were estimated to have been infected. In Japan in 2007, there were 80,912 immigrants from Brazil, 15,281 from Peru, and 19,413 from other South American countries whose country of origin was not identified, a portion of whom may have been also infected. In 15 countries of Europe in 2005, excluding Spain, 2.9% of the 483,074 legal Latin American immigrants were estimated to be infected with T. cruzi. By 2008, Spain had received 1,678,711 immigrants from Latin American endemic countries; of these, 5.2% were potentially infected with T. cruzi and 17,390 may develop Chagas disease. Further, it was estimated that 24-92 newborns delivered by South American T. cruzi infected mothers in Spain may have been congenitally infected with T. cruzi in 2007. In the USA we estimated that 1.9% of approximately 13 million Latin American immigrants in 2000, and 2% of 17 million in 2007, were potentially infected with T. cruzi. Of these, 49,157 and 65,133 in 2000 and 2007 respectively, may have or may develop symptoms and signs of chronic Chagas disease. Governments should implement policies to prevent donations of blood and organs from T. cruzi infected donors. In addition, an infrastructure that assures detection and treatment of acute and chronic cases as well as congenital infection should be developed.

  14. [Possible oral transmission of Chagas disease among hydrocarbons sector workers in Casanare, Colombia, 2014].

    PubMed

    Zuleta-Dueñas, Liliana Patricia; López-Quiroga, Ángela Johana; Torres-Torres, Fernando; Castañeda-Porras, Oneida

    2017-06-01

    Trypanosoma cruzi, the etiological agent for Chagas disease, can be transmitted by oral intake of contaminated food or drinks. During epidemiological week 14 of 2014, two cases of acute Chagas disease were notified among hydrocarbons sector workers in Paz de Ariporo, Casanare. To characterize the affected population, to establish control and prevention measures and to confirm the outbreak. We conducted an outbreak investigation that included the following components: a) Search for symptomatic people compatible with Chagas disease according to the case definition for their referral to medical services; b) entomological survey (192/197 houses); c) sanitary inspection and microbiological analysis of food samples; and d) study of reservoirs. Data management and analysis were done with Epi-Info 7.1.5 using descriptive statistics. We also calculated intradomicile and peridomicile triatomine infestation indexes. We detected 552 exposed people; 40 had the disease (7.2%), of whom seven were women (17,5%) and 33, men (82.5%), i.e., a male-female ratio of 5:1. The mean age was 39.1 ± 10.8 years; the attack rate was 7.2% and lethality, 5% (2/40). Symptoms included fever (100% of cases), headache (80%), myalgia and arthralgia (65%), facial edema (55%), and abdominal pain (37.5%). The mean incubation time was 17 days (range: 3-21). Rhodnius prolixus domiciliary infestation index was 3.3 % and 2.2% in the peridomicile. In the five restaurants inspected sanitary conditions were deficient and food samples were microbiologically non-conforming. We found a dog and two opossums positive for IgG antibodies by ELISA. Environmental, sanitary and epidemiological conditions at the place confirmed an outbreak of Chagas diseases related to occupational exposure, possibly by oral transmission, which may be the largest to date in Colombia.

  15. Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease

    PubMed Central

    Ferreira, Adaliene Versiani Matos; Segatto, Marcela; Menezes, Zélia; Macedo, Andréa Mara; Gelape, Cláudio; de Oliveira Andrade, Luciana; Nagajyothi, Fnu; Scherer, Philipp E.; Teixeira, Mauro Martins; Tanowitz, Herbert B.

    2013-01-01

    Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected experimental animals and humans. Here we demonstrate the persistence of the parasite in adipose tissue from of three of 10 elderly seropositive patients with chronic chagasic heart disease. Nine control patients had no parasites in the fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro. Thus, in humans as in mice the parasite may persist in adipose tissue for decades and become a reservoir of infection. PMID:21726660

  16. Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease.

    PubMed

    Ferreira, Adaliene Versiani Matos; Segatto, Marcela; Menezes, Zélia; Macedo, Andréa Mara; Gelape, Cláudio; de Oliveira Andrade, Luciana; Nagajyothi, Fnu; Scherer, Philipp E; Teixeira, Mauro Martins; Tanowitz, Herbert B

    2011-11-01

    Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected experimental animals and humans. Here we demonstrate the persistence of the parasite in adipose tissue from of three of 10 elderly seropositive patients with chronic chagasic heart disease. Nine control patients had no parasites in the fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro. Thus, in humans as in mice the parasite may persist in adipose tissue for decades and become a reservoir of infection.

  17. [Regression of acute Chagas cardiopathy in an infant with a suspected transfusion infection].

    PubMed

    Gónzalez-Zambrano, H; Amador Mena, J E; Delgadillo Jaime, C B

    1999-01-01

    Chagas disease was described in Mexico by Mazzotti in 1940. Post-transfusional cases have not been described. We report proved case of acute chagasic cardiopathy in a nine months old infant with suspected transfusional infection during neonatal period. She was treated with nifurtimox with disappearance of parasites and regression of cardiopathy. She is asymptomatic nine years afterwards with normal growth and negative parasitology and serology.

  18. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease

    PubMed Central

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado

    2016-01-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC–poly(d,l-lactide)–polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC–poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease. PMID:27324760

  19. The Prevalence of Chagas Heart Disease in a Central Bolivian Community Endemic for Trypanosoma Cruzi

    PubMed Central

    Yager, Jessica E.; Lozano Beltran, Daniel F.; Torrico, Faustino; Gilman, Robert H.; Bern, Caryn

    2015-01-01

    Background Though the incidence of new Trypanosoma cruzi infections has decreased significantly in endemic regions in the Americas, medical professionals continue to encounter a high burden of resulting Chagas disease among infected adults. The current prevalence of Chagas heart disease in a community setting is not known; nor is it known how recent insecticide vector control measures may have impacted the progression of cardiac disease in an infected population. Objectives and Methods Nested within a community serosurvey in rural and periurban communities in central Bolivia, we performed a cross-sectional cardiac substudy to evaluate adults for historical, clinical, and electrocardiographic evidence of cardiac disease. All adults between the ages of 20 and 60 years old with T. cruzi infection and those with a clinical history, physical exam, or ECG consistent with cardiac abnormalities were also scheduled for echocardiography. Results and conclusions Of the 604 cardiac substudy participants with definitive serology results, 183 were seropositive for infection with T. cruzi (30.3%). Participants who were seropositive for T. cruzi infection were more likely to have conduction system defects (1.6% versus 0 for complete right bundle branch block and 10.4% versus 1.9% for any bundle branch block; p=0.008 and p<0.001, respectively). However, there was no statistically significant difference in the prevalence of bradycardia among seropositive versus seronegative participants. Echocardiogram findings were not consistent with a high burden of Chagas cardiomyopathy: valvulopathies were the most common abnormality, and few participants were found to have low ejection fraction or left ventricular dilatation. No participants had significant heart failure. Though almost one third of adults in the community were seropositive for T. cruzi infection, few had evidence of Chagas heart disease. PMID:26407509

  20. Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease.

    PubMed

    Assíria Fontes Martins, Tassiane; de Figueiredo Diniz, Lívia; Mazzeti, Ana Lia; da Silva do Nascimento, Álvaro Fernando; Caldas, Sérgio; Caldas, Ivo Santana; de Andrade, Isabel Mayer; Ribeiro, Isabela; Bahia, Maria Terezinha

    2015-01-01

    The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.

  1. Chagas disease in Ecuador: a sylvatic focus in the Amazon region.

    PubMed

    Amunárriz, M; Chico, M E; Guderian, R H

    1991-06-01

    A sylvatic focus of Chagas disease is reported in the Amazon region of Ecuador (provinces of Napo and Sucumbios). During 1987-1989, 10 cases of acute infection were diagnosed by direct visualization of Trypanosoma cruzi in peripheral blood smears during routine malaria checks. Also in that region, three triatomine bugs, Rhodnius pictipes, Rhodnius robustus and Panstrongylus geniculatus were found naturally infected with T. cruzi suggesting that the human cases represent an autochthonous focus of active transmission.

  2. A Scientometric Evaluation of the Chagas Disease Implementation Research Programme of the PAHO and TDR

    PubMed Central

    Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E.

    2013-01-01

    The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

  3. A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors

    PubMed Central

    Farrow, Anitra L.; Peng, Binghao J.; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L.

    2016-01-01

    Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi’s amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the “Antigen Capsid-Incorporation” strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

  4. Overcoming research barriers in Chagas disease-designing effective implementation science.

    PubMed

    Henao-Martínez, Andrés F; Colborn, Kathryn; Parra-Henao, Gabriel

    2017-01-01

    Chagas disease is a complex tropical parasitic infection. It affects a significant portion of the population in Latin America, especially in areas of poverty and poor access to health care. It also affects immigrants in high-income countries who lack access to health care due to their legal status. Millions of people are at risk of contracting the disease, and approximately 30 % of chronically infected patients will develop cardiomyopathy. The cost of caring for patients that have been infected is substantial. Basic science research has introduced new concepts and knowledge for the parasite and vector biology as well as better understanding of the pathophysiology of the disease. These research findings nevertheless require effective and timely translation into clinical practice. Likewise, the design of new research projects should account for the multiple system-based barriers. Implementation science facilitates the applicability of research findings and identifies barriers to its execution. Creation of implementation science measures to reach and sustain research programs with greater potential to impact Chagas disease are lacking. This point of view proposes opportunities for implementation science in Chagas disease and strategies for researching effective interventions for preventing and treating the disease.

  5. First century of Chagas' disease: an overview on novel approaches to nifurtimox and benzonidazole delivery systems.

    PubMed

    Salomon, Claudio J

    2012-03-01

    Hundred years after the discovery of Chagas' disease, there is a lack of effective treatment to control this neglected disease caused by the parasite Trypanosoma cruzi. The transmission is primarily through vector-borne blood transfusion or during pregnancy, producing high mortality and morbidity among poor people in many countries of Latin America. In the last decades, the efforts have been focused mainly on the elimination of vectors. At the same time, screening of blood donors in order to avoid transfusional transmission has been improved all over the world. However, Chagas' disease is still a major public health problem, with estimates of nearly 90 million people at risk of infection and more than eight million infected in 18 endemic countries. Despite the high incidence in endemic regions and the dissemination of neglected diseases in North America and Europe, to date, there are only two drugs developed and prescribed for the treatment of Chagas' disease, nifurtimox (tablets of 120 mg) and benzonidazole (tablets of 100 mg). In this review, different approaches carried out in the last decades for developing novel pharmaceutical formulations for the delivery of nifurtimox and benznidazole are discussed.

  6. Positive deviance study to inform a Chagas disease control program in southern Ecuador

    PubMed Central

    Nieto-Sanchez, Claudia; Baus, Esteban G; Guerrero, Darwin; Grijalva, Mario J

    2015-01-01

    Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region. PMID:25807468

  7. Positive deviance study to inform a Chagas disease control program in southern Ecuador.

    PubMed

    Nieto-Sanchez, Claudia; Baus, Esteban G; Guerrero, Darwin; Grijalva, Mario J

    2015-05-01

    Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region.

  8. Current Understanding of Immunity to Trypanosoma cruzi Infection and Pathogenesis of Chagas Disease

    PubMed Central

    Machado, Fabiana S.; Dutra, Walderez O.; Esper, Lisia; Gollob, Kenneth; Teixeira, Mauro M.; Factor, Stephen M.; Weiss, Louis M.; Nagajyothi, Fnu; Tanowitz, Herbert B.; Garg, Nisha J.

    2012-01-01

    Chagas disease caused by Trypanosoma cruzi remains an important neglected tropical disease and a cause of significant morbidity and mortality. No longer confined to endemic areas of Latin America, it is now found in non-endemic areas due to immigration. The parasite may persist in any tissue, but in recent years there has been increased recognition of adipose tissue both as an early target of infection and a reservoir of chronic infection. The major complications of this disease are cardiomyopathy and megasyndromes involving the gastrointestinal tract. The pathogenesis of Chagas disease is complex and multifactorial involving many interactive pathways. The significance of innate immunity, including the contributions of cytokines, chemokines, reactive oxygen species, and oxidative stress, has been emphasized. The role of the components of the eicosanoid pathway such as thromboxane A2 and the lipoxins has been demonstrated to have profound effects as both pro-and anti-inflammatory factors. Additionally, we discuss the vasoconstrictive actions of thromboxane A2 and endothelin-1n Chagas disease. Human immunity to T. cruzi infection and its role in pathogen control and disease progression have not been fully investigated. However, recently, it was demonstrated that a reduction in the anti-inflammatory cytokine IL-10 was associated with clinically significant chronic chagasic cardiomyopathy. PMID:23076807

  9. Chagas disease in the 21st Century: a public health success or an emerging threat?

    PubMed Central

    Bonney, Kevin M.

    2014-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health burden in Latin America and a potentially serious emerging threat to a number of countries throughout the world. Although public health programs have significantly reduced the prevalence of Chagas disease in Latin America in recent decades, the number of infections in the United States and non-endemic countries in Europe and the Western Pacific Region continues to rise. Moreover, there is still no vaccine or highly effective cure available for the approximately 10 million people currently infected with T. cruzi, a third of which will develop potentially fatal cardiomyopathy and/or severe digestive tract disorders. As Chagas disease becomes an increasingly globalized public health issue in the twenty-first century, continued attentiveness from governmental and health organizations as well as improved diagnostic tools, expanded surveillance and increased research funding will be required to maintain existing public health successes and stymie the spread of the disease to new areas and populations. PMID:24626257

  10. Evaluation of Adult Chronic Chagas' Heart Disease Diagnosis by Molecular and Serological Methods ▿

    PubMed Central

    Ramírez, Juan David; Guhl, Felipe; Umezawa, Eufrosina Setsu; Morillo, Carlos A.; Rosas, Fernando; Marin-Neto, Jose A.; Restrepo, Silvia

    2009-01-01

    Chagas' disease caused by Trypanosoma cruzi is endemic in Latin America. T. cruzi presents heterogeneous populations and comprises two main genetic lineages, named T. cruzi I and T. cruzi II. Diagnosis in the chronic phase is based on conventional serological tests, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), and diagnosis in the acute phase based on parasitological methods, including hemoculture. The objective of this study was to evaluate the diagnostic procedures of Chagas' disease in adult patients in the chronic phase by using a PCR assay and conventional serological tests, including TESA-blot as the gold standard. Samples were obtained from 240 clinical chronic chagasic patients. The sensitivities, compared to that of TESA-blot, were 70% for PCR using the kinetoplast region, 75% for PCR using the nuclear repetitive region, 99% for IIF, and 95% for ELISA. According to the serological tests results, we recommend that researchers assess the reliability and sensitivity of the commercial kit Chagatest ELISA recombinant, version 3.0 (Chagatest Rec v3.0; Wiener Lab, Rosario, Argentina), due to the lack of sensitivity. Based on our analysis, we concluded that PCR cannot be validated as a conventional diagnostic technique for Chagas' disease. These data have been corroborated by low levels of concordance with serology test results. It is recommended that PCR be used only for alternative diagnostic support. Using the nuclear repetitive region of T. cruzi, PCR could also be applicable for monitoring patients receiving etiologic treatment. PMID:19846646

  11. [American human trypanosomiasis 90 years after its discovery by Carlos Chagas. I. Epidemiology and control].

    PubMed

    Pays, J F

    1998-01-01

    It was in 1909 that Carlos Chagas described the disease which now bears his name. During the ensuing 90 years, our knowledge of this apparently whimsical, protozoan disease has grown enormously but many points remain unclear. Epidemiologically speaking, current knowledge is poor about the mechanisms and markers of variability of Trypanosoma cruzi, mechanisms allowing the organism to survive in the host, and susceptibility of infected individuals to disabling or fatal late complications. With regard to vector control, it is increasingly obvious that success will be more difficult than previously thought due to the likelihood that, as domestic species are exterminated, they will be replaced by semi-domesticated or wild species. Two other factors that have significantly changed the conventional epidemiological profile of Chagas'disease on the subcontinent over the past 50 years are human intervention in the environment and population migration from rural to urban zones. Despite the breakthroughs achieved in the last decade. Chagas'disease, with its multiple modes of transmission (vector-borne, congenital, and transfusional to name but the most important), diverse reservoir involving over 175 species, and potential for course of the disease in man, will remain a major health problem in Latin America countries for many years to come.

  12. Chagas disease in the 21st century: a public health success or an emerging threat?

    PubMed

    Bonney, Kevin M

    2014-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health burden in Latin America and a potentially serious emerging threat to a number of countries throughout the world. Although public health programs have significantly reduced the prevalence of Chagas disease in Latin America in recent decades, the number of infections in the United States and non-endemic countries in Europe and the Western Pacific Region continues to rise. Moreover, there is still no vaccine or highly effective cure available for the approximately 10 million people currently infected with T. cruzi, a third of which will develop potentially fatal cardiomyopathy and/or severe digestive tract disorders. As Chagas disease becomes an increasingly globalized public health issue in the twenty-first century, continued attentiveness from governmental and health organizations as well as improved diagnostic tools, expanded surveillance and increased research funding will be required to maintain existing public health successes and stymie the spread of the disease to new areas and populations. © K.M. Bonney, published by EDP Sciences, 2014.

  13. [The control of the transmission by transfusion of Chagas' disease in the Southern Cone Initiative].

    PubMed

    Dias, J C; Schofield, C J

    1998-01-01

    The Southern Cone Initiative against Chagas' disease, was launched in 1991. The aim was to interrupt the transmission of Chagas disease by elimination of domestic populations of the major vector, Triatoma infestans, and by improved screening of blood donors. As a result of these activities, a marked reduction in the risk of transfusional transmission can now be seen throughout the programme area. In addition to specific legislation concerning the quality of transfused blood, a series of national and regional reference laboratories have been set up with the help of PAHO in order to improve the quality of pre-transfusional serodiagnosis. Results indicate a progressive reduction in the overall infection prevalence of blood donors, and show that the age-prevalence curve has shifted towards older age-groups. In this paper we analyse the changes in infection prevalence in the Southern Cone countries, drawing attention to the situation in Bolivia which has the highest indices of infection and lowest levels of coverage by the control programme. In this situation chemoprophylaxis of blood prior to transfusion may be recommended in accordance with PAHO criteria. In the medium term however, interruption of human Chagas disease transmission may be expected over most of the Southern Cone region, as long as the control activities are continued and consolidated through effective epidemiological surveillance.

  14. Modelling inter-human transmission dynamics of Chagas disease: analysis and application.

    PubMed

    Fabrizio, M C; Schweigmann, N J; Bartoloni, N J

    2014-05-01

    Transmission of Trypanosoma cruzi, the causal agent of Chagas disease, has expanded from rural endemic to urban areas due to migration. This so-called urban Chagas is an emerging health problem in American, European, Australian and Japanese cities. We present a mathematical model to analyse the dynamics of urban Chagas to better understand its epidemiology. The model considers the three clinical stages of the disease and the main routes of inter-human transmission. To overcome the complexities of the infection dynamics, the next-generation matrix method was developed. We deduced expressions which allowed estimating the number of new infections generated by an infected individual through each transmission route at each disease stage, the basic reproduction number and the number of individuals at each disease stage at the outbreak of the infection. The analysis was applied to Buenos Aires city (Argentina). We estimated that 94% of the new infections are generated by individuals in the chronic indeterminate stage. When migration was not considered, the infection disappeared slowly and R0 = 0.079, whereas when migration was considered, the number of individuals in each stage of the infection tended to stabilize. The expressions can be used to estimate different numbers of infected individuals in any place where only inter-human transmission is possible.

  15. Multi-epitope proteins for improved serological detection of Trypanosoma cruzi infection and Chagas Disease.

    PubMed

    Duthie, Malcolm S; Guderian, Jeffery A; Vallur, Aarthy C; Misquith, Ayesha; Liang, Hong; Mohamath, Raodoh; Luquetti, Alejandro O; Carter, Darrick; Tavares, Suelene N B; Reed, Steven G

    2016-03-01

    We previously reported that tandem repeat (TR) proteins from Trypanosoma cruzi could serve as targets of the antibody response and be useful as diagnostic indicators. To optimize reagents for detecting T. cruzi infection we evaluated individual TR proteins and identified several that were recognized by the majority of Chagas patient's sera collected from individuals form Brazil. We then produced novel, recombinant fusion proteins to combine the reactive TR proteins into a single diagnostic product. Direct comparison of the antibody response of serum samples that were readily detected by the established fusion antigen used in commercial detection of Chagas disease, TcF, revealed strong responses to TcF43 and TcF26 proteins. While the TcF43 and TcF26 antigens enhanced detection and strength of signal, they did not compromise the specificity of detection compared to that obtained with TcF. Finally, it was apparent by testing against a panel of 84 serum samples assembled on the basis of moderate or weak reactivity against TcF (mostly signal:noise <5) that TcF43 and TcF26 could more strongly detected by many of the sera that had low TcF antibody levels. Taken together, these data indicate that TcF43 and TcF26 could be used to enhance the detection of T. cruzi infection as well as supporting a diagnosis of Chagas disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Implantable cardioverter defibrillators and Chagas' disease: results of the ICD Registry Latin America.

    PubMed

    Muratore, Claudio A; Batista Sa, Luiz A; Chiale, Pablo A; Eloy, Ricardo; Tentori, Maria Cristina; Escudero, Jaime; Lima, Antonio Malan Cavalcanti; Medina, Luis E; Garillo, Raúl; Maloney, Jennifer

    2009-02-01

    Chagas' disease is an endemic parasitic affliction in Latin America. It is frequently associated with ventricular tachyarrhythmia and sudden death. The aim of this study is to assess the evolution of patients with Chagas' disease treated with an implantable cardioverter defibrillator (ICD). Eighty-nine chagasic patients with ICD were included for analysis from the Medtronic ICD Registry Latin America. At implant, mean age was 59 +/- 10 years, and 72% were male. Eighty-one patients (91%) had secondary prevention indications. Mean left ventricular ejection fraction was 40 +/- 11%, and mean follow-up was 12 +/- 7 months. During follow-up, six patients died (6.7%); three due to congestive heart failure, one due to sudden death, and two due to non-cardiac cause. Hospitalization occurred in seven patients. Thirty-eight patients (42%) received appropriate ICD therapies. A total of 737 episodes were detected by the ICD. The mean period between ICD implantation and the first appropriate therapy was 104 days. Electrical storms were observed in 14 of the 89 patients (15.7%). Inappropriate therapies were observed in seven patients. This registry confirms that ICD therapy provides protection by effectively terminating life-threatening arrhythmias in patients with Chagas' disease. This is especially so when patients receive the device for secondary prevention.

  17. The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions - A comprehensive review

    PubMed Central

    Coura, José Rodrigues

    2015-01-01

    This review deals with transmission of Trypanosoma cruzi by the most important domestic vectors, blood transfusion and oral intake. Among the vectors, Triatoma infestans, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidiata, Triatoma brasiliensis, Triatoma pseudomaculata, Triatoma sordida, Triatoma maculata, Panstrongylus geniculatus, Rhodnius ecuadoriensis and Rhodnius pallescens can be highlighted. Transmission of Chagas infection, which has been brought under control in some countries in South and Central America, remains a great challenge, particularly considering that many endemic countries do not have control over blood donors. Even more concerning is the case of non-endemic countries that receive thousands of migrants from endemic areas that carry Chagas disease, such as the United States of America, in North America, Spain, in Europe, Japan, in Asia, and Australia, in Oceania. In the Brazilian Amazon Region, since Shaw et al. (1969) described the first acute cases of the disease caused by oral transmission, hundreds of acute cases of the disease due to oral transmission have been described in that region, which is today considered to be endemic for oral transmission. Several other outbreaks of acute Chagas disease by oral transmission have been described in different states of Brazil and in other South American countries. PMID:25466622

  18. Chagas disease and housing improvement in northeastern Brazil: a cross-sectional survey.

    PubMed

    Lima, Marli M; Carvalho-Costa, Filipe A; Toma, Helena K; Borges-Pereira, José; de Oliveira, Tiago Guedes; Sarquis, Otília

    2015-05-01

    Chagas disease was investigated in two new settlements of landless rural workers inhabiting prefabricated, triatomine-proof houses and in four neighboring older communities where mud huts were still well suitable for vectors. Through a cross-sectional survey and entomological assessment, we surveyed 148 houses/families in the two new settlements and in 47 houses/families in the four older localities. We determined seroprevalence of Chagas disease through IFI and Elisa (eluates) assays and searched for vectors in the domestic and peridomestic environments. Seroprevalence reached 0.6% (3/466) in the new settlements and 0.8% (1/115) in the older communities. Triatomines were not found in the new settlements, while 7 Triatoma brasiliensis, 4 T. pseudomaculata, 1 Panstrongylus lutzi, and 145 Rhodnius nasutus were collected in the older localities. In addition, a colony of T. brasiliensis (n = 55) was encountered inside a school attended by children of the region. Parasite strains isolated from the insects were characterized as T. cruzi I. Despite the low prevalence of Chagas disease in both scenarios, entomological surveillance must be strengthened and housing improvement reinforced in order to control vector transmission. The risk of infection by the vectors was lower in the settlements of improved homes, where conditions for colonization of the peridomestic environment by transmitting insects were not observed.

  19. Oesophageal motility disorders in infected immigrants with Chagas disease in a non-endemic European area

    PubMed Central

    Valerio, Lluís; Vallès, Xavier; Morales, Betty; Garcia-Diaz, M Immaculada; Pedro-Botet, M Luisa; Serra, Jordi

    2016-01-01

    Background Immigration-related new diseases pose a growing challenge for healthcare services in receptor countries. Following Latin American migration, Chagas disease has inevitably appeared in Europe. Aim To determine the prevalence and characteristics of oesophageal motility disorders in immigrants infected with Trypanosoma cruzi, using high resolution oesophageal manometry (HREM). Methods In all newly-diagnosed cases with chronic Chagas infection referring upper digestive symptoms, a protocolized clinical evaluation and complementary tests including barium oesophagogram and HREM were carried out. As control group, 14 healthy subjects from the same endemic areas were studied with HREM. Results We included 61 patients (46 female, 15 male; age range 26–63 years). Only seven patients (11%) had a minor alteration on barium oesophagogram. By contrast, 23 (37%) patients showed an alteration in oesophageal manometry, mainly minor motility disorders (34%). Only one healthy control (7%) had a minor motility disorder at HREM (p = 0.029 vs. patients). Conclusions Oesophageal motor disorders in infected immigrants with Chagas disease are common, and mainly characterized by a minor motility disorder that is not detected by barium oesophagogram. Hence, as well as barium oesophagogram examination, HREM should be considered, to assess oesophageal damage in this specific group of patients. PMID:27536373

  20. [Knowledge of vector-borne diseases (dengue, rickettsiosis and Chagas disease) in physicians].

    PubMed

    Lugo-Caballero, César I; Dzul-Rosado, Karla; Dzul-Tut, Irving; Balam-May, Ángel; Zavala-Castro, Jorge

    2017-01-01

    The ecological conditions of Yucatan made it a suitable region for the acquisition of vector-borne diseases such as dengue, rickettsiosis, and Chagas disease. As the epidemiological burden of these diseases shows an alarming increase of severe cases, the early establishment of diagnosis and therapeutics by first-contact physicians is a critical step that is not being fulfilled due to several reasons, including poor knowledge. To determine the level of knowledge related to dengue, Chagas disease, and rickettsiosis among rural first-contact physicians of Yucatan. A survey was applied to 90 first-contact physicians from rural clinics of Yucatan, which included 32 items related to the diagnosis, treatment, and prevention of dengue, rickettsiosis, and Chagas disease. Answers were analyzed by central tendency statistics. Differences were observed among every category, however; diagnosis and therapeutics showed the lower values. Globally, 62.5% of respondents showed moderate knowledge, 37.5% poor knowledge, and 0% adequate knowledge. Results suggest that a strong campaign for a continuous diffusion of knowledge regarding these diseases is needed. In regions with high prevalence of these kinds of diseases, like Yucatan, the impact of these results on the epidemiological burden of these diseases must be evaluated.

  1. Chagas disease in Europe: A review for the internist in the globalized world.

    PubMed

    Antinori, Spinello; Galimberti, Laura; Bianco, Roberto; Grande, Romualdo; Galli, Massimo; Corbellino, Mario

    2017-05-11

    Chagas disease (CD) or American trypanosomiasis identified in 1909 by Carlos Chagas, has become over the last 40years a global health concern due to the huge migration flows from Latin America to Europe, United States, Canada and Japan. In Europe, most migrants from CD-endemic areas are concentrated in Spain, Italy, France, United Kingdom and Switzerland. Pooled seroprevalence studies conducted in Europe show an overall 4.2% prevalence, with the highest infection rates observed among individuals from Bolivia (18.1%). However, in most European countries the disease is neglected with absence of screening programmes and low access to diagnosis and treatment. Physicians working in Europe should also be aware of the risk of autochthonous transmission of Trypanosoma cruzi to newborns by their infected mothers and to recipients of blood or transplanted organs from infected donors. Finally, physicians should be able to recognize and treat the most frequent and serious complications of chronic Chagas disease, namely cardiomyopathy, megacolon and megaesophagus. This review aims to highlights the problem of CD in Europe by reviewing papers published by European researchers on this argument, in order to raise the awareness of internists who are bound to increasingly encounter patients with the disease in their routine daily activities. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  2. Evaluation of a Recombinant Trypanosoma cruzi Mucin-Like Antigen for Serodiagnosis of Chagas' Disease ▿

    PubMed Central

    De Marchi, Claudia R.; Di Noia, Javier M.; Frasch, Alberto C. C.; Amato Neto, Vicente; Almeida, Igor C.; Buscaglia, Carlos A.

    2011-01-01

    Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and is one of the most important endemic problems in Latin America. Lately, it has also become a health concern in the United States and Europe. Currently, a diagnosis of Chagas' disease and the screening of blood supplies for antiparasite antibodies are achieved by conventional serological tests that show substantial variation in the reproducibility and reliability of their results. In addition, the specificity of these assays is curtailed by antigenic cross-reactivity with sera from patients affected by other endemic diseases, such as leishmaniasis. Here we used a highly sensitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to evaluate a recombinant protein core of a mucin-like molecule (termed trypomastigote small surface antigen [TSSA]) for the detection of specific serum antibodies in a broad panel of human sera. The same samples were evaluated by CL-ELISA using as the antigen either a mixture of native T. cruzi trypomastigote mucins or an epimastigote extract and, for further comparison, by conventional serologic tests, such as an indirect hemagglutination assay and indirect immunofluorescence assay. TSSA showed ∼87% sensitivity among the seropositive Chagasic panel, a value which was increased up to >98% when only parasitologically positive samples were considered. More importantly, TSSA showed a significant increase in specificity (97.4%) compared to those of currently used assays, which averaged 80 to 90%. Overall, our data demonstrate that recombinant TSSA may be a useful antigen for the immunodiagnosis of Chagas' disease. PMID:21880857

  3. Prevalence and Risk Factors for Chagas Disease in Pregnant Women in Casanare, Colombia

    PubMed Central

    Cucunubá, Zulma M.; Flórez, Astrid C.; Cárdenas, Ángela; Pavía, Paula; Montilla, Marleny; Aldana, Rodrigo; Villamizar, Katherine; Ríos, Lyda C.; Nicholls, Rubén S.; Puerta, Concepción J.

    2012-01-01

    Knowledge of the prevalence and risk factors associated with maternal infection is the first step to develop a surveillance system for congenital transmission of Chagas disease. We conducted a cross-sectional study in Casanare, a disease-endemic area in Colombia. A total of 982 patients were enrolled in the study. A global prevalence of Trypanosoma cruzi infection of 4.0% (95% confidence interval [CI] = 2.8–5.3%) was found. Multivariate analysis showed that the most important risk-associated factors were age > 29 years (adjusted odds ratio [aOR] = 3.4, 95% CI = 0.9–12.4), rural residency (aOR = 2.2, 95% CI = 1.0–4.6), low education level (aOR = 10.2, 95% CI = 1.6–82.7), and previous knowledge of the vector (aOR = 2.2, 95% CI = 1.0–4.9). Relatives and siblings of infected mothers showed a prevalence of 9.3%. These findings may help physicians to investigate congenital cases, screen Chagas disease in siblings and relatives, and provide early treatment to prevent the chronic complications of Chagas disease. PMID:23033397

  4. Understanding transmissibility patterns of Chagas disease through complex vector-host networks.

    PubMed

    Rengifo-Correa, Laura; Stephens, Christopher R; Morrone, Juan J; Téllez-Rendón, Juan Luis; González-Salazar, Constantino

    2017-01-12

    Chagas disease is one of the most important vector-borne zoonotic diseases in Latin America. Control strategies could be improved if transmissibility patterns of its aetiologic agent, Trypanosoma cruzi, were better understood. To understand transmissibility patterns of Chagas disease in Mexico, we inferred potential vectors and hosts of T. cruzi from geographic distributions of nine species of Triatominae and 396 wild mammal species, respectively. The most probable vectors and hosts of T. cruzi were represented in a Complex Inference Network, from which we formulated a predictive model and several associated hypotheses about the ecological epidemiology of Chagas disease. We compiled a list of confirmed mammal hosts to test our hypotheses. Our tests allowed us to predict the most important potential hosts of T. cruzi and to validate the model showing that the confirmed hosts were those predicted to be the most important hosts. We were also able to predict differences in the transmissibility of T. cruzi among triatomine species from spatial data. We hope our findings help drive efforts for future experimental studies.

  5. Seroprevalence of Triatoma virus (Dicistroviridae: Cripaviridae) antibodies in Chagas disease patients.

    PubMed

    Querido, Jailson F B; Echeverría, María G; Marti, Gerardo A; Costa, Rita Medina; Susevich, María L; Rabinovich, Jorge E; Copa, Aydee; Montaño, Nair A; Garcia, Lineth; Cordova, Marisol; Torrico, Faustino; Sánchez-Eugenia, Rubén; Sánchez-Magraner, Lissete; Muñiz-Trabudua, Xabier; López-Marijuan, Ibai; Rozas-Dennis, Gabriela S; Diosque, Patricio; de Castro, Ana M; Robello, Carlos; Rodríguez, Julio S; Altcheh, Jaime; Salazar-Schettino, Paz M; Bucio, Marta I; Espinoza, Bertha; Guérin, Diego M A; Silva, Marcelo Sousa

    2015-01-17

    Chagas disease is caused by Trypanosoma cruzi, and humans acquire the parasite by exposure to contaminated feces from hematophagous insect vectors known as triatomines. Triatoma virus (TrV) is the sole viral pathogen of triatomines, and is transmitted among insects through the fecal-oral route and, as it happens with T. cruzi, the infected insects release the virus when defecating during or after blood uptake. In this work, we analysed the occurrence of anti-TrV antibodies in human sera from Chagas disease endemic and non-endemic countries, and developed a mathematical model to estimate the transmission probability of TrV from insects to man, which ranged between 0.00053 and 0.0015. Our results confirm that people with Chagas disease living in Bolivia, Argentina and Mexico have been exposed to TrV, and that TrV is unable to replicate in human hosts. We presented the first experimental evidence of antibodies against TrV structural proteins in human sera.

  6. Prevalence of Chagas Disease in Latin-American Migrants Living in Europe: A Systematic Review and Meta-analysis

    PubMed Central

    Requena-Méndez, Ana; Aldasoro, Edelweiss; de Lazzari, Elisa; Sicuri, Elisa; Brown, Michael; Moore, David A. J.; Gascon, Joaquim; Muñoz, Jose

    2015-01-01

    Background Few studies have assessed the burden of Chagas disease in non-endemic countries and most of them are based on prevalence estimates from Latin American (LA) countries that likely differ from the prevalence in migrants living in Europe. The aim of this study was to systematically review the existing data informing current understanding of the prevalence of Chagas disease in LA migrants living in European countries. Methods We conducted a systematic review and meta-analysis of studies reporting prevalence of Chagas disease in European countries belonging to the European Union (EU) before 2004 in accordance with the MOOSE guidelines and based on the database sources MEDLINE and Global Health. No restrictions were placed on study date, study design or language of publication. The pooled prevalence was estimated using random effect models based on DerSimonian & Laird method. Results We identified 18 studies conducted in five European countries. The random effect pooled prevalence was 4.2% (95%CI:2.2-6.7%); and the heterogeneity of Chagas disease prevalence among studies was high (I2 = 97%,p<0.001). Migrants from Bolivia had the highest prevalence of Chagas disease (18.1%, 95%CI:13.9–22.7%). Conclusions Prevalence of Chagas in LA migrants living in Europe is high, particularly in migrants from Bolivia and Paraguay. Data are highly heterogeneous dependent upon country of origin and within studies of migrants from the same country of origin. Country-specific prevalence differs from the estimates available from LA countries. Our meta-analysis provides prevalence estimates of Chagas disease that should be used to estimate the burden of disease in European countries. PMID:25680190

  7. Effects of aspirin-triggered resolvin D1 on peripheral blood mononuclear cells from patients with Chagas' heart disease.

    PubMed

    Ogata, Haline; Teixeira, Maxelle Martins; Sousa, Rodrigo Cunha de; Silva, Marcos Vinícius da; Correia, Dalmo; Rodrigues Junior, Virmondes; Levy, Bruce David; Rogério, Alexandre de Paula

    2016-04-15

    Chagas disease is caused by Trypanosoma cruzi (T. cruzi). In some patients with Chagas disease, symptoms progress to chronic chagasic cardiomyopathy. Endogenously, inflammation is resolved in the presence of lipid mediators such as aspirin-triggered RvD1 (AT-RvD1) which has anti-inflammatory and pro-resolution effects. Here, we demonstrated, for the first time, the effects of AT-RvD1 on T. cruzi antigen-stimulated peripheral blood mononuclear cells (PBMCs) from patients with Chagas heart disease. The levels of IFN-γ, TNF-α, IL-10, and IL-13 increased in PBMCs from cardiac-form Chagas patients in stage B1 (patients with fewer heart abnormalities) stimulated with T. cruzi antigen compared to those in non-stimulated PBMCs. AT-RvD1 reduced the IFN-γ concentrations in PBMCs from patients with Chagas disease stimulated with T. cruzi antigen compared to stimulated with T. cruzi antigen cells. AT-RvD1 treatment resulted in no observable changes in TNF-α, IL-10, and IL-13 levels. AT-RvD1 significantly decreased the percentage of necrotic cells and caused a significant reduction in the proliferation rate of T. cruzi antigen-stimulated PBMCs from patients with Chagas disease. These findings demonstrate that AT-RvD1 modulates the immune response in Chagas disease patients and might have potential to be used as an alternative approach for slowing the development of further heart damage. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The immunology of experimental Chagas' disease. IV. Production of lesions in rabbits similar to those of chronic Chagas' disease in man.

    PubMed Central

    Teixeira, A. R.; Teixeira, M. L.; Santos-Buch, C. A.

    1975-01-01

    Eight rabbits that received a single inoculation of trypomastigotes of a virulent strain of Trypanosoma cruzi first developed a transient acute illness associated with parasitemia; later, 4 of these rabbits died with chronic myocarditis and/or with megacolon in the absence of demonstrable parasitemia or encysted parasites in tissues. Two of these rabbits with chronic myocarditis died unexpectedly. Three of the inoculated rabbits that survived the infection were sacrificed 18 months later and showed similar but less severe microscopic lesions. The remaining rabbit is alive and well at the time of writing (26 months) with negative blood cultures but high hemagglutinating antibody titers to T. cruzi antigens. The natural course of T. cruzi infection in rabbits and the lesions observed postmortem are similar to those recorded for humans with chronic Chagas' disease. Multiple injections of particulate subcellular antigens of T. cruzi in rabbits resulted in microscopic lesions similar to those observed in rabbits that survived protozoan infection. Sera of rabbits inoculated with T. cruzi have antibodies to striated and smooth muscle structures. However, evidence provided in this and in other experiments strongly suggest that the lesions of chronic Chagas' disease are produced by delayed hypersensitivity to T. cruzi antigens. Images Figure 1 Figure 2 Figures 3-4 Figure 5 Figure 6 Figure 7 PMID:808136

  9. Chagas' disease diagnosis: a multicentric evaluation of Chagas Stat-Pak, a rapid immunochromatographic assay with recombinant proteins of Trypanosoma cruzi.

    PubMed

    Luquetti, Alejandro O; Ponce, Carlos; Ponce, Elisa; Esfandiari, Javan; Schijman, Alejandro; Revollo, Susana; Añez, Nestor; Zingales, Bianca; Ramgel-Aldao, Rafael; Gonzalez, Antonio; Levin, Mariano J; Umezawa, Eufrosina S; Franco da Silveira, José

    2003-08-01

    A rapid serologic test for diagnosis of T. cruzi infection (Chagas Stat Pak) was developed using recombinant proteins in an immunochromatographic assay. This cassette format test was evaluated first in blind with a panel of 393 coded serum samples. The Chagas Stat-Pak identified 197 infected (98.5% sensitivity) and 183 non-infected individuals (94.8% specificity). A second evaluation was performed with 352 sera from four Latin America countries tested independently in each country, showing a sensitivity of 100% and specificity of 98.6%. A third set of tests comparing sera with plasma and eluates from filter paper as well as serum preserved in 50% glycerol did show identical results as those obtained with serum. This rapid test (15 min) uses one device per sample, does not require refrigeration nor a laboratory structure or specialized skills to be performed, accepts different types of samples and may be stored for long periods of time for result checking and documentation. These attributes together with the high sensitivity and specificity demonstrated herein, make this test a suitable tool for field studies, small laboratories and emergencies at blood banks in the countryside of endemic areas.

  10. BNP, NTproBNP, CMBK, and MMP-2 predict mortality in severe Chagas cardiomyopathy

    PubMed Central

    Sherbuk, Jacqueline E.; Okamoto, Emi E.; Marks, Morgan A.; Fortuny, Enzo; Clark, Eva H.; Galdos-Cardenas, Gerson; Vasquez-Villar, Angel; Fernandez, Antonio B.; Crawford, Thomas C.; Do, Rose Q.; Flores-Franco, Jorge Luis; Colanzi, Rony; Gilman, Robert H.; Bern, Caryn

    2015-01-01

    Background Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival. Objectives Our study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital. Methods The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, ECG findings, medications, and serum cardiac biomarker levels (BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2) were ascertained. Echocardiograms were preferentially performed on those with cardiac symptoms or electrocardiogram abnormalities. Participants were contacted by phone approximately 1 year after initial evaluation; deaths were reported by family members. Receiver operating characteristic curves were used to optimize cut-off values for each marker. For markers with area under curve > 0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality. Results The median follow-up time was 14.1 months (interquartile range 12.5- 16.7 months). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy, 20 (40%) had died. Higher baseline levels of BNP (HR[95% CI]:3.1 [1.2, 8.4]), NTproBNP (4.4[1.8,11.0]), CKMB (3.3[1.3, 8.0]), and MMP-2 (4.2[1.5, 11.8]) were significantly associated with subsequent mortality. Conclusions Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NTproBNP, CKMB and MMP2 have added predictive value for mortality, even in the presence of

  11. Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses.

    PubMed

    Chaves, Ana Thereza; de Assis Silva Gomes Estanislau, Juliana; Fiuza, Jacqueline Araújo; Carvalho, Andréa Teixeira; Ferreira, Karine Silvestre; Fares, Rafaelle Christine Gomes; Guimarães, Pedro Henrique Gazzinelli; de Souza Fagundes, Elaine Maria; Morato, Maria José; Fujiwara, Ricardo Toshio; da Costa Rocha, Manoel Otávio; Correa-Oliveira, Rodrigo

    2016-04-30

    Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis

  12. Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period.

    PubMed

    Duschak, Vilma G

    2016-01-01

    The American trypanosomiasis, Chagas disease, is a parasitic infection typically spread by triatomine vectors affecting millions of people all over Latin America. Existing chemotherapy is centered on the nitroaromatic compounds benznidazole and nifurtimox that provide unsatisfactory results and substantial side effects. So, the finding and exploration of novel ways to challenge this neglected disease is a main priority. The biologic and biochemical progress in the scientific knowledge of Trypanosoma cruzi in the period comprising last 15-years has increased the identification of multiple targets for Chagas´ disease chemotherapy. In the middle of the best encouraging targets for trypanocidal drugs, ergosterol biosynthesis pathway and cruzipain, a key cysteine protease (CP) of T. cruzi, have been pointed out. Unfortunately, recent clinical trials investigating the administration of pozoconazole and ravuconazole to chronic indeterminate Chagas disease patients revealed their inferiority compared to the standard drug Benznidazole. In view of the information gained in the preceding years, a reasonable approach for the fast development of novel anti-T. cruzi chemotherapy would be focused on K777, the cysteine proteinase inhibitor (CPI) near to enter to clinical trials, and founded on the clinical evaluation of combination of known drugs with existing trypanocidal agents to obtain more efficiency and less secondary effects. Top series of xanthine have been recently identified as clinical candidate for Chagas disease. In addition, trypanothione biosynthesis, thiol-dependant redox and polyamine metabolism, the glycolytic, glyconeogenic, pentose phosphate, lipidic and polyisoprenoid biosynthetic pathways, and the enzymes from biosynthetic glycoconjugates pathways have been studied. Several specific enzymes from these particular biosynthetic pathways such as hypoxanthine-guaninephosphoribosyl- transferase and farnesyl-pyrophosphate synthase, among others, have also been

  13. Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease.

    PubMed

    García-Bournissen, Facundo; Moroni, Samanta; Marson, Maria Elena; Moscatelli, Guillermo; Mastrantonio, Guido; Bisio, Margarita; Cornou, Laura; Ballering, Griselda; Altcheh, Jaime

    2015-01-01

    Benznidazole (BNZ) is safe and effective for the treatment of paediatric Chagas disease. Treatment of adults is also effective in many cases, but discouraged in breastfeeding women because no information on BNZ transfer into breast milk is available. We aimed to evaluate the degree of BNZ transfer into breast milk in lactating women with Chagas disease. Prospective cohort study of lactating women with Chagas disease treated with BNZ administered for 30 days. Patients and their breastfed infants were evaluated at admission, the 7th and 30th day of treatment (and monthly thereafter, for 6 months). BNZ was measured in plasma and milk by high performance liquid chromatography. The protocol was registered in ClinicalTrials.gov (#NCT01547533). 12 lactating women with chronic Chagas disease were enrolled (median age 28.5 years, range 20-34). Median BNZ dose was 5.65 mg/kg/day twice daily. Five mothers had adverse drug events (45%), but no adverse drug reactions or any untoward outcomes were observed in the breastfed infants. Median milk BNZ concentration was 3.8 mg/L (range 0.3-5.9) and 6.26 mg/L (range 0.3-12.6) in plasma. Median BNZ milk to plasma ratio was 0.52 (range 0.3-2.79). Median relative BNZ dose received by the infant (assuming a daily breast milk intake of 150 mL/kg/day) was 12.3% of the maternal dose per kg (range 5.5%-17%). The limited transference of BNZ into breast milk and the reassuring normal clinical evaluation of the breastfed babies suggest that maternal BNZ treatment for Chagas disease during breast feeding is unlikely to present a risk for the breastfed infant. ClinicalTrials.gov NCT01547533. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Upscale or downscale: applications of fine scale remotely sensed data to Chagas disease in Argentina and schistosomiasis in Kenya

    PubMed Central

    Kitron, Uriel; Clennon, Julie A.; Cecere, M. Carla; Gürtler, Ricardo E.; King, Charles H.; Vazquez-Prokopec, Gonzalo

    2007-01-01

    Depending on the research question or the public health application, the appropriate resolution of the data varies temporally, spatially, and, for satellite data, spectrally and radiometrically. Regardless of the scale used to address a research or public health question, the temptation is always there to extrapolate from fine-resolution data or to interpolate from coarse resolution studies. In both cases, the relevance of data and analyses conducted on one spatial level to other levels cannot be taken for granted. Spatial heterogeneity on the micro-scale may not be detected using coarse spatial resolution, and conversely, general patterns on the macro-scale may not be detected using fine spatial resolution. Two studies are described where the transmission dynamics and risk of infection was assessed on the micro-scale starting with household level studies in one community, and the study area was extended gradually to consider several communities and sources for vectors or intermediate hosts. In a study of Chagas disease in northwest Argentina, the reinfestation process of communities by the main domestic vector was analyzed using spatial statistics; sources within and outside communities as well as the distance of reinfestation were identified. In a study of urinary schistosomiasis in coastal Kenya, age dependent and directional focal clustering of infections was detected around some aquatic habitats, and a hydrological model was developed to detect least cost dispersal routes that allow snails to reinfest dried-up habitats. Some general aspects of focal statistics are discussed. Several general questions need to be considered in geospatial health studies, including the following: (i) what are the best criteria for selecting the spatial (and temporal) unit of intervention and analysis? (ii) how do the key measures of risk and transmission dynamics vary with scale? (iii) how do we integrate processes occurring at diverse spatial and temporal scales? All of these

  15. Clinical forms of Trypanosoma cruzi infected individuals in the chronic phase of Chagas disease in Puebla, Mexico.

    PubMed

    Sánchez-Guillén, María Del Carmen; López-Colombo, Aurelio; Ordóñez-Toquero, Guillermo; Gomez-Albino, Isidoro; Ramos-Jimenez, Judith; Torres-Rasgado, Enrique; Salgado-Rosas, Hilda; Romero-Díaz, Mónica; Pulido-Pérez, Patricia; Pérez-Fuentes, Ricardo

    2006-11-01

    In Mexico, despite the relatively high seroprevalence of Trypanosoma cruzi infection in humans in some areas, reported morbidity of Chagas disease is not clear. We determined clinical stage in 71 individuals seropositive to T. cruzi in the state of Puebla, Mexico, an area endemic for Chagas disease with a reported seroprevalence of 7.7%. Diagnosis of Chagas disease was made by two standardized serological tests (ELISA, IHA). Individuals were stratified according to clinical studies. All patients were submitted to EKG, barium swallow, and barium enema. Groups were identified as indeterminate form (IF) asymptomatic individuals without evidence of abnormalities (n = 34 cases); those with gastrointestinal alterations (12 patients) including symptoms of abnormal relaxation of the lower esophageal sphincter and absent peristalsis in the esophageal body, grade I megaesophagus, and/or megacolon; patients with clinical manifestations and documented changes of chronic Chagas heart disease who were subdivided as follows: mild (8 patients)--mild electrocardiographic changes of ventricular repolarization, sinus bradychardia); moderate (6 patients)--left bundle branch block, right bundle branch block associated with left anterior fascicular block); severe (8 patients)--signs of cardiomegaly, dilated cardiomyopathy); and the associated form (3 cases) that included presence of both cardiomyopathy and megaesophagus. These data highlight the importance of accurate evaluation of the prevalence and clinical course of Chagas disease in endemic and non-endemic areas of Mexico.

  16. [Knowledge and risk factors related to Chagas' disease in two Panamanian communities where Rhodnius pallescens is the main vector].

    PubMed

    Hurtado, Lisbeth A; Calzada, José E; Pineda, Vanessa; González, Kadir; Santamaría, Ana María; Cáceres, Lorenzo; Wald, Coridalia; Saldaña, Azael

    2014-01-01

    The implementation of surveillance, control and prevention measures for Chagas´ disease requires an integrated approach. The sustainability of programs depends on community participation supported on a basic understanding of the problem. To evaluate the knowledge of people interviewed which facilitates or limits the surveillance, prevention and control of Chagas' disease in two endemic Panamanian communities where Rhodnius pallescens is the main vector. A questionnaire assessed the knowledge and risk factors related to Chagas' disease in 201 people over 10 years of age from the endemic communities of Las Pavas and Lagartera Grande located on the western shore of Panama Canal. Additionally, with the help of the residents, the presence of triatomine bugs in 93 dwellings was evaluated during a year. Of those interviewed, 69.2% (139/201) had poor or very poor knowledge about Chagas' disease. Nearly 93% (187/201) was exposed to moderate or high risk factors. Triatomine bugs were collected in 20.4% (19/93) of the evaluated homes; 80% (66/76) of them were R. pallescens. Significant association was found between the presence of triatomines inside the houses and precarious housing (p<0.01). Despite having been exposed to health education-related programs, it is necessary to strengthen the basic knowledge about Chagas' disease in the two communities before establishing prevention and surveillance measures which involve active participation of its inhabitants.

  17. Clinical, electrocardiographic and echocardiographic abnormalities in Latin American migrants with newly diagnosed Chagas disease 2005-2009, Barcelona, Spain.

    PubMed

    Valerio, L; Roure, S; Sabria, M; Balanzo, X; Valles, X; Seres, L

    2011-09-22

    Following Latin American migration, Chagas disease has inevitably appeared in non-endemic countries in Europe and elsewhere. New policies are necessary to prevent transmission in those countries but the long, often undetected chronic period of the early stages of the disease also renders epidemiological studies important. The main objective of our study was to determine the presence of clinical, electrocardiogram (ECG) and echocardiographic abnormalities in a population of Latin American migrants infected with Trypanosoma cruzi at the moment of diagnosis. We performed a hospital-based observational study of 100 adult patients with newly diagnosed Chagas infection between January 2005 and December 2009. Thirty-seven patients were classified within the Brazilian Consensus on Chagas cardiomyopathy early cardiac stages (A or B1) and 49 presented pathological findings (stage B2) according to the Panamerican Health Organization Classification. Overall, 49 patients showed ECG and/or echocardiographic alterations. The presence of ECG and ecocardiographic alterations were significantly associated (p=0.038). The most frequent ECG and echocardiographic findings were right bundle branch block (12 cases) and impaired left ventricular wall relaxation (24 cases), respectively. In conclusion, ECG and echocardiographic alterations coherent with Chagas cardiomyopathy were found in a large proportion of newly diagnosed Latin American migrants infected with T. cruzi. In the mid-term, Chagas disease might become an important cause of chronic cadiomyopathy in our attendance area.

  18. [A study of the antiherpetic activity of the chaga mushroom (Inonotus obliquus) extracts in the Vero cells infected with the herpes simplex virus].

    PubMed

    Polkovnikova, M V; Nosik, N N; Garaev, T M; Kondrashina, N G; Finogenova, M P; Shibnev, V A

    2014-01-01

    The chaga mushroom (Inonotus obliquus) contains a wide range of excellent bioactive compounds. However, limited information exists on the antiviral activity of the compounds extracted from chaga. A number of subfractions of chaga were obtained using different solvents and different procedures. The subfractions of chaga extracted with water, alcohol, alkali were tested for their toxicity for the Vero cell culture and antiviral effect in the Vero cells infected with the Herpes simplex virus (HSV), Type 1. It was shown that most of the subfractions were not toxic for the Vero cells and had protective effect on the Vero cells infected with HSV. The subfraction IV in the concentration 5 microg/ml protected the Vero cells from cytodestructive action of HSV and no viral DNA was detected in infected cells treated with chaga extracts. Best protective effect was observed when compound was added before or within one hour after the Vero cells were infected with HSV.

  19. Coronary Microvascular Disease in Chronic Chagas Cardiomyopathy Including an Overview on History, Pathology, and Other Proposed Pathogenic Mechanisms

    PubMed Central

    Rossi, Marcos A.; Tanowitz, Herbert B.; Malvestio, Lygia M.; Celes, Mara R.; Campos, Erica C.; Blefari, Valdecir; Prado, Cibele M.

    2010-01-01

    This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease. PMID:20824217

  20. [How health activities view man and how man rethinks them: an anthropological analysis of Chagas disease control].

    PubMed

    Magnani, Claudia; Dias, João Carlos Pinto; Gontijo, Eliane Dias

    2009-09-01

    This anthropological study addresses the cultural perceptions of a group of residents in the city of Bambuí, Minas Gerais State, Brazil, in relation to experience with Chagas disease and the impact of health measures on social life. The ethnographic study was based on open interviews, seeking to identify individual perceptions among 35 inhabitants of Bambuí (with and without Chagas disease) living in the region since the 1940s, when Chagas disease control activities were launched. Within a broad analysis of social perceptions concerning the effect of these health measures, the study sought to observe the cultural representations of the illness process. The study is intended to contribute to comprehensive work in health interventions, including the target population's socio-cultural characteristics. The cultural perspective plays an important role in preventing social distress.

  1. Impact of Helminth Infection on the Clinical and Microbiological Presentation of Chagas Diseases in Chronically Infected Patients

    PubMed Central

    Salvador, Fernando; Sulleiro, Elena; Sánchez-Montalvá, Adrián; Martínez-Gallo, Mónica; Carrillo, Eugenia; Molina, Israel

    2016-01-01

    Abstract Background Helminth infections are highly prevalent in tropical and subtropical countries, coexisting in Chagas disease endemic areas. Helminth infections in humans may modulate the host immune system, changing the Th1/Th2 polarization. This immunological disturbance could modify the immune response to other infections. The aim of this study is to evaluate the relationship between clinical, microbiological and epidemiological characteristics of Chagas disease patients, with the presence of helminth infection. Methods A prospective observational study was conducted at Vall d’Hebron University Hospital (Barcelona, Spain). Inclusion criteria were: age over 18 years, diagnosis of Chagas disease, and not having received specific treatment for Chagas disease previously to the inclusion. The study protocol included Chagas disease assessment (cardiac and digestive evaluation, detection of T. cruzi DNA measured by PCR in peripheral blood), and helminth infection diagnosis (detection of IgG anti-Strongyloides stercoralis by ELISA, microscopic examination of stool samples from three different days, and specific faecal culture for S. stercoralis larvae). Results Overall, 65 patients were included, median age was 38 years, 75.4% were women and most of them came from Bolivia. Cardiac and digestive involvement was present in 18.5% and 27.7% of patients respectively. T. cruzi PCR was positive in 28 (43.1%) patients. Helminth infection was diagnosed in 12 (18.5%) patients. No differences were observed in clinical and epidemiological characteristics between patients with and without helminth infection. Nevertheless, the proportion of patients with positive T. cruzi PCR was higher among patients with helminth infection compared with patients without helminth infection (75% vs 35.8%, p = 0.021). Conclusions We observed a high prevalence of S. stercoralis infection among chronic Chagas disease patients attended in our tropical medicine unit. Strongyloidiasis was associated

  2. Stroke history and Chagas disease are independent predictors of silent cerebral microembolism in patients with congestive heart failure.

    PubMed

    Jesus, Pedro A P; Neville, Iuri; Cincurá, Carolina; Menezes, Daniela F; Vieira-de-Melo, Rodrigo M; Lacerda, Amanda M; Viana, Leila C; Pereira, Davidson F; Ribeiro-dos-Santos, Valter; Reis, Francisco J F B; Macedo, Cristiano; Oliveira-Filho, Jamary

    2011-01-01

    Chagas disease is endemic in South and Central America, where 18 million individuals are infected by Trypanosoma cruzi, causing congestive heart failure (CHF) and cardioembolic stroke. Transcranial Doppler (TCD) is able to detect real-time microembolic signals (MES) to the brain vessels and may represent a surrogate marker of stroke risk. We aimed to determine predictors of MES in a population of patients with CHF. Consecutive CHF patients from a university-based cardiomyopathy clinic underwent TCD recording of the middle cerebral artery for 60 min by a single investigator who was blinded to all clinical data including cardiomyopathy etiology. Predictors of MES were sought by multivariable logistic regression analysis. From April 2004 to February 2009, 144 patients were studied, including 62 (44.6%) patients with Chagas disease. MES were detected in 9 (6.2%) patients and were more frequent in patients with Chagas disease than in patients with other causes of CHF (12.9 vs. 1.2%, p = 0.005). In multivariate analysis corrected for age and left-ventricular ejection fraction, predictors of MES were Chagas disease (odds ratio = 1.15, 95% confidence interval = 1.05-1.26, p = 0.004) and stroke history (odds ratio = 1.27, 95% confidence interval = 1.08-1.50, p = 0.005). Chagas disease and stroke history are risk factors for MES independent of cardiac disease severity. Other mechanisms besides structural cardiac disease may be operative, increasing embolic risk in Chagas disease. Copyright © 2010 S. Karger AG, Basel.

  3. Evaluation of the Chagas disease control program in Açucena Municipality, Rio Doce Valley, State of Minas Gerais, Brazil.

    PubMed

    Santos, Adriana dos; Letro, Rejane Balmant; Lemos do Bem, Vitor Antônio; Azeredo, Bernardino Vaz de Melo; Coelho, George Luiz Lins Machado; Diotaiuti, Liléia; Machado-de-Assis, Girley Francisco; de Lana, Marta

    2014-01-01

    Açucena Municipality, Rio Doce Valley, State of Minas Gerais, Brazil temporarily (2001-2005) interrupted epidemiological surveillance for Chagas disease. The objective of this work was to evaluate the Chagas Disease Control Program (CDCP) in Açucena and to offer suggestions for improving local epidemiological surveillance. This study was conducted in three phases: I) a serological investigation of schoolchildren aged 5 to 15 years using an enzyme-linked immunosorbent assay (ELISA) test performed on blood collected on filter paper followed by ELISA, indirect immunofluorescence (IIF) and indirect hemaglutination (IHA) on venous blood for borderline cases and those in the gray zone of reactivity; II) vector evaluation using the data obtained by local health agents during 2006-2010; and III) examination by ELISA, IIF and IHA of serum samples from the inhabitants of houses where infected Triatoma vitticeps was found and evaluation of their knowledge about Chagas disease. Five individuals had inconclusive results in the ELISA screening but were seronegative for Chagas disease. The triatomine evaluation revealed the presence of three species: Triatoma vitticeps, Panstrongylus megistus and Panstrongylus diasi. Triatoma vitticeps was the most prevalent and widespread, with a higher (67%) index of Trypanosoma cruzi flagellates and evidence of colonization. Most of the inhabitants of the infested houses recognized triatomines and had basic knowledge about Chagas disease. Although T. vitticeps is not clearly associated with Chagas disease transmission, these results highlight the importance of maintaining CDCP in endemic areas and the need for greater emphasis on epidemiological surveillance, especially in areas with important vectorial changes or that have been modified by human intervention.

  4. Impact of Helminth Infection on the Clinical and Microbiological Presentation of Chagas Diseases in Chronically Infected Patients.

    PubMed

    Salvador, Fernando; Sulleiro, Elena; Sánchez-Montalvá, Adrián; Martínez-Gallo, Mónica; Carrillo, Eugenia; Molina, Israel

    2016-04-01

    Helminth infections are highly prevalent in tropical and subtropical countries, coexisting in Chagas disease endemic areas. Helminth infections in humans may modulate the host immune system, changing the Th1/Th2 polarization. This immunological disturbance could modify the immune response to other infections. The aim of this study is to evaluate the relationship between clinical, microbiological and epidemiological characteristics of Chagas disease patients, with the presence of helminth infection. A prospective observational study was conducted at Vall d'Hebron University Hospital (Barcelona, Spain). Inclusion criteria were: age over 18 years, diagnosis of Chagas disease, and not having received specific treatment for Chagas disease previously to the inclusion. The study protocol included Chagas disease assessment (cardiac and digestive evaluation, detection of T. cruzi DNA measured by PCR in peripheral blood), and helminth infection diagnosis (detection of IgG anti-Strongyloides stercoralis by ELISA, microscopic examination of stool samples from three different days, and specific faecal culture for S. stercoralis larvae). Overall, 65 patients were included, median age was 38 years, 75.4% were women and most of them came from Bolivia. Cardiac and digestive involvement was present in 18.5% and 27.7% of patients respectively. T. cruzi PCR was positive in 28 (43.1%) patients. Helminth infection was diagnosed in 12 (18.5%) patients. No differences were observed in clinical and epidemiological characteristics between patients with and without helminth infection. Nevertheless, the proportion of patients with positive T. cruzi PCR was higher among patients with helminth infection compared with patients without helminth infection (75% vs 35.8%, p = 0.021). We observed a high prevalence of S. stercoralis infection among chronic Chagas disease patients attended in our tropical medicine unit. Strongyloidiasis was associated with significantly higher proportion of positive T

  5. How universal is coverage and access to diagnosis and treatment for Chagas disease in Colombia? A health systems analysis.

    PubMed

    Cucunubá, Zulma M; Manne-Goehler, Jennifer M; Díaz, Diana; Nouvellet, Pierre; Bernal, Oscar; Marchiol, Andrea; Basáñez, María-Gloria; Conteh, Lesong

    2017-02-01

    Limited access to Chagas disease diagnosis and treatment is a major obstacle to reaching the 2020 World Health Organization milestones of delivering care to all infected and ill patients. Colombia has been identified as a health system in transition, reporting one of the highest levels of health insurance coverage in Latin America. We explore if and how this high level of coverage extends to those with Chagas disease, a traditionally marginalised population. Using a mixed methods approach, we calculate coverage for screening, diagnosis and treatment of Chagas. We then identify supply-side constraints both quantitatively and qualitatively. A review of official registries of tests and treatments for Chagas disease delivered between 2008 and 2014 is compared to estimates of infected people. Using the Flagship Framework, we explore barriers limiting access to care. Screening coverage is estimated at 1.2% of the population at risk. Aetiological treatment with either benznidazol or nifurtimox covered 0.3-0.4% of the infected population. Barriers to accessing screening, diagnosis and treatment are identified for each of the Flagship Framework's five dimensions of interest: financing, payment, regulation, organization and persuasion. The main challenges identified were: a lack of clarity in terms of financial responsibilities in a segmented health system, claims of limited resources for undertaking activities particularly in primary care, non-inclusion of confirmatory test(s) in the basic package of diagnosis and care, poor logistics in the distribution and supply chain of medicines, and lack of awareness of medical personnel. Very low screening coverage emerges as a key obstacle hindering access to care for Chagas disease. Findings suggest serious shortcomings in this health system for Chagas disease, despite the success of universal health insurance scale-up in Colombia. Whether these shortcomings exist in relation to other neglected tropical diseases needs investigating

  6. Major Trypanosoma cruzi antigenic determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope.

    PubMed Central

    Mesri, E A; Levitus, G; Hontebeyrie-Joskowicz, M; Dighiero, G; Van Regenmortel, M H; Levin, M J

    1990-01-01

    A Trypanosoma cruzi lambda gt11 cDNA clone, JL5, expressed a recombinant protein which was found to react predominantly with chronic Chagas' heart disease sera. The cloned 35-residue-long peptide was identified as the carboxyl-terminal portion of a T. cruzi ribosomal P protein. The JL5 13 carboxyl-terminal residues shared a high degree of homology with the systemic lupus erythematosus (SLE) ribosomal P protein epitope. Synthetic peptides comprising the 13 (R-13), 10 (R-10), and 7 (R-7) carboxyl-terminal residues of the JL5 protein were used to study, by enzyme-linked immunosorbent assay, the specificity of the Chagas' disease anti-JL5 and SLE anti-P antibodies. The R-13 peptide defined a linear antigenic determinant of the JL5 recombinant protein. As was proved for JL5, R-13 defined antibody specificities which were significantly increased in chronic Chagas' heart disease patients. Only SLE anti-P positive sera were found to react with JL5 and R-13. Fine epitope mapping showed that Chagas' disease anti-JL5 and SLE anti-P antibodies define similar epitopes within the R-13 peptide. The binding of the SLE sera to JL5 was completely blocked by the R-13 peptide, indicating that the shared specificity between anti-JL5 and anti-P autoantibodies was exclusively limited to the conserved linear epitope(s) within the R-13 peptide. The prevalence of high anti-R-13 antibody titers in Chagas' heart disease patients supports the hypothesis that postulates the existence of autoimmune disorders in Chagas' heart disease. PMID:1696282

  7. Microsatellite markers from the Chagas disease vector, Rhodnius prolixus (Hemiptera, Reduviidae), and their applicability to Rhodnius species.

    PubMed

    Harry, M; Roose, C L; Vautrin, D; Noireau, F; Romaña, C A; Solignac, M

    2008-05-01

    Ten microsatellites were isolated and characterized from a partial genomic library of Rhodnius prolixus, the principal Chagas disease vector in Venezuela, Colombia and Central America. These polymorphic molecular markers could be particularly useful in Chagas disease control initiatives. A wider applicability of the primer-pairs isolated was shown, from 6 to 10 loci being amplifiable in five out of the ten Rhodnius species tested, namely R. domesticus, R. nasutus, R. neglectus, R. neivai and R. robustus. Interestingly, all the loci were amplified in the latter. These markers may be of interest to trace the colonization of human dwellings from triatomine sylvatic populations in order to better define epidemiological risk patterns.

  8. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole.

    PubMed

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-03-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruzi quantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective.

  9. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole

    PubMed Central

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-01-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective. PMID:26982179

  10. American trypanosomiasis, or Chagas disease, in Panama: a chronological synopsis of ecological and epidemiological research.

    PubMed

    Rodriguez, Indra G; Loaiza, Jose R

    2017-10-10

    American trypanosomiasis, or Chagas disease, is a growing public health problem in Panama, and further forest degradation due to human population growth is expected to worsen the situation. Most people infected with the parasite Trypanosoma cruzi are silently ill, and their life expectancy is severely compromised, which contributes to further deterioration of living conditions in endemic regions. Here, we review the outcomes of nearly 100 years of ecological and epidemiological investigation about Chagas disease in Panama, in an attempt to highlight progress, identify needs, and re-orient future efforts. Rhodnius pallescens and Triatoma dimidiata are both primary vectors of T. cruzi in Panama, but R. pallescens seems more efficient in human-altered forest ecosystems due to a greater degree of association with Attalea butyracea. In contrast, T. dimidiata transmits T. cruzi efficiently under more sylvatic conditions (e.g. settlements inside old-growth or secondary forest patches), where its populations reach considerable numbers irrespective of the absence of A. butyracea. A trend of increasing forest degradation, suburbanization, and development of tourism in Panama favoring the establishment of A. butyracea and other palm tree species (Acrocomia sp.) suggests that a colonist species like R. pallescens will continue to play a more prominent role in the transmission of T. cruzi than a forest specialist like T. dimidiata. However, studies about the taxonomic status and ecology of these vectors are still needed in Panama to address their transmission potential fully. The implementation of an active surveillance system and education programs could greatly minimize the risk of Chagas disease transmission in Panama, preventing fatal infections in children from endemic areas.

  11. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.

    PubMed

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard; Supek, Frantisek

    2015-10-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates.

  12. Cancer cell cytotoxicity of extracts and small phenolic compounds from Chaga [Inonotus obliquus (persoon) Pilat].

    PubMed

    Nakajima, Yuki; Nishida, Hiroshi; Matsugo, Seiichi; Konishi, Tetsuya

    2009-06-01

    Previously, we studied the antioxidant potential of Chaga mushroom [Inonotus obliquus (persoon) Pilat] extracts and isolated several small (poly)phenolic compounds as the major antioxidant components in the 80% methanol (MeOH) extract. In the present study, these isolated phenolic ingredients together with several other types of Chaga extracts were examined for cytotoxic effects against normal (IMR90) and cancer (A549, PA-1, U937, and HL-60) cell lines. Results revealed decoctions from both the fruiting body (FB) and sclerotium (ST) parts of Chaga, especially the ST part, showed considerable cytotoxicity toward tumor cells, but the cytotoxicity appeared to be stronger against normal cells than cancer cells. The 80% MeOH ST extract also showed the same trend. On the other hand, the 80% MeOH extract of FB showed significant cytotoxicity towards tumor cell lines without affecting normal cells, for example, the 50% lethal dose was 49.4 +/- 2.9 microg/mL for PA-1 cells versus 123.6 +/- 13.8 microg/mL for normal cells. The phenolic components isolated from the 80% MeOH extracts had markedly greater cancer cell toxicity than the extracts themselves. In particular, two out of seven compounds showed strong cytotoxicity towards several tumor cell lines without giving rise to significant cell toxicity toward normal cells. For example, the 50% lethal dose for 3,4-dihydroxybenzalacetone was 12.2 micromol/L in PA-1 cells but was 272.8 micromol/L in IMR90 cells. Fluorescence-activated cell sorting analysis further revealed these phenolic ingredients have high potentiality for apoptosis induction in PA-1 cells.

  13. [What do the numbers tell us about the temporal evolution of Chagas' disease?

    PubMed

    Canals, Mauricio; González, Christian; Canals, Lucia; Canals, Andrea; Cáceres, Dante; Alvarado, Sergio; Cattan, Pedro E; Saavedra, Miguel; Zulantay, Inés; Apt, Werner

    2017-04-01

    Chagas disease remains highly prevalent in Chile, especially between the regions of Arica and Parinacota, and Coquimbo. Since 1999 it is considered that in Chile the vector transmission was interrupted. Under this premise, the epidemiological dynamics should be changing. We analyzed the evolution of the prevalence of Chagas' disease analyzing 64,995 xenodiagnosis performed in the laboratory of Parasitology of the Faculty of Medicine of the University of Chile between 1949 and 2014. The evolution of the mortalities and incidences from the databases of the Ministry of Health in the periods in which it was analyzed. The rates of domiciliary infestation and the number of vector insects sent to the Public Health Institute and its trypano-triatomine indices were also analyzed. The prevalence of Chagas' disease in inhabitants of risk areas remained stable in this period as well as mortality. The incidence rate shows a progressive increase with a tendency towards stabilization. A significant decrease in sampling effort was found, declining by two orders of magnitude, especially since 2000. The progressive increase in morbidity had no clear relation to the interruption of the vector chain nor to the greater diagnostic effort occurred in 2009, since it was evident from before. While home infestation declines, reports of intrusion of solitary individuals and wild foci of T. infestans have increased. Trypano-triatomine indices were maintained with high values in all vector species. This study shows a worrying situation, for while on the one hand the interruption of the vector transmission and improvement in the research systems is emphasized, the concern for this disease seems to be decreasing with less diagnostic efforts and lower education at the higher level, and by the other hand the numbers show that the problem if it is not increasing, at least maintains its careless historical magnitude.

  14. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas.

    PubMed

    Péneau, Julie; Nguyen, Anne; Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

    2016-02-01

    The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species.

  15. Chagas disease: national survey of seroprevalence in children under five years of age conducted in 2008.

    PubMed

    Russomando, Graciela; Cousiño, Blanca; Sanchez, Zunilda; Franco, Laura X; Nara, Eva M; Chena, Lilian; Martínez, Magaly; Galeano, María E; Benitez, Lucio

    2017-05-01

    Since the early 1990s, programs to control Chagas disease in South America have focused on eradicating domiciliary Triatoma infestans, the main vector. Seroprevalence studies of the chagasic infection are included as part of the vector control programs; they are essential to assess the impact of vector control measures and to monitor the prevention of vector transmission. To assess the interruption of domiciliary vector transmission of Chagas disease by T. infestans in Paraguay by evaluating the current state of transmission in rural areas. A survey of seroprevalence of Chagas disease was carried out in a representative sample group of Paraguayans aged one to five years living in rural areas of Paraguay in 2008. Blood samples collected on filter paper from 12,776 children were tested using an enzyme-linked immunosorbent assay. Children whose serology was positive or undetermined (n = 41) were recalled to donate a whole blood sample for retesting. Their homes were inspected for current triatomine infestation. Blood samples from their respective mothers were also collected and tested to check possible transmission of the disease by a congenital route. A seroprevalence rate of 0.24% for Trypanosoma cruzi infection was detected in children under five years of age among the country's rural population. Our findings indicate that T. cruzi was transmitted to these children vertically. The total number of infected children, aged one to five years living in these departments, was estimated at 1,691 cases with an annual incidence of congenital transmission of 338 cases per year. We determined the impact of vector control in the transmission of T. cruzi, following uninterrupted vector control measures employed since 1999 in contiguous T. infestans-endemic areas of Paraguay, and this allowed us to estimate the degree of risk of congenital transmission in the country.

  16. Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease

    PubMed Central

    da Mota, Fabio Faria; Marinho, Lourena Pinheiro; Moreira, Carlos José de Carvalho; Lima, Marli Maria; Mello, Cícero Brasileiro; Garcia, Eloi Souza; Carels, Nicolas; Azambuja, Patricia

    2012-01-01

    Background Chagas disease is a trypanosomiasis whose agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous bugs known as triatomines. Even though insecticide treatments allow effective control of these bugs in most Latin American countries where Chagas disease is endemic, the disease still affects a large proportion of the population of South America. The features of the disease in humans have been extensively studied, and the genome of the parasite has been sequenced, but no effective drug is yet available to treat Chagas disease. The digestive tract of the insect vectors in which T. cruzi develops has been much less well investigated than blood from its human hosts and constitutes a dynamic environment with very different conditions. Thus, we investigated the composition of the predominant bacterial species of the microbiota in insect vectors from Rhodnius, Triatoma, Panstrongylus and Dipetalogaster genera. Methodology/Principal Findings Microbiota of triatomine guts were investigated using cultivation-independent methods, i.e., phylogenetic analysis of 16s rDNA using denaturing gradient gel electrophoresis (DGGE) and cloned-based sequencing. The Chao index showed that the diversity of bacterial species in triatomine guts is low, comprising fewer than 20 predominant species, and that these species vary between insect species. The analyses showed that Serratia predominates in Rhodnius, Arsenophonus predominates in Triatoma and Panstrongylus, while Candidatus Rohrkolberia predominates in Dipetalogaster. Conclusions/Significance The microbiota of triatomine guts represents one of the factors that may interfere with T. cruzi transmission and virulence in humans. The knowledge of its composition according to insect species is important for designing measures of biological control for T. cruzi. We found that the predominant species of the bacterial microbiota in triatomines form a group of low complexity whose structure

  17. Free-roaming kissing bugs, vectors of Chagas disease, feed often on humans in the Southwest.

    PubMed

    Klotz, Stephen A; Schmidt, Justin O; Dorn, Patricia L; Ivanyi, Craig; Sullivan, Katherine R; Stevens, Lori

    2014-05-01

    Kissing bugs, vectors of Trypanosoma cruzi, the parasite that causes Chagas disease, are common in the desert Southwest. After a dispersal flight in summer, adult kissing bugs occasionally gain access to houses where they remain feeding on humans and pets. How often wild, free-roaming kissing bugs feed on humans outside their homes has not been studied. This is important because contact of kissing bugs with humans is one means of gauging the risk for acquisition of Chagas disease. We captured kissing bugs in a zoological park near Tucson, Arizona, where many potential vertebrate hosts are on display, as well as being visited by more than 300,000 humans annually. Cloacal contents of the bugs were investigated for sources of blood meals and infection with T. cruzi. Eight of 134 captured bugs were randomly selected and investigated. All 8 (100%) had human blood in their cloacae, and 7 of 8 (88%) had fed on various vertebrates on display or feral in the park. Three bugs (38%) were infected with T. cruzi. Three specimens of the largest species of kissing bug in the United States (Triatoma recurva) were captured in a cave and walking on a road; 2 of 3 (67%) had fed on humans. No T. recurva harbored T. cruzi. This study establishes that free-roaming kissing bugs, given the opportunity, frequently feed on humans outside the confines of their homes in the desert Southwest and that some harbored T. cruzi. This could represent a hitherto unrecognized potential for transmission of Chagas disease in the United States. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Free-roaming Kissing Bugs, Vectors of Chagas Disease, Feed Often on Humans in the Southwest

    PubMed Central

    Klotz, Stephen A; Schmidt, Justin O.; Dorn, Patricia L.; Ivanyi, Craig; Sullivan, Katherine R.; Stevens, Lori

    2014-01-01

    BACKGROUND Kissing bugs, vectors of Trypanosoma cruzi, the parasite that causes Chagas disease, are common in the desert Southwest. After a dispersal flight in summer, adult kissing bugs occasionally gain access to houses where they remain feeding on humans and pets. How often wild, free-roaming kissing bugs feed on humans outside their homes has not been studied. This is important because contact of kissing bugs with humans is one means of gauging the risk for acquisition of Chagas disease. METHODS We captured kissing bugs in a zoological park near Tucson, Arizona, where many potential vertebrate hosts are on display, as well as being visited by more than 300,000 humans annually. Cloacal contents of the bugs were investigated for sources of blood meals and infection with T. cruzi. RESULTS Eight of 134 captured bugs were randomly selected and investigated. All 8 (100%) had human blood in their cloacae, and 7 of 8 (88%) had fed on various vertebrates on display or feral in the park. Three bugs (38%) were infected with T. cruzi. Three specimens of the largest species of kissing bug in the United States (Triatoma recurva) were captured in a cave and walking on a road; 2 of 3 (67%) had fed on humans. No T. recurva harbored T. cruzi. CONCLUSIONS This study establishes that free-roaming kissing bugs, given the opportunity, frequently feed on humans outside the confines of their homes in the desert Southwest and that some harbored T. cruzi. This could represent a hitherto unrecognized potential for transmission of Chagas disease in the United States. PMID:24398362

  19. The Prevalence of Atrial Fibrillation and Conduction Abnormalities in Chagas' Disease: A Meta-Analysis.

    PubMed

    Cardoso, Rhanderson; Garcia, Daniel; Fernandes, Gilson; He, L I; Lichtenberger, Paola; Viles-Gonzalez, Juan; Coffey, James O; Mitrani, Raul D

    2016-02-01

    Chagas' disease (CD) has been associated with atrial fibrillation (AF) and electrocardiographic (ECG) conduction defects. However, prior studies have shown conflicting results. We performed a meta-analysis comparing the prevalence of AF and conduction abnormalities between CD and non-CD patients. PubMed, EMBASE, Cochrane Central, and Latin American databases were searched for studies that directly compared the prevalence of AF and conduction defects in CD and non-CD patients. Odds ratios (OR) were computed using random-effects model due to anticipated heterogeneity. We further performed subanalyses limited to studies that included only patients with cardiomyopathy. A total of 17,238 patients from 30 studies were included, of whom 6,840 (40%) had a positive serology for CD. In the pooled data, AF was significantly more prevalent in the CD group (OR 1.62; 95%CI 1.21-2.15; P = 0.001). However, no significant difference was observed between groups when the analysis included only patients with cardiomyopathy (OR 1.21; 95%CI 0.97-1.50; P = 0.08) or heart failure (OR 1.09; 95%CI 0.81-1.47; P = 0.55). The combination of right bundle branch block (RBBB) and left anterior fascicular block (LAFB) had the highest OR for increased prevalence in patients with Chagas' cardiomyopathy compared to non-CD etiologies (OR 5.31; 95%CI 1.23-22.86; P = 0.03). Our meta-analysis suggests that the prevalence of AF in patients with Chagas' cardiomyopathy is not significantly different from non-CD cardiomyopathies. The pattern of RBBB and LAFB in patients with cardiomyopathy of unknown etiology and epidemiologic risk factors should raise the possibility of CD and prompt specific diagnostic testing. © 2015 Wiley Periodicals, Inc.

  20. Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy.

    PubMed

    de Oliveira, Luciano Fonseca Lemos; Romano, Minna Moreira Dias; de Carvalho, Eduardo Elias Vieira; Cabeza, Jorge Mejia; Salgado, Hélio Cesar; Fazan Júnior, Rubens; Costa, Renata Sesti; da Silva, João Santana; Higuchi, Maria de Lourdes; Maciel, Benedito Carlos; Cunha-Neto, Edécio; Marin-Neto, José Antônio; Simões, Marcus Vinícius

    2016-01-21

    Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters. Female Syrian hamsters (n=34) infected with 3.5×10(4) or 10(5) blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (r=-0.63; P<0.0001) than with the extent of fibrosis (r=-0.36; P=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9±5.5%), 8 (33%) showed segmental WMA predominating in the apical, inferior, and posterolateral segments. The segments exhibiting WMA, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3±5.7% and 7±6.3%, P<0.0001) and an even greater intensity of inflammation (218.0±111.6 and 124.5±84.8 nuclei/mm², P<0.0001). Isolated WMA with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

    PubMed Central

    Viotti, Rodolfo; Vigliano, Carlos; Álvarez, María Gabriela; Lococo, Bruno; Petti, Marcos; Bertocchi, Graciela; Armenti, Alejandro; De Rissio, Ana María; Cooley, Gretchen; Tarleton, Rick; Laucella, Susana

    2011-01-01

    Background The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion, achieved many years post-treatment. One of the main limitations in evaluating treatment for chronic Chagas disease is the lack of reliable tests to ensure parasite clearance and to examine the effects of treatment. However, declines in conventional serological titers and a new multiplex assay can be useful tools to monitor early the treatment impact. Methodology/Principal Findings Changes in antibody levels, including seronegative conversion as well as declines in titers, were serially measured in 53 benznidazole-treated and 89 untreated chronic patients in Buenos Aires, Argentina with a median follow-up of 36 months. Decrease of titers (34/53 [64%] treated vs. 19/89 [21%] untreated, p<0.001) and seronegative conversion (21/53, [40%] treated vs. 6/89, [7%] untreated, p<0.001) in at least one conventional serological test were significantly higher in the benznidazole-treated group compare with the untreated group. When not only complete seronegative conversion but also seronegative conversion on 2 tests and the decreases of titers on 2 or 3 tests were considered, the impact of treatment on conventional serology increased from 21% (11/53 subjects) to 45% (24/53 subjects). A strong concordance was found between the combination of conventional serologic tests and multiplex assay (kappa index 0.60) to detect a decrease in antibody levels pos-treatment. Conclusions/Significance Treatment with benznidazole in subjects with chronic Chagas disease has a major impact on the serology specific for T. cruzi infection in a shorter follow-up period than previously considered, reflected either by a complete or partial seronegative conversion or by a significant decrease in the levels of T. cruzi antibodies, consistent with a possible elimination or reduction of parasite load. PMID:21909451

  2. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas

    PubMed Central

    Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

    2016-01-01

    The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species. PMID:26867025

  3. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease

    PubMed Central

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard

    2015-01-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates. PMID:26239982

  4. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

    PubMed Central

    Khare, Shilpi; Roach, Steven L.; Barnes, S. Whitney; Hoepfner, Dominic; Walker, John R.; Chatterjee, Arnab K.; Neitz, R. Jeffrey; Arkin, Michelle R.; McNamara, Case W.; Ballard, Jaime; Lai, Yin; Fu, Yue; Molteni, Valentina; Yeh, Vince; McKerrow, James H.; Glynne, Richard J.; Supek, Frantisek

    2015-01-01

    Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease. PMID:26186534

  5. Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

    PubMed Central

    Silva, A. R.; Do Bem, V. A. L.; Bahia, M. T.; Martins-Filho, O. A.; Dias, J. C. P.; Albajar-Viñas, P.; Torres, R. M.; Lana, M.

    2012-01-01

    We performed a critical study of conventional serology, followed by supplementary serological, parasitological, and molecular tests, to assess the response to etiologic treatment of Chagas' disease. A group of 94 Chagas' disease patients treated with benznidazole at least 10 years earlier were evaluated from the laboratory and clinical points of view. When conventional serology (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IIF], and indirect hemagglutination [IHA]) and classic criteria (consistent results with any two of the three tests) or more rigorous criteria (consistent results from the three tests) were used, 10.6% and 8.5% of patients were considered treated and cured (TC) by classic and rigorous criteria, respectively. Patients were then evaluated using supplementary (recombinant ELISA and Trypanosoma cruzi excreted-secreted antigen blotting [TESA-blot]), parasitological (hemoculture), and molecular (PCR) tests. The results of recombinant ELISA were similar to those with the rigorous criterion (three consistent test results). The TESA-blot group showed a higher percentage (21.3%) of negative results than the groups defined by either cure criterion. Hemoculture and PCR gave negative results for all treated and cured (TC) patients, regardless of the criterion used. Recombinant ELISA and TESA-blot tests showed negative results for 70% and 87.5% of the patients categorized as TC by the classic and three-test criteria, respectively. For patients with discordant conventional serology, the supplementary serological and molecular tests were the decisive factor in determining therapeutic failure. Clinical evaluation showed that 62.5% of TC patients presented with the indeterminate form of the disease. Additionally, treated patients with negative TESA-blot results should be reevaluated later with all methodologies used here to verify whether TESA-blot is a reliable way to determine early parasitological cure of Chagas' disease. PMID

  6. Chagas disease: national survey of seroprevalence in children under five years of age conducted in 2008

    PubMed Central

    Russomando, Graciela; Cousiño, Blanca; Sanchez, Zunilda; Franco, Laura X; Nara, Eva M; Chena, Lilian; Martínez, Magaly; Galeano, María E; Benitez, Lucio

    2017-01-01

    BACKGROUND Since the early 1990s, programs to control Chagas disease in South America have focused on eradicating domiciliary Triatoma infestans, the main vector. Seroprevalence studies of the chagasic infection are included as part of the vector control programs; they are essential to assess the impact of vector control measures and to monitor the prevention of vector transmission. OBJECTIVE To assess the interruption of domiciliary vector transmission of Chagas disease by T. infestans in Paraguay by evaluating the current state of transmission in rural areas. METHODS A survey of seroprevalence of Chagas disease was carried out in a representative sample group of Paraguayans aged one to five years living in rural areas of Paraguay in 2008. Blood samples collected on filter paper from 12,776 children were tested using an enzyme-linked immunosorbent assay. Children whose serology was positive or undetermined (n = 41) were recalled to donate a whole blood sample for retesting. Their homes were inspected for current triatomine infestation. Blood samples from their respective mothers were also collected and tested to check possible transmission of the disease by a congenital route. FINDINGS A seroprevalence rate of 0.24% for Trypanosoma cruzi infection was detected in children under five years of age among the country’s rural population. Our findings indicate that T. cruzi was transmitted to these children vertically. The total number of infected children, aged one to five years living in these departments, was estimated at 1,691 cases with an annual incidence of congenital transmission of 338 cases per year. MAIN CONCLUSION We determined the impact of vector control in the transmission of T. cruzi, following uninterrupted vector control measures employed since 1999 in contiguous T. infestans-endemic areas of Paraguay, and this allowed us to estimate the degree of risk of congenital transmission in the country. PMID:28443980

  7. Electrocardiographic and echocardiographic abnormalities in residents of rural Bolivian communities hyperendemic for Chagas disease

    PubMed Central

    Fernandez, Antonio B.; Nunes, Maria Carmo P.; Clark, Eva H.; Samuels, Aaron; Menacho, Silvio; Gomez, Jesus; Gutierrez, Ricardo W. Bozo; Crawford, Thomas C.; Gilman, Robert H.; Bern, Caryn

    2015-01-01

    Background Chagas disease is a neglected and preventable tropical disease that causes significant cardiac morbidity and mortality in Latin America. Our objective in this study was to describe cardiac findings among inhabitants of rural communities of the Bolivian Chaco. Methods The cardiac study drew participants from an epidemiologic study in 7 indigenous Guarani communities. All infected participants 10 years or older were asked to undergo a brief physical examination and 12-lead electrocardiogram. A subset had echocardiograms (ECGs). ECGs and echocardiograms were read by one or more cardiologists. Results Of 1137 residents 10 years or older, 753 (66.2%) had T. cruzi infection. Cardiac evaluations were performed for 398 infected participants 10 years or older. Fifty-five (13.8%) participants had one or more ECG abnormality suggestive of Chagas cardiomyopathy. The most frequent abnormalities were bundle branch blocks in 42 (11.3%), followed by rhythm disturbances or ventricular ectopy in 13 (3.3%) and atrioventricular blocks (AVB) in 10 (2.6%) participants. The prevalence of any abnormality rose from 1.1% among those 10-19 years old to 14.2%, 17.3% and 26.4% among those 20-39, 40-59 and older than 60 years, respectively. First degree AVB was seen most frequently in participants 60 years or older, but the 4 patients with 3rd degree AVB were all under 50 years old. Eighteen and two participants had a left ventricular ejection fraction of 40-54% and <40%, respectively. An increasing number of ECG abnormalities was associated with progressively larger left ventricular end-diastolic dimensions and lower left ventricular ejection fraction. Conclusions We found a high prevalence of ECG abnormalities and substantial evidence of Chagas cardiomyopathy. Programs to improve access to basic cardiac care (annual ECGs, antiarrhythmics, pacemakers) could have an immediate impact on morbidity and mortality in these highly endemic communities. PMID:26407511

  8. ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

    PubMed Central

    2010-01-01

    Background Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance. Methods A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease. Results Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied. Conclusions Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore

  9. ABO, Secretor and Lewis histo-blood group systems influence the digestive form of Chagas disease.

    PubMed

    Bernardo, Cássia Rubia; Camargo, Ana Vitória Silveira; Ronchi, Luís Sérgio; de Oliveira, Amanda Priscila; de Campos Júnior, Eumildo; Borim, Aldenis Albanez