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Sample records for acute chagas disease

  1. Acute Chagas Disease in a Returning Traveler

    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.

  2. Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice

    Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; de Castro-Faria-Neto, Hugo Caire; Pereira, Mirian Claudia de Souza; Tibiriçá, Eduardo; Garzoni, Luciana Ribeiro

    2014-01-01

    Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perf...

  3. Chagas Disease

    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 ...

  4. Distantiae Transmission of Trypanosoma cruzi: A New Epidemiological Feature of Acute Chagas Disease in Brazil

    Xavier, Samanta Cristina das Chagas; Roque, André Luiz Rodrigues; Bilac, Daniele; de Araújo, Vitor Antônio Louzada; Neto, Sócrates Fraga da Costa; Lorosa, Elias Seixas; da Silva, Luiz Felipe Coutinho Ferreira; Jansen, Ana Maria

    2014-01-01

    Background The new epidemiological scenario of orally transmitted Chagas disease that has emerged in Brazil, and mainly in the Amazon region, needs to be addressed with a new and systematic focus. Belém, the capital of Pará state, reports the highest number of acute Chagas disease (ACD) cases associated with the consumption of açaí juice. Methodology/Principal Findings The wild and domestic enzootic transmission cycles of Trypanosoma cruzi were evaluated in the two locations (Jurunas and Val-...

  5. Distantiae transmission of Trypanosoma cruzi: a new epidemiological feature of acute Chagas disease in Brazil.

    Samanta Cristina das Chagas Xavier; André Luiz Rodrigues Roque; Daniele Bilac; Vitor Antônio Louzada de Araújo; Sócrates Fraga da Costa da Costa Neto; Elias Seixas Lorosa; Luiz Felipe Coutinho Ferreira da Silva; Ana Maria Jansen

    2014-01-01

    BACKGROUND: The new epidemiological scenario of orally transmitted Chagas disease that has emerged in Brazil, and mainly in the Amazon region, needs to be addressed with a new and systematic focus. Belém, the capital of Pará state, reports the highest number of acute Chagas disease (ACD) cases associated with the consumption of açaí juice. METHODOLOGY/PRINCIPAL FINDINGS: The wild and domestic enzootic transmission cycles of Trypanosoma cruzi were evaluated in the two locations (Jurunas and Va...

  6. Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon

    Rita de Cássia de Souza-Lima

    2013-10-01

    Full Text Available Introduction Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. Methods We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. Results There were 15 males (average age, 31.3 years, all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. Conclusions All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

  7. Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon

    Rita de Cassia de Souza-Lima

    2013-07-01

    Full Text Available Introduction Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. Methods We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. Results There were 15 males (average age, 31.3 years, all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. Conclusions All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

  8. FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO STATE, BRAZIL

    Luiz Henrique Conde SANGENIS

    2015-08-01

    Full Text Available SUMMARY Chagas disease (CD is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro.

  9. Chagas disease

    Insect control with insecticides and houses that are less likely to have high insect populations will help control the spread of the disease. Blood banks in Central and South America screen donors for ...

  10. In vivo studies of 5-arylethenylbenzofuroxans in acute murine models of Chagas' disease.

    Boiani, Lucía; Davies, Carolina; Arredondo, Carolina; Porcal, Williams; Merlino, Alicia; Gerpe, Alejandra; Boiani, Mariana; Pacheco, José Pedro; Basombrío, Miguel Angel; Cerecetto, Hugo; González, Mercedes

    2008-10-01

    5-arylethenylbenzofuroxan derivatives with high in vitro anti-Trypanosoma cruzi activity were studied in vivo using acute murine models of Chagas' disease. The selected compounds, as pure isomeric forms, 1, 2, 3 and 4, or as equimolecular mixture of geometric isomers, 1:2, 3:4, 5:6 were studied against different T. cruzi strains. Consequently, Tulahuen 2 strain, Colombiana strain (resistant to Nifurtimox and Benznidazole), and two different wild strains, one isolated from the wild reservoir Didelphis marsupialis and another one from Uruguayan patients, were selected. No relevant signs of in vivo toxicity were observed with the benzofuroxans orally administered. Compound 1 and the mixture of isomers 1:2 were the best for treating infection against the four studied strains. PMID:18255195

  11. Spatiotemporal analysis of reported cases of acute Chagas disease in the State of Pernambuco, Brazil, from 2002 to 2013

    Fred Luciano Neves Santos

    2015-04-01

    Full Text Available INTRODUCTION: Control strategies to eliminate the transmission of Chagas disease by insect vectors have significantly decreased the number of reported acute cases in Brazil. However, data regarding the incidence and distribution of acute Chagas disease cases in the State of Pernambuco are unavailable in the literature. METHODS: A geographical information system was used to delineate the spatiotemporal distribution profile of the cases from 2002 to 2013 in 185 municipalities of Pernambuco based on the municipality where notification occurred. The results were presented in digital maps generated by the TerraView software (INPE. RESULTS: A total of 302 cases of acute disease were recorded in 37.8% of the municipalities, for a total of 0.13 cases per 1,000,000 inhabitants per year. Out of the 302 cases, 99.3% were reported between 2002 and 2006. The most affected municipalities were Carnaubeira da Penha, Mirandiba and Terra Nova. The risk maps showed a significant decrease in the number of notifications and a concentration of cases in the Midwest region. CONCLUSIONS: This study highlights a significant decrease in new cases of acute Chagas disease in Pernambuco starting in 2006 when Brazil received an international certification for the interruption of vectorial transmission by Triatoma infestans. However, control strategies should still be encouraged because other triatomine species can also transmit the parasite; moreover, other transmission modes must not be neglected.

  12. Extraction of Trypanosoma cruzi DNA from food: a contribution to the elucidation of acute Chagas disease outbreaks

    Renata Trotta Barroso Ferreira; Aline Martins Melandre; Maria Luiza Cabral; Maria Regina Branquinho; Paola Cardarelli-Leite

    2016-01-01

    Abstract: INTRODUCTION: Before 2004, the occurrence of acute Chagas disease (ACD) by oral transmission associated with food was scarcely known or investigated. Originally sporadic and circumstantial, ACD occurrences have now become frequent in the Amazon region, with recently related outbreaks spreading to several Brazilian states. These cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with Trypanosoma cruzi in endemic areas. Altho...

  13. Chagas Disease, France

    Lescure, François-Xavier; Canestri, Ana; Melliez, Hugues; Jauréguiberry, Stéphane; Develoux, Michel; Dorent, Richard; Guiard-Schmid, Jean-Baptiste; Bonnard, Philippe; Ajana, Faïza; Rolla, Valeria; Carlier, Yves; Gay, Frederick; Elghouzzi, Marie-Hélène; Danis, Martin; Pialoux, Gilles

    2008-01-01

    Chagas disease (CD) is endemic to Latin America; its prevalence is highest in Bolivia. CD is sometimes seen in the United States and Canada among migrants from Latin America, whereas it is rare in Europe. We report 9 cases of imported CD in France from 2004 to 2006.

  14. Chagas' disease and AIDS

    Vaidian, Anil K; Louis M Weiss; Tanowitz, Herbert B.

    2004-01-01

    Chagas' disease caused by Trypanosoma cruzi is an opportunistic infection in the setting of HIV/AIDS. Some individuals with HIV and chronic T. cruzi infection may experience a reactivation, which is most commonly manifested by meningoencephalitis. A reactivation myocarditis is the second most common manifestation. These presentations may be difficult to distinguish from toxoplasmosis in individuals with HIV/AIDS. The overlap of HIV and Trypanosoma cruzi infection occurs not only in endemic ar...

  15. Immunosuppression and Chagas disease: a management challenge.

    María-Jesús Pinazo

    Full Text Available Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been

  16. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.

    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas

    2016-05-01

    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection. PMID:26852285

  17. Ventricular arrhythmias in Chagas disease

    Marco Paulo Tomaz Barbosa

    2015-02-01

    Full Text Available Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

  18. Control of Chagas disease vectors

    JM Ramsey; CJ Schofield

    2003-01-01

    Most Latin American countries are making dramatic progress in controlling Chagas disease, through a series of national and international initiatives focusing on elimination of domestic populations of Triatominae, improved screening of blood donors, and clinical support and treatment of persons infected with Trypanosoma cruzi. Some countries, particularly Uruguay, Chile and Brazil, are sufficiently advanced in their programmes to initiate detailed planning of the subsequent phases of Chagas di...

  19. Experimental Chagas' disease in rhesus monkeys. I. Clinical, parasitological, hematological and anatomo-pathological studies in the acute and indeterminate phase of the disease.

    Bonecini-Almeida, M da G; Galvão-Castro, B; Pessoa, M H; Pirmez, C; Laranja, F

    1990-01-01

    Rhesus monkeys (Macaca mulatta) were infected subcutaneously with 1.0 x 10(4) to 1.5 x 10(4) metacyclic trypomastigotes of Trypanosoma cruzi (Colombian strain). Parasitological and immunological parameters were evaluated in these animals for periods of 1 month to over 3 years. A chagoma was observed between the 3rd and the 13th day after infection (a.i.) and patent parasitaemia between the 13th and 59th day a.i.. Thereafter, parasites were demonstrated only by haemoculture and/or xenodiagnosis. Circulating specific IgM and IgG antibodies were observed as early as in the 2nd week a.i. IgG levels persisted until the end of the experiment, but IgM antibodies were detectable nine months a.i. Haematological alterations comprised leucocytosis and lymphocytosis. Electrocardiographic alterations were minor and transient, similar to those observed in non-lethal human acute Chagas' myocarditis. Myocarditis and myositis, characterized by multiple foci of lympho-histiocyte inflammatory infiltrate, were present in monkeys sacrificed on the 41st, 70th and 76th day but not in the animal sacrificed 3 years and 3 months a. i.. The results suggest that Chagas' disease in rhesus monkeys reproduces the acute and indeterminate phases of human Chagas' disease. PMID:2128360

  20. Experimental chagas' disease in rhesus monkeys. I. Clinical parasitological, hematological and anatomo-pathological studies in the acute and indeterminate phase of the disease

    Maria da Glória Bonecine-Almeida

    1990-06-01

    Full Text Available Rhesus monkeys (macaca mulatta were infected subcutaneously with 1.0 x 10**4 to 1.5 x 10**4 metacyclic trypomastigotes of Trypanosoma cruzi (Colombian strain. Parasitological and immunological parameters were evaluated in these animals for periods of 1 month to over 3 years. a chagona was observed between the 3 rd and the 13th day after infection (a.i and patent parasitaemia between the 13th and 59th day a.i.. Thereafter, parasites were demonstrated only by haemoculture and/or xenodiagnosis. Circulating specifc IgM and IgC antibodies were observed as early as in the 2nd week a. i. IgG levels persisted until the end of the expriment, but IgM antibodies were detectable nine months a. i. Haematological alterations comprised leucocytosis and lymphocytosis. Eletrocardiographic alterations were minor and transient, similar to those observe in non-lethal human acute Chagas' myocarditis. Myocarditis and myositis, characterized by multiple foci of lympho-histiocyte inflammatory infiltrate, were present in monkeys sacrificed on the 41 th, 70th and 76 th day but not in the animal sacrificed 3 years and 3 months a. i.. The results suggest that Chagas' disease in rhesus monkeys reproduces the acute and indeterminate phases of human Chagas' disease.

  1. Trypanosoma cruzi IV causing outbreaks of acute Chagas disease and infections by different haplotypes in the Western Brazilian Amazonia.

    Wuelton Marcelo Monteiro

    Full Text Available BACKGROUND: Chagas disease is an emergent tropical disease in the Brazilian Amazon Region, with an increasing number of cases in recent decades. In this region, the sylvatic cycle of Trypanosoma cruzi transmission, which constitutes a reservoir of parasites that might be associated with specific molecular, epidemiological and clinical traits, has been little explored. The objective of this work is to genetically characterize stocks of T. cruzi from human cases, triatomines and reservoir mammals in the State of Amazonas, in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 96 T. cruzi samples from four municipalities in distant locations of the State of Amazonas. Molecular characterization of isolated parasites from cultures in LIT medium or directly from vectors or whole human blood was performed by PCR of the non-transcribed spacer of the mini-exon and of the 24 S alfa ribosomal RNA gene, RFLP and sequencing of the mitochondrial cytochrome c oxidase subunit II (COII gene, and by sequencing of the glucose-phosphate isomerase gene. The T. cruzi parasites from two outbreaks of acute disease were all typed as TcIV. One of the outbreaks was triggered by several haplotypes of the same DTU. TcIV also occurred in isolated cases and in Rhodnius robustus. Incongruence between mitochondrial and nuclear phylogenies is likely to be indicative of historical genetic exchange events resulting in mitochondrial introgression between TcIII and TcIV DTUs from Western Brazilian Amazon. TcI predominated among triatomines and was the unique DTU infecting marsupials. CONCLUSION/SIGNIFICANCE: DTU TcIV, rarely associated with human Chagas disease in other areas of the Amazon basin, is the major strain responsible for the human infections in the Western Brazilian Amazon, occurring in outbreaks as single or mixed infections by different haplotypes.

  2. Alterações quantitativas das células de purkinje na moléstia de chagas experimental no camundongo Quantitative study of Purkinje cells in the acute phase of experimental Chagas' disease

    Edymar Jardim

    1967-09-01

    Full Text Available O autor estudou quantitativamente as células de Purkinje em cortes semi-seriados do cerebelo de camundongos inoculados experimentalmente com T. cruzi,tendo verificado considerável destruição neuronal na fase aguda da enfermidade.A quantitative study of Purkinje cells was done through semi-serial sections of cerebellum of mice experimentally innoculated by Trypanosoma cruzi. Avery marked neuronal destruction was found in the acute phase of Chagas' disease.

  3. Control of Chagas disease vectors

    Ramsey JM

    2003-01-01

    Full Text Available Most Latin American countries are making dramatic progress in controlling Chagas disease, through a series of national and international initiatives focusing on elimination of domestic populations of Triatominae, improved screening of blood donors, and clinical support and treatment of persons infected with Trypanosoma cruzi. Some countries, particularly Uruguay, Chile and Brazil, are sufficiently advanced in their programmes to initiate detailed planning of the subsequent phases of Chagas disease control, while others such as Peru, Ecuador, and Mexico, are currently applying only the initial phases of the control campaigns. In this review, we seek to provide a brief history of the campaigns as a basis for discussion of future interventions. Our aim is to relate operational needs to the underlying biological aspects that have made Chagas disease so serious in Latin America but have also revealed the epidemiological vulnerability of this disease.

  4. Chagas Disease: No Longer Exotic

    2008-04-03

    This podcast is designed to inform health care providers about Chagas disease, diagnosis, and treatment and to assist in identifying infected patients.  Created: 4/3/2008 by National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED).   Date Released: 4/8/2008.

  5. Chagas disease in the Amazon Region

    Hugo Marcelo Aguilar

    2007-10-01

    Full Text Available The risk that Chagas disease becomes established as a major endemic threat in Amazonia (the world's largest tropical biome, today inhabited by over 30 million people relates to a complex set of interacting biological and social determinants. These include intense immigration from endemic areas (possibly introducing parasites and vectors, extensive landscape transformation with uncontrolled deforestation, and the great diversity of wild Trypanosoma cruzi reservoir hosts and vectors (25 species in nine genera, which maintain intense sylvatic transmission cycles. Invasion of houses by adventitious vectors (with infection rates > 60% is common, and focal adaptation of native triatomines to artificial structures has been reported. Both acute (~ 500 and chronic cases of autochthonous human Chagas disease have been documented beyond doubt in the region. Continuous, low-intensity transmission seems to occur throughout the Amazon, and generates a hypoendemic pattern with seropositivity rates of ~ 1-3%. Discrete foci also exist in which transmission is more intense (e.g., in localized outbreaks probably linked to oral transmission and prevalence rates higher. Early detection-treatment of acute cases is crucial for avoiding further dispersion of endemic transmission of Chagas disease in Amazonia, and will require the involvement of malaria control and primary health care systems. Comprehensive eco-epidemiological research, including prevalence surveys or the characterization of transmission dynamics in different ecological settings, is still needed. The International Initiative for Chagas Disesae Surveillance and Prevention in the Amazon provides the framework for building up the political and scientific cooperation networks required to confront the challenge of preventing Chagas disease in Amazonia.

  6. Nanotechnological approaches against Chagas disease.

    Romero, Eder Lilia; Morilla, Maria Jose

    2010-03-18

    Over several thousand years, the flagellated Trypanosome cruzi-causative agent of Chagas disease-developed a complex life cycle between the reduviidae vectors and its human hosts. Due to their silent and hidden location, the intracellular amastigotes are mainly responsible for the nearly 50,000 annual deaths caused by the chronic chagasic cardiomyopathy. Chagas disease is the most important parasitic disease in the Americas, though treatments have not evolved towards a more efficient pharmacotherapy that (i) eradicates the scarce amastigotes present at the indeterminate/chronic form and (ii) employs less toxic drugs than benznidazole or nifurtimox. Nano-drug delivery systems (nanoDDS) represent useful means to selectively deliver the drug to intracellular targets. However, preclinical research in Chagas must be extended in order to improve the chances of a clinical implementation. The stages involved in this process are (i) selection of the appropriate drug for a specific parasite, (ii) development of a drug-loaded nanoDDS structure that displays the adequate pharmacokinetics, biodistribution and intracellular transit and (iii) selection of the right parasite form to target and the right stage of the disease for the treatment to be started. In this review we will critically overview the few research works published in the last 20years in the context of nanotechnology and Chagas diseases and highlight the gaps in knowledge towards the design of more efficient medicines to address this endemic. PMID:19941920

  7. Extraction of Trypanosoma cruzi DNA from food: a contribution to the elucidation of acute Chagas disease outbreaks

    Renata Trotta Barroso Ferreira

    2016-04-01

    Full Text Available Abstract: INTRODUCTION: Before 2004, the occurrence of acute Chagas disease (ACD by oral transmission associated with food was scarcely known or investigated. Originally sporadic and circumstantial, ACD occurrences have now become frequent in the Amazon region, with recently related outbreaks spreading to several Brazilian states. These cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with Trypanosoma cruzi in endemic areas. Although guidelines for processing the fruit to minimize contamination through microorganisms and parasites exist, açai-based products must be assessed for quality, for which the demand for appropriate methodologies must be met. METHODS: Dilutions ranging from 5 to 1,000 T. cruzi CL Brener cells were mixed with 2mL of acai juice. Four Extraction of T. cruzi DNA methods were used on the fruit, and the cetyltrimethyl ammonium bromide (CTAB method was selected according to JRC, 2005. RESULTS: DNA extraction by the CTAB method yielded satisfactory results with regard to purity and concentration for use in PCR. Overall, the methods employed proved that not only extraction efficiency but also high sensitivity in amplification was important. CONCLUSIONS: The method for T. cruzi detection in food is a powerful tool in the epidemiological investigation of outbreaks as it turns epidemiological evidence into supporting data that serve to confirm T. cruzi infection in the foods. It also facilitates food quality control and assessment of good manufacturing practices involving acai-based products.

  8. Control of Chagas disease.

    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. PMID:16735164

  9. Chagas disease risk in Texas.

    Sahotra Sarkar

    Full Text Available 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

  10. Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.

    Novaes, Rômulo Dias; Sartini, Marcus Vinicius Pessoa; Rodrigues, João Paulo Ferreira; Gonçalves, Reggiani Vilela; Santos, Eliziária Cardoso; Souza, Raquel Lopes Martins; Caldas, Ivo Santana

    2016-06-01

    Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy. PMID:27001816

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

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

    2016-05-01

    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. PMID:26976879

  12. Involvement of the autonomic nervous system in Chagas heart disease

    Edison Reis Lopes

    1983-12-01

    Full Text Available The autonomic nervous system and especially the intracardiac autonomic nervous system is involved in Chagas' disease. Ganglionitis and periganglionitis were noted in three groups ofpatients dying with Chagas'disease: 1 Those in heart failure; 2 Those dying a sudden, non violent death and; 3 Those dying as a consequence ofaccidents or homicide. Hearts in the threegroups also revealed myocarditis and scattered involvement of intramyocardial ganglion cells as well as lesions of myelinic and unmyelinic fibers ascribable to Chagas'disease. In mice with experimentally induced Chagas' disease weobserved more intensive neuronal lesions of the cardiac ganglia in the acute phase of infection. Perhaps neuronal loss has a role in the pathogenesis of Chagas cardiomyopathy. However based on our own experience and on other data from the literature we conclude that the loss of neurones is not the main factor responsible for the manifestations exhibited by chronic chagasic patients. On the other hand the neuronal lesions may have played a role in the sudden death ofone group of patients with Chagas'disease but is difficult to explain the group of patients who did not die sudderly but instead progressed to cardiac failure.

  13. Cell Therapy in Chagas Disease

    Antonio C. Campos de Carvalho

    2009-01-01

    Full Text Available Chagas disease which is caused by the parasite Trypanosoma cruzi is an important cause of cardiomyopathy in Latin America. In later stages chagasic cardiomyopathy is associated with congestive heart failure which is often refractory to medical therapy. In these individuals heart transplantation has been attempted. However, this procedure is fraught with many problems attributable to the surgery and the postsurgical administration of immunosuppressive drugs. Studies in mice suggest that the transplantation of bone-marrow-derived cells ameliorates the inflammation and fibrosis in the heart associated with this infection. Cardiac magnetic resonance imaging reveals that bone marrow transplantation ameliorates the infection induced right ventricular enlargement. On the basis of these animal studies the safety of autologous bone marrow transplantation has been assessed in patients with chagasic end-stage heart disease. The initial results are encouraging and more studies need to be performed.

  14. Chagas Disease Cardiomyopathy: Immunopathology and Genetics

    Edecio Cunha-Neto

    2014-01-01

    Full Text Available 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.

  15. Tratamiento de la enfermedad de Chagas TREATMENT OF CHAGAS DISEASES

    Werner Apt

    1999-07-01

    visualice. En niños menores de 10 años con infección crónica reciente el NF durante 60 días ha dado buenos resultados al igual que en el BNZ a dosis de 5mg/kg día por 60 días en niños de 6-12 años con la forma indeterminada. En adultos el itraconazol a dosis de 6 mg/kg al día por 120 días, repartido en dos dosis ha permitido una curación del 60%. El BNZ a dosis de 5mg/kg día por 30 días ha demostrado disminuir las alteraciones electrocardiográ-ficas nuevas de los cardiopatas crónicos. Es importante señalar que por lo general en el período crónico no hay negativización de la serología convencional y el criterio de curación se debe basar en dos o más de los siguientes parametros, que se deben mantener así por varios años y siempre que no exista posibilidad de reinfección: 1 Negativización del xenodiagnóstico 2 Negativización de los hemocultivos 3 Viraje del PCR de (+ a (- 4 Viraje de los anticuerpos líticos de (+ a (- 5 Mejoría clínica y del ECG. Especialmente en cardiopatías recientes.Up to day, it is accepted that human Chagas disease must be treated in any of its evolution periods , with the only exception of the chronical terminal phase In the acute clinical period infection of less than two months and in the biological period with demonstration of parasites in fresh blood smears, stick drop, with positive conventional serology and positive IgM. Treatment is with nifurtimox (NF 8-10 mg/kg per day in adults and 15 mg/kg per day in children for 60-90 days. The dosis is given in three daily intakes. The clinical and serology cure 60%. In Brazil where this drug is not used benznidazol (BNZ is prescribed at dosis of 5 mg/kg per day for adults and 5-10 mg/kg per day in children during 60 days. In congenital infection therapy must be applied as soon as the dignosis is confirmed by clinic and demonstration of parasites at fresh blood, smear microstraut, etc. In the new born often the dignosis is done when he has the chronic period of the infection

  16. Distribution and characterization of canine Chagas disease in Texas.

    Kjos, S A; Snowden, K F; Craig, T M; Lewis, B; Ronald, N; Olson, J K

    2008-04-15

    Although acute and chronic cases of canine Chagas disease have been reported from multiple areas in the southern region of the United States, little data are available on current disease occurrence patterns in endemic areas. Therefore, a study to assess frequency, geographic distribution, signalment, and clinical spectrum of Chagas disease in domestic dogs from Texas was conducted. Serology, histopathology, and clinical case records from multiple institutions for the time period 1993-2007 were analyzed. A total of 537 serologically and/or histopathologically confirmed cases were documented. Cases were reported from 48 of 254 counties within Texas, covering all major geographic regions. Forty-eight dog breeds were represented among the cases, primarily in the sporting and working groups. In histopathologically confirmed cases, acute death occurred in 42%, approximately half of which were ecoregions of Texas, affecting a broad range of dog breeds and age groups. PMID:18255233

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

    Jose Rodrigues Coura

    2013-12-01

    Full Text Available 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

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

    José Rodrigues Coura

    2012-03-01

    Full Text Available 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.

  19. Chagas disease. A new pathophysiological assessment

    Background: There is scarce information on myocardial perfusion abnormalities and on the coronary vasomotor condition in Chagas disease patients. Aims: To assess regional perfusion abnormalities and the coronary vasomotor response of patients in the chronic phase of Chagas disease. Methods: With the use of 99mTc-sestamibi SPECT imaging and cold pressor test and intracoronary acetylcoline (ACH) perfusion, we studied 9 patients aged 42,6±12 years, 4 males, in the chronic stage of Chagas disease (5 with the indeterminate form and 4 with heart lesion) with normal coronary arteries. Vasomotor responses to intracoronary increasing doses of ACH and to a single dose of nitroglycerine (NTG) were assessed with digital quantitative angiography. Regional myocardial perfusion was evaluated at rest and after cold pressor test by a semi quantitative score analysis in an 18-segment model with 99mTc-sestamibi SPECT images. Results were expressed as mean ± 2SD. Differences between continuous variables were measured by two tails Student's t test for paired variables and the significance level was set at 5 %. Results: All patients had regional perfusion defects and abnormal vasomotor response. The diameter of the left anterior descending artery decreased 34% from a basal diameter of 3.66∫0.95 mm down to 2.42±0.74 mm after maximal response to ACH (p<0.002). NTG infusion augmented its diameter to 3.86±0.77 mm (p<0.0002) that is a 60% increase from post ACH diameter. Myocardial perfusion score was 1∫2.66 at rest and 6.22±3.6 after cold pressor test (p<0.0001). Conclusions: This group of patients in the chronic phase of Chagas disease showed an abnormal vasoconstrictive response to intracoronary ACH and cold-induced perfusion defects suggesting that endothelial dysfunction plays a role in the pathophysiology of chronic Chagas heart disease

  20. A Paratransgenic Strategy for the Control of Chagas Disease

    Ivy Hurwitz; Annabeth Fieck; Nichole Klein; Christo Jose; Angray Kang; Ravi Durvasula

    2012-01-01

    Chagas disease results from infection with the parasite Trypanosoma cruzi. This disease remains a significant cause of morbidity and mortality in central and south America. Chagas disease now exists and is detected worldwide because of human migration. Control of Chagas disease has relied mainly on vector eradication however, the development of insect resistance to pesticides, coupled with cost and adverse health effects of insecticide treatments, has prompted our group to investigate novel m...

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

    Janine M Ramsey

    2014-04-01

    Full Text Available 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.

  2. The ecology of Chagas disease in Chile.

    Schofield, C J; Apt, W; Miles, M A

    1982-01-01

    Chagas disease probably affects over half a million people in Chile, principally in rural communities in the fertile valleys of the arid 'norte chico' region, north of Santiago. The main domestic vector is Triatoma infestans, but Triatoma spinolai, although mainly in rocky sylvatic and peridomestic ecotopes, also invades houses. Since the Spanish invasion in the sixteenth century, and particularly during the last 100 years, the endemic region has suffered an ecological breakdown, largely due to excessive timbering and over-grazing, which has led to a denuded landscape with severe loss of agricultural productivity. This breakdown, combined with uneconomically sized farms and poor marketing, exacerbates the poverty of the rural communities. As in other similar areas of Latin America, the combination of poverty and poor education discourages improvements in housing which would reduce the risk of vector-transmitted Chagas disease. This paper reviews the historical and ecological background of the endemic region of Chile, both as a basis for further work, and as a point of comparison with other endemic areas. The review attempts to show how the current status of Chagas disease is likely to be maintained through its association with poor quality housing, poverty and ecological degradation, drawing parallels with other endemic++ areas and suggesting ways by which the ecological damage might be reversed. PMID:6821391

  3. Uruguay declared free of Chagas disease transmission.

    1998-06-01

    According to 1997 entomological and sero-epidemiological data, the transmission of Chagas disease has been interrupted in Uruguay; this has been certified by an independent commission appointed by the Pan American Health Organization/World Health Organization (PAHO/WHO). Transmission of Chagas disease, which is endemic in Uruguay, is via the vector Triatoma infestans or through transfusion with infected blood. In 1983, T. infestans lived in dwellings in 80% of Uruguay; in 1996, in all departments except Tacuarembo, house infestation rates decreased to below 0.1% (a reduction equivalent to 95%). The vector is found around the home, rather than in it, in Tacuarembo; therefore, its presence does not have any significance for transmission. The number of infected blood donors is now negligible, and there is 100% coverage via compulsory blood screening. Uruguay is the first Southern Cone country to have achieved the goals established by the Ministries of Health of Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay to eliminate the transmission of Chagas disease. PMID:12321803

  4. Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

    Anis Rassi Jr

    2009-07-01

    Full Text Available Chagas heart disease (CHD results from infection with the protozoan parasite Trypanosoma cruzi and is the leading cause of infectious myocarditis worldwide. It poses a substantial public health burden due to high morbidity and mortality. CHD is also the most serious and frequent manifestation of chronic Chagas disease and appears in 20-40% of infected individuals between 10-30 years after the original acute infection. In recent decades, numerous clinical and experimental investigations have shown that a low-grade but incessant parasitism, along with an accompanying immunological response [either parasite-driven (most likely or autoimmune-mediated], plays an important role in producing myocardial damage in CHD. At the same time, primary neuronal damage and microvascular dysfunction have been described as ancillary pathogenic mechanisms. Conduction system disturbances, atrial and ventricular arrhythmias, congestive heart failure, systemic and pulmonary thromboembolism and sudden cardiac death are the most common clinical manifestations of chronic Chagas cardiomyopathy. Management of CHD aims to relieve symptoms, identify markers of unfavourable prognosis and treat those individuals at increased risk of disease progression or death. This article reviews the pathophysiology of myocardial damage, discusses the value of current risk stratification models and proposes an algorithm to guide mortality risk assessment and therapeutic decision-making in patients with CHD.

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

    Reinaldo B. Bestetti

    2016-01-01

    Full Text Available Abstract 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.

  6. [Investigation of vectors and reservoirs in an acute Chagas outbreak due to possible oral transmission in Aguachica, Cesar, Colombia].

    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. PMID:24896050

  7. Série de casos agudos de doença de Chagas atendidos num serviço terciário de Manaus, Estado do Amazonas, de 1980 a 2006 Series of acute Chagas' disease cases attended at a tertiary-level clinic in Manaus, State of Amazonas, from 1980 to 2006

    Wuelton Marcelo Monteiro

    2010-04-01

    Full Text Available INTRODUÇÃO: A doença de Chagas é um problema emergente e negligenciado na Região Amazônica. MÉTODOS: Descreve-se uma série de casos agudos autóctones de doença de Chagas atendidos na Fundação de Medicina Tropical do Amazonas, Manaus, de 1980 a 2006. RESULTADOS: Registraram-se 29 casos, sendo 19 do sexo masculino e 10 casos do sexo feminino. Quinze eram casos isolados e 14 provenientes de surtos. Os sinais/sintomas mais freqüentes foram febre, fadiga, cefaléia, mialgia, calafrios, palidez, dispnéia e edema de face e de membros inferiores. Não foi registrado nenhum óbito. CONCLUSÕES: A doença incidiu com frequência em jovens. Os métodos parasitológicos mostraram elevada sensibilidade.INTRODUCTION: Chagas disease is an emerging and neglected problem in the Brazilian Amazon region. METHODS: This study describes a series of acute autochthonous cases of Chagas disease that were attended at the Tropical Medicine Foundation of Amazonas, Manaus, between 1980 and 2006. RESULTS: Twenty-nine cases were recorded: 19 (65.5% were male and 10 (34.5% cases were female. Fifteen (51.7% were isolated cases and 14 (48.3% were from outbreaks. The commonest signs and symptoms were fever, fatigue, headache, myalgia, chills, pallor, dyspnea and edema of the face and lower limbs. No deaths were recorded. CONCLUSIONS: The disease occurred frequently among young people. The parasitological methods showed high sensitivity.

  8. Melatonin in Chagas´ disease: Possible therapeutic value

    Daniel P. Cardinali

    2011-10-01

    Full Text Available 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.

  9. Chagas disease and globalization of the Amazon.

    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. PMID:17308715

  10. Update on Chagas' disease in Mexico

    Dumonteil Eric

    1999-01-01

    Full Text Available Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, represents a major public health problem in most of the American continent. As transmission of the parasite is being interrupted in most of South America, the disease remains endemic in various areas of Mexico. We review here some of the information gathered in recent years. Seroprevalence of T. cruzi infection in humans remains relatively high in some areas, and there has been a general increase in the number of chronic cases reported to health authorities in recent years. In fact, chronic chagasic cardiomyopathy appears to be affecting a large number of patients with heart disease, but many cases may be misreported because of the unspecific nature of the clinical symptoms. Epidemiological monitoring of vector and reservoir populations, as well as of human cases is helping focus on endemic areas, but a better coordination and development of these efforts is still needed. Recent studies of parasite biology are in agreement with previous work showing the great diversity of parasite characteristics, and support the need for a regional approach to this zoonosis. Strong and continuing support from health and academic authorities is thus still needed to further improve our understanding of Chagas' disease in Mexico and implement efficient control programs.

  11. Cognitive impairment in human chronic Chagas' disease

    C.A. Mangone

    1994-06-01

    Full Text Available We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD. No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area was compared using the Mini Mental State Exam (MMSE, Weschler Memory Scale (WMS and the Weschler Adult Intelligent Scale (WAIS. Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. Results: Chagasic patients showed lower MMSE scores (p<004, poor orientation (p<.004, and attention (p<.007. Lower WMS MQ were associated with CCD (Chi2 5.9; p<.01; Fisher test p<.02. Lower WAIS IQ were associated with CCD (Chi2 6.3, p<.01; Fisher test p<.01 being the digit symbol (p<.03, picture completion (p<.03, picture arrangement (p<.01 and object assembly (p<.03 subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.

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

    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. PMID:26777312

  13. Immune Response to Trypanosoma cruzi Shed Acute Phase Antigen in Children from an Endemic Area for Chagas' Disease in Bolivia

    Simone Frédérique Brenière

    1997-07-01

    Full Text Available A field study of the immune response to the shed acute phase antigen (SAPA of Trypanosoma cruzi was carried out in the locality of Mizque, Cochabamba department, Bolivia. Schoolchildren (266, with an average of 8.6 ± 3.6 years, were surveyed for parasitological and serological diagnosis, as well as antibodies directed against SAPA using the corresponding recombinant protein in ELISA. The antibodies against SAPA were shown in 82% of patients presenting positive serological diagnosis (IgG specific antibodies. The positive and negative predictive values were 0.88. Antibodies anti-SAPA were shown in 80.8% of the chagasic patients in the initial stage of the infection (positive IgM serology and/or positive buffy coat (BC test and in 81.4% of the patients in the indeterminate stage of the infection (positive IgG serology with negative BC and IgM tests. These results show that the anti-SAPA response is not only present during the initial stage of the infection (few months but extends some years after infection

  14. A cost-benefit analisys of chagas disease control

    C. J. Schofield

    1991-09-01

    Full Text Available Chagas disease transmission can be effetively interrupted by insecticidal control of its triatomine bug vectors. We present here a simple model comparing the costs and benefits of such a programme, designed to eliminate domestic populations of Triatoma infestans throughout its known area of distribution over the seven southernmost countries of Latin America. The model has been simplified to require only four financial estimates relating to the unit cost of housing spraying and benefits due to avoidance of premature death in the acute phase of the disease, avoidance of supportive treatment and care in the chronic phase of the disease, and avoidance of corrective digestive and cardiac surgery. Exceptfor these direct medical costs, al other potential benefits have been ignored. Nevertheless, the model shows that the direct financial benefits of such a programme would far outweigh the costs, and the project would support a remarkably high internal rate of return under the least optimistic estimates.

  15. Oral Transmission of Chagas Disease by Consumption of Açaí Palm Fruit, Brazil

    Nóbrega, Aglaêr A.; Garcia, Marcio H.; Tatto, Erica; Marcos T Obara; 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.

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

    ... mainly, in rural areas of Latin America where poverty is widespread). Chagas disease ( T. cruzi infection) is ... Prevention 1600 Clifton Rd. Atlanta, GA 30329-4027, USA 800-CDC-INFO (800-232-4636) TTY: (888) ...

  17. Chagas' disease in the Amazon Basin: V. Periurban palms as habitats of Rhodnius robustus and Rhodnius pictipes - triatomine vectors of Chagas' disease

    M. A. Miles

    1983-12-01

    Full Text Available Trypanosoma cruzi infected Rhodnius robustus and/or Rhodnius pictipes were commonly found, in large numbers, in the Brazilian Amazonian palms Maximiliana regia ("inajá", Acrocomia sclerocarpa ("mucajá" and Orbignya speciosa ("babaçu". The common opossum, Didelphis marsupialis, was the animal most frequently associated with triatomine infested palms. R. pictipes, frequently light-attracted into houses from palm trees, was the probable source of an acute case of Chagas' disease in the vicinity of Belém. It is considered that triatomine infested palms are likely to cause some cases of acute Chagas' disease in the States of Amazonas and Rondônia. Possible control methods are suggested.Rhodnius robustus e/ou Rhodnius pictipes, infectados com Trypanosoma cruzi foram comumente encontrados, em grande numero, nas palmeiras Maximiliana regia (inaja, Acrocomia sclerocarpa (mucaja e Orbignya speciosa (babacu na Amazonia brasileira. O marsupial Didelphis marsupialis foi o animal encontrado mais frequentemente nas palmeiras associadas a alta prevalencia de triatomineos. R. pictipes que e atraido pela luz nas residencias de palmeiras vizinhas, provavelmente e a fonte de um caso agudo de doenca de Chagas nas vizinhancas de Belem. Sugere-se que as palmeiras albergando triatomineos poderiam ser relacionadas com infeccoes humanas de doenca de Chagas nos Estados de Amazonas e Rondonia. Sugere-se, tambem, possiveis metodos de controle.

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

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

    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 a...

  19. Prophylactic and therapeutic DNA vaccines against Chagas disease

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

    2015-01-01

    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-lik...

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

    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

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

    Belkisyolé Alarcón de Noya

    2015-05-01

    Full Text Available 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.

  2. Chagas disease: Central American initiative launched.

    1998-02-01

    An initiative to interrupt the transmission of Chagas disease in Central America was launched at a meeting held October 22-24, 1997, in Tegucigalpa, Honduras. Sponsored by the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR), the meeting was attended by government delegates from Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama. The initiative was launched within the framework of Resolution 13 of the Meeting of Ministers of Health of the Central American Countries, held in Belize in September 1997. Detailed plans of activities were prepared for each country for the period 1998-2001, for approval by the various ministries of health, while operational, epidemiological, and entomological research priorities were also agreed upon. Research projects to help improve disease control will be sponsored by TDR. The first meeting of the Technical Intergovernment Commission established to meet annually to assess progress in control activities will occur in October 1998 in Guatemala. Vector and infection rate data are briefly presented on each country represented at the meeting. PMID:12348564

  3. Megabladder in experimental Chagas disease: pathological features of the bladder wall

    Scremin Luciano Henrique Gazoni; Corbett Carlos Eduardo Pereira; Laurenti Márcia Dallastra; Nunes Elizabeth Visone; Gama-Rodrigues Joaquim José; Okumura Masayuki

    1999-01-01

    Mega-organs, primarily in the digestive tract, are well known to occur in chronic Chagas disease. Acute experimental infection with Trypanosoma cruzi results in parasitism of a wide range of cells, tissues, and organs, including the urinary bladder. Infection of BALB/c mice with 100,000 bloodstream forms of the Y strain of T. cruzi induced acute infection with intense parasitism of all layers of the urinary bladder. Parasites were found in the mucosa, lamina propria, muscular, adventitial con...

  4. Behavioural biology of Chagas disease vectors

    Claudio Ricardo Lazzari

    2013-01-01

    Full Text Available 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.

  5. Chronic Chagas disease: from basics to laboratory medicine.

    Haberland, Annekathrin; Saravia, Silvia Gilka Munoz; Wallukat, Gerd; Ziebig, Reinhard; Schimke, Ingolf

    2013-02-01

    Chagas disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10-30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemo therapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed. PMID:23045386

  6. Long term evaluation of etiological treatment of Chagas disease with benznidazole

    Cançado J Romeu

    2002-01-01

    The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for...

  7. A new era for chagas disease drug discovery?

    Keenan, Martine; Chaplin, Jason H

    2015-01-01

    Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed. PMID:25727705

  8. Nanomedicines against Chagas disease: an update on therapeutics, prophylaxis and diagnosis.

    Morilla, Maria Jose; Romero, Eder Lilia

    2015-02-01

    Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi. After a mostly clinically silent acute phase, the disease becomes a lifelong chronic condition that can lead to chronic heart failure and thromboembolic phenomena followed by sudden death. Antichagasic treatment is only effective in the acute phase but fails to eradicate the intracellular form of parasites and causes severe toxicity in adults. Although conventional oral benznidazol is not a safe and efficient drug to cure chronic adult patients, current preclinical data is insufficient to envisage if conventional antichagasic treatment could be realistically improved by a nanomedical approach. This review will discuss how nanomedicines could help to improve the performance of therapeutics, vaccines and diagnosis of Chagas disease. PMID:25707979

  9. Perinatal Screening for Chagas Disease in Southern Texas.

    Edwards, Morven S; Rench, Marcia A; Todd, Charles W; Czaicki, Nancy; Steurer, Francis J; Bern, Caryn; Montgomery, Susan P

    2015-03-01

    Perinatal screening for Trypanosoma cruzi in a cohort of 4000 predominantly Hispanic women in southern Texas revealed that Chagas disease occurs with sufficient frequency (0.25%) that targeted perinatal screening should be considered to identify infected mothers and infants at risk for congenital infection. PMID:26407360

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

    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

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

    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. PMID:26801589

  12. Chagas cardiomyopathy in the context of the chronic disease transition.

    Alicia I Hidron

    Full Text Available 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 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.

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

    Ludmila; Rodrigues; Pinto; Ferreira; Amanda; Farage; Frade; Monique; Andrade; Baron; Isabela; Cunha; Navarro; Jorge; Kalil; Christophe; Chevillard; Edecio; Cunha-Neto

    2014-01-01

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

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

    Ferreira, Ludmila Rodrigues Pinto; Frade, Amanda Farage; Baron, Monique Andrade; Navarro, Isabela Cunha; Kalil, Jorge; Chevillard, Christophe; Cunha-Neto, Edecio

    2014-08-26

    Chagas disease cardiomyopathy (CCC), the main consequence of Trypanosoma cruzi (T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon (IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease. PMID:25228957

  15. Interactive Media on Chagas Disease: Development and Content

    Claudinei Caetano de Souza

    2013-10-01

    Full Text Available An interactive media on Chagas disease was developed as an educational tool, on the context of the scientific research and dissemination actions of the National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases (INBEQMeDI. Different computational resources were used either in terms of hardware and software. The media contains 13 videos that range from 30 seconds to 4 minutes, all with information about Chagas disease, showing the social and economic aspects; the research made by the INBEQMeDI group; different aspects of the disease illustrated by slides arranged in a mobile carousel, and radio programs, with funny skits. The target audience for use of this feature is students aged 10 to 17 years. Teachers of areas of science and biology, through a partnership with the Agency of Education of the State of São Paulo, will be invited to plan a strategy for media use with their students.

  16. Chagas Heart Disease Pathogenesis: One Mechanism or Many?

    Bonney, Kevin M.; David M. Engman

    2008-01-01

    Chagas heart disease (CHD), caused by the protozoan parasite Trypanosoma cruzi, is the leading cause of infectious myocarditis in the world. The etiology of CHD is unclear and multiple mechanisms have been proposed to explain the pathogenesis of the disease. This review describes the proposed mechanisms of CHD pathogenesis and evaluates the historical significance and evidence supporting each. Although the majority of CHD-related pathologies are currently attributed to parasite persistence in...

  17. Elimination of vector-borne transmission of Chagas disease

    AC Silveira; MC Vinhaes

    1999-01-01

    The control of the vector-borne transmission of Chagas disease in Brazil was organized as a national program in 1975, when two large entomological and sero-epidemiological surveys were conducted in the country in order to identify areas at highest risk of transmission and to guide inerventions regarding the chemical treatment of domestic vectors of the disease. The authors present the baseline data gathered through these studies and compare them with more recent data. The evaluation performed...

  18. Chagas disease, migration and community settlement patterns in Arequipa, Peru.

    Angela M Bayer

    Full Text Available 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

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

    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

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

    Jaime-Andrade G. J.

    1997-01-01

    Full Text Available 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 triatomines (Triatoma longipennis Usinger infected with Trypanosoma cruzi collected within 5 meters from the place where the animal lived in the city of Guadalajara.

  1. Assessment and epidemiology of Chagas' disease in patients treated in Araguaina - Tocantins

    Chagas disease (AD) was described by Carlos Chagas in 1909. It is caused by a parasite T. cruzi, transmitted by bugs, by blood transfusion, vertical and orally. The DC has two phases: acute and chronic. The evolution to the cardiac form occurs in about 30% of chronic cases and is the largest cause of mortality in chronic Chagas disease. The aim of this study was to Chagas' disease in patients of Tocantins, compared with other heart patients and asymptomatic from the standpoint of non-invasive exams using radiant energies such as echocardiography and ECG and RX. The descriptive study included 80 patients, 20 chronic form of Chagas disease, 20 indeterminate, 20 with other heart diseases, and 20 controls. There was a prevalence of 9.5% of chagasic patients treated in outpatient cardiology at Araguaina Tocantins, and 7.3% in chronic and 2.21% in the indeterminate. Of the chronic patients in the study 50% had mega esophagus and megacolon 4 (20%). Most patients had no family history of AD, nor was a smoker or drinker. Major electrocardiographic abnormalities found refer to driving. The evaluation of ICT, the chronic chagasic showed that increased by 40% of patients, 40% had esophageal changes and 20% of patients had megacolon s. The echocardiogram was abnormal in 42%). 27% of patients had EF below 55% changed. Changes in segmental contractility and Asynchrony septum were found in 80% of chronic Chagas disease. In 80% of the patients was observed diastolic dysfunction. The valvular changes occurred in 75%. Electrocardiographic abnormalities occurred in 80% of patients with CCC, while the other heart had ECG changes. Arterial hypertension had an incidence of 45% in patients with CCC and 40% in FCI. The systolic and diastolic ventricular dysfunction was more prevalent in groups that had an abnormal ECG and arrhythmia. Observed that the group of chagasic decreased ejection fraction is correlated to a higher incidence of arrhythmias besides diastolic dysfunction and related

  2. Molecular epidemiology of human oral Chagas disease outbreaks in Colombia.

    Juan David Ramírez

    Full Text Available 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.

  3. A Paratransgenic Strategy for the Control of Chagas Disease

    Ivy Hurwitz

    2012-01-01

    Full Text Available Chagas disease results from infection with the parasite Trypanosoma cruzi. This disease remains a significant cause of morbidity and mortality in central and south America. Chagas disease now exists and is detected worldwide because of human migration. Control of Chagas disease has relied mainly on vector eradication however, the development of insect resistance to pesticides, coupled with cost and adverse health effects of insecticide treatments, has prompted our group to investigate novel methods of transmission control. Our laboratory has been instrumental in the development of the paratransgenic strategy to control vectorial transmission of T. cruzi. In this paper, we discuss various components of the paratransgenic approach. Specifically, we describe classes of molecules that can serve as effectors, including antimicrobial peptides, endoglucanases, and highly specific single chain antibodies that target surface glycoprotein tags on the surface of T. cruzi. Furthermore, we address evolving concepts related to field dispersal of engineered bacteria as part of the paratransgenic control strategy and attendant risk assessment evaluation.

  4. A cost-benefit analisys of chagas disease control

    C.J. Schofield; J.C.P. Dias

    1991-01-01

    Chagas disease transmission can be effetively interrupted by insecticidal control of its triatomine bug vectors. We present here a simple model comparing the costs and benefits of such a programme, designed to eliminate domestic populations of Triatoma infestans throughout its known area of distribution over the seven southernmost countries of Latin America. The model has been simplified to require only four financial estimates relating to the unit cost of housing spraying and benefits due to...

  5. Epicuticular lipids induce aggregation in Chagas disease vectors

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

    2009-01-01

    Abstract 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-ex...

  6. Chagas disease: what is known and what is needed - A background article

    José Rodrigues Coura

    2007-10-01

    Full Text Available Chagas disease began millions of years ago as an enzootic disease of wild animals and started to be transmitted to man accidentally in the form of an anthropozoonosis when man invaded wild ecotopes. Endemic Chagas disease became established as a zoonosis over the last 200-300 years through forest clearance for agriculture and livestock rearing and adaptation of triatomines to domestic environments and to man and domestic animals as a food source. It is estimated that 15 to 16 million people are infected with Trypanosoma cruzi in Latin America and 75 to 90 million people are exposed to infection. When T. cruzi is transmitted to man through the feces of triatomines, at bite sites or in mucosa, through blood transfusion or orally through contaminated food, it invades the bloodstream and lymphatic system and becomes established in the muscle and cardiac tissue, the digestive system and phagocytic cells. This causes inflammatory lesions and immune responses, particularly mediated by CD4+, CD8+, interleukin-2 (IL and IL-4, with cell and neuron destruction and fibrosis, and leads to blockage of the cardiac conduction system, arrhythmia, cardiac insufficiency, aperistalsis, and dilatation of hollow viscera, particularly the esophagus and colon. T. cruzi may also be transmitted from mother to child across the placenta and through the birth canal, thus causing abortion, prematurity, and organic lesions in the fetus. In immunosuppressed individuals, T. cruzi infection may become reactivated such that it spreads as a severe disease causing diffuse myocarditis and lesions of the central nervous system. Chagas disease is characterized by an acute phase with or without symptoms, and with entry point signs (inoculation chagoma or Romaña's sign, fever, adenomegaly, hepatosplenomegaly, and evident parasitemia, and an indeterminate chronic phase (asymptomatic, with normal results from electrocardiogram and x-ray of the heart, esophagus, and colon or with a

  7. Long term evaluation of etiological treatment of chagas disease with benznidazole.

    Cancado, J Romeu

    2002-01-01

    The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of

  8. Long term evaluation of etiological treatment of Chagas disease with benznidazole

    CANÇADO J. Romeu

    2002-01-01

    Full Text Available The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of

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

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

    2016-01-01

    Abstract: INTRODUCTION 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. METHODS 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 ...

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

    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. PMID:23484340

  11. Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy

    Álvaro Moncayo

    2009-07-01

    Full Text Available Chagas disease, named after Carlos Chagas, who first described it in 1909, exists only on the American Continent. It is caused by a parasite, Trypanosoma cruzi, which is transmitted to humans by blood-sucking triatomine bugs and via blood transfusion. Chagas disease has two successive phases: acute and chronic. The acute phase lasts six-eight weeks. Several years after entering the chronic phase, 20-35% of infected individuals, depending on the geographical area, will develop irreversible lesions of the autonomous nervous system in the heart, oesophagus and colon, and of the peripheral nervous system. Data on the prevalence and distribution of Chagas disease improved in quality during the 1980s as a result of the demographically representative cross-sectional studies in countries where accurate information was not previously available. A group of experts met in Brasilia in 1979 and devised standard protocols to carry out countrywide prevalence studies on human T. cruzi infection and triatomine house infestation. Thanks to a coordinated multi-country programme in the Southern Cone countries, the transmission of Chagas disease by vectors and via blood transfusion was interrupted in Uruguay in 1997, in Chile in 1999 and in Brazil in 2006; thus, the incidence of new infections by T. cruzi across the South American continent has decreased by 70%. Similar multi-country initiatives have been launched in the Andean countries and in Central America and rapid progress has been reported towards the goal of interrupting the transmission of Chagas disease, as requested by a 1998 Resolution of the World Health Assembly. The cost-benefit analysis of investment in the vector control programme in Brazil indicates that there are savings of US$17 in medical care and disabilities for each dollar spent on prevention, showing that the programme is a health investment with very high return. Many well-known research institutions in Latin America were key elements of a

  12. Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

    Florencia del Puerto

    Full Text Available BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG, and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD, and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

  13. Aspectos neurológicos da doença de chagas: sistema nervoso central Neurological aspects of Chagas' disease: central nervous system

    Sylvio de Vergueiro Forjaz

    1967-09-01

    Full Text Available The lesions of the nervous system in the Trypanosomiasis Cruzi are quite frequent and are not only limited to the encephalo-spinal-axis. Actually, they are much more common in the peripheral representations of the autonomic nervous system, resulting in the so-called enteromegalies (mega-esophagus, megacolon, etc. so frequent in Brazil. However, only the clinical manifestations due to the encephalic and spinal lesions have been included in the neurological aspects of Chagas' disease (as formerly contended for by Carlos Chagas. In the acute phase of the central nervous system infestation, the Trypanosoma cruzi,as leishmanias, is found in cellular elements of the neuroglia (microglia, astroglia and may be isolated from the peripheral blood and cerebrospinal fluid (inoculation in sensitive animals. The corresponding clinical manifestations are the severe difuse meningo-encephalo-myelitis with a high degree of lethality and also signs of infection, hepatomegaly and splenomegaly. The infants from endemic areas are much more compromised. The clinical-pathologic as well as experimental confirmations on that acute phase of the disease are numerous and irrefutable. In the chronic phase of the disease, the neurological manifestations are not very clear. Early in 1909, Chagas, impressed with the great number of cases of infantile encephalopathy found in infested regions, imputed to the T. cruzithe etiology of such cases of encephalopathy and considered them as pertaining to a chronic phase of the disease. This has not been confirmed by other investigations, and even if the etiologic agent were the T. cruzithe clinical manifestations have no evolutive character and seem more sequelae than symptoms of a real chronic nervous phase. Even experimentally it has not been possible to demonstrate the presence of parasites in the nervous system of infested animals after clearing of the signs of the acute phase. In patients with chronic Chagas' disease with lesions in

  14. Doença de Chagas no Brasil Chagas disease in Brazil

    Márcio C. Vinhaes

    2000-01-01

    Full Text Available Sumariam-se os dados da Fundação Nacional de Saúde (FNS sobre o estado atual dos vetores da doença de Chagas no Brasil, verificando-se que após vinte anos de controle químico continuado houve franca redução dos índices triatomínico-tripanosômicos, particularmente para esp��cies como Triatoma infestans e Panstrongylus megistus. Em paralelo, dados de sorologia escolar, de internações e de mortalidade pela doença indicam descenso nas taxas de incidência e impacto médico social da protozoose, restando áreas mais preocupantes, como o Nordeste e resíduos de T. infestans. Impõe-se urgente uma vigilância epidemiológica efetiva, a ser realizada por estados e municípios ante o processo de descentralização da FNS.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.

  15. Enfermedad de Chagas congenita en la Ciudad de Salta, Argentina Congenital Chagas' disease in Salta, Argentina

    Mario Zaidenberg

    1993-02-01

    presence of T. cruzi in blood, explored in fresh smears by serial micro-hematocrite and/or by xenodiagnosis, was the only criterion to define infection in NB. All NB were followed up by direct agglutination (DA with or without 2 mercaptoethanol (DA-w2ME, DA-wo2ME and IIF in order to establish the specific antibody kinetics. Clinical studies on NB with T. cruzi infection include routine laboratory tests. Benznidazole (3 to 7 mg/kg/day and, in 1 case, nifurtimox (15 mg/kg/day were employed as therapeutic agents. T. cruzi infection was confirmed in 149 PW (15.9%, table I. These chagasic mothers delivered 6 chagasic NB (CCHD-NB, (4%. Diagnosis of congenital Chagas' disease accounted for a total of 12 NB out of the 968 studied. 4 out of them were positive by both micro-hematocrite and blood smears and 7 by micro-hematocrite alone. Xenodiagnosis was performed in 2 NB resulting positive in both cases, table II. The most usual clinical findings included hepatomegaly (present in all cases, splenomegaly 8/12, jaundice 10/12 and prematurity 5/12, table 3. Laboratory findings showed anemia to be of hypochromic microcytic type in all cases. Other laboratory findings included lymphocytosis, normal erythrosedimentation, slight to moderate increase of transaminases in all cases, and elevated indirect bilirrubin in cases with jaundice, table 4. Analysis of cerebro spinal fluid in 6 CCh-NB revealed the presence of T. cruzi in 2 cases, plus abnormal cytochemical content in one of them, table 4. The serological reactions of infected and treated NB became negative between 4th and 8th month in all but 1 case that remained positive until 14th, fig. 1. A close correlation was found between DA and IIF. DA-w2ME liter showed a significant drop during the initial phase of the controls. Benznidazole was successful in 11 out of the 12 CCh-NB. The remaining NB was effectively treated with nifurtimox. Therapeutic tolerance was satisfactory for both agents. These observations showed that congenital Chagas

  16. Travelers' Health: Trypanosomiasis, American (Chagas Disease)

    ... Guide Learn About Destination See a Doctor Pre-Travel Appointment Your Health Status How Diseases Spread Pack Smart Plan Ahead ... During Trip After Your Trip CDC-TV Videos Travel to the Olympics ... Presentations for Health Professionals Yellow Fever Vaccine Course About the Yellow ...

  17. Chagas disease and globalization of the Amazon La enfermedad de Chagas y la globalización de la Amazonia

    Roberto Briceño-León

    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 mod...

  18. Aspectos neurológicos da moléstia de chagas Neurological aspects of Chagas disease

    Fritz Köberle

    1967-09-01

    Full Text Available Carlos Chagas related in more than two 200 cases, what he called "nervous forms" of trypanosomiasis, that is neurological manifestations from central origin (idiotism, infantilism, pseudo-bulbar paralysis, aphasia, cerebellar ataxia, atetosis, espostic or paralytic diplegia, disbasia. At that time Chagas expressed his concepts as follows: "In relation to the frequency of trypanosomiasis nervous forms we have performed many observations which allow us to state that this disease is the one which causes the largest number of organic affections of the central nervous system, in human pathology". We are plenty convinced by Chagas's statement. By experiments on animals of laboratory we have very often noticed a rather varied neurological symptomatology, being worth point out identical syndromes to those observed by Chagas. Our autopsy material non-rarely include chronic Chagas cases presenting a most varied symtomatology. Among them we have named only three cases of discerebral nanism, a rather rare affection in other parts of the world and relatively frequent in our material. The fact which we have demonstrated, i.e., a relatively great decreasing of number of nervous cells in the peripheral system could happen in the central nervous system as well. Provided that there are only two quantitative works on neuron number diminishing in the central nervous system in mice and rats we decline to go into further details about central neuropathies in man. We emphasized the necessity to perform researches on this field by means of intimate collaboration between clinicians and pathologists, as the only way to confirm on scientific basis all that was observed by the panoramic and genial vision of Carlos Chagas.

  19. Urban transmission of Chagas disease in Cochabamba, Bolivia

    N Medrano-Mercado

    2008-08-01

    Full Text Available Chagas disease is a major public health problem in Bolivia. In the city of Cochabamba, 58% of the population lives in peripheral urban districts ("popular zones" where the infection prevalence is extremely high. From 1995 to 1999, we studied the demographics of Chagas infections in children from five to 13 years old (n = 2218 from the South zone (SZ and North zone (NZ districts, which differ in social, environmental, and agricultural conditions. Information gathered from these districts demonstrates qualitative and quantitative evidence for the active transmission of Trypanosoma cruzi in urban Cochabamba. Seropositivity was high in both zones (25% in SZ and 19% in NZ. We observed a high risk of infection in children from five to nine years old in SZ, but in NZ, a higher risk occurred in children aged 10-13, with odds ratio for infection three times higher in NZ than in SZ. This difference was not due to triatomine density, since more than 1,000 Triatoma infestans were captured in both zones, but was possibly secondary to the vector infection rate (79% in SZ and 37% in NZ. Electrocardiogram abnormalities were found to be prevalent in children and pre-adolescents (SZ = 40%, NZ = 17%, indicating that under continuous exposure to infection and re-infection, a severe form of the disease may develop early in life. This work demonstrates that T. cruzi infection should also be considered an urban health problem and is not restricted to the rural areas and small villages of Bolivia.

  20. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.

    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. PMID:26239982

  1. IL18 Gene Variants Influence the Susceptibility to Chagas Disease

    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

  2. Leptin levels in different forms of Chagas' disease

    F. Fernandes

    2007-12-01

    Full Text Available Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG, and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001 in the CHF group (1.4 ± 0.8 ng/mL when compared to the IF group (5.3 ± 5.3 ng/mL, ECG group (9.7 ± 10.7 ng/mL, and control group (8.1 ± 7.8 ng/mL. NT-proBNP levels were significantly higher (P < 0.001 in the CHF group (831.8 ± 800.1 pg/mL when compared to the IF group (53.2 ± 33.3 pg/mL, ECG group (83.3 ± 57.4 pg/mL, and control group (32 ± 22.7 pg/mL. Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

  3. Different Infective Forms Trigger Distinct Immune Response in Experimental Chagas Disease

    Vieira, Paula Melo de Abreu; Francisco, Amanda Fortes; Machado, Evandro Marques de Meneses; Nogueira, Nívia Carolina; Fonseca, Kátia da Silva; Reis, Alexandre Barbosa; Teixeira-Carvalho, Andrea; Martins-Filho, Olindo Assis; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2012-01-01

    Although metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-α and later of IFN-γ by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-γ, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease. PMID:22412949

  4. Long term evaluation of etiological treatment of Chagas disease with benznidazole Avaliação a longo prazo do tratamento etiológico da doença de Chagas com benznidazol

    J. Romeu CANÇADO

    2002-01-01

    The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for...

  5. Integrate Study of a Bolivian Population Infected by Trypanosoma cruzi, the Agent of Chagas Disease

    Simone Frédérique Brenière

    2002-04-01

    Full Text Available A cross section of a human population (501 individuals selected at random, and living in a Bolivian community, highly endemic for Chagas disease, was investigated combining together clinical, parasitological and molecular approaches. Conventional serology and polymerase chain reaction (PCR indicated an active transmission of the infection, a high seroprevalence (43.3% ranging from around 12% in 45 years, and a high sensitivity (83.8% and specificity of PCR. Abnormal ECG tracing was predominant in chagasic patients and was already present among individuals younger than 13 years. SAPA (shed acute phase antigen recombinant protein and the synthetic peptide R-13 were used as antigens in ELISA tests. The reactivity of SAPA was strongly associated to Trypanosoma cruzi infection and independent of the age of the patients but was not suitable neither for universal serodiagnosis nor for discrimination of specific phases of Chagas infection. Anti-R-13 response was observed in 27.5% only in chagasic patients. Moreover, anti-R13 reactivity was associated with early infection and not to cardiac pathology. This result questioned previous studies, which considered the anti-R-13 response as a marker of chronic Chagas heart disease. The major clonets 20 and 39 (belonging to Trypanosoma cruzi I and T. cruzi II respectively which circulate in equal proportions in vectors of the studied area, were identified in patients' blood by PCR. Clonet 39 was selected over clonet 20 in the circulation whatever the age of the patient. The only factor related to strain detected in patients' blood, was the anti-R-13 reactivity: 37% of the patients infected by clonet 39 (94 cases had anti-R13 antibodies contrasting with only 6% of the patients without clonet 39 (16 cases.

  6. Radioisotopic exploration of patients suffering from chronic Chagas' disease

    The importance of Chagas' disease - a histic and haematic parasitosis endemic in extensive areas of Latin America, with 60 million people exposed to it and 20 million infected - stems from the high sickness and mortality rates affecting mainly rural and fringe populations. Nevertheless, progressive urbanization of the disease due to population migration and blood transfusion is being observed. The authors studied 56 cases of patients with Chagas' disease, 45 of whom were detected asymptomatically when donating blood by immunoserological reactions involving complement fixation and haemagglutination. Radiotracers were used to explore ventricular function in 56 cases; oesophageal transit in 29 cases; the upper urinary tract in 25 cases; and bladder function in 22 cases. All four procedures were applied to 19 patients. In 40 patients a study was made of the left and right ventricular function, the left being found altered in 17% of the cases, the right ventricular function in 22% and both in 25%. In 26 cases (65%) anomalies were encountered in at least one of the two ventricles. Oesophageal transit was altered in 20 patients, 16 of them asymptomatically. In 6 of them it was prolonged, in 4 it was adynamic and in 10 cases uncoordinated. The upper urinary tract showed abnormalities (pyelic dilation, pyelo-ureteral dyskinesia, ureteral dyskinesia, ureteral dilation and/or vesico-ureteral reflux) in 22 patients, in all cases asymptomatically. Bladder function was abnormal in 18 asymptomatic patients, basically represented by a residual decompensated cystopathy with a hypotonicity of different degrees. Of the 45 patients without symptoms detected when donating blood, there was alteration of ventricular function in 49%, of oesophageal transit in 68%, of the upper urinary tract in 90%, and of bladder function in 78%, with an overall figure of 66% abnormal examinations from 106 radioisotopic studies

  7. Ecological aspects of the vectorial control of Chagas' disease in Brazil

    João Carlos P. Dias

    1994-01-01

    The feasibility and most important ecological aspects of vectorial Chagas' disease control are discussed. The spread and maintenance of this disease involve multiple ecological and sociopolitical factors that must be taken into account when control programs are planned, executed and evaluated. In spite of its complexity, Chagas disease can be controlled using methods that target specific mechanisms of transmission, the most important being vectorial and transfusional. Major ecological problem...

  8. The potential for emergence of Chagas disease in the United States

    Rebecca Click Lambert

    2008-05-01

    Full Text Available To determine the risk for Chagas disease (American trypanosomiasis in the United States, the characteristics that make the triatomine vector effective and the areas most at risk for transmission were delineated. In addition, the status of Chagas disease awareness among physicians in areas with a potential risk for the disease was determined. A geographical information system (GIS was used to analyze three triatomine species within the United States known to harbor Trypanosoma cruzi and that exhibit qualities of domesticity. An analysis of the minimum temperature threshold for increased triatomine activity delineates the current population at increased risk, and by incorporating temperature predictions for 2030, the population at risk under a future climate scenario was also delineated. Considering both environmental and social factors, a vignette-based physician survey, based on the results of the GIS analysis, was used to gauge the level of awareness of Chagas disease within the delineated higher risk range. The current area at increased risk for Chagas disease includes much of the southern United States, and the higher risk range is expected to expand into the central United States based upon the 1°C (1.8°F increase in temperature predicted by the Intergovernmental Panel on Climate Change (IPCC by the year 2030. Survey results indicate a limited consideration of Chagas disease during differential diagnosis, illustrating that the low number of Chagas disease cases discovered in the United States may be attributable to a lack of disease awareness as opposed to a lack of disease threat. This study combines GIS and survey analyses to evaluate the role that temperature variability and disease awareness among physicians play in the potential emergence of Chagas disease in the United States. This approach indicates that there is a potential for Chagas disease to emerge in the United States.

  9. Cerebral evoked potentials in human chronic Chagas' disease

    O. M. Genovese

    1989-09-01

    Full Text Available Seventy five patients with the diagnosis of chronic Chagas' disease were studied by employing EPs techniques. Two of them had delayed arrival of the signal to the Erb's point and one to the spinal cord when looking at SEPs. TWo patients had increment of the time interval between waves 1st and IIIrd, when studying PEATs. These findings were interpreted as due to peripheral nerve fibers damage, a feature described in previous papers. The, most striking finding was the prolonged time interval between waves N13 and N20 (SEPs found in two patients and between waves IIIrd and Vth (PEAT seen in 7 affected subjects. These observations suggested the development of some sort of CNS involvement, perhaps related to myelin damage, in patients who reached the chronic state of the infection.

  10. Cost-effectiveness analysis in Chagas' disease vectors control interventions

    A. M. Oliveira Filho

    1989-01-01

    Full Text Available After a large scale field trial performed in central Brazil envisaging the control of Chagas' disease vectors in an endemic area colonized by Triatoma infestans and T. sordida the cost-effectiveness analysis for each insecticide/formulation was performed. It considered the operational costs and the prices of insecticides and formulations, related to the activity and persistence of each one. The end point was considered to be less than 90% of domicilliary unitis (house + annexes free of infestation. The results showed good cost-effectiveness for a slow-release emulsifiable suspension (SRES based on PVA and containing malathion as active ingredient, as well as for the pyrethroids tested in this assay-cyfluthrin, cypermethrin, deltamethrin and permethrin.

  11. [Association of encephalic vascular accidents and Chagas disease].

    Lopes, E R; Marquez, J O; da Costa Neto, B; Menezes, A A; Chapadeiro, M E

    1991-01-01

    The frequency of strokes was studied in chronic chagasic and years of age, non-chagasic patients, older than 15 coming to necropsy in Uberaba, from 1979 than 1988. The study consisted of paired sex and age matched controls. Two hundred and eight pairs were analysed. Either ischemic or hemorrhagic strokes were found in 41 (19.7%) of the chagasics and in 55 (26.4%) of the non-chagasic, a difference not significant at the level of 5%. Twelve (75%) of the former had infarcts and 4 (25%) had brain hemorrhage; five (31.3%) of the non-chagasics had ischemic strokes and 11 (68.7%) had hemorrhagic strokes. The differences were significant to the level of 5%. The results indicate a high frequency of ischemic strokes in human Chagas' disease and demonstrate a lesser frequency of hemorrhagic stroke in chagasics when compared with non-chagasics. PMID:1841424

  12. Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation

    Guimaro, M.C.; Alves, R. J. V.; Rose, E.; Sousa, A.O.; Rosa, A.D.; Hecht, M.M.; Sousa, M.V.; Andrade, R.R.; Vital, T.; Plachý, Jiří; Nitz, N.; Hejnar, Jiří; Gomes, C.C.; Teixeira, A.R.L.

    2014-01-01

    Roč. 8, č. 12 (2014). ISSN 1935-2735 Institutional support: RVO:68378050 Keywords : Chagas disease * inbred chicken * adoptive transfer of immunity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.446, year: 2014

  13. Mapping of Chagas disease research: analysis of publications in the period between 1940 and 2009

    José Manuel Ramos

    2011-12-01

    Full Text Available INTRODUCTION: Publications are often used as a measure of success in research work. Chagas disease occurs in Central and Southern America. However, during the past years, the disease has been occurring outside Latin America due to migration from endemic zones. This article describes a bibliometric review of the literature on Chagas disease research indexed in PubMed during a 70-year period. METHODS: Medline was used via the PubMed online service of the U.S. National Library of Medicine from 1940 to 2009. The search strategy was: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH]. RESULTS: A total of 13,989 references were retrieved. The number of publications increased steadily over time from 1,361 (1940-1969 to 5,430 (2000-2009 (coefficient of determination for linear fit, R²=0.910. Eight journals contained 25% of the Chagas disease literature. Of the publications, 64.2% came from endemic countries. Brazil was the predominant country (37%, followed by the United States (17.6% and Argentina (14%. The ranking in production changed when the number of publications was normalized by estimated cases of Chagas disease (Panama and Uruguay, population (Argentina and Uruguay, and gross domestic product (Bolivia and Brazil. CONCLUSIONS: Several Latin American countries, where the prevalence of T. cruzi infection was not very high, were the main producers of the Chagas disease literature, after adjusting for economic and population indexes. The countries with more estimated cases of Chagas disease produced less research on Chagas disease than some developed countries.

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

    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. PMID:26513769

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

    Guillermo Moscatelli

    2015-08-01

    Full Text Available 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 cruziinfection 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.

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

    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, transcript...

  17. Aortic distensibility measured by pulse-wave velocity is not modified in patients with Chagas' disease

    Arteaga Edmundo

    2006-06-01

    Full Text Available Abstract Background Experimental studies demonstrate that infection with trypanosoma cruzi causes vasculitis. The inflammatory lesion process could hypothetically lead to decreased distensibility of large and small arteries in advanced Chagas' disease. We tested this hypothesis. Methods and results We evaluated carotid-femoral pulse-wave velocity (PWV in 53 Chagas' disease patients compared with 31 healthy volunteers (control group. The 53 patients were classified into 3 groups: 1 16 with indeterminate form of Chagas' disease; 2 18 with Chagas' disease, electrocardiographic abnormalities, and normal systolic function; 3 19 with Chagas' disease, systolic dysfunction, and mild-to-moderate congestive heart failure. No difference was noted between the 4 groups regarding carotid-femoral PWV (8.4 ± 1.1 vs 8.2 ± 1.5 vs 8.2 ± 1.4 vs 8.7 ± 1.6 m/s, P = 0.6 or pulse pressure (39.5 ± 7.6 vs 39.3 ± 8.1 vs 39.5 ± 7.4 vs 39.7 ± 6.9 mm Hg, P = 0.9. A positive, significant, similar correlation occurred between PWV and age in patients with Chagas' disease (r = 0.42, P = 0.002, in controls (r = 0.48, P = 0.006, and also between PWV and systolic blood pressure in both groups (patients with Chagas' disease, r = 0.38, P = 0.005; healthy subjects, r = 0.36, P = 0.043. Conclusion Carotid femoral pulse-wave velocity is not modified in patients with Chagas' disease, suggesting that elastic properties of large arteries are not affected in this disorder.

  18. Geographic Distribution of Chagas Disease Vectors in Brazil Based on Ecological Niche Modeling

    Rodrigo Gurgel-Gonçalves

    2012-01-01

    Full Text Available Although Brazil was declared free from Chagas disease transmission by the domestic vector Triatoma infestans, human acute cases are still being registered based on transmission by native triatomine species. For a better understanding of transmission risk, the geographic distribution of Brazilian triatomines was analyzed. Sixteen out of 62 Brazilian species that both occur in >20 municipalities and present synanthropic tendencies were modeled based on their ecological niches. Panstrongylus geniculatus and P. megistus showed broad ecological ranges, but most of the species sort out by the biome in which they are distributed: Rhodnius pictipes and R. robustus in the Amazon; R. neglectus, Triatoma sordida, and T. costalimai in the Cerrado; R. nasutus, P. lutzi, T. brasiliensis, T. pseudomaculata, T. melanocephala, and T. petrocchiae in the Caatinga; T. rubrovaria in the southern pampas; T. tibiamaculata and T. vitticeps in the Atlantic Forest. Although most occurrences were recorded in open areas (Cerrado and Caatinga, our results show that all environmental conditions in the country are favorable to one or more of the species analyzed, such that almost nowhere is Chagas transmission risk negligible.

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

    Pedro Emmanuel Alvarenga Americano do Brasil

    2016-06-01

    Full Text Available Abstract: INTRODUCTION 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. METHODS 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. RESULTS 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. CONCLUSIONS: 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.

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

    José Rodrigues Coura

    2012-06-01

    Full Text Available 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.

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

    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

  2. Evaluation of the rabbit as a model for Chagas disease - II: histopathologic studies of the heart, digestive tract and skeletal muscle

    Arnaldo Moreira da Silva; Luiz Eduardo Ramirez; Marlene Vargas; Edmundo Chapadeiro; Zigman Brener

    1996-01-01

    In order to investigate the value of the rabbit as an experimental model for Chagas' disease, seventy one animals were inoculated with different Trypanosoma cruzi strains and routes. The rabbits were submitted to necropsy in acute (earlier than three months of infection), recent chronic (three to six months) and late chronic (later than six months) phases. Myocarditis, generally focal and endomysial, occurred in 94.1%, 66.7% and 70.8% of the infected rabbits respectively in the acute, recent ...

  3. Melatonin in Chagas´ disease: Possible therapeutic value La melatonina en la enfermedad de Chagas: Su posible valor terapéutico

    Daniel P. Cardinali

    2011-10-01

    Full Text Available 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.La enfermedad de Chagas es un problema grave de salud en América Latina, causando cerca de 50 000 muertes al año y unos 18 millones de infectados. Alrededor del 25-30% de los pacientes infectados con Trypanosoma cruzi desarrollan la forma crónica de la enfermedad. La respuesta de defensa ante el T. cruzi depende de la inmunidad innata y adquirida con la participación de macrófagos, células “natural killer”, linfocitos T y B, y la producción de citoquinas proinflamatorias de tipo Th-1. Además, el aumento en la producción de óxido nítrico (NO en los macrófagos lleva a una acci

  4. Viability study of a multiplex diagnostic platform for Chagas disease.

    Foti, Leonardo; Fonseca, Bruna de Paula Fonseca e; Nascimento, Lilian Dias; Marques, Christiane de Fatima Silva; da Silva, Edmilson Domingos; Duarte, Cesar Augusto Barros; Probst, Christian M; Goldenberg, Samuel; Pinto, Antônio Gomes; Krieger, Marco Aurélio

    2009-07-01

    A new multiplex assay platform was evaluated to detect Trypanosoma cruzi infection using the recombinant antigens CRA, FRA, CRAFRA fusion and parasite lysate. The antigens presented different sensitivity and specificity in a singleplex test when compared to a serial dilution of two pools comprising 10 positive serum samples and one pool of 10 negative samples. The recombinant protein CRA presented lower sensitivity (55%) in contrast to the 100% specificity and sensitivity of FRA, CRAFRA and T. cruzi lysate. These antigens also showed good results in a duplex test and the duplex test with CRAFRA/T. cruzi lysate showed better performance with 100% specificity and sensitivity, as well as a lower cut-off value in comparison to the other duplex test, FRA/T. cruzi lysate. Hence, when the antigens were used in duplex format, both tests showed decreased cut-off values and no interference between different bead sets, resulting in increasing sensitivity and specificity. The results of these multiplex tests show that they could be an alternative to singleplex detection for Chagas disease, and also indicate the necessity of using multiplex diagnostic tools to increase the sensitivity and specificity for diagnostic tests. Emerging data from the T. cruzi genome and from its ORFeome project will also allow the identification of new antigens for this disease detection application. PMID:19753468

  5. Viability study of a multiplex diagnostic platform for Chagas disease

    Leonardo Foti

    2009-07-01

    Full Text Available A new multiplex assay platform was evaluated to detect Trypanosoma cruzi infection using the recombinant antigens CRA, FRA, CRAFRA fusion and parasite lysate. The antigens presented different sensitivity and specificity in a singleplex test when compared to a serial dilution of two pools comprising 10 positive serum samples and one pool of 10 negative samples. The recombinant protein CRA presented lower sensitivity (55% in contrast to the 100% specificity and sensitivity of FRA, CRAFRA and T. cruzi lysate. These antigens also showed good results in a duplex test and the duplex test with CRAFRA/T. cruzi lysate showed better performance with 100% specificity and sensitivity, as well as a lower cut-off value in comparison to the other duplex test, FRA/T. cruzi lysate. Hence, when the antigens were used in duplex format, both tests showed decreased cut-off values and no interference between different bead sets, resulting in increasing sensitivity and specificity. The results of these multiplex tests show that they could be an alternative to singleplex detection for Chagas disease, and also indicate the necessity of using multiplex diagnostic tools to increase the sensitivity and specificity for diagnostic tests. Emerging data from the T. cruzi genome and from its ORFeome project will also allow the identification of new antigens for this disease detection application.

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

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

    2012-01-01

    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 wit...

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

    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

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

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

    2013-02-01

    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

  9. Chagas Disease Vector Control in Tupiza, Southern Bolivia

    G Guillen

    1997-01-01

    Full Text Available 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

  10. Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

    Luiz Fernando Junqueira Junior

    2012-04-01

    Full Text Available INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

  11. Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries

    Moncayo Alvaro

    2003-01-01

    Full Text Available Chagas disease, named after Carlos Chagas who first described it in 1909, exists only on the American Continent. It is caused by a parasite, Trypanosoma cruzi, transmitted to humans by blood-sucking triatomine bugs and by blood transfusion. Chagas disease has two successive phases, acute and chronic. The acute phase lasts 6 to 8 weeks. After several years of starting the chronic phase, 20% to 35% of the infected individuals, depending on the geographical area will develop irreversible lesions of the autonomous nervous system in the heart, esophagus, colon and the peripheral nervous system. Data on the prevalence and distribution of Chagas disease improved in quality during the 1980's as a result of the demographically representative cross-sectional studies carried out in countries where accurate information was not available. A group of experts met in Brasília in 1979 and devised standard protocols to carry out countrywide prevalence studies on human T. cruzi infection and triatomine house infestation. Thanks to a coordinated multi-country program in the Southern Cone countries the transmission of Chagas disease by vectors and by blood transfusion has been interrupted in Uruguay in1997, in Chile in 1999, and in 8 of the 12 endemic states of Brazil in 2000 and so the incidence of new infections by T. cruzi in the whole continent has decreased by 70%. Similar control multi-country initiatives have been launched in the Andean countries and in Central America and rapid progress has been recorded to ensure the interruption of the transmission of Chagas disease by 2005 as requested by a Resolution of the World Health Assembly approved in 1998. The cost-benefit analysis of the investments of the vector control program in Brazil indicate that there are savings of US$17 in medical care and disabilities for each dollar spent on prevention, showing that the program is a health investment with good return. Since the inception in 1979 of the Steering

  12. [José Lima Pedreira de Freitas and the redefinition and control of Chagas disease].

    Rocha, Juan Stuardo Yazlle

    2016-08-01

    A brief overview of the evolution of knowledge about Chagas disease since its discovery by Carlos Chagas in 1909 until the mid-1940s is presented. The trajectory of physician Pedreira de Freitas and his growing involvement in research in the area led to his contributions to laboratory diagnosis - which lent consistency and security to epidemiological surveys of Chagas disease - and the redefinition of the scale of the disease in Brazil and the Americas with its terrible social and economic impact. His proposal for the disease prevention model - based on selective purging in the application of insecticide - was adopted nationally and internationally and made it possible to bring the disease under control in Brazil and other countries. He devoted himself with equal intensity to enhancing the teaching of medical practices in the community and was a pioneer in the implementation of preventive medicine in medical education in Brazil. PMID:27557035

  13. Scintigraphy for the detection of myocardial damage in the indeterminate form of Chagas disease

    Pedroso, Enio Roberto Pietra; Rezende, Nilton Alves de, E-mail: narezende@terra.com.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Abuhid, Ivana Moura [Instituto de Medicina Nuclear e Diagnostico Molecular, Belo Horizonte, MG (Brazil)

    2010-07-15

    Background: non-invasive cardiological methods have been used for the identification of myocardial damage in Chagas disease. Objective: to verify whether the rest/stress myocardial perfusion scintigraphy is able to identify early myocardial damage in the indeterminate form of Chagas disease. Methods: eighteen patients with the indeterminate form of Chagas Disease and the same number of normal controls, paired by sex and age, underwent rest/stress myocardial scintigraphy using sestamibi-99mTc, aiming at detecting early cardiac damage. Results: the results did not show perfusion or ventricular function defects in patients at the indeterminate phase of Chagas disease and in the normal controls, except for a patient who presented signs of ventricular dysfunction in the myocardial perfusion scintigraphy with electrocardiographic gating. Conclusion: the results of this study, considering the small sample size, showed that the rest/stress myocardial scintigraphy using sestamibi-99mTc is not an effective method to detect early myocardial alterations in the indeterminate form of Chagas disease (author)

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

    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. PMID:27044564

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

    Jennifer M Manne

    Full Text Available 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

  16. Study of the hypothalamic - hypophyseal - thyroid axis by the administration of TRH to Chagas' disease patients

    The TSH and T3 response to synthetic TRH was evaluated in two groups of patients: normal and with Chagas' disease, from the urban area of Sao Paulo (Brazil). Plasma T4, PBI and TSH values were within the normal range, when compared with those found in the controls: So were the thyroid uptakes of 2 and 24 hours; the basal levels of T3 where within the normal range except in three subjects whose values were higher than normal. After TRH administration the amount of TSH secretion in patients with Chagas' disease was increased when compared to normal ones, while T3 secretion was unaltered. It is suggested that in the Chagas' disease there is an increase in the pituitary TSH, while the thyroid reserve is preserved. This increase could be due to a difference in the regulation rate of TRH, which is determined by the neuronal degeneration caused by the disease itself. (author)

  17. Antigenicity and Diagnostic Potential of Vaccine Candidates in Human Chagas Disease

    Shivali Gupta; Xianxiu Wan; Zago, Maria P.; Martinez Sellers, Valena C.; Silva, Trevor S.; Dadjah Assiah; Monisha Dhiman; Sonia Nuñez; Petersen, John R; Vázquez-Chagoyán, Juan C.; Jose G Estrada-Franco; Nisha Jain Garg

    2013-01-01

    BACKGROUND: Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease. METHODS AND RESULTS: Sera samples f...

  18. Congenital Chagas disease of second generation in Santiago, Chile. Report of two cases

    SCHENONE Hugo

    2001-01-01

    Full Text Available Congenital Chagas disease (CChD has been reported in different countries, mostly in Latin America. In 1987 a fatal case of CChD of second generation (CChDSG was published. Within a period of six months - 1989-1990 - two cases of CChDSG were diagnosed and studied in the city of Santiago. Two premature newborns, sons of two sisters, with moderate liver and spleen enlargement, were found to have positive serology for Chagas disease and xenodiagnoses. The mothers, urban residents all their lives, without antecedents of triatomine bugs contact or blood transfusions, showed positive serology and xenodiagnoses. Their mother (grandmother of the infants, lived 20 years in a Northern rural Chagas disease endemic locality, in a triatomine infested house. Afterwards, she moved to Santiago, where she married and has resided up to now. Serology and xenodiagnoses were also positive. All the Trypanosoma cruzi infected individuals were successfully treated with nifurtimox.

  19. Trypanosoma cruzi, causal agent of Chagas disease: The borderline between wild and domestic cycles in Venezuela.

    Leidi eHerrera

    2014-11-01

    Full Text Available American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi, occurs between triatomine vectors and mammals, including man. T. cruzi has 150 Ma in America with almost 10 million of infected people today. The overlapping of its wild and domestic ecotopes is increasing. The host-parasite imbrications has been discerned by the study of infection patterns, transmissibility and transmission cycles in natural and laboratory models, through to parasitological and molecular tests. This article describes specific parasite niches, as plant biocenosis or biological corridors between domestic and wild ecotopes and helps distinguish Chagas disease risks and the borderline between wild and domestic transmission cycles, with emphasis on Venezuelan studies.

  20. Necroscopic study of a Chagas' disease chronic case with normal electrocardiograms

    The morphological changes in the postmortem study of a man probably with the indeterminate form of Chagas' disease are described. The heart exhibited lesions of the epicardium, myocardium and endocardium, as well as of the conduction system, primarily small inflammatory foci. There was mild fibrosis of the myocardium, atrioventricular node, and left bundle branch (at its origin). These alterations, although mild, were similar, in quality, to those described in the other chronic forms of Chagas' disease, and suggest active lesions, with a potential for further development. In the esophagus, among other features, a striking reduction of the number of neurons was observed. (author)

  1. Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection.

    Camandaroba, Edson Luiz P; Pinheiro Lima, Clarissa M; Andrade, Sonia G

    2002-01-01

    Oral transmission of Trypanosoma cruzi has been suspected when epidemic episodes of acute infection were observed in areas devoid of domiciled insect vectors. Considering that the distribution of T. cruzi biodemes differs in sylvatic and domestic cycles, results of studies on biodemes can be of interest regarding oral transmission. The infectivity of T. cruzi strains of different biodemes was tested in mice subjected to infection by the digestive route (gavage). Swiss mice were infected either with the Peruvian strain (Biodeme Type I, Z2b) or the Colombian strain (Biodeme Type III, Z1, or T. cruzi I); for control, intraperitoneal inoculation was performed in a group of mice. The Colombian strain revealed a similar high infectivity and pathogenicity when either route of infection was used. However, the Peruvian strain showed contrasting levels of infectivity and pathogenicity, being high by intraperitoneal inoculation and low when the gastric route was used. The higher infectivity of the Colombian strain (Biodeme Type III) by gastric inoculation is in keeping with its role in the epidemic episodes of acute Chagas disease registered in the literature, since strains belonging to Biodeme III are most often found in sylvatic hosts. PMID:12048547

  2. Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection

    CAMANDAROBA Edson Luiz P.

    2002-01-01

    Full Text Available Oral transmission of Trypanosoma cruzi has been suspected when epidemic episodes of acute infection were observed in areas devoid of domiciled insect vectors. Considering that the distribution of T. cruzi biodemes differs in sylvatic and domestic cycles, results of studies on biodemes can be of interest regarding oral transmission. The infectivity of T. cruzi strains of different biodemes was tested in mice subjected to infection by the digestive route (gavage. Swiss mice were infected either with the Peruvian strain (Biodeme Type I, Z2b or the Colombian strain (Biodeme Type III, Z1, or T. cruzi I; for control, intraperitoneal inoculation was performed in a group of mice. The Colombian strain revealed a similar high infectivity and pathogenicity when either route of infection was used. However, the Peruvian strain showed contrasting levels of infectivity and pathogenicity, being high by intraperitoneal inoculation and low when the gastric route was used. The higher infectivity of the Colombian strain (Biodeme Type III by gastric inoculation is in keeping with its role in the epidemic episodes of acute Chagas disease registered in the literature, since strains belonging to Biodeme III are most often found in sylvatic hosts.

  3. Epidemiological characteristics of patients with Chagas Disease Características epidemiológicas dos pacientes com Doença de Chagas

    Fabíola Adriane Souza Oliveira

    2010-11-01

    Full Text Available

    The Chagas Disease is an infection caused by Trypanosoma cruzy, transmitted to a hematophague insect, transfused blood or birth, with evolution divided in acute and chronic phases. Object: Analyses variables from patients with Chagas Disease (CD: age, gender, education, prevalence, and presence of co morbid and work. Methodology: The study region is constituted by many peripheral neighborhoods from Montes Claros City- Minas Gerais- Brazil. The study was made with 7150 registered people in the local health unit (Programa Saúde da Família, Tancredo Neves. The information about Chagas Disease was obtaining from ‘A’ files, this present in virtual information program. Take a part in the study only patients with the confirmed diagnostic of Chagas Disease in two diagnostic methods different. Results: The prevalence of Chagas Disease were 1% (86 patients, 60% of cases belong of female gender. The middle age at the men was 47,5 years and the woman was 48,6 years. The main occupation were: retired 9,3%, general services 51,1%, house-wife 17,4%, unemployment 18,5%, students 1,1% and autonomous 1,1%. The analysis of schooling demonstrates: 27,9% was illiterate, 68,6% does not have completely the primary school and 2,3% has completely the second school. The co morbid more seen were the Systemic Hypertension Arterial (SHA. Conclusion: The epidemiological profile in the study site is of the an adult patient with the age between 40-50 years, female gender, with schooling low, working in general services and with SHA were the co morbid.

    A Doença de Chagas (DC é uma infecção causada pelo Trypanosoma cruzi, transmitida por um inseto hematófago, adquirida por transfusão sanguínea ou congenitamente, com evolução dividida em fase aguda e crônica. Objetivo: Analisar as seguintes variáveis dos pacientes portadores da Doença de Chagas (DC: idade, sexo, escolaridade, prevalência, comorbidades associadas e ocupação. Metodologia: A região do

  4. Irradiated T. cruzi and resistant consomic animals can be useful in Chagas disease studies

    Human Chagas disease is considered the most significant parasitic disease in Latin America. It is estimated that 16-18 million people are infected by T. cruzi. As a consequence, approximately 50,000 deaths occur every year. The acute infection usually goes unrecognized and enters into a chronic stage that persists throughout the host's life span. However, roughly 30% of infected individuals eventually will develop disease with an array of possible manifestations affecting the heart, the digestive tract, and/or the peripheral nervous system. This disease is commonly modeled in inbred mice even though mouse strains used to simulate experimental infection vary considerably. In this way, Wrightsman and Trischmann showed that chromosome 17 was directly involved in a T. cruzi resistance, showing the influence of host's genetic constitution on disease severity. Additionally, in 2003, Passos and Graefe, working separately, quantified parasite burdens in resistant and susceptible strains and applied a backcross strategy to map the genomic loci linked to susceptibility and resistance in inbred mice. The genomes of the animals were scanned with microsatellite markers and the results found by these authors showed that the resistance mechanism is polygenic and is under the control of a complex network. In the particular case of Y strain, in vivo assays indicated that survival was related to the chromosomes 7,11,14,17 and 19. In order to evaluate the influence of each isolated chromosome as well as their interactions, we employed susceptible isogenic mice to construct consomic lineages for each one of those chromosomes. The consomic strains were injected with irradiated and native forms of Y strain T. cruzi, and the infectivity parameters were evaluated by quantitative methods. Radiation caused inability of trypanosomes to infect and kill mice, when these parasites were irradiated with 1 kGy of gamma rays from a 60Co source. In this experiment we used 101, 102, 103, 104 and 105

  5. Chagas disease and globalization of the Amazon La enfermedad de Chagas y la globalización de la Amazonia

    Roberto Briceño-León

    2007-01-01

    Full Text Available 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.El incremento de casos autóctonos de la enfermedad de Chagas en la Amazonia a partir de los años setenta hace temer que pueda convertirse en un novedoso problema de salud pública en la región. Este cambio del patrón epidemiológico de la enfermedad en la región amazónica debe ser explicado por las transformaciones ambientales y sociales que han ocurrido en los pasados treinta años. Este artículo utiliza la teoría sociológica de los efectos perversos para explicar esos cambios como el resultado indeseado del cambio de modelo de desarrollo "hacia adentro", que había existido hasta los años setenta, por otro "hacia fuera" que está orientado por las fuerzas de la producción y el comercio internacional que conocemos como globalización. El art

  6. Fase aguda da doença de Chagas na Amazônia brasileira: estudo de 233 casos do Pará, Amapá e Maranhão observados entre 1988 e 2005 Acute phase of Chagas disease in the Brazilian Amazon region: study of 233 cases from Pará, Amapá and Maranhão observed between 1988 and 2005

    Ana Yecê das Neves Pinto

    2008-12-01

    Full Text Available Foram estudados 233 casos de fase aguda da doença de Chagas, oriundos do Pará, Amapá e Maranhão, observados no período de 1988 a 2005, cento e sessenta deles retrospectivamente de 1988 a 2002 e setenta e três prospectivamente de 2003 a 2005. Entre os casos estudados 78,5% (183/233 faziam parte de surtos provavelmente por transmissão oral, acometendo em média 4 pessoas e 21,5% (50/233 eram casos isolados. Foram considerados casos agudos aqueles que apresentaram exames parasitológicos diretos (a fresco, gota espessa ou Quantitative Buffy Coat - QBC e/ou IgM anti-Trypanosoma cruzi positivos. Foram feitos ainda xenodiagnósticos em 224 pacientes e hemoculturas em 213. Todos foram avaliados clinica e epidemiologicamente. As manifestações clínicas mais freqüentes foram febre (100%, cefaléia (92,3%, mialgia (84,1%, palidez (67%, dispnéia (58,4%, edema de membros inferiores (57,9%, edema de face (57,5% dor abdominal (44,2%, miocardite (39,9% e exantema (27%. O eletrocardiograma mostrou alterações de repolarização ventricular em 38,5% dos casos, baixa voltagem de QRS em 15,4% e desvio de SAQRS em 11,5%, extra-sístoles ventriculares em 5,8%, bradicardia em 5,8% e taquicardia em 5,8%, bloqueio de ramo direito em 4,8% e fibrilação atrial em 4,8%. A alteração mais freqüente vista no ecocardiograma foi o derrame pericárdico em 46,2% dos casos. Treze (5,6% pacientes evoluíram para o óbito, 10 (76,9% dos quais por comprometimento cardiovascular, dois por complicações de origem digestiva e um de causa mal definida.Two hundred and thirty-three cases of the acute phase of Chagas disease, from Pará, Amapá and Maranhão, were observed between 1988 and 2005. One hundred and sixty were studied retrospectively from 1988 to 2002 and seventy-three were prospectively followed up from 2003 to 2005. Among the cases studied, 78.5% (183/233 formed part of outbreaks, probably due to oral transmission (affecting a mean of 4 individuals, and 21

  7. Update on Chagas' disease in Mexico Actualización sobre la enfermedad de Chagas en México

    Eric Dumonteil

    1999-07-01

    Full Text Available Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, represents a major public health problem in most of the American continent. As transmission of the parasite is being interrupted in most of South America, the disease remains endemic in various areas of Mexico. We review here some of the information gathered in recent years. Seroprevalence of T. cruzi infection in humans remains relatively high in some areas, and there has been a general increase in the number of chronic cases reported to health authorities in recent years. In fact, chronic chagasic cardiomyopathy appears to be affecting a large number of patients with heart disease, but many cases may be misreported because of the unspecific nature of the clinical symptoms. Epidemiological monitoring of vector and reservoir populations, as well as of human cases is helping focus on endemic areas, but a better coordination and development of these efforts is still needed. Recent studies of parasite biology are in agreement with previous work showing the great diversity of parasite characteristics, and support the need for a regional approach to this zoonosis. Strong and continuing support from health and academic authorities is thus still needed to further improve our understanding of Chagas' disease in Mexico and implement efficient control programs.La enfermedad de Chagas, causada por el parásito protozoario Trypanosoma cruzi, constituye un importante problema de salud pública en el continente americano. La transmisión del parásito se ha ido interrumpiendo en la mayor parte de América del Sur, pero la enfermedad sigue siendo endémica en varias regiones de México. En este artículo se revisa la información más reciente sobre dicha enfermedad. La seroprevalencia de la infección por T. cruzi se ha mantenido a niveles relativamente altos en algunas regiones, y se observa un aumento general en el número de casos reportados a las autoridades de salud en los últimos a

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

    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…

  9. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

    Iván Darío BRAVO-TOBAR

    2015-10-01

    Full Text Available 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.

  10. A doença de Chagas em Minas Gerais: esbôco crítico dos trabalhos publicados até 1951 Chagas' disease in Minas Geraes: a critical sudy of the papers published up to 1951

    J. Pellegrino

    1953-12-01

    Lassance were carried out by Chagas and its co-workers of the Oswaldo Cruz Institute. During this period they described the various clinical features of the new disease, made a detailed study of its agent and the biology of the transmitting insects, and experiments and studies on the pathogeny and pathology of the disease; they developed diagnostic methods, analysed the role of domiciliary and wild reservoirs, and insistently showed the social significance of this sanitary problem. 2 The research work made on Chagas' disease in Bambuí contributed decisively for the growing interest on the study of this disease during the last few years. Although the work in Bambuí was carried out continuously since its beginning in 1940, the researches may be divided into two groups, namely the preliminary made before the installation in the mentioned city of the Center for the Study and Prophylaxis of Chagas' Disease in November 1943, and the work done after the installation of the Center. The first group represents the first contribution after the researches carried out in Lassance, towards a formal study of acute cases of Chagas' disease in the State .The finding of numerous acute cases at Bambuí led the direction of the Oswaldo Cruz Institute to create a Center of Studies in that city. An outstanding contribution on the clinical, epidemiological and prophylactic fields was brought about by investigators of Manguinhos with the abundant material supplied by the Bambuí Center. The chief contributions from Bambuí were of three kinds: a The individualization of the chronic Chagas' heart disease on clinical, anatomo-pathological, electrocardiographic and experimental basis; the demonstration of its great frequency in infected individuals and the verification that in certain rural areas schizotrypanosis is one of the most important etiological factors of heart disease. b The experience acquired with the use of the complement fixation reaction with antigens of cultures of Schizotripanum

  11. Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism

    Teixeira, A.R.L.; Gomes, C.; Nitz, N.; Sousa, A.O.; Alvez, R.M.; Guimaro, M.C.; Cordeiro, C.; Bernal, F.M.; Rosa, A.C.; Hejnar, Jiří; Leonardecz, E.; Hecht, M.M.

    2011-01-01

    Roč. 5, č. 3 (2011), e1000. ISSN 1935-2735 Institutional research plan: CEZ:AV0Z50520514 Keywords : Chagas disease * Trypanosoma cruzi * kDNA minicircles * inbred chicken Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.716, year: 2011

  12. [Serologic study of the diagnosis of Chagas disease in Nicaraguan students in the Juventud island].

    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. PMID:2518003

  13. Chagas' Disease and HIV Co-infection: Genotypic Characterization of the Trypanosoma cruzi Strain

    Pacheco Raquel S

    1998-01-01

    Full Text Available In the past few years, new aspects of the immunopathology of Chagas' disease have been described in immunosuppressed patients, such as fatal central nervous system lesions related to the reactivation of the parasite. This article is the first description of the genotypic characterization, at the strain level, of Trypanosoma cruzi isolated from a patient with Chagas` disease/AIDS co-infection. The presence of four hypodense lesions was observed in the cranial compute tomographic scan. The diagnosis of AIDS was assessed by the detection of anti-HIV antibodies using enzyme-linked immunosorbent assay (ELISA and Western blot techniques. The CD4+ lymphocyte counts were maintained under 200 cells/mm3 during one year demonstrating the severity of the state of immunosuppression. Chagas' disease was confirmed by serological and parasitological methods. Trypomastigote forms were visualized in a thick blood smear. The parasite isolated is genotypically similar to the CL strain. The paper reinforces that cerebral Chagas' disease can be considered as another potential opportunistic infection in AIDS resulting from the reactivation of a dormant T. cruzi infection acquired years earlier.

  14. Chronic phase of Chagas disease: why should it be treated? A comprehensive review

    José Rodrigues Coura

    2011-09-01

    Full Text Available The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii promote tissue regeneration to prevent fibrosis, (iii reverse existing fibrosis, (iv prevent cardiomyopathy, megaoesophagus and megacolon and (v reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

  15. Esophageal striated muscle contractions in patients with Chagas' disease and idiopathic achalasia

    R.O. Dantas

    2002-06-01

    Full Text Available Chagas' disease causes degeneration and reduction of the number of intrinsic neurons of the esophageal myenteric plexus, with consequent absent or partial lower esophageal sphincter relaxation and loss of peristalsis in the esophageal body. The impairment of esophageal motility is seen mainly in the distal smooth muscle region. There is no study about esophageal striated muscle contractions in the disease. In 81 patients with heartburn (44 with esophagitis taken as controls, 51 patients with Chagas' disease (21 with esophageal dilatation and 18 patients with idiopathic achalasia (11 with esophageal dilatation we studied the amplitude, duration and area under the curve of esophageal proximal contractions. Using the manometric method and a continuous perfusion system we measured the esophageal striated muscle contractions 2 to 3 cm below the upper esophageal sphincter after swallows of a 5-ml bolus of water. There was no significant difference in striated muscle contractions between patients with heartburn and esophagitis and patients with heartburn without esophagitis. There was also no significant difference between patients with heartburn younger or older than 50 years or between men and women or in esophageal striated muscle contractions between patients with heartburn and Chagas' disease. The esophageal proximal amplitude of contractions was lower in patients with idiopathic achalasia than in patients with heartburn. In patients with Chagas' disease there was no significant difference between patients with esophageal dilatation and patients with normal esophageal diameter. Esophageal striated muscle contractions in patients with Chagas' disease have the same amplitude and duration as seen in patients with heartburn. Patients with idiopathic achalasia have a lower amplitude of contraction than patients with heartburn.

  16. Upper esophageal sphincter pressure in patients with Chagas' disease and primary achalasia

    Dantas R.O.

    2000-01-01

    Full Text Available The most important component of the upper esophageal sphincter (UES is the cricopharyngeal muscle. During the measurement of sphincter pressure the catheter passed through the sphincter affects the pressure value. In Chagas' disease and primary achalasia there is an esophageal myenteric plexus denervation which may affect UES pressure. We measured the UES pressure of 115 patients with Chagas' disease, 28 patients with primary achalasia and 40 healthy volunteers. We used a round manometric catheter with continuous perfusion and the rapid pull-through method, performed in triplicate during apnea. Pressures were measured in four directions, and the direction with the highest pressure (anterior/posterior and the average of the four directions were measured. The highest UES pressure in Chagas' disease patients without abnormalities upon radiologic esophageal examination (N = 63 was higher than in normal volunteers (142.8 ± 47.4 mmHg vs 113.0 ± 46.0 mmHg, mean ± SD, P<0.05. There was no difference in UES pressure between patients with primary achalasia and patients with Chagas' disease and similar esophageal involvement and normal volunteers (P>0.05. There was no difference between patients with or without esophageal dilation. In the group of subjects less than 50 years of age the UES pressure of primary achalasia (N = 21 was lower than that of Chagas' disease patients with normal radiologic esophageal examination (N = 41, measured at the site with the highest pressure (109.3 ± 31.5 mmHg vs 149.6 ± 45.3 mmHg, P<0.01 and as the average of the four directions (64.2 ± 17.1 mmHg vs 83.5 ± 28.6 mmHg, P<0.05. We conclude that there is no difference in UES pressure between patients with Chagas' disease, primary achalasia and normal volunteers, except for patients with minor involvement by Chagas' disease, for whom the UES pressure at the site with the highest pressure was higher than the pressure of normal volunteers and patients with primary

  17. Effects of aspirin-triggered resolvin D1 on peripheral blood mononuclear cells from patients with Chagas' heart disease.

    Ogata, Haline; Teixeira, Maxelle Martins; de Sousa, Rodrigo Cunha; da Silva, Marcos Vinícius; Correia, Dalmo; Rodrigues Junior, Virmondes; Levy, Bruce David; de Paula Rogério, Alexandre

    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. PMID:26927755

  18. Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological Confirmation of Chagas Disease

    Granjon, Elodie; Dichtel-Danjoy, Marie-Laure; Saba, Esber; Sabino, Ester; Campos de Oliveira, Lea; Zrein, Maan

    2016-01-01

    Background Chagas disease is due to the parasite Trypanosoma cruzi, a protist disseminated by a Triatome vector. This disease is endemic to Latin America and considered by WHO as one of the 17 world’s neglected diseases. In Europe and in North America, imported cases are also detected, due to migration of population outside of the endemic region. Diagnosis of T. cruzi infection is usually made indirectly by the detection of specific antibodies to T. cruzi antigens. Following initial diagnosti...

  19. VFV as a New Effective CYP51 Structure-Derived Drug Candidate for Chagas Disease and Visceral Leishmaniasis.

    Lepesheva, Galina I; Hargrove, Tatiana Y; Rachakonda, Girish; Wawrzak, Zdzislaw; Pomel, Sébastien; Cojean, Sandrine; Nde, Pius N; Nes, W David; Locuson, Charles W; Calcutt, M Wade; Waterman, Michael R; Daniels, J Scott; Loiseau, Philippe M; Villalta, Fernando

    2015-11-01

    Sterol 14α-demethylases (CYP51) are the enzymes essential for sterol biosynthesis. They serve as clinical targets for antifungal azoles and are considered as targets for treatment of human Trypanosomatidae infections. Recently, we have shown that VNI, a potent and selective inhibitor of trypanosomal CYP51 that we identified and structurally characterized in complex with the enzyme, can cure the acute and chronic forms of Chagas disease. The purpose of this work was to apply the CYP51 structure/function for further development of the VNI scaffold. As anticipated, VFV (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide, the derivative designed to fill the deepest portion of the CYP51 substrate-binding cavity, reveals a broader antiprotozoan spectrum of action. It has stronger antiparasitic activity in cellular experiments, cures the experimental Chagas disease with 100% efficacy, and suppresses visceral leishmaniasis by 89% (vs 60% for VNI). Oral bioavailability, low off-target activity, favorable pharmacokinetics and tissue distribution characterize VFV as a promising new drug candidate. PMID:25883390

  20. Bolivian migrants with Chagas disease in Barcelona, Spain: a qualitative study of dietary changes and digestive problems.

    Posada, Elizabeth; Pell, Christopher; Angulo, Nataly; Pinazo, María Jesús; Gimeno, Faust; Elizalde, Ignasi; Gysels, Marjolein; Muñoz, Jose; Pool, Robert; Gascón, Joaquim

    2011-12-01

    Due to international migration, Chagas disease, endemic in Latin America, has become more common in non-endemic areas. Chronic Chagas disease can cause damage to the digestive system leading to constipation. However, a range of factors influences constipation and a better understanding of the role of non-Chagas related factors is required to improve management of Chagas-related digestive problems. This study explores perceptions of constipation and changes in food and exercise habits amongst Bolivians in Barcelona, Spain. Bolivian migrants attending the Tropical Medicine Unit (Hospital Clínic, Barcelona) were interviewed about their food habits in Spain and Bolivia, migratory experience, work and leisure activities. Chagas seropositive participants also received radiological examinations. Bolivian migrants experienced dietary changes, influenced by work-related factors, which included reductions in quantities of food and liquid consumed. Almost half the participants reported changes in digestive rhythm since arriving in Spain. Constipation, which was common, in some cases was only recounted during interviews. Bolivian migrants' constipation may be associated with chronic Chagas disease or migration-related dietary changes. Careful questioning using the Rome III criteria is however required to ensure its diagnosis. Radiological studies are also required to confirm the role of Chagas disease and identify potentially serious intestinal damage. PMID:24038501

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

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

    2016-05-01

    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

  2. A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera)

    Ribeiro, J.M.C.; Schwarz, Alexandra; Francischetti, I.M.B.

    2015-01-01

    Roč. 52, č. 3 (2015), s. 351-358. ISSN 0022-2585 R&D Projects: GA MŠk LH12002; GA ČR GPP302/11/P798 Institutional support: RVO:60077344 Keywords : Chagas disease * vector biology * saliva ry gland * transcriptome * medical entomology Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 1.953, year: 2014

  3. The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

    Milena B. P. Soares; LAIN PONTES-DE-CARVALHO; RICARDO RIBEIRO-DOS-SANTOS

    2001-01-01

    Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC), the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstit...

  4. Biology, diversity and strategies for the monitoring and control of triatomines - Chagas disease vectors

    Jane Costa; Marcelo Lorenzo

    2009-01-01

    Despite the relevant achievements in the control of the main Chagas disease vectors Triatoma infestans and Rhodnius prolixus, several factors still promote the risk of infection. The disease is a real threat to the poor rural regions of several countries in Latin America. The current situation in Brazil requires renewed attention due to its high diversity of triatomine species and to the rapid and drastic environmental changes that are occurring. Using the biology, behaviour and diversity of ...

  5. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas

    Péneau, Julie; Nguyen, Anne; 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 triato-mines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status an...

  6. A scientometric evaluation of the Chagas disease implementation research programme of the PAHO and TDR.

    Ana Laura Carbajal-de-la-Fuente

    2013-11-01

    Full Text Available 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.

  7. La enfermedad de Chagas en las Américas: una perspectiva de ecosalud Chagas disease in the Americas: an ecohealth perspective

    Roberto Briceño-León

    2009-01-01

    Full Text Available El proceso de transmisión de la enfermedad de Chagas ha estado históricamente relacionado con los patrones de ocupación territorial de los asentamientos humanos. En las áreas rurales puede ocurrir más fácilmente el encuentro del vector, los agentes patógenos y los seres humanos, por las condiciones de la vivienda y la pobreza existente en estas zonas. Los procesos migratorios permanentes o estacionales han jugado un papel igualmente importante en el transporte de los vectores y en la infección de la población en las zonas urbanas. Las nuevas fronteras agrícolas del Amazonas se han establecido nuevas áreas de transmisión de la enfermedad. La atención dada a los bancos de sangre ha permitido disminuir la transmisión transfusional, pero la inmigración internacional ha cambiado la situación epidemiológica, pues en Estados Unidos y España viven miles de enfermos que habían sido infectados décadas antes y no encuentran adecuada atención. Los avances en el conocimiento y el control de la enfermedad son mostrados en el artículo, señalando las limitaciones existentes en cuanto al mejoramiento de las condiciones ambientales y de vivienda de los pobres.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

  8. Brain Chagas'disease: increasing differential diagnosis of brain mass in immunosuppressed patients - a case report and literature revision

    The authors present a case of Chagas'disease as tumor-like lesion of the brain, in a patient with Aids, simulating the lesions most frequently found in these patients, as toxoplasmosis, lymphoma and cryptococcosis. Furthermore, the case reported have peculiarity to be the only with lesion documented in cerebellum, and unusual due to be secondary by reactivation of chronic Chagas disease. Moreover, emphasize analysis of cerebrospinal fluid with realization of sorologic tests to Chagas's disease, as simple as effective method, to make use of biopsy with stereotaxia in unfinished cases and bad evolution. Finally, after a wide world literature review about Chagas'disease as a tumor-like lesion of the brain, emphasizing this publication as the first written in a radiology journal of specialty. (author). 40 refs., 3 figs., 1 tab

  9. Discrepancies and consequences of indirect hemagglutination, indirect immunofluorescence and Elisa tests for the diagnosis of Chagas disease

    Regina Maia de Souza; Vicente Amato Neto

    2012-01-01

    Using the indirect hemagglutination (IH), indirect immunofluorescence (IIF) and enzyme linked immunosorbent assay (ELISA) tests for the diagnosis of Chagas disease, 4000 serum samples were examined. This study was conducted with different purposes: clinical interest, research support and parasitological monitoring of those patients with Chagas disease who were treated with heart transplantations. The tests occurred without patient selection and in accordance with the medical requests. The res...

  10. Chagas' disease in the Brazilian Amazon: I - a short review Doença de Chagas na Amazônia Brasileira: I. revisão

    José Rodrigues Coura; Angela Cristina Verissimo Junqueira; Cristina Maria Giordano; Ilra Renata Komoda Funatsu

    1994-01-01

    At least eighteen species of triatominae have been found in the Brazilian Amazon, nine of them naturally infected with Trypanosoma cruzi or "cruzi-like" trypanosomes and associated with numerous wild reservoirs. Despite the small number of human cases of Chagas' disease described to date in the Brazilian Amazon the risk that the disease will become endemic in this area is increasing for the following reasons: a) uncontrolled deforestation and colonization altering the ecological balance betwe...

  11. A therapeutic nanoparticle vaccine against Trypanosoma cruzi in a BALB/c mouse model of Chagas disease.

    Barry, Meagan A; Wang, Qian; Jones, Kathryn M; Heffernan, Michael J; Buhaya, Munir H; Beaumier, Coreen M; Keegan, Brian P; Zhan, Bin; Dumonteil, Eric; Bottazzi, Maria Elena; Hotez, Peter J

    2016-04-01

    Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system. PMID:26890466

  12. Chagas Disease in a Non-endemic Country: A Multidisciplinary Research, Bologna, Italy.

    Di Girolamo, Chiara; Martelli, Giulia; Ciannameo, Anna; Vocale, Caterina; Fini, Marco; Stefanini, Angelo; Landini, Maria Paola; Viale, Pierluigi; Verucchi, Gabriella

    2016-06-01

    Global processes have brought about a substantial change in the epidemiological landscape of Chagas disease, spreading it to non-endemic areas. Italy is the second country in Europe in terms of Latin American migrants and expected infection rate. Given that scenario, the Bologna University Teaching Hospital undertaken a study aimed at providing preliminary data on the prevalence and investigating the knowledge and the subjective perceptions of Chagas disease, migration pathways and other relevant ill-health experiences. A cross-sectional study was undertaken in association with an ethnographic research. Between November 2010 and May 2013 Chagas disease testing was offered to people who attended the hospital and data were collected to investigate the broader socio-demographic and cultural factors. 151 individuals were screened for anti T. cruzi antibodies; 12 of them, 10 Bolivians and 2 Argentinians, were seroreactive, resulting in an overall prevalence of 7.94 %. Both the quantitative and the qualitative analysis revealed a degree of heterogeneity in terms of knowledge and perceptions of the disease as well as of migration pathways. The results are comparable with those reported by previous studies with similar characteristics and highlight the relevance of such public health issue in a non-endemic context. Moreover, the interdisciplinary approach has greatly helped to unveil the complex social and cultural implications of Chagas disease, to explain the subjective ill-health experiences, and to understand the ways in which the broader socio-economic and cultural context affects an intervention and its potential for success or failure. PMID:25935443

  13. Assessment and epidemiology of Chagas' disease in patients treated in Araguaina - Tocantins; Avaliacao e epidemiologia da cardiopatia chagasica em pacientes atendidos em Araguaina - Tocantins

    Correa, Valeria Rita

    2010-07-01

    Chagas disease (AD) was described by Carlos Chagas in 1909. It is caused by a parasite T. cruzi, transmitted by bugs, by blood transfusion, vertical and orally. The DC has two phases: acute and chronic. The evolution to the cardiac form occurs in about 30% of chronic cases and is the largest cause of mortality in chronic Chagas disease. The aim of this study was to Chagas' disease in patients of Tocantins, compared with other heart patients and asymptomatic from the standpoint of non-invasive exams using radiant energies such as echocardiography and ECG and RX. The descriptive study included 80 patients, 20 chronic form of Chagas disease, 20 indeterminate, 20 with other heart diseases, and 20 controls. There was a prevalence of 9.5% of chagasic patients treated in outpatient cardiology at Araguaina Tocantins, and 7.3% in chronic and 2.21% in the indeterminate. Of the chronic patients in the study 50% had mega esophagus and megacolon 4 (20%). Most patients had no family history of AD, nor was a smoker or drinker. Major electrocardiographic abnormalities found refer to driving. The evaluation of ICT, the chronic chagasic showed that increased by 40% of patients, 40% had esophageal changes and 20% of patients had megacolon s. The echocardiogram was abnormal in 42%). 27% of patients had EF below 55% changed. Changes in segmental contractility and Asynchrony septum were found in 80% of chronic Chagas disease. In 80% of the patients was observed diastolic dysfunction. The valvular changes occurred in 75%. Electrocardiographic abnormalities occurred in 80% of patients with CCC, while the other heart had ECG changes. Arterial hypertension had an incidence of 45% in patients with CCC and 40% in FCI. The systolic and diastolic ventricular dysfunction was more prevalent in groups that had an abnormal ECG and arrhythmia. Observed that the group of chagasic decreased ejection fraction is correlated to a higher incidence of arrhythmias besides diastolic dysfunction and

  14. Mode of death on Chagas heart disease: comparison with other etiologies. a subanalysis of the REMADHE prospective trial.

    Silvia M Ayub-Ferreira

    Full Text Available 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.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.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.ClinicalTrials.gov NCT00505050 (REMADHE.

  15. Population differentiation of the Chagas disease vector Triatoma maculata (Erichson, 1848) from Colombia and Venezuela.

    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. PMID:27232127

  16. Chagas disease: from bush to huts and houses. Is it the case of the Brazilian amazon?

    José Rodrigues Coura

    1999-09-01

    Full Text Available Two of the major problems facing the Amazon - human migration from the other areas and uncontrolled deforestation - constitute the greatest risk for the establishment of endemic Chagas disease in this part of Brazil. At least 18 species of triatomines had been found in the Brazilian Amazon, 10 of them infected with Trypanosoma cruzi, associated with numerous wild reservoirs. With wide-range deforestation, wild animals will perforce be driven into other areas, with tendency for triatomines to become adapted to alternative food sources in peri and intradomicilies. Serological surveys and cross-sectional studies for Chagas disease, carried out in rural areas of the Rio Negro, in the Brazilian Amazon, showed a high level of seropositivity for T. cruzi antibodies. A strong correlation of seroreactivity with the contact of gatherers of piaçava fibers with wild triatomines could be evidenced.

  17. [Urbanization of chagas disease in Peru: experiences in prevention and control].

    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. PMID:25123876

  18. Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in chagas disease patients.

    Tomas Duffy

    Full Text Available 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 10(6 and 10(7 for Silvio X10 cl1 (T. cruzi I and Cl Brener stocks (T. cruzi IIe, respectively, an efficiency of 99%, and a coefficient of determination (R(2 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.

  19. Exposure to Citral, Cinnamon and Ruda Disrupts the Life Cycle of a Vector of Chagas Disease

    C. I. Abramson; E. Aldana; E. Sulbaran

    2007-01-01

    The main vector of Chagas disease in Venezuela was exposed to the odors of citral, cinnamon and ruda. Cinnamon was found to stop the life cycle of Rhodnius prolixus relative to untreated animals. Citral and ruda also influenced the life cycle but not to the extent of animals exposed to cinnamon. We suggest that future research be directed toward using cinnamon in field and toxicity tests.

  20. PREVALENCE OF CHAGAS DISEASE IN A RURAL AREA IN THE STATE OF CEARA, BRAZIL

    Erlane Chaves FREITAS; Maria de Fátima OLIVEIRA; Mônica Coelho ANDRADE; VASCONCELOS, Arduina Sofia Ortet de Barros; José Damião da SILVA FILHO; CÂNDIDO, Darlan da Silva; PEREIRA, Laíse dos Santos; João Paulo Ramalho CORREIA; José Napoleão Monte da CRUZ; Cavalcanti, Luciano Pamplona de Góes

    2015-01-01

    SUMMARY Chagas disease is caused by Trypanosoma cruzi and affects about two to three million people in Brazil, still figuring as an important public health problem. A study was conducted in a rural area of the municipality of Limoeiro do Norte - CE, northeastern Brazil, aiming to determine the prevalence of T. cruzi infection. Of the inhabitants, 52% were examined, among whom 2.6% (4/154) were seropositive in at least two serological tests. All seropositive individuals were older than 50 year...

  1. Irradiated T. cruzi and resistant consomic animals can be useful in Chagas disease studies

    Dias, Viviane Liotti; Passos, Luiz Augusto Correa; Salgado, Andreia Ruis [Universidade Estadual de Campinas, SP (Brazil). Centro Multidisciplinar para a Investigacao Biologica (CEMIB/UNICAMP)], e-mail: viviliotti@cemib.unicamp.br; Spencer, Patrick Jack; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Human Chagas disease is considered the most significant parasitic disease in Latin America. It is estimated that 16-18 million people are infected by T. cruzi. As a consequence, approximately 50,000 deaths occur every year. The acute infection usually goes unrecognized and enters into a chronic stage that persists throughout the host's life span. However, roughly 30% of infected individuals eventually will develop disease with an array of possible manifestations affecting the heart, the digestive tract, and/or the peripheral nervous system. This disease is commonly modeled in inbred mice even though mouse strains used to simulate experimental infection vary considerably. In this way, Wrightsman and Trischmann showed that chromosome 17 was directly involved in a T. cruzi resistance, showing the influence of host's genetic constitution on disease severity. Additionally, in 2003, Passos and Graefe, working separately, quantified parasite burdens in resistant and susceptible strains and applied a backcross strategy to map the genomic loci linked to susceptibility and resistance in inbred mice. The genomes of the animals were scanned with microsatellite markers and the results found by these authors showed that the resistance mechanism is polygenic and is under the control of a complex network. In the particular case of Y strain, in vivo assays indicated that survival was related to the chromosomes 7,11,14,17 and 19. In order to evaluate the influence of each isolated chromosome as well as their interactions, we employed susceptible isogenic mice to construct consomic lineages for each one of those chromosomes. The consomic strains were injected with irradiated and native forms of Y strain T. cruzi, and the infectivity parameters were evaluated by quantitative methods. Radiation caused inability of trypanosomes to infect and kill mice, when these parasites were irradiated with 1 kGy of gamma rays from a {sup 60}Co source. In this experiment we used 10{sup 1

  2. Working conditions of Chagas' disease patients in a large Brazilian city

    Maria Elena Guariento

    1999-04-01

    Full Text Available This study evaluated the working conditions of Chagas' disease patients in the city of Campinas, São Paulo, focusing on two-hundred-fifty patients with steady employment and treated at the University Hospital (HC-FCM/Unicamp: 98% were working-age and 77.6% were men. The origin of the patients reflected the migratory process occurring among this population. Most of the patients had limited professional skills, while 63.6% had not finished primary school and 21.6% were illiterate. However, 63.6% were regularly employed under duly processed work contracts. Their jobs were mainly in general services (21.6% and heavy industry (21.2%. Some 55% of the patients reported a monthly income less than or equal to U$100.00, and 40.4% reported having been fired at least once during the last ten years, in 8.9% of the cases because of a diagnosis of Chagas' disease. Of the patients undergoing pre-hiring physical examinations (57.2%, 9.1% were refused, 92.3% of whom due to positive serology for T. cruzi. Finally, 78.4% reported not belonging to a labor union. The study demonstrated the precarious working conditions and discrimination experienced by workers with Chagas' disease.

  3. Positive deviance study to inform a Chagas disease control program in southern Ecuador.

    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. PMID:25807468

  4. Positive deviance study to inform a Chagas disease control program in southern Ecuador

    Claudia Nieto-Sanchez

    2015-05-01

    Full Text Available 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.

  5. Chagas disease and housing improvement in northeastern Brazil: a cross-sectional survey.

    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. PMID:25673077

  6. A Case of Vertical Transmission of Chagas Disease Contracted via Blood Transfusion in Canada

    Margaret A Fearon

    2013-01-01

    Full Text Available Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is endemic in many countries in Latin America, where infected bugs of the Triatominea subfamily carry the parasite in the gut and transmit it to humans through fecal contamination of a bite. However, vertical transmission and transmission through blood transfusion and organ transplantation is well documented. Increasing immigration from endemic countries to North America has prompted blood operators, including Canadian Blood Services and Hema Quebec, to initiate blood donor testing for Chagas antibody. In the present report, an unusual case of vertical transmission from a mother, most likely infected through blood transfusion, and detected as part of a concurrent seroprevalence study in blood donors is described.

  7. Multi-epitope proteins for improved serological detection of Trypanosoma cruzi infection and Chagas Disease.

    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 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. PMID:26658314

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

    Andréa Teixeira-Carvalho

    Full Text Available 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.

  9. Training Systems Modelers through the Development of a Multi-scale Chagas Disease Risk Model

    Hanley, J.; Stevens-Goodnight, S.; Kulkarni, S.; Bustamante, D.; Fytilis, N.; Goff, P.; Monroy, C.; Morrissey, L. A.; Orantes, L.; Stevens, L.; Dorn, P.; Lucero, D.; Rios, J.; Rizzo, D. M.

    2012-12-01

    The goal of our NSF-sponsored Division of Behavioral and Cognitive Sciences grant is to create a multidisciplinary approach to develop spatially explicit models of vector-borne disease risk using Chagas disease as our model. Chagas disease is a parasitic disease endemic to Latin America that afflicts an estimated 10 million people. The causative agent (Trypanosoma cruzi) is most commonly transmitted to humans by blood feeding triatomine insect vectors. Our objectives are: (1) advance knowledge on the multiple interacting factors affecting the transmission of Chagas disease, and (2) provide next generation genomic and spatial analysis tools applicable to the study of other vector-borne diseases worldwide. This funding is a collaborative effort between the RSENR (UVM), the School of Engineering (UVM), the Department of Biology (UVM), the Department of Biological Sciences (Loyola (New Orleans)) and the Laboratory of Applied Entomology and Parasitology (Universidad de San Carlos). Throughout this five-year study, multi-educational groups (i.e., high school, undergraduate, graduate, and postdoctoral) will be trained in systems modeling. This systems approach challenges students to incorporate environmental, social, and economic as well as technical aspects and enables modelers to simulate and visualize topics that would either be too expensive, complex or difficult to study directly (Yasar and Landau 2003). We launch this research by developing a set of multi-scale, epidemiological models of Chagas disease risk using STELLA® software v.9.1.3 (isee systems, inc., Lebanon, NH). We use this particular system dynamics software as a starting point because of its simple graphical user interface (e.g., behavior-over-time graphs, stock/flow diagrams, and causal loops). To date, high school and undergraduate students have created a set of multi-scale (i.e., homestead, village, and regional) disease models. Modeling the system at multiple spatial scales forces recognition that

  10. Chagas Disease: Challenges in Developing New Trypanocidal Lead Compounds [Doença de Chagas: Desafios no Desenvolvimento de Novas Substâncias Líderes Tripanomicidas

    Fernando de C. da Silva

    2012-03-01

    Full Text Available Chagas disease cycle was fully elucidated by Carlos Chagas in 1909, when he reported his discovery to the scientific community in two seminal papers. Today remains innumerous factors that limit its therapeutic treatment. One of them is the lack of new drugs in the market since is well known that the existing drugs are poorly active with low efficacy and considerable side effects. Nowadays, many efforts have been done in combinatorial chemistry and synthesis of new compounds searching for new lead compounds. The present review intends to show that a wide variety of synthetic strategies are being used for the preparation of pharmaceutically active compounds against several strains of T. cruzi with a range of potential clinical applications.

  11. Seroprevalence and sociocultural conditionants of Chagas disease in school aged children of marginal zones of Asunción

    Vera Ninfa I.

    1998-01-01

    Full Text Available Chagas disease is becoming a public health problem in Latin America due to the wide distribution, the high prevalence, the magnitude of the damage caused and the difficulties to control it. In Paraguay, the disease is mainly distributed in the departments of Paraguari, Cordillera and Central. Prevalence in marginal zones, where migrations from rural populations and endemic areas make possible the urbanization of the disease, has no been studied yet. This is a descriptive study with a cross-sectional sampling and a probabilistic system recruitment carried out in school aged children from marginal zones of Asuncion to determine the prevalence of Chagas' disease. Serological methods, parasite isolation and questionnaires were used to achieve the goals. Nine hundred and fifty three children were studied to determine the prevalence of Chagas' disease in marginal zones which was 1.4%.

  12. Serum-Mediated Activation of Macrophages Reflects TcVac2 Vaccine Efficacy against Chagas Disease

    Gupta, Shivali; Silva, Trevor S.; Osizugbo, Jessica E.; Tucker, Laura; Spratt, Heidi M.; Garg, Nisha J.

    2014-01-01

    Chagas disease is endemic in Latin America and an emerging infectious disease in the United States. No effective treatments are available. The TcG1, TcG2, and TcG4 antigens are highly conserved in clinically relevant Trypanosoma cruzi isolates and are recognized by B and T cells in infected hosts. Delivery of these antigens as a DNA prime/protein boost vaccine (TcVac2) elicited lytic antibodies and type 1 CD8+ T cells that expanded upon challenge infection and provided >90% control of parasit...

  13. Aptamer based, non-PCR, non-serological detection of Chagas disease biomarkers in Trypanosoma cruzi infected mice.

    Rana Nagarkatti

    Full Text Available Chagas disease affects about 5 million people across the world. The etiological agent, the intracellular parasite Trypanosoma cruzi (T. cruzi, can be diagnosed using microscopy, serology or PCR based assays. However, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. It is well documented that several parasite proteins called T. cruzi Excreted Secreted Antigens (TESA, are released into the blood of an infected host. These circulating parasite antigens could thus be used as highly specific biomarkers of T. cruzi infection. In this study, we have demonstrated that, using a SELEx based approach, parasite specific ligands called aptamers, can be used to detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer (ELA assay, similar to ELISA, was developed using biotinylated aptamers to demonstrate that these RNA ligands could interact with parasite targets. Aptamer L44 (Apt-L44 showed significant and specific binding to TESA as well as T. cruzi trypomastigote extract and not to host proteins or proteins of Leishmania donovani, a related trypanosomatid parasite. Our result also demonstrated that the target of Apt-L44 is conserved in three different strains of T. cruzi. In mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of binding compared to non-infected mice suggesting that it could detect a biomarker of T. cruzi infection. Additionally, Apt-L44 could detect these circulating biomarkers in both the acute phase, from 7 to 28 days post infection, and in the chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44 could thus be used in a qualitative ELA assay to detect biomarkers of Chagas disease.

  14. Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

    Garcia, Simone; Ramos, Carolina O.; Senra, Juliana F. V.; Vilas-Boas, Fabio; Rodrigues, Maurício M.; Campos-de-Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo; Soares, Milena B. P.

    2005-01-01

    Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2β, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of β1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy. PMID:15793134

  15. Cultivation-independent methods reveal differences among bacterial gut microbiota in triatomine vectors of Chagas disease.

    Fabio Faria da Mota

    Full Text Available 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

  16. Chronic Chagas' heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine.

    Muñoz-Saravia, Silvia Gilka; Haberland, Annekathrin; Wallukat, Gerd; Schimke, Ingolf

    2012-01-01

    Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease. PMID:21165698

  17. Chagas' disease: the rural environment and vector control in the state of São Paulo, Brazil Doença de Chagas: meio rural e controle de vetores no Estado de São Paulo, Brasil

    Dalva Marli V. Wanderley

    1993-01-01

    In the first half of this century - a period of expanding coffee cultivation - there was a close relationship between the growth of cleared spaces, the domestication of triatomines, and the establishment of Chagas' disease in the state of São Paulo. However, the initiation of control mesuares in 1950 coincided with a period characterized by a progressive reversal of the conditions that had facilitated the establishment of Chagas' disease in the first place. Alterations were taking place in th...

  18. Combining Public Health Education and Disease Ecology Research: Using Citizen Science to Assess Chagas Disease Entomological Risk in Texas.

    Rachel Curtis-Robles

    2015-12-01

    Full Text Available Chagas disease is a zoonotic parasitic disease well-documented throughout the Americas and transmitted primarily by triatomine 'kissing bug' vectors. In acknowledgment of the successful history of vector control programs based on community participation across Latin America, we used a citizen science approach to gain novel insight into the geographic distribution, seasonal activity, and Trypanosoma cruzi infection prevalence of kissing bugs in Texas while empowering the public with information about Chagas disease.We accepted submissions of kissing bugs encountered by the public in Texas and other states from 2013-2014 while providing educational literature about Chagas disease. In the laboratory, kissing bugs were identified to species, dissected, and tested for T. cruzi infection. A total of 1,980 triatomines were submitted to the program comprised of at least seven species, of which T. gerstaeckeri and T. sanguisuga were the most abundant (85.7% of submissions. Triatomines were most commonly collected from dog kennels and outdoor patios; Overall, 10.5% of triatomines were collected from inside the home. Triatomines were submitted from across Texas, including many counties which were not previously known to harbor kissing bugs. Kissing bugs were captured primarily throughout April-October, and peak activity occurred in June-July. Emails to our dedicated account regarding kissing bugs were more frequent in the summer months (June-August than the rest of the year. We detected T. cruzi in 63.3% of tested bugs.Citizen science is an efficient approach for generating data on the distribution, phenology, and infection prevalence of kissing bugs-vectors of the Chagas disease parasite-while educating the public and medical community.

  19. Training the Next Generation of Scientists: System Dynamics Modeling of Chagas Disease (American Trypanosomiasis) transmission.

    Goff, P.; Hulse, A.; Harder, H. R.; Pierce, L. A.; Rizzo, D.; Hanley, J.; Orantes, L.; Stevens, L.; Justi, S.; Monroy, C.

    2015-12-01

    A computational simulation has been designed as an investigative case study by high school students to introduce system dynamics modeling into high school curriculum. This case study approach leads users through the forensics necessary to diagnose an unknown disease in a Central American village. This disease, Chagas, is endemic to 21 Latin American countries. The CDC estimates that of the 110 million people living in areas with the disease, 8 million are infected, with as many as 300,000 US cases. Chagas is caused by the protozoan parasite, Trypanosoma cruzi, and is spread via blood feeding insect (vectors), that feed on vertebrates and live in crevasses in the walls and roofs of adobe homes. One-third of the infected people will develop chronic Chagas who are asymptomatic for years before their heart or GI tract become enlarged resulting in death. The case study has three parts. Students play the role of WHO field investigators and work collaboratively to: 1) use genetics to identify the host(s) and vector of the disease 2) use a STELLA™ SIR (Susceptible, Infected, Recovered) system dynamics model to study Chagas at the village scale and 3) develop management strategies. The simulations identify mitigation strategies known as Ecohealth Interventions (e.g., home improvements using local materials) to help stakeholders test and compare multiple optima. High school students collaborated with researchers from the University of Vermont, Loyola University and Universidad de San Carlos, Guatemala, working in labs, interviewing researchers, and incorporating mulitple field data as part of a NSF-funded multiyear grant. The model displays stable equilibria of hosts, vectors, and disease-states. Sensitivity analyses show measures of household condition and presence of vertebrates were significant leverage points, supporting other findings by the University research team. The village-scale model explores multiple solutions to disease mitigation for the purpose of producing

  20. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas.

    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. PMID:26867025

  1. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas.

    Julie Péneau

    2016-02-01

    Full Text Available 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.

  2. Advanced megaesophagus (Group III secondary to vector-borne Chagas disease in a 20-month-old infant

    Anis Rassi

    2012-04-01

    Full Text Available The authors report the case of a female infant with Group III (or Grade III megaesophagus secondary to vector-borne Chagas disease, resulting in severe malnutrition that reversed after surgery (Heller technique. The infant was then treated with the antiparasitic drug benznidazole, and the infection was cured, as demonstrated serologically and parasitologically. After follow-up of several years without evidence of disease, with satisfactory weight and height development, the patient had her first child at age 23, in whom serological tests for Chagas disease yielded negative results. Thirty years after the initial examination, the patient's electrocardiogram, echocardiogram, and chest radiography remained normal.

  3. Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

    Budni, Patrícia, E-mail: budnip@gmail.com [Universidade Federal de Santa Catarina, Florianópolis, SC (Brazil); Pedrosa, Roberto Coury [Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil); Dalmarco, Eduardo Monguilhott; Dalmarco, Juliana Bastos; Frode, Tânia Sílvia; Wilhelm, Danilo Filho [Universidade Federal de Santa Catarina, Florianópolis, SC (Brazil)

    2013-10-15

    Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. The decrease in oxidative

  4. Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

    Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. The decrease in oxidative

  5. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups

  6. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    Tassi, Eduardo Marinho, E-mail: etassi@ibest.com.br [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Continentino, Marcelo Abramoff [Hospital Frei Galvão, Guaratinguetá, SP (Brazil); Nascimento, Emília Matos do; Pereira, Basílio de Bragança [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Coppe - Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia - UFRJ, Rio de Janeiro, RJ (Brazil); Pedrosa, Roberto Coury [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2014-05-15

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups.

  7. ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

    Hasslocher-Moreno Alejandro M

    2010-11-01

    Full Text Available Abstract 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

  8. Health-related quality of life in patients with Chagas disease

    Bruna Guimarães Oliveira; Mery Natali Silva Abreu; Claudia Drummond Guimarães Abreu; Manoel Otavio da Costa Rocha; Antonio Luiz Ribeiro

    2011-01-01

    INTRODUCTION: Chagas disease (ChD) is a chronic illness related to significant morbidity and mortality that can affect the quality of life (QoL) of infected patients. However, there are few studies regarding QoL in ChD. The objectives of this study are to construct a health-related QoL (HRQoL) profile of ChD patients and compare this with a non-ChD (NChD) group to identify factors associated with the worst HRQoL scores in ChD patients. METHODS: HRQoL was investigated in 125 patients with ChD ...

  9. Impact of Helminth Infection on the Clinical and Microbiological Presentation of Chagas Diseases in Chronically Infected Patients

    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

  10. Evaluation of the Chagas Disease Control Program in Açucena Municipality, Rio Doce Valley, State of Minas Gerais, Brazil

    Adriana dos Santos

    2014-04-01

    Full Text Available Introduction 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. Methods 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. Results 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. Conclusions 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.

  11. Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva, Switzerland.

    Yves Jackson

    Full Text Available BACKGROUND: Migration of Latin Americans to the USA, Canada and Europe has modified Chagas disease distribution, but data on imported cases and on risks of local transmission remain scarce. We assessed the prevalence and risk factors for Chagas disease, staged the disease and evaluated attitudes towards blood transfusion and organ transplant among Latin American migrants in Geneva, Switzerland. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included all consecutive Latin American migrants seeking medical care at a primary care facility or attending two Latino churches. After completing a questionnaire, they were screened for Chagas disease with two serological tests (Biomérieux ELISA cruzi; Biokit Bioelisa Chagas. Infected subjects underwent a complete medical work-up. Predictive factors for infection were assessed by univariate and multivariate logistic regression analysis.1012 persons (females: 83%; mean age: 37.2 [SD 11.3] years, Bolivians: 48% [n = 485] were recruited. 96% had no residency permit. Chagas disease was diagnosed with two positive serological tests in 130 patients (12.8%; 95%CI 10.8%-14.9%, including 127 Bolivians (26.2%; 95%CI 22.3%-30.1%. All patients were in the chronic phase, including 11.3% with cardiac and 0.8% with digestive complications. Predictive factors for infection were Bolivian origin (OR 33.2; 95%CI 7.5-147.5, reported maternal infection with T. cruzi (OR 6.9; 95%CI 1.9-24.3, and age older than 35 years (OR 6.7; 95%CI 2.4-18.8. While 22 (16.9% infected subjects had already donated blood, 24 (18.5% and 34 (26.2% considered donating blood and organs outside Latin America, respectively. CONCLUSIONS: Chagas disease is highly prevalent among Bolivian migrants in Switzerland. Chronic cardiac and digestive complications were substantial. Screening of individuals at risk should be implemented in nonendemic countries and must include undocumented migrants.

  12. Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

    Silvana de Araújo Silva

    2007-11-01

    Full Text Available A case-control study on chronic Chagas heart disease (CCHD was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD. Fourty-six patients (51.1% with Chagas heart disease (anomalous ECG were assigned to the case group and 44 (48.9% were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin, epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking, and clinical (systemic hypertension variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age - presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61 - and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23. Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

  13. Stairway to Heaven or Hell? Perspectives and Limitations of Chagas Disease Chemotherapy.

    Salomao, Kelly; Menna-Barreto, Rubem Figueiredo Sadok; de Castro, Solange Lisboa

    2016-01-01

    In this review, we intend to provide a general view of the evolution of experimental studies in the area of chemotherapy for Chagas disease. We can follow the process of drug development through three phases. The first phase began almost at the same time as the discovery made by Carlos Chagas and proceeds to 1970, during which time an extensive list of compounds was subjected to preclinical and clinical trials. The second phase began with the introduction of nifurtimox and benznidazole into the clinical setting, followed with the search for alternative drugs. In this phase, a dichotomy existed between rational and empirical approaches in preclinical studies. The third phase began with the unravelling of the T. cruzi genome. The development of transgenic parasites has allowed the development of solid HTS protocols, and the establishment of bioluminescent T. cruzi has allowed in vivo drug evaluations using a reduced number of animals. Among the wide variety of compounds subjected to preclinical studies, we have discovered azolic and non-azolic inhibitors of sterol C14α-demethylase (CYP51) and nitro compounds. Two compounds evaluated during the second phase, namely, MK-436 and allopurinol, could be revisited. Clinical studies of posaconazole and E1224 yielded disappointing results, and it is critical to understand the reason for their failure as a monotherapy. Currently, the combination and repositioning of drugs with different mechanisms of action are complementary approaches. The use of drug combinations, particularly those of nitro compounds with CYP51 inhibitors, is considered a real alternative for the treatment of Chagas disease. PMID:27072716

  14. Suicide risk and alcohol and drug abuse in outpatients with HIV infection and Chagas disease

    Patrícia M. Guimarães

    2014-05-01

    Full Text Available Objective: To evaluate psychiatric comorbidities in outpatients receiving care for HIV and Chagas disease at Instituto de Pesquisa Clínica Evandro Chagas (IPEC, Fundação Oswaldo Cruz (Fiocruz, Rio de Janeiro, Brazil. Methods: Cross-sectional study with a consecutive sample of 125 patients referred to an outpatient psychiatric clinic from February to December 2010. The Mini International Neuropsychiatric Interview (MINI was used. Factors associated with more frequent mental disorders were estimated by odds ratios (OR with 95% confidence intervals (95%CI by multiple logistic regression. Results: Seventy-six (60.8% patients with HIV, 40 (32% patients with Chagas disease, and nine (7.2% patients with human T-lymphotropic virus were interviewed. The majority were women (64%, with up to 8 years of formal education (56%, and unemployed (81.6%. The median age was 49 years. Suicide risk (n=71 (56%, agoraphobia (n=65 (52%, major depressive episode (n=56 (44.8%, and alcohol/drug abuse (n=43 (34.4% predominated, the latter being directly associated with lower family income (OR = 2.64; 95%CI 1.03-6.75 and HIV infection (OR = 5.24; 95%CI 1.56-17.61. Suicide risk was associated with non-white skin color (OR = 2.21; 95%CI 1.03-4.75, unemployment (OR = 2.72; 95%CI 1.01-7.34, and diagnosis of major depression (OR = 3.34; 95%CI 1.54-7.44. Conclusion: Measures targeting adverse socioeconomic conditions and psychiatric and psychological monitoring and care should be encouraged in this population, considering the association with abuse of alcohol/other psychoactive drugs and suicide risk.

  15. Acute radiation disease

    Features of clinical trends in acute period of radiation disease at personnel who suffered from Chernobyl accident are considered. The main attention is paid to the results of 10 year observation of organs, systems and metabolic processes in patients. Used therapeutic, rehabilitation and preventive actions in stationary, ambulatory and sanatorium - health resort stages are described

  16. All-around care for patients with Chagas disease: a challenge for the XXI century

    Wilson de Oliveira Jr

    2009-07-01

    Full Text Available In 1987, the University of Pernambuco's Oswaldo Cruz Hospital in Recife, Brazil opened its Chagas Disease and Heart Failure Outpatient Clinic with the aim of providing its patients all-around care through adoption of a biopsychosocial model of care. All-around care involves caring for the patient as a whole human being in the context of the biological, psychological and social factors present, which are an inherent part of the human condition. One prerequisite for the proposed model of care is the participation of a multidisciplinary team of trained technical staff committed to this framework. Although the main focus of the service is on care, teaching and research are also an important part of its work. The Pernambuco Association of Chagas Disease Patients is guided by the same model of care and has been carrying out educational activities relating to the disease, its treatment and support for patients and family members for several years. This Association plays an important role in advocating to public authorities on behalf of patients. The accumulated experience of the past 22 years has shown us that a broad vision of health care can help clinicians and policy makers to make decisions that are more in tune with the everyday reality of the patient, which in turn has a positive impact on adherence to treatment and quality of life.

  17. Chagas' disease in the Brazilian Amazon: I - a short review Doença de Chagas na Amazônia Brasileira: I. revisão

    José Rodrigues Coura

    1994-08-01

    Full Text Available At least eighteen species of triatominae have been found in the Brazilian Amazon, nine of them naturally infected with Trypanosoma cruzi or "cruzi-like" trypanosomes and associated with numerous wild reservoirs. Despite the small number of human cases of Chagas' disease described to date in the Brazilian Amazon the risk that the disease will become endemic in this area is increasing for the following reasons: a uncontrolled deforestation and colonization altering the ecological balance between reservoir hosts and wild vectors; b the adaptation of reservoir hosts of T.cruzi and wild vectors to peripheral and intradomiciliary areas, as the sole feeding alternative; c migration of infected human population from endemic areas, accompanied by domestic reservoir hosts (dogs and cats or accidentally carrying in their baggage vectors already adapted to the domestic habitat. In short, risks that Chagas' disease will become endemic to the Amazon appear to be linked to the transposition of the wild cycle to the domestic cycle in that area or to transfer of the domestic cycle from endemic areas to the Amazon.Pelo menos dezoito espécies de triatomíneos foram encontradas na Amazônia brasileira, nove das quais infectadas com Trypanosoma cruzi ou semelhante ("cruzi-like", associadas com numerosos reservatórios silvestres. A despeito do pequeno número de casos humanos da doença de Chagas descritos até agora na Amazônia brasileira, o risco que essa doença se torne endêmica é cada vez maior, pelas seguintes razões: a desmatamentos e colonização descontrolados, alterando o balanço entre reservatórios e vetores; b adaptação de reservatórios e vetores silvestres com T.cruzi ao peridomicílio, como única alternativa alimentar; c migração de populações humanas infectadas com T.cruzi acompanhadas de reservatórios domésticos (cães e gatos ou de vetores de suas regiões de origem na bagagem, já adaptados ao domicílio. Em resumo, o risco de que

  18. Gas exchange during exercise in different evolutional stages of chronic Chagas' heart disease

    Fátima Palha de Oliveira

    2000-12-01

    Full Text Available OBJECTIVE: To compare gas exchange at rest and during exercise in patients with chronic Chagas' heart disease grouped according to the Los Andes clinical/hemodynamic classification. METHODS: We studied 15 healthy volunteers and 52 patients grouped according to the Los Andes clinical/hemodynamic classification as follows: 17 patients in group IA (normal electrocardiogram/echocardiogram, 9 patients in group IB (normal electrocardiogram and abnormal echocardiogram, 14 patients in group II (abnormal electrocardiogram/echocardiogram, without congestive heart failure, and 12 patients in group III (abnormal electrocardiogram/echocardiogram with congestive heart failure. The following variables were analyzed: oxygen consumption (V O2, carbon dioxide production (V CO2, gas exchange rate (R, inspiratory current volume (V IC, expiratory current volume (V EC, respiratory frequency, minute volume (V E, heart rate (HR, maximum load, O2 pulse, and ventilatory anaerobic threshold (AT. RESULTS: When compared with the healthy group, patients in groups II and III showed significant changes in the following variables: V O2peak, V CO2peak, V ICpeak, V ECpeak, E, HR, and maximum load. Group IA showed significantly better results for these same variables as compared with group III. CONCLUSION: The functional capacity of patients in the initial phase of chronic Chagas' heart disease is higher than that of patients in an advanced phase and shows a decrease that follows the loss in cardiac-hemodynamic performance.

  19. The effect of Ageratum fastigiatum extract on Rhodnius nasutus, vector of Chagas disease

    Bethânia A. Avelar-Freitas

    2013-04-01

    Full Text Available Control of Chagas disease is based on insecticide spraying in domiciles in order to exterminate triatomine populations. However, since the vectors differ in susceptibility to currently used insecticides, the screening of the toxic potential of Brazilian flora may identify new molecules lethal to triatomines. This study evaluated the toxicity of ethanolic extract of Ageratum fastigiatum (Gardner R.M. King & H. Rob., Asteraceae, on Rhodnius nasutus, a known vector of Chagas disease. Ethanolic extracts of the aerial parts of A. fastigiatum were prepared at 25 and 50 mg/mL concentrations, and 5 µL was applied to fifth-instar nymphs of R. nasutus (n=30. Controls included nymphs that were treated with 5 µL ethanol (n=30 or left untreated (n=30. The percentage of dead insects in each group was observed at 24, 48, 72, 96 and 120 h after application. The extracts of A. fastigiatum showed a mortality rate of about 37% and 77% after 120 h, at concentrations of 25 and 50 mg/mL, respectively. In control groups, the mortality rate remained under 7%. The extract of A. fastigiatum contains a coumarin, a molecule with recognized toxicity in insects, and which may be responsible for killing the triatomines.

  20. [Epidemiological status of Chagas disease in the endemic area from Region II of Antofagasta].

    Cáceres, J; Burchard, L; Bahamonde, M I; Contreras, M C; García, A; Rojas, A; Schenone, H; Lorca, M

    1999-01-01

    During 1997 a seroepidemiological study on Chagas' disease was carried out in 18 localities of three provinces (Tocopilla, El Loa and Antofagasta) of Region II (20 degrees 56'-26 degrees South Lat.; 70 degrees 38'-67 degrees West Long.), in order to assess the impact of the control program against Triatoma infestans launched in 1988, based on insecticide spraying of dwellings. By means of ELISA and an indirect hemagglutination test for Chagas' disease blood samples from 1,034 children under 10 years of age were examined, arising a 0.5% (3 cases) positivity. Test resulted positive in 2 (0.9%) children from the locality of San Pedro de Atacama and 1 (0.4%) from Calama city, all in the age group 6-10 year-old. However, none of their dwellings were found infested with T. infestants. These results indicate that the control program has a good possibility to prevent new human infections. It is advisable to continue the seroepidemiological and entomological vigilance and remark the necessity of increasing the effort in the study of transmission through other routes, to adopt or reinforce the pertinent preventive measures. PMID:10488587

  1. Conventional serological performance in diagnosis of Chagas' disease in southern Brazil

    Anelise Bergmann Araújo

    2013-04-01

    Full Text Available Results of Chagas' disease diagnosis show disagreement. The aim of this study was to compare commercial tests for Chagas' disease serodiagnosis in southern Brazil. A total of 161 samples were evaluated. Three enzyme-linked immunosorbent assays, one indirect hemagglutination and one indirect immunofluorescence were assessed. Trypomastigote excreted-secreted antigen-blot was a confirmatory method. From 161 samples, 65.84% were positive in all tests, while 34.16% presents mismatch result in at least one of the tests. All techniques tested presented false-positive and/or false-negative results as follows: Enzyme-linked immunosorbent assay 1 had more false-positive results (lower specificity, indirect immunofluorescence had the highest rate of false-negative results (lower sen sitivity, enzyme-linked immunosorbent assays had fewer false-negative results (higher sensitivity, while indirect hemagglutination showed no false-positive result (higher specificity. Knowing the characteristics of techniques make it possible to combine them and obtain more reliable diagnosis. Therefore, it seems useful to combine techniques for diagnosing this infection.

  2. Impact of Chagas Disease in Bolivian Immigrants Living in Europe and the Risk of Stigmatization

    Rafael M. Ortí-Lucas

    2014-01-01

    Full Text Available Background. The prevalence of Chagas disease in endemic countries varies with the kind of vector involved and the socioeconomic conditions of the population of origin. Due to recent immigration it is an emerging public health problem in Europe, especially in those countries which receive immigrant populations with a high prevalence of carriers. The study reviews the impact of the disease on Bolivian immigrants living in Europe, the preventive measures and regulations applied in European countries, and their repercussion on possible stigmatization of certain population groups. Methods. The Bolivian immigrant population resident in 2012 was estimated and the affected population in different European countries was calculated with data on carrier prevalence that were recently published. The preventive measures and regulations available in Europe were also reviewed. MEDLINE-PubMed, GoPubMed, and Embase were consulted for the literature review. Results. The Bolivian immigrant population has the highest prevalence of Chagas carriers (6.7%–25% compared to the overall Latin American population (1.3%–2.4%. Only in Spain, France, Belgium, UK, Portugal, Italy, Switzerland, The Netherlands, and Germany, preventive measures are applied to this population. The established regulations are insufficient and completely different criteria are applied in the different countries and this could reflect a certain degree of stigmatization.

  3. I Latin American Guidelines for the diagnosis and treatment of Chagas' heart disease: executive summary.

    Andrade, Jadelson Pinheiro de; Marin Neto, Jose Antonio; Paola, Angelo Amato Vincenzo de; Vilas-Boas, Fábio; Oliveira, Glaucia Maria Moraes; Bacal, Fernando; Bocchi, Edimar Alcides; Almeida, Dirceu Rodrigues; Fragata Filho, Abilio Augusto; Moreira, Maria da Consolação Vieira; Xavier, Sergio Salles; Oliveira Junior, Wilson Alves de; Dias, João Carlos Pinto

    2011-06-01

    Much has been achieved in one century after Carlos Chagas' discovery. However, there is surely much to be done in the next decades. At present, we are witnessing many remarkable efforts to monitor the epidemiology of the disease, to better understand the biology of the T. cruzi and its interaction with human beings as well as the pathogenesis and pathophysiology of the complications in the chronic phase, and deal more appropriately and effectively with late cardiac and digestive manifestations. Although the vector and transfusion-derived transmission of the disease has been controlled in many countries, there remains a pressing need for sustained surveillance of the measures that led to this achievement. It is also necessary to adopt initiatives that enable appropriate management of social and medical conditions resulting from the migration of infected individuals to countries where the disease formerly did not exist. It's also necessary to standardize the most reliable methods of detection of infection with T. cruzi, not only for diagnosis purposes, but more crucially, as a cure criterion. The etiological treatment of millions of patients in the chronic stage of the disease is also to be unraveled. A renewed interest in this area is observed, including prospects of studies focusing on the association of drugs with benznidazole. We also wait for full evidence of the actual effectiveness of the etiological treatment to impact favorably on the natural history of the disease in its chronic phase. Eventually, cardiologists are primarily responsible for improving the clinical management of their patients with Chagas' disease, judiciously prescribing drugs and interventions that respect, as much as possible, the peculiar pathophysiology of the disease, wasting no plausible therapeutic opportunities. PMID:21789345

  4. Polymorphic sites at the immunoregulatory CTLA-4 gene are associated with chronic chagas disease and its clinical manifestations.

    Fabrício C Dias

    Full Text Available BACKGROUND: Chagas disease affects approximately 10 million people mainly in Latin America. The immune regulation by the host seems to be an essential factor for disease evolution, and immune system inhibitory molecules such as CTLA-4 and PD-1 favor the maintenance of peripheral tolerance. Considering that polymorphisms at the immunoregulatory CTLA-4 and PDCD1 genes may alter their inhibitory function, we investigated the association of alleles, genotypes and haplotypes of polymorphic sites observed at the CTLA-4 and PDCD1 genes with different clinical manifestations of chronic Chagas disease (indeterminate, cardiac, digestive and mixed. METHODS: The polymorphisms at the CTLA-4 (-1722T/C, -318C/T and +49A/G and PDCD1 (PD-1.3G/A genes were typed using TaqMan methodology in 277 chronic Chagas disease patients classified into four groups, according to clinical characteristics, and 326 non-infected controls. RESULTS: Our results showed that CTLA-4 -1722CC genotype (22%, -1722C allele (27% and CTLA-4 TCG (8.6%, TCA (26% and CCA (15% haplotypes were strongly associated with the indeterminate form, while the CTLA-4-318CT genotype (82% and CTLA-4-318T allele (47% were found mainly in patients with the mixed form of the disease. The CTLA-4 TCG haplotype (10.2% was associated with the digestive form. On the other hand, the PD-1.3G/A polymorphism was not associated with chronic Chagas disease and its clinical manifestations. CONCLUSIONS: Here, we showed that alleles, genotypes and haplotypes reported to increase the expression of the regulatory molecule CTLA-4 were associated with the indeterminate form of the disease. Taken together, our data support the idea that polymorphic sites at immunoregulatory genes may influence the development of Chagas disease variants.

  5. Opportunities for improved chagas disease vector control based on knowledge, attitudes and practices of communities in the yucatan peninsula, Mexico.

    Kathryn Rosecrans

    2014-03-01

    Full Text Available BACKGROUND: Chagas disease is a vector-borne parasitic disease of major public health importance. Current prevention efforts are based on triatomine vector control to reduce transmission to humans. Success of vector control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to improved vector control strategies in the Yucatan peninsula, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: We employed a sequence of qualitative and quantitative research methods to investigate knowledge, attitudes and practices surrounding Chagas disease, triatomines and vector control in three rural communities. Our combined data show that community members are well aware of triatomines and are knowledgeable about their habits. However, most have a limited understanding of the transmission dynamics and clinical manifestations of Chagas disease. While triatomine control is not a priority for community members, they frequently use domestic insecticide products including insecticide spray, mosquito coils and plug-in repellents. Families spend about $32 US per year on these products. Alternative methods such as yard cleaning and window screens are perceived as desirable and potentially more effective. Screens are nonetheless described as unaffordable, in spite of a cost comparable to the average annual spending on insecticide products. CONCLUSION/SIGNIFICANCE: Further education campaigns and possibly financing schemes may lead families to redirect their current vector control spending from insecticide products to window screens. Also, synergism with mosquito control efforts should be further explored to motivate community involvement and ensure sustainability of Chagas disease vector control.

  6. Regulatory T Cells Phenotype in Different Clinical Forms of Chagas' Disease

    Teixeira-Carvalho, Andréa; Renato Zuquim Antas, Paulo; Assis Silva Gomes, Juliana; Sathler-Avelar, Renato; Otávio Costa Rocha, Manoel; Elói-Santos, Silvana Maria; Pinho, Rosa Teixeira; Correa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis

    2011-01-01

    CD25High CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In this review, we summarize data obtained by the investigation of Treg cells in different clinical forms of Chagas' disease. Ex vivo immunophenotyping of whole blood, as well as after stimulation with Trypanosoma cruzi antigens, demonstrated that individuals in the indeterminate (IND) clinical form of the disease have a higher frequency of Treg cells, suggesting that an expansion of those cells could be beneficial, possibly by limiting strong cytotoxic activity and tissue damage. Additional analysis demonstrated an activated status of Treg cells based on low expression of CD62L and high expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. cruzi antigenic stimulation. Moreover, there was an increase in the frequency of the population of Foxp3+ CD25HighCD4+ cells that was also IL-10+ in the IND group, whereas in the cardiac (CARD) group, there was an increase in the percentage of Foxp3+ CD25High CD4+ cells that expressed CTLA-4. These data suggest that IL-10 produced by Treg cells is effective in controlling disease development in IND patients. However, in CARD patients, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient to control the progression of the disease. These data suggest that Treg cells may play an important role in controlling the immune response in Chagas' disease and the balance between regulatory and effector T cells may be important for the progression and development of the disease. Additional detailed analysis of the mechanisms on how these cells are activated and exert their function will certainly give insights for the rational design of procedure to achieve the appropriate balance between protection and pathology during parasite

  7. Health-related quality of life in patients with Chagas disease: a review of the evidence

    Giovane Rodrigo Sousa

    2015-04-01

    Full Text Available Chagas disease (ChD, a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi (T. cruzi, remains a serious public health issue in Latin America and is an emerging disease in several non-endemic countries, where knowledge of the condition and experience with its clinical management are limited. Regionally, the disease is the major cause of disability secondary to tropical diseases in young adults. Health-related quality of life (HRQoL impairment is common in patients with ChD, especially in those with Chagas dilated cardiomyopathy, the most severe manifestation of the disease, which frequently leads to heart failure. The aim of this review was to conduct a literature search for studies that have evaluated the determining factors of HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and experimental studies, as well as clinical trials that evaluated the HRQoL in ChD patients aged 18 to 60 years and are presenting an explicit description of statistical analysis. Using a combination of keywords based on Descriptors in Health Sciences (DeCS and Medical Subject Headings (MeSH for searches in PubMed and the Scientific Electronic Library Online (SciELO, 148 studies were found. After exclusions, 12 studies were selected for analysis. Three main findings were extracted from these studies: 1 cardiac involvement is associated with a worse HRQoL in ChD patients; 2 HRQoL is associated with the patients' functional capacity; and 3 simple and inexpensive therapeutic measures are effective for improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the effectiveness of non-surgical conservative treatment, and cardiac involvement are important determining factors for the HRQoL in ChD patients.

  8. The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease

    J Antonio Marin-Neto

    2009-07-01

    Full Text Available Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project - Benznidazole Evaluation for Interrupting Trypanosomiasis - is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease.

  9. Effects of an exercise program on blood pressure in patients with treated hypertension and chronic Chagas' heart disease

    Claudia Rosa de Oliveira; Andréa Silvestre de Sousa; Bráulio Santos; Paloma Hargreaves Fialho; Carla Cristiane Soares dos Santos; Juliana Rega de Oliveira; Marcus Vinícius Souza

    2012-01-01

    INTRODUCTION: Previous studies describe an imbalance of the autonomic nervous system in Chagas' disease causing increased sympathetic activity, which could influence the genesis of hypertension. However, patients undergoing regular physical exercise could counteract this condition, considering that exercise causes physiological responses through autonomic and hemodynamic changes that positively affect the cardiovascular system. This study aimed to evaluate the effects of an exercise program o...

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

    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

    Some individuals with Chagas disease develop right precordial lead ST segment elevation in response to an ajmaline challenge test, and the prevalence of right bundle branch block (RBBB) is also high in Chagas disease. Because these same electrocardiographic abnormalities occur in the Brugada syndrome, which involves genetically defective cardiac sodium channels, acquired damage to cardiac sodium channels may also occur in Chagas disease. We studied several conventional and advanced resting 12-lead/derived Frank-lead ECG parameters in 34 patients with Chagas -related heart disease (mean age 39 14 years) and in 34 age-/gender-matched healthy controls. All ECG recordings were of 5-10 min duration, obtained in the supine position using high fidelity hardware/software (CardioSoft, Houston, TX). Even after excluding those Chagas patients who had resting BBBs, tachycardia and/or pathologic arrhythmia (n=8), significant differences remained in multiple conventional and advanced ECG parameters between the Chagas and control groups (n=26/group), especially in their respective QT interval variability indices, maximal spatial QRS-T angles and low frequency HRV powers (p=0.0006, p=0.0015 and p=0.0314 respectively). In relation to the issue of potential damage to cardiac sodium channels, the Chagas patients had: 1) greater than or equal to twice the incidence of resting ST segment elevation in leads V1-V3 (n=10/26 vs. n=5/26) and of both leftward (n=5/26 versus n=0/26) and rightward (n=7/26 versus n=3/26) QRS axis deviation than controls; 2) significantly increased filtered (40-250 Hz) QRS interval durations (92.1 8.5 versus 85.3 plus or minus 9.0 ms, p=0.022) versus controls; and 3) significantly decreased QT and especially JT interval durations versus controls (QT interval: 387.5 plus or minus 26.4 versus 408.9 plus or minus 34.6 ms, p=0.013; JT interval: 290.5 plus or minus 26.3 versus 314.8 plus or minus 31.3 ms; p=0.0029). Heart rates and Bazett-corrected QTc/JTc intervals

  11. A field trial of alternative targeted screening strategies for Chagas disease in Arequipa, Peru.

    Gabrielle C Hunter

    2012-01-01

    Full Text Available BACKGROUND: Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment. METHODS: We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1 infected vectors; 2 high vector densities; 3 low vector densities; and 4 no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m around seropositive individuals, and collected data on costs of implementation for each strategy. RESULTS: Infection was detected in 21 of 923 (2.28% participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively. Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041, time lived in a rural location (OR 1.04; p = 0.022, and time lived in an infested area (OR 1.04; p = 0.008. No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others. CONCLUSIONS: Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the

  12. Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.

    Shivali Gupta

    Full Text Available BACKGROUND: Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease. METHODS AND RESULTS: Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd-phase for antibody response to the recombinant antigens (individually or mixed by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175. The IgG antibodies to TcG1, TcG2, and TcG4 (individually and TcG(mix were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%, TcG2- (96%, TcG4- (94.6% and TcG(mix- (98% based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8% in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects. CONCLUSIONS: Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.

  13. Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic, Clinical, and Serological Evolution of Chagas Disease.

    Abilio Augusto Fragata-Filho

    2016-03-01

    Full Text Available Chagas disease is one of the most important endemic parasitic diseases in Latin America. In its chronic phase, progression to cardiomyopathy has high morbidity and mortality. The persistence of a normal electrocardiogram (ECG provides a similar prognosis to that of a non-diseased population. Benznidazole (BNZ is the only drug with trypanocidal action available in Brazil.A group of 310 patients with chronic Chagas disease who had normal ECGs at the first medical visit performed before 2002 were included. There were 263 patients treated with BNZ and 47 untreated. The follow-up period was 19.59 years. Univariate analyses showed that those treated were younger and predominantly male. As many as 79.08% of those treated and 46.81% of those untreated continued with normal electrocardiograms (p <0.0001. The occurrence of electrocardiographic abnormalities and relevant clinical events (heart failure, stroke, total mortality, and cardiovascular death was less prevalent in treated patients (p <0.001, p: 0.022, p: 0.047 respectively. In multivariate analyses, the parasiticide treatment was an independent variable for persistence of a normal ECG pattern, which was an independent variable in the prevention of significant clinical events. The immunofluorescence titers decreased with the parasitological treatment. However, the small number of tests in untreated patients did not allow the correlation of the decrease of these titers with electrocardiographic alterations.These data suggest that treatment with benznidazole prevents the occurrence of electrocardiographic alterations. On the other hand, patients who develop ECG abnormalities present with more significant clinical events.

  14. Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological Confirmation of Chagas Disease

    Granjon, Elodie; Dichtel-Danjoy, Marie-Laure; Saba, Esber; Sabino, Ester; Campos de Oliveira, Lea; Zrein, Maan

    2016-01-01

    Background Chagas disease is due to the parasite Trypanosoma cruzi, a protist disseminated by a Triatome vector. This disease is endemic to Latin America and considered by WHO as one of the 17 world’s neglected diseases. In Europe and in North America, imported cases are also detected, due to migration of population outside of the endemic region. Diagnosis of T. cruzi infection is usually made indirectly by the detection of specific antibodies to T. cruzi antigens. Following initial diagnostic evaluation or screening test (qualifying or discarding blood donation), a confirmation test is performed for samples initially reactive. The test presented in this study aims at the confirmation/refutation of the infectious status of human blood samples and will permit taking appropriate clinical measures. Methodology/Principal Findings We designed a novel array of twelve antigens and printed these antigens onto 96-well plates. We tested 248 positive samples T. cruzi, 94 unscreened blood donors’ samples from non-endemic area, 49 seronegative blood donors, 7 false-positive and 3 doubtful samples. The observed reactivities were analyzed to propose a decision-tree algorithm that correctly classifies all the samples, with the potential to discriminate false-positive results and sticky samples. We observed that antibodies levels (Sum of all antigens) was significantly higher for PCR positive than for PCR negative samples in all studied groups with Multi-cruzi. Conclusion/Significance The results described in this study indicate that the Multi-cruzi improves the serological confirmation of Chagas disease. Moreover the “sum of all antigens” detected by Multi-cruzi could reflect parasitemia level in patients–like PCR signals does—and could serve as an indicator of parasite clearance in longitudinal follow-ups. Validation of this assay is still required on an independent large collection of well characterized samples including typical false-reactive samples such as

  15. Histological and endoscopic features of the stomachs of patients with Chagas disease in the era of Helicobacter pylori

    Fernanda Machado Fonseca

    2014-12-01

    Full Text Available Introduction Most studies that have evaluated the stomachs of patients with Chagas disease were performed before the discovery of Helicobacter pylori and used no control groups. This study compared the gastric features of chagasic and non-chagasic patients and assessed whether gastritis could be associated with Chagas disease. Methods Gastric biopsy samples were taken from patients who underwent endoscopy for histological analysis according to the Updated Sydney System. H. pylori infection was assessed by histology, 16S ribosomal ribonucleic acid (rRNA polymerase chain reaction (PCR, serology and the 13C-urea breath test. Patients were considered H. pylori-negative when all of these diagnostic tests were negative. Clinical and socio-demographic data were obtained by reviewing medical records and using a questionnaire. Results The prevalence of H. pylori infection (70.3% versus 71.7% and chronic gastritis (92.2% versus 85% was similar in the chagasic and non-chagasic groups, respectively; such as peptic ulcer, atrophy and intestinal metaplasia. Gastritis was associated with H. pylori infection independent of Chagas disease in a log-binomial regression model. However, the chagasic H. pylori-negative patients showed a significantly higher grade of mononuclear (in the corpus and polymorphonuclear (PMN (in the antrum cell infiltration. Additionally, the patients with the digestive form of Chagas disease showed a significantly lower prevalence of corpus atrophy than those with other clinical forms. Conclusions The prevalence of H. pylori infection and of gastric histological and endoscopic features was similar among the chagasic and non-chagasic patients. Additionally, this is the first controlled study to demonstrate that H. pylori is the major cause of gastritis in patients with Chagas disease.

  16. Chagas disease

    ... the walls Living in Central or South America Poverty Receiving a blood transfusion from a person who ... heart or digestive problems. Abnormal heart rhythms may cause sudden death. Once heart failure develops, death usually ...

  17. Modeling horizontal gene transfer (HGT in the gut of the Chagas disease vector Rhodnius prolixus

    Durvasula Ravi V

    2011-05-01

    Full Text Available Abstract Background Paratransgenesis is an approach to reducing arthropod vector competence using genetically modified symbionts. When applied to control of Chagas disease, the symbiont bacterium Rhodococcus rhodnii, resident in the gut lumen of the triatomine vector Rhodnius prolixus (Hemiptera: Reduviidae, is transformed to export cecropin A, an insect immune peptide. Cecropin A is active against Trypanosoma cruzi, the causative agent of Chagas disease. While proof of concept has been achieved in laboratory studies, a rigorous and comprehensive risk assessment is required prior to consideration of field release. An important part of this assessment involves estimating probability of transgene horizontal transfer to environmental organisms (HGT. This article presents a two-part risk assessment methodology: a theoretical model predicting HGT in the gut of R. prolixus from the genetically transformed symbiont R. rhodnii to a closely related non-target bacterium, Gordona rubropertinctus, in the absence of selection pressure, and a series of laboratory trials designed to test the model. Results The model predicted an HGT frequency of less than 1.14 × 10-16 per 100,000 generations at the 99% certainty level. The model was iterated twenty times, with the mean of the ten highest outputs evaluated at the 99% certainty level. Laboratory trials indicated no horizontal gene transfer, supporting the conclusions of the model. Conclusions The model treats HGT as a composite event, the probability of which is determined by the joint probability of three independent events: gene transfer through the modalities of transformation, transduction, and conjugation. Genes are represented in matrices and Monte Carlo method and Markov chain analysis are used to simulate and evaluate environmental conditions. The model is intended as a risk assessment instrument and predicts HGT frequency of less than 1.14 × 10-16 per 100,000 generations. With laboratory studies that

  18. Chagas disease in an area of recent occupation in Cochabamba, Bolivia

    Albarracin-Veizaga Hugo

    1999-01-01

    Full Text Available INTRODUCTION: A descriptive, entomological and seroepidemiological study on Chagas disease was conducted in a place of recent occupation on the outskirts of Cochabamba, Bolivia: Avaroa/Primer de Mayo (population:3,000, where the socio-economic level is low and no control measures have been made available. METHODS: The immunofluorescent antibody test (IFAT was used for IgG and IgM anti-Trypanosoma cruzi antibodies in filter paper bloodspot eluates from 128 subjects (73 females, 55 males selected by systematic sampling. Concerning each subject age, gender, birthplace, occupation, duration of residence and building materials used in their houses were recorded. Vectors were captured both in domestic and peridomestic environments. RESULTS: Seropositive, 12.5% (16/128: females, 15.1% (11/73; males, 9.1% (5/55. Average time of residence: 6.1 years for the whole population sample and 7.4 years for the seropositive subjects. Most houses had adobe walls (76.7% , n= 30, galvanized iron rooves (86.7% and earthen floors (53.4% 80% of the walls had crevices. One hundred forty seven specimens of Triatoma infestans were captured, of which 104 (70.7% were domestic, and 1 peridomestic Triatoma sordida. Precipitin host identification: birds, 67.5%; humans, 27.8%; rodents, 11.9%; dogs, 8.7%; cats, 1.6%. House infestation and density indices were 53.3 and 493.0 respectively. We found 21 (14.3% specimens of T. infestans infected with trypanosomes, 18 (85.7% of which in domestic environments. DISCUSSION: The elements for the vector transmission of Chagas disease are present in Avaroa/Primer de Mayo and the ancient custom of keeping guinea pigs indoors adds to the risk of human infection. In neighboring Cochabamba, due to substandard quality control, contaminated blood transfusions are not infrequent, which further aggravates the spread of Chagas disease. Prompt action to check the transmission of this infection, involving additionally the congenital and transfusional

  19. Analysis of Children's Perception of Triatomine Vectors of Chagas Disease through Drawings: Opportunities for Targeted Health Education

    Yevstigneyeva, Violetta; Camara-Mejia, Javier; Dumonteil, Eric

    2014-01-01

    Background Chagas disease is a tropical parasitic disease affecting about 10 million people, mostly in the Americas, and transmitted mainly by triatomine bugs. Insect vector control with indoor residual insecticides and the promotion of housing improvement is the main control intervention. The success of such interventions relies on their acceptance and appropriation by communities, which depends on their knowledge and perceptions of both the disease and the vector. In this study, we investig...

  20. Analysis of children's perception of triatomine vectors of chagas disease through drawings: opportunities for targeted health education.

    Violetta Yevstigneyeva; Javier Camara-Mejia; Eric Dumonteil

    2014-01-01

    Chagas disease is a tropical parasitic disease affecting about 10 million people, mostly in the Americas, and transmitted mainly by triatomine bugs. Insect vector control with indoor residual insecticides and the promotion of housing improvement is the main control intervention. The success of such interventions relies on their acceptance and appropriation by communities, which depends on their knowledge and perceptions of both the disease and the vector. In this study, we investigated school...

  1. Enfermedad de Chagas en poblaciones prehistóricas del norte de Chile Chagas disease in prehistoric populations of northern Chile

    NANCY ORELLANA-HALKYER

    2010-12-01

    Full Text Available La enfermedad de Chagas es producida por el parásito Trypanosoma cruzi, el cual afecta tanto a seres humanos como a animales, en particular mamíferos marsupiales y placentarios. Las vías de transmisión son diversas, siendo una de las más importantes la vía vectorial, en la que participan insectos infectados con este parásito, animales y humanos. En este artículo de revisión discutimos los postulados sobre la vía de transmisión oral, los hallazgos de T. cruzi en momias de América y especialmente en las del norte de Chile. Presentamos además información que apunta a que la enfermedad de Chagas estuvo presente mucho antes de la conquista europea y de la construcción de viviendas de adobe. Comentamos las hipótesis sobre el vector domiciliado más importante de Sudamérica, Triatoma infestans, su antigüedad en la costa de Arica y los reportes más recientes de otros vectores silvestres. También se discute la información relacionada a la participación en el ciclo de T. cruzi de distintos mamíferos silvestres de Chile y asimismo proponemos el estudio paleoparasitológico en restos zooarqueológicos para conocer las especies de mamíferos reservónos de T. cruzi en la antigüedad.Chagas diseases is produced by a parasite named Trypanosoma cruzi, that affects humans and other marsupial and placental mammals. Transmission routes are diverse, but the most important transmission is the vector route, which involves the triatomine insects, wild and domestic infected animáis, and humans. Here we review the data about oral transmission route and the evidences of the etiological agent (Trypanosoma cruzi of Chagas disease in pre-Columbian American mummies, making a critical review of the infection in northern Chile. Moreover, we comment on the hypotheses suggested in relation to the most important vector of the infection in South América Triatoma infestans, its antiquity in the Arica coast, and the recent reports about other wild infected

  2. Prevalence of Cardiac Arrhythmias During and After Pregnancy in Women with Chagas' Disease without Apparent Heart Disease

    Achá Renato Enrique Sologuren

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate cardiac arrhythmias during and after pregnancy in women with Chagas' disease without apparent heart disease using dynamic electrocardiography. METHODS: Twenty pregnant women with Chagas' disease without apparent heart disease aged 19 to 42 years (26.96 ± 3.6 and a control group of 20 non-chagasic pregnant patients aged 16 to 34 years (22.5 ± 4.8. The patients were submitted to passive hemagglutination and indirect immunofluorescence for the detection of Trypanosoma cruzi evaluation, and electrocardiography, echocardiography and 24-h dynamic electrocardiography. RESULTS: Supraventricular premature depolarizations were observed in 18 (90% patients and ventricular premature depolarization in 11 (55% patients of both groups during pregnancy. After delivery, supraventricular premature depolarizations were present in 13 (60% chagasic patients and in 16 (89.4% control patients (P<=0.05. Ventricular premature depolarization were observed in 9 (45% chagasic patients and 11 (57.8% control patients. CONCLUSION: The prevalence of ventricular premature depolarization was similar for the chagasic and control groups during and after pregnancy. The incidence of supraventricular premature depolarizations was similar in the two groups during pregnancy, while after delivery a predominance was observed in the control group compared to the chagasic group.

  3. Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

    Rassi, Daniela do Carmo, E-mail: dani.rassi@hotmail.com [Faculdade de Medicina e Hospital das Clínicas da Universidade Federal de Goiás (UFG), Goiânia, GO (Brazil); Vieira, Marcelo Luiz Campos [Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil); Arruda, Ana Lúcia Martins [Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil); Hotta, Viviane Tiemi [Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil); Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador [Faculdade de Medicina e Hospital das Clínicas da Universidade Federal de Goiás (UFG), Goiânia, GO (Brazil)

    2014-03-15

    Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m{sup 2} were associated with a significant increase in mortality (log rank p < 0.0001). The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.

  4. Chagas' disease: an emergent urban zoonosis. The caracas valley (Venezuela) as an epidemiological model.

    Urdaneta-Morales, Servio

    2014-01-01

    The unprecedented emergence of important public health and veterinary zoonoses is usually a result of exponential population growth and globalization of human activities. I characterized Chagas' disease as an emergent zoonosis in the Caracas Valley (Venezuela) due to the following findings: the presence of reservoirs (Didelphis marsupialis, Rattus rattus) and vectors (Panstrongylus geniculatus, Panstrongylus rufotuberculatus) infected with Trypanosoma cruzi in urbanized or marginalized areas; the elevated contact between P. geniculatus and human beings detected by parasitological and molecular examinations of triatomine feces demonstrated the possibility of transmission risks; a study of outbreaks of urban Chagas' disease reported the first proven case of oral transmission of T. cruzi to human beings; the risk of transmission of glandular metacyclic stages from marsupials by experimental ocular and oral instillation; mice genitalia infected with T. cruzi contaminated blood resulted in the formation of amastigotes very close to the lumen suggesting that there may be a possibility of infection via their release into the urine and thence to the exterior; the ubiquitous histotropism and histopathology of T. cruzi was demonstrated using a mouse model; the presence of experimental T. cruzi pseudocysts in adipose, bone-cartilage, and eye tissue indicated a potential risk for transplants. Socio-sanitary programs that include improvements in housing, vector control, and access to medical treatment, as well as strategies aimed at combating social inequalities, poverty, and underdevelopment should be undertaken in those areas where zoonoses are most prevalent. Disciplines, such as Ecology, Epidemiology, Medical Entomology, Human and Veterinary Medicine, Environmental Studies, Public Health, Social and Political Studies, Immunology, Microbiology, and Pharmacology could all provide important contributions that aim to reduce the occurrence of factors governing the spread of

  5. Present situation and new strategies for Chagas disease chemotherapy: a proposal

    José Rodrigues Coura

    2009-07-01

    Full Text Available Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914 and up to the drugs currently in use (nifurtimox and benznidazole, along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles, in separate form. Several diseases such as tuberculosis, leprosy and AIDS only came under control after they were treated with associations of drugs with different mechanisms of action. This not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .To this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i nifurtimox (8 mg/kg/day + benznidazole (5 mg/kg/day x 60 consecutive days; (ii nifurtimox (8 mg/kg/day or benznidazole (5 mg/kg/day + allopurinol (8-10 mg/kg/day x 60 days and (iii nifurtimox (8 mg/kg/day or benznidazole (5 mg/kg/day + ketoconazole, fluconazole or itraconazole (5-6 mg/kg/day x 60 consecutive days. The doses of the drugs and the treatment schedules for the clinical trials must be adapted according to the side effects. From these, other double or triple associations could be made, using drugs with different mechanisms of action. This proposal does not exclude investigations on new drugs over the median and long terms, targeting other aspects of the metabolism of Trypanosoma cruzi. Until such time as the ideal drug for specific treatment of Chagas disease might be discovered, we need to develop new strategies for achieving greater efficacy with the old drugs in associations and to develop rational experimentation with new drugs.

  6. Development of a Fluorescence-based Trypanosoma cruzi CYP51 Inhibition Assay for Effective Compound Triaging in Drug Discovery Programmes for Chagas Disease.

    Jennifer Riley; Stephen Brand; Michael Voice; Ivan Caballero; David Calvo; Kevin D Read

    2015-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life threatening global health problem with only two drugs available for treatment (benznidazole and nifurtimox), both having variable efficacy in the chronic stage of the disease and high rates of adverse drug reactions. Inhibitors of sterol 14α-demethylase (CYP51) have proven effective against T. cruzi in vitro and in vivo in animal models of Chagas disease. Consequently two azole inhibitors of CYP51 (posaco...

  7. Longitudinal study of the indirect immunofluorescence and complement fixation tests for diagnosis of chagas' disease in immunosuppressed patients submitted to renal transplantation

    José Fernando de Castro Figueiredo; Adhemar Mário Fiorillo; Agenor Spallini Ferraz

    1993-01-01

    Clinical and serological follow-up of 7 patients submitted to renal transplantation and presenting positive serological reactions to Chagas 'disease before immunossupression did not show significant changes in indirect immunofluorescence and complement fixation titres for Chagas ' disease, or signs and symptoms indicating exacerbation of the disease during follow- up. In addition, 18 of 66 recipients of renal transplants considered to be non-chagasic before immunosuppression showed at least o...

  8. Epidemiology of and impact of insecticide spraying on Chagas disease in communities in the Bolivian Chaco.

    Aaron M Samuels

    Full Text Available BACKGROUND: Chagas disease control campaigns relying upon residual insecticide spraying have been successful in many Southern American countries. However, in some areas, rapid reinfestation and recrudescence of transmission have occurred. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey in the Bolivian Chaco to evaluate prevalence of and risk factors for T. cruzi infection 11 years after two rounds of blanket insecticide application. We used a cubic B-spline model to estimate change in force of infection over time based on age-specific seroprevalence data. Overall T. cruzi seroprevalence was 51.7%. The prevalence was 19.8% among children 2-15, 72.7% among those 15-30 and 97.1% among participants older than 30 years. Based on the model, the estimated annual force of infection was 4.3% over the two years before the first blanket spray in 2000 and fell to 0.4% for 2001-2002. The estimated annual force of infection for 2004-2005, the 2 year period following the second blanket spray, was 4.6%. However, the 95% bootstrap confidence intervals overlap for all of these estimates. In a multivariable model, only sleeping in a structure with cracks in the walls (aOR = 2.35; 95% CI = 1.15-4.78, age and village of residence were associated with infection. CONCLUSIONS/SIGNIFICANCE: As in other areas in the Chaco, we found an extremely high prevalence of Chagas disease. Despite evidence that blanket insecticide application in 2000 may have decreased the force of infection, active transmission is ongoing. Continued spraying vigilance, infestation surveillance, and systematic household improvements are necessary to disrupt and sustain interruption of infection transmission.

  9. Lineage analysis of circulating Trypanosoma cruzi parasites and their association with clinical forms of Chagas disease in Bolivia.

    Ramona del Puerto

    Full Text Available BACKGROUND: The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU: Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. METHODS AND FINDINGS: Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon. DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA was amplified from 196 out of 306 samples (64.1%, of which 104 (53.3% were Tc IId, 4 (2.0% Tc I, 7 (3.6% Tc IIb, 1 (0.5% Tc IIe, 26 (13.3% Tc I/IId, 1 (0.5% Tc I/IIb/IId, 2 (1.0% Tc IIb/d and 51 (25.9% were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%, TPK like (48.9% and Bug-like (1.5%. There was no significant association between Tc types and clinical manifestations of disease. CONCLUSIONS: None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia.

  10. Analysis of children's perception of triatomine vectors of chagas disease through drawings: opportunities for targeted health education.

    Violetta Yevstigneyeva

    2014-10-01

    Full Text Available Chagas disease is a tropical parasitic disease affecting about 10 million people, mostly in the Americas, and transmitted mainly by triatomine bugs. Insect vector control with indoor residual insecticides and the promotion of housing improvement is the main control intervention. The success of such interventions relies on their acceptance and appropriation by communities, which depends on their knowledge and perceptions of both the disease and the vector. In this study, we investigated school-aged children's knowledge and perception on triatomine vectors and Chagas disease to further understand how communities view this vector and the disease in Yucatan, Mexico.We performed an analysis of children's drawings on the theme of triatomines and their house in several rural villages, to explore in an open-ended manner their views, understanding and misconceptions. A total of 261 drawings were collected from children ages 6-12 from four villages. We found that children are very familiar with triatomine vectors, and know very well many aspects of their biology and ecology, and in particular their blood-feeding habits. On the other hand, their drawings suggest that the role of triatomines as vectors of a chronic and severe cardiac disease is less understood, and the main perceived health threat appears limited to the bite itself, as previously observed in adults.These results have important implications for the specific design of future education materials and campaigns, and for the promotion of the inclusion of children in raising Chagas disease awareness in these endemic communities.