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Sample records for chagas departamento general

  1. Chagas disease

    MedlinePlus

    Kirchhoff LV. Chagas' disease. In: Goldman L, Schafer AI, eds. Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 355. Kirchhoff LV. Trypanosoma species (American trypanosomiasis, Chagas' disease): Biology ...

  2. Chagas Disease

    MedlinePlus

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

  3. Chagas disease

    MedlinePlus

    ... help control the spread of the disease. Blood banks in Central and South America screen donors for ... if the donor has the parasite. Most blood banks in the United States began screening for Chagas ...

  4. Chagas Disease (American trypanosomiasis)

    MedlinePlus

    ... Features Commentaries 2014 Multimedia Contacts Chagas disease (American trypanosomiasis) Fact sheet Updated March 2016 Key facts About ... is essential. Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by ...

  5. Chagas' disease.

    PubMed Central

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

    1992-01-01

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

  6. Carlos Chagas: biographical sketch.

    PubMed

    Moncayo, Alvaro

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. Immunology of Chagas' disease*

    PubMed Central

    1974-01-01

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

  9. Rapidly Progressing Chagas Cardiomyopathy.

    PubMed

    Hollowed, John; McCullough, Matthew; Sanchez, Daniel; Traina, Mahmoud; Hernandez, Salvador; Murillo, Efrain

    2016-04-01

    Chagas disease, caused by the parasiteTrypanosoma cruzi, can cause a potentially life-threatening cardiomyopathy in approximately 10-40% of afflicted individuals. The decline in cardiac function characteristically progresses over the course of many years. We report a case of Chagas disease in which the patient experienced an atypical rapid deterioration to severe cardiomyopathy over the course of 16 months. This case argues the need for increased routine surveillance for patients with confirmedT. cruziinfection, who are determined to be at high-risk for worsening cardiomyopathy. PMID:26856912

  10. The history of Chagas disease.

    PubMed

    Steverding, Dietmar

    2014-01-01

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

  11. The history of Chagas disease

    PubMed Central

    2014-01-01

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

  12. Acute Chagas Disease in a Returning Traveler

    PubMed Central

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

    2012-01-01

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

  13. Control of Chagas disease vectors.

    PubMed

    Ramsey, J M; Schofield, C J

    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 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. The English version of this paper is available too at: http://www.insp.mx/salud/index.html. PMID:12736992

  14. Nanotechnological approaches against Chagas disease.

    PubMed

    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

  15. Duodenogastric reflux in Chagas' disease

    SciTech Connect

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

    1988-10-01

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

  16. Heterologous Infection During Chagas' Disease

    NASA Astrophysics Data System (ADS)

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

    2007-05-01

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

  17. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

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

  18. The Chronic Gastrointestinal Manifestations of Chagas Disease

    PubMed Central

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

    2009-01-01

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

  19. The Vasculature in Chagas Disease

    PubMed Central

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

    2013-01-01

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

  20. [Globalization, inequity and Chagas disease].

    PubMed

    Dias, João Carlos Pinto

    2007-01-01

    Chagas disease (American trypanosomiasis) bears a close relationship to multiple social and political aspects involving issues of globalization and inequity. Such relations concern the process of disease production and control in parallel with medical management. Despite the poverty in Latin America and various problems related to inequities and globalization, Chagas disease has been controlled in several areas, a fact that reinforces the countries' self-reliance. Several problems and challenges related to the disease can be expected in the future, mainly concerning medical care for already infected individuals and the sustainability of effective epidemiological surveillance. Both points depend heavily on improved performance by the national health systems, principally in terms of their efficiency and their capacity to overcome inequity. A particularly important role has been attributed to the Latin American scientific and academic community in the implementation and sustainability of efficient control policies. Control activities have now evolved towards internationally shared initiatives, a major new stride forward in the region's political context. PMID:17308713

  1. Economic evaluation of Chagas disease screening in Spain.

    PubMed

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

    2015-08-01

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

  2. Chaga mushroom-induced oxalate nephropathy.

    PubMed

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

    2014-06-01

    Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms. PMID:23149251

  3. Chagas' disease as a foodborne illness.

    PubMed

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

    2009-02-01

    Various researchers have studied the importance of the oral transmission of Chagas' disease since the mid-20th century. Only in recent years, due to an outbreak that occurred in the Brazilian State of Santa Catarina in 2005 and to various outbreaks occurring during the last 3 years in the Brazilian Amazon basin, mainly associated with the consumption of Amazonian palm berry or açaí (Euterpe oleracea Mart.) juice, has this transmission route aroused the attention of researchers. Nevertheless, reports published in the 1960s already indicated the possibility of Chagas' disease transmission via food in Brazil, mainly in the Amazonian region. Recently, in December 2007, an outbreak of Chagas' disease occurred in Caracas, Venezuela, related to ingestion of contaminated fruit juices. The objective of this article is to point out the importance of foodborne transmission in the etiology of Chagas' disease, on the basis of published research and Brazilian epidemiology data. PMID:19350996

  4. Chagas Heart Disease: Report on Recent Developments

    PubMed Central

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

    2011-01-01

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

  5. Chagas disease cardiomyopathy: immunopathology and genetics.

    PubMed

    Cunha-Neto, Edecio; Chevillard, Christophe

    2014-01-01

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

  6. Chagas Disease Cardiomyopathy: Immunopathology and Genetics

    PubMed Central

    Chevillard, Christophe

    2014-01-01

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

  7. Chagas disease in Andean countries.

    PubMed

    Guhl, Felipe

    2007-10-30

    The Andean Countries' Initiative (ACI) for controlling Chagas disease was officially created in 1997 within the framework of the Hipolito Unanue Agreement (UNANUE) between the Ministries of Health of Colombia, Ecuador, Peru, and Venezuela. Its objective was to interrupt transmission via vector and transfusion in the region, taking into account that there are 12.5 million people at risk in the four Andean countries forming the initiative in the area and around 3 million people are infected by Trypanosoma cruzi. The progress of control activities for the vector species present in the Andean sub-region, for different reasons, has been slow and control interventions have still not been installed in all geographical areas occupied by the target species. This has been partly due to lack of knowledge about these vector populations' biological characteristics, and consequent uncertainty about which are the appropriate control measures and strategies to be implemented in the region. The main vector species present important similarities in Venezuela and Colombia and in Ecuador and Northern Peru and they can be approached in a similar way throughout the whole regions, basing approaches on and adapting them to the current strategies being developed in Venezuela during the 1960s which have been progressively adopted in the Southern Cone and Central-American region. Additional measures are needed for keeping endemic areas free from Rhodnius prolixus silvatic populations, widely spread in the Orinoco region in Colombia and Venezuela. Regarding aetiological treatment, it is worth mentioning that (with the exception of Colombia) none of the other countries forming the ACI have registered medicaments available for treating infected young people. There are no suitable follow-up programmes in the sub-region or for treating cases of congenital Chagas disease. An integral and integrated programme encompassing all the aspects including transmission by transfusion which seems to have

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2007-01-01

    Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general. PMID:18997282

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

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Parasites - American Trypanosomiasis (also known as Chagas Disease) Note: Javascript is ... see the DPDx Web site: Chagas disease (American Trypanosomiasis) Diagnostic Procedures: Blood Specimens Get Email Updates To ...

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

    MedlinePlus

    ... concerned about getting Chagas disease? Why are blood banks now screening for Chagas disease? The transmission of ... have the disease after all. Will the blood bank let me know if my blood tests positive ...

  12. Immunosuppression and Chagas Disease: A Management Challenge

    PubMed Central

    Pinazo, María-Jesús; Espinosa, Gerard; Cortes-Lletget, Cristina; Posada, Elizabeth de Jesús; Aldasoro, Edelweiss; Oliveira, Inés; Muñoz, Jose; Gállego, Montserrat; Gascon, Joaquim

    2013-01-01

    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 formally

  13. Chagas Disease and Breast-feeding

    PubMed Central

    López-Vélez, Rogelio

    2013-01-01

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

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

    PubMed Central

    Sosa-Estani, Sergio; Segura, Elsa Leonor

    2015-01-01

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

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

    PubMed

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

    2016-01-01

    In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute. PMID:26433162

  16. Paleoparasitology of Chagas disease--a review.

    PubMed

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

    2009-07-01

    One hundred years since the discovery of Chagas disease associated with Trypanosoma cruzi infection, growing attention has focused on understanding the evolution in parasite-human host interaction. This interest has featured studies and results from paleoparasitology, not only the description of lesions in mummified bodies, but also the recovery of genetic material from the parasite and the possibility of analyzing such material over time. The present study reviews the evidence of Chagas disease in organic remains excavated from archeological sites and discusses two findings in greater detail, both with lesions suggestive of chagasic megacolon and confirmed by molecular biology techniques. One of these sites is located in the United States, on the border between Texas and Mexico and the other in state of Minas Gerais, in the Brazilian cerrado (savannah). Dated prior to contact with Europeans, these results confirm that Chagas disease affected prehistoric human groups in other regions outside the Andean altiplanos and other transmission areas on the Pacific Coast, previously considered the origin of T. cruzi infection in the human host. PMID:19753453

  17. Uruguay declared free of Chagas disease transmission.

    PubMed

    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

  18. The ecology of Chagas disease in Chile.

    PubMed

    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

  19. The elimination of Chagas' disease from Brazil

    PubMed Central

    MASSAD, E.

    2008-01-01

    SUMMARY On 9 June 2006 the Pan American Health Organization (PAHO) presented the Minister of Health of Brazil with the International Elimination of Transmission of Chagas' Disease Certificate. This act was the culmination of an intensive process that began in 1991 with the Southern Cone Initiative, a joint agreement between the governments of Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay and Peru, to control Chagas' disease by the elimination of the main vector, Triatoma infestans. This initiative has been highly successful and the prevalence area of the vector diminished rapidly in the last years. As a consequence, the current seroprevalence in children aged between 0 and 5 years is of the order of 10−5, a clear indication that transmission, if it is occurring, is only accidental. In this review I calculate the basic reproduction number, R0, for Chagas' disease and demonstrate that its relatively low value (1·25) explains why vectorial transmission was interrupted relatively easily. In addition, I used a mathematical model to forecast how long the remaining cases of the disease, as well as the additional vertically transmitted cases will last. PMID:18053273

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

    PubMed

    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

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

    PubMed Central

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

    2013-01-01

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

  2. Respiratory sinus arrhythmia in Chagas disease.

    PubMed

    Neves, Victor Ribeiro; Peltola, Mirja; Huikuri, Heikki; Rocha, Manoel Otávio da Costa; Ribeiro, Antonio Luiz

    2014-10-01

    We applied the respiratory sinus arrhythmia (RSA) quantification algorithm to 24-hour ECG recordings of Chagas disease (ChD) patients with (G1, n=148) and without left ventricular dysfunction (LVD) (G2, n=33), and in control subjects (G0, n=28). Both ChD groups displayed a reduced RSA index; G1=299 (144-812); G2=335 (162-667), p=0.011, which was correlated with vagal indexes of heart rate variability analysis. RSA index is a marker of vagal modulation in ChD patients. PMID:25130950

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

    PubMed

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

    2016-04-01

    Human migration has been identified as a potential factor for increased Chagas disease risk and has transformed the disease from a Latin American problem to a global one. We conducted a systematic review of the scientific literature between 2004-2014 in order to: summarize recent seroprevalence estimates of Chagas disease among Latin American migrants, in both endemic and non-endemic settings; compare seroprevalence estimates in migrants to countrywide prevalence estimates; and identify risk factors for Chagas disease among migrants. A total of 320 studies were screened and 23 studies were included. We found evidence that the prevalence of Chagas disease is higher than expected in some migrant groups and that reliance on blood donor screening prevalence estimates underestimates the burden of disease. Overall there is a dearth of high quality epidemiologic studies on the prevalence of Chagas disease in migrants, especially among intra-regional migrants within Latin America. Given that this zoonotic disease cannot likely be eradicated, improved surveillance and reporting is vital to continuing control efforts. More accurate health surveillance of both Latin American migrants and the Chagas disease burden will help countries appropriately scale up their response to this chronic disease. Overall, improved estimates of Chagas disease among migrants would likely serve to highlight the real need for better screening, diagnostics, and treatment of individuals living with the disease. PMID:26777312

  4. Use of a Novel Chagas Urine Nanoparticle Test (Chunap) for Diagnosis of Congenital Chagas Disease

    PubMed Central

    Castro-Sesquen, Yagahira E.; Gilman, Robert H.; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Sánchez, Gerardo; Valencia Ayala, Edward; Liotta, Lance; Bern, Caryn; Luchini, Alessandra

    2014-01-01

    Background Detection of congenital T. cruzi transmission is considered one of the pillars of control programs of Chagas disease. Congenital transmission accounts for 25% of new infections with an estimated 15,000 infected infants per year. Current programs to detect congenital Chagas disease in Latin America utilize microscopy early in life and serology after 6 months. These programs suffer from low sensitivity by microscopy and high loss to follow-up later in infancy. We developed a Chagas urine nanoparticle test (Chunap) to concentrate, preserve and detect T. cruzi antigens in urine for early, non-invasive diagnosis of congenital Chagas disease. Methodology/Principal Findings This is a proof-of-concept study of Chunap for the early diagnosis of congenital Chagas disease. Poly N-isopropylacrylamide nano-particles functionalized with trypan blue were synthesized by precipitation polymerization and characterized with photon correlation spectroscopy. We evaluated the ability of the nanoparticles to capture, concentrate and preserve T. cruzi antigens. Urine samples from congenitally infected and uninfected infants were then concentrated using these nanoparticles. The antigens were eluted and detected by Western Blot using a monoclonal antibody against T. cruzi lipophosphoglycan. The nanoparticles concentrate T. cruzi antigens by 100 fold (western blot detection limit decreased from 50 ng/ml to 0.5 ng/ml). The sensitivity of Chunap in a single specimen at one month of age was 91.3% (21/23, 95% CI: 71.92%–98.68%), comparable to PCR in two specimens at 0 and 1 month (91.3%) and significantly higher than microscopy in two specimens (34.8%, 95% CI: 16.42%–57.26%). Chunap specificity was 96.5% (71/74 endemic, 12/12 non-endemic specimens). Particle-sequestered T. cruzi antigens were protected from trypsin digestion. Conclusion/Significance Chunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease. PMID

  5. Chagas disease and globalization of the Amazon.

    PubMed

    Briceño-León, Roberto

    2007-01-01

    The increasing number of autochthonous cases of Chagas disease in the Amazon since the 1970s has led to fear that the disease may become a new public health problem in the region. This transformation in the disease's epidemiological pattern in the Amazon can be explained by environmental and social changes in the last 30 years. The current article draws on the sociological theory of perverse effects to explain these changes as the unwanted result of the shift from the "inward" development model prevailing until the 1970s to the "outward" model that we know as globalization, oriented by industrial forces and international trade. The current article highlights the implementation of five new patterns in agriculture, cattle-raising, mining, lumbering, and urban occupation that have generated changes in the environment and the traditional indigenous habitat and have led to migratory flows, deforestation, sedentary living, the presence of domestic animals, and changes in the habitat that facilitate colonization of human dwellings by vectors and the domestic and work-related transmission of the disease. The expansion of Chagas disease is thus a perverse effect of the globalization process in the Amazon. PMID:17308715

  6. Chagas' Disease: Pregnancy and Congenital Transmission

    PubMed Central

    Hernández, Roberto

    2014-01-01

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

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

    PubMed

    Pays, J-F

    2016-08-01

    After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease". PMID:27376642

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

    PubMed

    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

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

    PubMed

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

    2012-01-01

    A new epidemiological scenario involving the oral transmission of Chagas disease, mainly in the Amazon basin, requires innovative control measures. Geospatial analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have been scarce. We applied interpolation and map algebra methods to evaluate mammalian fauna variables related to small wild mammals and the T. cruzi infection pattern in dogs to identify hotspot areas of transmission. We also evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease. Dogs (n = 649) were examined by two parasitological and three distinct serological assays. kDNA amplification was performed in patent infections, although the infection was mainly sub-patent in dogs. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 11-89% in different localities. The interpolation method and map algebra were employed to test the associations between the lower richness in mammal species and the risk of exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the reduction of the mammal fauna (richness and abundance) was associated with higher parasitemia in small wild mammals and higher exposure of dogs to infection. A Generalized Linear Model (GLM) demonstrated that species richness and positive hemocultures in wild mammals were associated with T. cruzi infection in dogs. Domestic canine infection rates differed significantly between areas with and without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by interpolation and map algebra methods proved to be a powerful tool in the evaluation of areas of T. cruzi transmission. Dog infection was shown to not only be an efficient indicator of reduction of wild mammalian fauna richness but to also act as a signal for the presence of small wild mammals with high parasitemia. The lower richness of small mammal species is discussed as a risk factor for the re-emergence of Chagas disease. PMID:22616021

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

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

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

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

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Parasites - American Trypanosomiasis (also known as Chagas Disease) Note: Javascript is ... cruzi infection) is also referred to as American trypanosomiasis. It is estimated that as many as 8 ...

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

    SciTech Connect

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

    1981-04-01

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

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

    SciTech Connect

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

    1981-04-01

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

  14. [Chagas disease: an emerging public health problem in Italy?].

    PubMed

    Guerri-Guttenberg, R A; Ciannameo, A; Di Girolamo, C; Milei, J J

    2009-03-01

    Chagas' disease is an endemic parasitic illness in the American continent, affecting around 16 to 18 million people. Given that 9.5% of immigrants to Italy are from Latin America and that the infection can be transmitted in non-endemic countries congenitally by organ donations and blood transfusions, Chagas disease should be regarded as an emerging public health problem in Italy. Clinical guidelines as well as health protocols are needed to deal with this rarely recognized disease. PMID:19359818

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

    PubMed

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

    2016-05-01

    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

  16. Chagas Disease: Still Many Unsolved Issues

    PubMed Central

    Álvarez, José M.; Fonseca, Raissa; Borges da Silva, Henrique; Marinho, Cláudio R. F.; Bortoluci, Karina R.; Sardinha, Luiz R.; Epiphanio, Sabrina; D'Império Lima, Maria Regina

    2014-01-01

    Over the past 20 years, the immune effector mechanisms involved in the control of Trypanosoma cruzi, as well as the receptors participating in parasite recognition by cells of the innate immune system, have been largely described. However, the main questions on the physiopathology of Chagas disease remain unanswered: “Why does the host immune system fail to provide sterile immunity?” and “Why do only a proportion of infected individuals develop chronic pathology?” In this review, we describe the mechanisms proposed to explain the inability of the immune system to eradicate the parasite and the elements that allow the development of chronic heart disease. Moreover, we discuss the possibility that the inability of infected cardiomyocytes to sense intracellular T. cruzi contributes to parasite persistence in the heart and the development of chronic pathology. PMID:25104883

  17. Antibodies to laminin in Chagas' disease

    PubMed Central

    1982-01-01

    We have found that sera from humans with Chagas' disease and Rhesus monkeys infected with Trypanosoma cruzi contain IgM and IgG antibodies, which react with structures in a variety of connective tissues. These antibodies react with laminin but not with various other purified connective tissue components like collagen types I, III, IV, and V, fibronectin, heparan sulfate (BM-1) proteoglycan, or chondronectin. The tissue-reacting antibodies were isolated by absorption to a laminin- Sepharose column. The bound fraction contained all the tissue-reacting antibodies. These antibodies strongly stained trypomastigotes and amastigotes, but weakly stained epimastigotes. These studies show that sera from T. cruzi-infected primates contain antilaminin antibodies, which may be produced by those host in response to a laminin-like molecule present in the parasite. PMID:6801186

  18. Old and new challenges in Chagas disease.

    PubMed

    Pérez-Molina, Jose A; Perez, Angela Martinez; Norman, Francesca F; Monge-Maillo, Begoña; López-Vélez, Rogelio

    2015-11-01

    Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected disease, which can lead to cardiomyopathy, arrhythmias, megaviscera, and more rarely, polyneuropathy in up to 30-40% of patients around 20 to 30 years after acute infection. Although it is endemic in the Americas, global population movements mean that it can be located wherever migrants from endemic areas settle. The disease was first described 100 years ago and still challenges clinicians worldwide, since diagnostic, therapeutic, and prognostic methods remain insufficient. Furthermore, factors such as HIV co-infection, immunosuppressive drugs, transplantation, and neoplastic disease can alter the natural course of the infection. We present the case of a Bolivian woman with chronic T cruzi infection diagnosed at our clinic in Madrid, Spain, who subsequently developed non-Hodgkin lymphoma. Our report illustrates the challenges of an increasingly common infection seen in non-endemic countries, and highlights both daily management dilemmas and associated difficulties that arise. PMID:26231478

  19. Prevention of congenital Chagas through treatment of girls and women of childbearing age

    PubMed Central

    Moscatelli, Guillermo; Moroni, Samanta; García-Bournissen, Facundo; Ballering, Griselda; Bisio, Margarita; Freilij, Héctor; Altcheh, Jaime

    2015-01-01

    It is currently unknown whether treatment of Chagas disease decreases the risk of congenital transmission from previously treated mothers to their infants. In a cohort of women with Chagas disease previously treated with benznidazole, no congenital transmission of the disease was observed in their newborns. This finding provides support for the treatment of Chagas disease as early as possible. PMID:25993401

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

    PubMed

    Nakajima, Yuki; Sato, Yuzo; Konishi, Tetsuya

    2007-08-01

    Inonotus obliquus (persoon) Pilat (Chaga, in Russia, kabanoanatake in Japan) is a fungus having been used as a folk medicine in Russia and said to have many health beneficial functions such as immune modulating and anti-cancer activities. In the present study, the antioxidant activity of hot water extract (decoction) of Chaga was precisely compared with those of other medicinal fungi (Agaricus blazei Mycelia, Ganoderma lucidum and Phellinus linteus) showing Chaga had the strongest antioxidant activity among fungi examined in terms of both superoxide and hydroxyl radicals scavenging activities. Further determination of the antioxidant potential of isolated fruiting body (brown part) and Sclerotium (black part) revealed the 80% MeOH extract of fruiting body had the highest potential as high as that of Chaga decoction. Finally, seven antioxidant components were isolated and purified from the 80% MeOH extract of Chaga fruiting body, and their chemical structures were determined as small phenolics as follows: 4-hydroxy-3,5-dimethoxy benzoic acid 2-hydroxy-1-hydroxymethyl ethyl ester (BAEE), protocatechic acid (PCA), caffeic acid (CA), 3,4-dihybenzaladehyde (DB), 2,5-dihydroxyterephtalic acid (DTA), syringic acid (SA) and 3,4-dihydroxybenzalacetone (DBL). Notably, BAEE was assigned as the new compound firstly identified from the natural source in the present study. PMID:17666849

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

    PubMed

    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

  2. Behavioural biology of Chagas disease vectors

    PubMed Central

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

    2013-01-01

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

  3. Highly effective serodiagnosis for Chagas' disease.

    PubMed

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

    2010-10-01

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

  4. Differential regional immune response in Chagas disease.

    PubMed

    de Meis, Juliana; Morrot, Alexandre; Farias-de-Oliveira, Désio Aurélio; Villa-Verde, Déa Maria Serra; Savino, Wilson

    2009-01-01

    Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells. This straight correlation between the kinetics of T cell response and the dynamics of lymphoid tissue cell numbers is a constant feature in acute infections yielded by pathogens that are cleared during the course of response. However, the regional dynamics of the immune response mounted against pathogens that are able to establish a persistent infection remain poorly understood. Herein we discuss the differential lymphocyte dynamics in distinct central and peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. While the thymus and mesenteric lymph nodes undergo a severe atrophy with massive lymphocyte depletion, the spleen and subcutaneous lymph nodes expand due to T and B cell activation/proliferation. These events are regulated by cytokines, as well as parasite-derived moieties. In this regard, identifying the molecular mechanisms underlying regional lymphocyte dynamics secondary to T. cruzi infection may hopefully contribute to the design of novel immune intervention strategies to control pathology in this infection. PMID:19582140

  5. Chagas disease: Central American initiative launched.

    PubMed

    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

  6. A new era for chagas disease drug discovery?

    PubMed

    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

  7. Quality assurance of the serologic diagnosis of Chagas' disease.

    PubMed

    Cura, E N; Segura, E L

    1998-04-01

    A quality assurance program of the Chagas' disease laboratory network of Argentina has been conducted by the National Reference Center since 1988, with the aim of assessing the reliability of serologic test results. Chagas' disease is endemic in Argentina, but the prevalence of seropositivity for Trypanosoma cruzi among 18- to 20-year-old men decreased from 5.8% in 1981 to 1.8% in 1994. About 600 laboratories form the Chagas' disease laboratory network, with main central laboratories in each of the 24 provinces in Argentina. The quality assurance program promotes regular use of good laboratory practice and internal and external quality control to improve performance of the participants; it also provides technical assistance and guidelines. Eventual corrective measures are discussed in workshops. Results of the first external evaluation by proficiency testing of serum panels and confirmation of results for 58 of the main laboratories reveal that from 1988 to 1994 the rate of agreement has increased. PMID:9608813

  8. VNI Cures Acute and Chronic Experimental Chagas Disease

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    1978-01-01

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

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

    PubMed

    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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Chagas parasite detection in blood images using AdaBoost.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. Lead identification to clinical candidate selection: drugs for Chagas disease.

    PubMed

    Neitz, R Jeffrey; Chen, Steven; Supek, Frantisek; Yeh, Vince; Kellar, Danielle; Gut, Jiri; Bryant, Clifford; Gallardo-Godoy, Alejandra; Molteni, Valentina; Roach, Steven L; Khare, Shilpi; Stinson, Monique; Chatterjee, Arnab K; Robertson, Stephanie; Renslo, Adam R; Arkin, Michelle; Glynne, Richard; McKerrow, James; Siqueira-Neto, Jair L

    2015-01-01

    Chagas disease affects 8 million people worldwide and remains a main cause of death due to heart failure in Latin America. The number of cases in the United States is now estimated to be 300,000, but there are currently no Food and Drug Administration (FDA)-approved drugs available for patients with Chagas disease. To fill this gap, we have established a public-private partnership between the University of California, San Francisco and the Genomics Institute of the Novartis Research Foundation (GNF) with the goal of delivering clinical candidates to treat Chagas disease. The discovery phase, based on the screening of more than 160,000 compounds from the GNF Academic Collaboration Library, led to the identification of new anti-Chagas scaffolds. Part of the screening campaign used and compared two screening methods, including a colorimetric-based assay using Trypanosoma cruzi expressing β-galactosidase and an image-based, high-content screening (HCS) assay using the CA-I/72 strain of T. cruzi. Comparing molecules tested in both assays, we found that ergosterol biosynthesis inhibitors had greater potency in the colorimetric assay than in the HCS assay. Both assays were used to inform structure-activity relationships for antiparasitic efficacy and pharmacokinetics. A new anti-T. cruzi scaffold derived from xanthine was identified, and we describe its development as lead series. PMID:25281737

  17. Perinatal Screening for Chagas Disease in Southern Texas.

    PubMed

    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

  18. Chagas Parasite Detection in Blood Images Using AdaBoost

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Coura, José Rodrigues

    2013-01-01

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

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

    PubMed

    Coura, José Rodrigues

    2013-12-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-01-30

    A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study. PMID:26801589

  5. Chagas' disease: trends in immunological research and prospects for immunoprophylaxis

    PubMed Central

    Teixeira, Antonio R. L.

    1979-01-01

    Acute infection with Trypanosoma cruzi usually subsides spontaneously but the mortality rate encountered in individuals with the chronic infection is high. Much evidence has accumulated in the last five years that autoimmunity plays an important role in the pathogenesis of the myocarditis that is common in the chronic phase. A negative relationship has been observed between the demonstrable parasitaemia and the presence of severe cardiac lesions. This myocarditis is characterized by lymphocytic infiltrates and destruction of normal heart cells, in the absence of the parasite in situ. Furthermore, the demonstration in vitro of heart cell lysis by T. cruzi-sensitized T lymphocytes is strong evidence of autoimmunity in Chagas' disease. Acquired immunity plays a major role in the course that T. cruzi infections may run in the mammalian host. As a result of the immune mechanisms induced by the parasite, the infection is controlled at subpatent levels, and the immune host does not develop acute T. cruzi infection again. At present there are several means of achieving immunoprotection against experimental T. cruzi infections, but it is not known whether vaccinated animals might develop chronic Chagas' disease and die many months or years later. Studies on immunoprotection against Chagas' disease should therefore not be limited only to the acute phase of the infection. Furthermore, the involvement of autoimmunity in the production of the lesions of Chagas' disease indicates that research in this area should be conducted with caution. The definition of an animal model for chronic Chagas' disease is essential to further development of immunological research devoted to immunoprophylaxis. PMID:120233

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2014-10-21

    Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries. PMID:25338155

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Bestetti, Reinaldo B; Cardinalli-Neto, Augusto

    2013-10-01

    Chagas disease was discovered by Carlos Chagas in 1909. Chagas worked at Oswaldo Cruz Institute, where the bases of experimental medicine were settled in Brazil, and that had no connection with the Faculty of Medicine of Rio de Janeiro. Chagas had several enemies at Oswaldo Cruz Institute mainly because of his election to Head of Service in 1910, and for the position of Oswaldo Cruz Directorship in 1917. Furthermore, Chagas gained enemies at Faculty of Medicine of Rio de Janeiro, which did not like to see the economical political autonomy of Oswaldo Cruz Institute. This allowed the Institute not only to perform top experimental research, but also to take the leadership of research in the country. Chagas was nominated to the Nobel Prize of 1921 in December, 1920. None was awarded the Nobel Prize in that year. He seems to have been evaluated by the Noble Committee of Karolinska Institute from March to May of 1921. At that time, his enemies were denying his discovery of Trypanosoma cruzi, a key point in Chagas' nomination by Karolinska Institute, and giving no epidemiological importance for the disease. By the same way, the obligation of small pox vaccination was tarnishing his public image. Having taken into account the epidemiologic importance of Chagas disease, the strong historical mistake in the process of Chagas evaluation, and the inequity behind all these facts, we insist on a posthumous Nobel Prize for the man who made the most complete medical-scientist discovery of all time. PMID:23410487

  11. [Representations, myths, and behaviors among Chagas disease patients with pacemakers].

    PubMed

    Magnani, Claudia; Oliveira, Bruna Guimarães; Gontijo, Eliane Dias

    2007-07-01

    This anthropological study aimed to evaluate the incorporation of pacemakers into the lives of individuals with Chagas disease. An ethnographic methodology was used, based on an open interview focusing on the personal perceptions of 15 patients with chronic Chagas cardiopathy who had required pacemaker implants at the Federal University Hospital in Belo Horizonte, Minas Gerais State, Brazil. As part of a broader quality of life analysis, the study investigated the cultural, physical, and psychological resources used by patients to confront, explain, and accept the disease process, including mental representations on the cultural perception of the illness and definition of social relations. The study was intended to contribute to comprehensive patient care by health professionals, including psychosocial aspects. Decoded and integrated orientation in the cultural sphere assumes an important role in order to prevent disinformation from perpetuating the dissemination of popular myths as active elements in patient stigmatization. PMID:17572811

  12. Novel cruzain inhibitors for the treatment of Chagas' disease.

    PubMed

    Rogers, Kathleen E; Keränen, Henrik; Durrant, Jacob D; Ratnam, Joseline; Doak, Allison; Arkin, Michelle R; McCammon, J Andrew

    2012-09-01

    The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, affects millions of individuals and continues to be an important global health concern. The poor efficacy and unfavorable side effects of current treatments necessitate novel therapeutics. Cruzain, the major cysteine protease of T. cruzi, is one potential novel target. Recent advances in a class of vinyl sulfone inhibitors are encouraging; however, as most potential therapeutics fail in clinical trials and both disease progression and resistance call for combination therapy with several drugs, the identification of additional classes of inhibitory molecules is essential. Using an exhaustive virtual-screening and experimental validation approach, we identify several additional small-molecule cruzain inhibitors. Further optimization of these chemical scaffolds could lead to the development of novel drugs useful in the treatment of Chagas' disease. PMID:22613098

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

    PubMed Central

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

    2012-01-01

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

  14. Challenges and perspectives of Chagas disease: a review

    PubMed Central

    2013-01-01

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

  15. Pathogenesis of Chagas disease: time to move on

    PubMed Central

    Machado, Fabiana S.; Tyler, Kevin M.; Brant, Fatima; Esper, Lisia; Teixeira, Mauro M.; Tanowitz, Herbert B.

    2012-01-01

    Trypanosoma cruzi is the etiologic agent of Chagas disease. The contributions of parasite and immune system for disease pathogenesis remain unresolved and controversial. The possibility that Chagas disease was an autoimmune progression triggered by T. cruzi infection led some to question the benefit of treating chronically T. cruzi-infected persons with drugs. Furthermore, it provided the rationale for not investing in research aimed at a vaccine which might carry a risk of inducing autoimmunity or exacerbating inflammation. This viewpoint was adopted by cash-strapped health systems in the developing economies where the disease is endemic and has been repeatedly challenged by researchers and clinicians in recent years and there is now a considerable body of evidence and broad consensus that parasite persistence is requisite for pathogenesis and that antiparasitic immunity can be protective against T. cruzi pathogenesis without eliciting autoimmune pathology. Thus, treatment of chronically infected patients is likely to yield positive outcomes and efforts to understand immunity and vaccine development should be recognized as a priority area of research for Chagas disease. PMID:22201990

  16. A case of Chagas' disease panniculitis after kidney transplantation.

    PubMed

    Campos, Fábio Prestes de; Pansard, Henry Mor; Arantes, Luiz Cláudio; Rodrigues, Arnaldo Teixeira; Daubermann, Melissa Falster; Azambuja, Marcos Felipe; Argenta, Laércio Cassol; Silva, Luiz Alberto Michet da

    2016-03-01

    Chagas' disease carries high morbidity and mortality due to acute parasitemia or cardiac, digestive, cutaneous or neurologic chronic lesions. Latin American countries have the majority of infected or at risk people. Transplanted patients using immunosuppressive agents may develop severe and even fatal forms of the disease. The available treatment causes frequent severe side-effects. A 59 years-old woman with end stage renal disease and positive serology for Chagas` disease, but without any clinical manifestation of this pathology, underwent kidney transplantation from a cadaveric donor and displayed three months later a thigh panniculitis from which a biopsy unveiled amastigote forms of Trypanosoma cruzi. The skin lesions disappeared following treatment with benzonidazole, but the drug was discontinued due to severe pancytopenia. Along with this, infection with E. faecalis and cytomegalovirus were treated with vancomicin and ganciclovir. The patient kept very well afterwards, with no new skin lesions and with good graft function. One year and three months after the transplant, she had an emergency surgery for an aortic dissecting aneurysm. Irreversible shock and death occurred in the immediate post-surgical period. It was not possible to establish or to rule out a relationship between the trypanosomiasis and the aortic lesions. Chagas` disease must be remembered in differential diagnosis of several clinical situations in transplant patients, mainly in endemic areas. The treatment can yeld good clinical response, but serious side-effects from the drugs may ensue. More effective and better tolerated options are in need for treatment or prophylaxis. PMID:27049374

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

    PubMed

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

    2016-07-01

    Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies. PMID:27216381

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    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 <1 year of age. Nearly all cases with histopathology data reported myocarditis (97.9%) and observation of Trypanosoma cruzi organisms (81.7%). Predominant clinical observations included enlarged heart, lethargy, anorexia, ascites, cardiac conduction disturbances, and respiratory difficulties. An increasing rate of serologic test submissions was noted over the study period, with an overall positive test prevalence of 20.3%. The study results provide strong evidence that an active canine Chagas disease transmission cycle is present throughout all ecoregions of Texas, affecting a broad range of dog breeds and age groups. PMID:18255233

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

    PubMed

    Edwards, James M; Gilner, Jennifer B; Hernandez, Jose; Kurtzberg, Joanne; Heine, R Phillips

    2016-08-01

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

  3. [Congenital ChagaśDisease: epidemiology, laboratorial diagnosis, prognosis and treatment].

    PubMed

    Reiche, E M; Inouye, M M; Bonametti, A M; Jankevicius, J V

    1996-01-01

    The authors review studies about epidemiology, clinical aspects and methods used in laboratorial diagnosis of congenital Chagas'disease, emphasizing the limitations in their specificity and sensibility, and suggest alternative methods to improve the accuracy and the quality of the laboratorial diagnosis of congenital Chagaśdisease, essential to an efficient treatment. PMID:14688943

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Ecological connectivity of Trypanosoma cruzi reservoirs and Triatoma pallidipennis hosts in an anthropogenic landscape with endemic Chagas disease.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Information on Vinchucas and Chagas disease.

    NASA Astrophysics Data System (ADS)

    Schenone, H.

    1981-12-01

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

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

    PubMed Central

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

    1977-01-01

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

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

    PubMed Central

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

    1980-01-01

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

  11. Further evidence of spontaneous cure in human Chagas disease.

    PubMed

    Dias, João Carlos Pinto; Dias, Emmanuel; Martins-Filho, Olindo Assis; Filho, Olindo M; Vitelli-Avelar, Danielle; Correia, Dalmo; Lages, Eliane; Prata, Aluízio

    2008-01-01

    An acute case of Chagas disease was studied in 1944, with clinical and laboratory follow-up until 2007, in Bambuí, Minas Gerais, Brazil. A five-year-old girl living in a rural hut that was highly infested with Triatoma infestans presented a febrile clinical condition compatible with the acute form of trypanosomiasis. She presented a positive thick blood smear, but never again showed serological and/or parasitological evidence of Trypanosoma cruzi infection, on several occasions. This patient never received any specific treatment and, to this day, she remains completely asymptomatic, with normal findings from clinical, electrocardiographic, X-ray and echocardiographic examinations. PMID:19009195

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

    PubMed

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

    2013-11-20

    Carlos Chagas, the discoverer of Chagas' disease was nominated to the Nobel Prize in 1921, but none did win the prize in that year. As a leader of a young scientist team, he discovered all aspects of the new disease from 1909 to 1920. It is still obscure why he did not win the Nobel Prize in 1921. Chagas was discarded by Gunnar Hedrèn on April 16, 1921. Hedrèn should have made a written report about the details of his evaluation to the Nobel Committee. However, such a document has not been found in the Nobel Committee Archives. No evidence of detractions made by Brazilian scientists on Chagas was found. Since Chagas nomination was consistent with the Nobel Committee requirements, as seen in the presentation letter by until now unknown Cypriano de Freitas, it become clear that Chagas did not win the Nobel Prize exclusively because the Nobel Committee did not perceive the importance of his discovery. Thus, it would be fair a posthumous Nobel Prize of 1921 to Carlos Chagas. A diploma of the Nobel Prize, as precedent with Dogmack in 1947, would recognize the merit of the scientist who made the most complete medical discovery of all times. PMID:24063910

  13. [American trypanosomiasis (Chagas disease) and the nervous system].

    PubMed

    Spina-Franca, A

    1988-01-01

    Ten to twelve million people irregularly distributed mainly through extensive rural areas of Latin America are afflicted by American trypanosomiasis (Chagas disease). Trypanosoma cruzi is the etiological agent, and it is naturally transmitted to humans by hematophagous hemiptera of Triatominae sub-family. These hemiptera feed by biting and usually defecate in the area near the puncture wound. Mucous membranes of breaks in the continuity of skin serve as passage ways for the parasite present in the excrement of the bug. Acute and chronic forms of American trypanosomiasis occur. Nervous system involvement in the acute form may give rise to meningoencephalitis. Central and/or peripheral signs of nervous system involvement can occur in the chronic form. Neuronal depopulation due to cell destruction by direct parasitism during the acute stage of the disease is the main pathogenetic way pointed out to explain chronic forms of nervous system involvement. Chronic Chagas cardiopathy usually produces mural thrombi. Fragments of thrombus situated in the left ventricle may become detached and migrate with the bloodstream to cause embolic phenomena in distant vessels--as in brain vessels--thus causing embolic cerebrovascular insults. Data on clinical and experimental studies are critically analysed. PMID:3143493

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html. PMID:23484340

  16. Squalene Synthase As a Target for Chagas Disease Therapeutics

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-05-01

    Data on the chemical composition of triterpenic and steroid compounds, isolated from the chaga mushroom grown in natural environment or in a synthetic culture have been summarized. Special attention has been paid to the biological activity of chaga mushroom extracts and these particular compounds against various cancer cell lines in vitro and in vivo. This analysis has demonstrated some common features in inhibition of growth of various cell lines by chaga mushroom components. In this context, the most active are triterpene compounds containing OH group at C-22 and a side chain unsaturated bond. PMID:27562990

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

    PubMed

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

    2013-04-01

    Chaga mushrooms (Inonotus obliquus) are hypothesised to exhibit general immune-potentiating, anti-inflammatory, and antitumor properties, but their anti-allergic activities are not fully understood. Therefore, this study investigated whether a chaga mushroom extract (C-HE) might have anti-allergic activity. This activity was assessed through the levels of the IgE Ab produced in response to an allergen (OVA). The administration of C-HE prophylactically inhibited the systemic anaphylactic shock induced by compound 48/80 in mice. The oral administration of C-HE significantly reduced the total IgE levels in mice and slightly affected the production of IgG1. Furthermore, spleen cell cultures harvested from OVA-sensitised mice that had received C-HE orally showed a significant increase in Th1-derived responses (IFN-γ production). Therefore, our results suggest that the chaga mushroom extract may be used as an anti-allergic functional food. PMID:23535020

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

    PubMed Central

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

    2014-01-01

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

  20. Prophet in his own country: Carlos Chagas and the Nobel Prize.

    PubMed

    Lewinsohn, Rachel

    2003-01-01

    In 1909, Carlos Chagas (1878-1934) discovered a new protozoon, Trypanosoma cruzi, and the (previously unknown) disease that it causes. Within a few months, virtually single-handed, he described the pathogen, its vector, and the clinical features of American trypanosomiasis (Chagas disease), a feat unique in medical history. He headed the Oswaldo Cruz Institute after the death of its founder (1917) until his own death; and from 1920 until 1926 he also directed the Brazilian Department of Public Health. His discovery brought him worldwide acclaim, but at home antagonism against Chagas, muted for years, finally flared up in a campaign that was acted out in the 1921-22 plenary sessions of the National Academy of Medicine. Chagas's name was repeatedly proposed for the Nobel Prize but he never received it; this hostile campaign may have been instrumental in costing him the award. PMID:14593222

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

    PubMed

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

    2015-11-01

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

  2. IL18 Gene Variants Influence the Susceptibility to Chagas Disease

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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

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

    PubMed Central

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

    2012-01-01

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

  11. Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic Trypanosoma cruzi–Seropositive Former Blood Donors

    PubMed Central

    Sabino, Ester C.; Ribeiro, Antonio L.; Salemi, Vera M.C.; Di Lorenzo Oliveira, Claudio; Antunes, Andre P.; Menezes, Marcia M.; Ianni, Barbara M.; Nastari, Luciano; Fernandes, Fabio; Patavino, Giuseppina M.; Sachdev, Vandana; Capuani, Ligia; de Almeida-Neto, Cesar; Carrick, Danielle M.; Wright, David; Kavounis, Katherine; Goncalez, Thelma T.; Carneiro-Proietti, Anna Barbara; Custer, Brian; Busch, Michael P.; Murphy, Edward L.

    2013-01-01

    Background Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi–infected persons. Methods and Results We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi–seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of São Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S3 heart sound. Conclusions There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi–seropositive blood donors, although disease was mild at diagnosis. PMID:23393012

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. SQ109, a New Drug Lead for Chagas Disease

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

    Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients. PMID:27044564

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

    PubMed Central

    Chatelain, Eric; Konar, Nandini

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Forsyth, Colin

    2015-11-01

    Dressler (2001:456) characterizes medical anthropology as divided between two poles: the constructivist, which focuses on the "meaning and significance that events have for people," and the structuralist, which emphasizes socioeconomic processes and relationships. This study synthesizes structuralist and constructivist perspectives by investigating how structural processes impact explanatory models of Chagas disease in a highly endemic area. The research took place from March-June 2013 through the Centro Medico Humberto Parra, a non-profit clinic servicing low income populations in Palacios, Bolivia and surrounding communities. Semistructured interviews (n = 68) and consensus analysis questionnaires (n = 48) were administered to people dealing with Chagas disease. In the interview narratives, respondents link Chagas disease with experiences of marginalization and rural poverty, and describe multilayered impediments to accessing treatment. They often view the disease as incurable, but this reflects inconsistent messages from the biomedical system. The consensus analysis results show strong agreement on knowledge of the vector, ethnomedical treatment, and structural factors related to Chagas disease. In interpreting Chagas disease, respondents account for the structural factors which place them at risk and impede access to care. PMID:26432176

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

    PubMed Central

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    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

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

    PubMed

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

    2014-08-22

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

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

    PubMed

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

    2015-01-01

    Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies. PMID:25385865

  5. A 9,000-year record of Chagas' disease

    PubMed Central

    Aufderheide, Arthur C.; Salo, Wilmar; Madden, Michael; Streitz, John; Buikstra, Jane; Guhl, Felipe; Arriaza, Bernardo; Renier, Colleen; Wittmers, Lorentz E.; Fornaciari, Gino; Allison, Marvin

    2004-01-01

    Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from ≈9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, ≈450 B.P. (≈1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite. PMID:14766963

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

    PubMed

    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

  7. Genomic Changes of Chagas Disease Vector, South America

    PubMed Central

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

    2004-01-01

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

  8. Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice

    PubMed Central

    Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; 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 perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD. PMID:25010691

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

    PubMed Central

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

    1983-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas' Disease▿

    PubMed Central

    Davies, Carolina; Cardozo, Rubén Marino; Negrette, Olga Sánchez; Mora, María Celia; Chung, Man Chin; Basombrío, Miguel Ángel

    2010-01-01

    The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent. PMID:20566772

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

    PubMed

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

    2013-09-01

    Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area. PMID:24080893

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

    PubMed

    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

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

    PubMed

    Briceno, Luis; Mosca, Walter

    2016-05-01

    A conservative estimation indicates that more than 400 000 Latin American immigrants are living in Italy. Several studies have shown that among these, the prevalence of Chagas disease is between 3.9% and 17%, so it is not unlikely to find a patient with this disease during a cardiology visit. How many patients from Latin America are diagnosed with heart failure in Italy and no one has ever thought about a possible Chagas disease? This brief review describes the situation of the disease in Italy, its characteristics, the etiology of this disease and its treatment. The latter aspect will be discussed considering the recent published results of the BENEFIT study, where it was found that treatment with benznidazole in patients with Chagas' cardiomyopathy is able to reduce significantly the detection of parasites in the blood, but it is not able to prevent clinical deterioration during 5 years of follow-up. The possible implications of these results will be discussed. PMID:27310907

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-02-01

    The inter-relations between man and the environment are among the main themes currently debated by the Brazilian public health. On such horizon, the questions concerning Chagas's disease are found to remain specially in the scope of the directed actions of control to the triatomine, the anti-vectorial fight , though already a century since its first description by Carlos Chagas, a major epidemiological problem in Latin America. Based on these considerations the present article will seek to discuss the main ecological aspects related to the American trypanosomiasis, emphasizing the control of the vectorial transmission in the context of the deep ecology. PMID:21340344

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2009-01-01

    Inonotus obliquus is a mushroom commonly known as Chaga that is widely used in folk medicine in Siberia, North America, and North Europe. Here, we evaluated the antimutagenic and antioxidant capacities of subfractions of Inonotus obliquus extract. The ethyl acetate extract was separated by vacuum chromatography into three fractions, and the fraction bearing the highest antimutagenic activity was subsequently separated into four fractions by reversed phase (ODS-C18) column chromatography. The most antimutagenic fraction was then separated into two subfractions (subfractions 1 and 2) by normal phase silica gel column chromatography. Ames test analysis revealed that the subfractions were not mutagenic. At 50 μg/plate, subfractions 1 and 2 strongly inhibited the mutagenesis induced in Salmonella typhimurium strain TA100 by the directly acting mutagen MNNG (0.4 μg/plate) by 80.0% and 77.3%, respectively. They also inhibited 0.15 μg/plate 4NQO-induced mutagenesis in TA98 and TA100 by 52.6-62.0%. The mutagenesis in TA98 induced by the indirectly acting mutagens Trp-P-1 (0.15 μg/plate) and B(α)P (10 μg/plate) was reduced by 47.0-68.2% by the subfractions, while the mutagenesis in TA100 by Trp-P-1 and B(α)P was reduced by 70.5-87.2%. Subfraction 1 was more inhibitory than subfraction 2 with regard to the mutagenic effects of 4NQO, Trp-P-1, and B(α)P. Subfractions 1 and 2 also had a strong antioxidant activity against DPPH radicals and were identified by MS, 1H NMR and 13C NMR analyses as 3β-hydroxy-lanosta-8, 24-dien-21-al and inotodiol, respectively. Thus, we show that the 3beta-hydroxy-lanosta-8, 24-dien-21-al and inotodiol components of Inonotus obliquus bear antimutagenic and antioxidative activities. PMID:18992843

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

    PubMed Central

    Cordovez, Juan M; Sanabria, Camilo

    2014-01-01

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

  20. Fexinidazole: A Potential New Drug Candidate for Chagas Disease

    PubMed Central

    Bahia, Maria Terezinha; de Andrade, Isabel Mayer; Martins, Tassiane Assíria Fontes; do Nascimento, Álvaro Fernando da Silva; Diniz, Lívia de Figueiredo; Caldas, Ivo Santana; Talvani, André; Trunz, Bernadette Bourdin; Torreele, Els; Ribeiro, Isabela

    2012-01-01

    Background New safe and effective treatments for Chagas disease (CD) are urgently needed. Current chemotherapy options for CD have significant limitations, including failure to uniformly achieve parasitological cure or prevent the chronic phase of CD, and safety and tolerability concerns. Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi. Methods and Findings We investigated the in vivo activity of fexinidazole against T. cruzi, using mice as hosts. The T. cruzi strains used in the study were previously characterized in murine models as susceptible (CL strain), partially resistant (Y strain), and resistant (Colombian and VL-10 strains) to the drugs currently in clinical use, benznidazole and nifurtimox. Our results demonstrated that fexinidazole was effective in suppressing parasitemia and preventing death in infected animals for all strains tested. In addition, assessment of definitive parasite clearance (cure) through parasitological, PCR, and serological methods showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain, and 77.8% against Colombian strain among animals treated during acute phase, and 70% (VL-10 strain) in those treated in chronic phase. Benznidazole had a similar effect against susceptible and partially resistant T. cruzi strains. Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses. Conclusions Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and resistant T

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

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

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

    PubMed

    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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Increasing Access to Treatment for Chagas Disease: The Case of Morelos, Mexico

    PubMed Central

    Manne-Goehler, Jennifer; Ramsey, Janine M.; Salgado, Marco Ocampo; Wirtz, Veronika J.; Reich, Michael R.

    2014-01-01

    Chagas disease is a neglected vector-borne disease with an estimated prevalence of 1.1 million cases in Mexico. Recent research showed that access to treatment of Chagas disease is limited in Mexico, with < 0.5% of infected cases treated. This brief report used quantitative data from the Morelos Program on Chagas disease and qualitative analysis of key informant interviews to examine strategies to increase treatment access for infected patients in Morelos, Mexico. From 2007 to 2011, 263 (9.2%) of the registered cases of Chagas disease in Mexico occurred in Morelos. Among these, 152 (57.8%) were treated and 97.3% of those treated received benznidazole. The assessment finds that state officials decided to directly purchase benznidazole from the distributor to increase access and improve clinical quality of treatment of patients in their state. They also faced significant barriers, especially in regulation and health system organization, which limited efforts to make high quality treatment available. PMID:25266353

  9. Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects

    PubMed Central

    Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, BT; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto

    2013-01-01

    Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children’s Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA. PMID:23151163

  10. Triatoma sanguisuga Blood Meals and Potential for Chagas Disease, Louisiana, USA

    PubMed Central

    Suarez, Julianne; Richards, Bethany; Dorn, Patricia L.

    2014-01-01

    To evaluate human risk for Chagas disease, we molecularly identified blood meal sources and prevalence of Trypanosoma cruzi infection among 49 Triatoma sanguisuga kissing bugs in Louisiana, USA. Humans accounted for the second most frequent blood source. Of the bugs that fed on humans, ≈40% were infected with T. cruzi, revealing transmission potential. PMID:25418456

  11. Chagas disease in 2 geriatric rhesus macaques (Macaca mulatta) housed in the Pacific Northwest.

    PubMed

    Dickerson, Mary F; Astorga, Nestor Gerardo; Astorga, Nestor Rodrigo; Lewis, Anne D

    2014-08-01

    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission. PMID:25296019

  12. Trypanosoma cruzi strain TcI is associated with chronic Chagas disease in the Brazilian Amazon

    PubMed Central

    2014-01-01

    Background Chagas disease in the Amazon region is considered an emerging anthropozoonosis with a predominance of the discrete typing units (DTUs) TcI and TcIV. These DTUs are responsible for cases of acute disease associated with oral transmission. Chronic disease cases have been detected through serological surveys. However, the mode of transmission could not be determined, or any association of chronic disease with a specific T. cruzi DTU’s. The aim of this study was to characterize Trypanosoma cruzi in patients with chronic Chagas disease in the State of Amazonas, Brazil. Methods Blood culture and xenodiagnosis were performed in 36 patients with positive serology for Chagas disease who participated in a serological survey performed in urban and rural areas of Manaus, Amazonas. DNA samples were extracted from the feces of triatomines used for xenodiagnosis, and the nontranscribed spacer of the mini-exon gene and the mitochondrial gene cytochrome oxidase subunit II (COII) were amplified by PCR and sequenced. Results Blood culture and xenodiagnosis were negative in 100% of samples; however, molecular techniques revealed that in 13 out of 36 (36%) fecal samples from xenodiagnosis, T. cruzi was characterized as the DTU TcI, and different haplotypes were identified within the same DTU. Conclusion The DTU TcI, which is mainly associated with acute cases of Chagas disease in the Amazon region, is also responsible for chronic infection in patients from a region in the State of Amazonas. PMID:24916362

  13. Dynamics of the antibody-T.cruzi competition during Chagas infection: Prognostic relevance of intracellular replication

    NASA Astrophysics Data System (ADS)

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

    2005-02-01

    A recently proposed model for the competitive parasite-antibody interactions in Chagas disease is extended by separately describing the parasitic intracellular and extracellular phases. The model solutions faithfully reproduce available population data and yield predictions for parasite-induced cardiac cell damage.

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

    PubMed Central

    LOPES, Patrícia da Silva; RAMOS, Eliezer Lucas Pires; GÓMEZ-HERNÁNDEZ, César; FERREIRA, Gabriela Lícia Santos; REZENDE-OLIVEIRA, Karine

    2015-01-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results. PMID:27049698

  15. Chaga mushroom extract inhibits oxidative DNA damage in human lymphocytes as assessed by comet assay.

    PubMed

    Park, Yoo Kyoung; Lee, Hyang Burm; Jeon, Eun-Jae; Jung, Hack Sung; Kang, Myung-Hee

    2004-01-01

    The Chaga mushroom (Inonotus obliquus) is claimed to have beneficial properties for human health, such as anti-bacterial, anti-allergic, anti-inflammatory and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protection of cell components against free radicals. We evaluated the effect of aqueous Chaga mushroom extracts for their potential for protecting against oxidative damage to DNA in human lymphocytes. Cells were pretreated with various concentrations (10, 50, 100 and 500 microg/mL) of the extract for 1 h at 37 degrees C. Cells were then treated with 100 microM of H2O2 for 5 min as an oxidative stress. Evaluation of oxidative damage was performed using single-cell gel electrophoresis for DNA fragmentation (Comet assay). Using image analysis, the degree of DNA damage was evaluated as the DNA tail moment. Cells pretreated with Chaga extract showed over 40% reduction in DNA fragmentation compared with the positive control (100 micromol H2O2 treatment). Thus, Chaga mushroom treatment affords cellular protection against endogenous DNA damage produced by H2O2. PMID:15630179

  16. Oral transmission of Chagas disease by consumption of açaí palm fruit, Brazil.

    PubMed

    Nóbrega, Aglaêr A; Garcia, Marcio H; Tatto, Erica; Obara, Marcos T; Costa, Elenild; Sobel, Jeremy; Araujo, Wildo N

    2009-04-01

    In 2006, a total of 178 cases of acute Chagas disease were reported from the Amazonian state of Pará, Brazil. Eleven occurred in Barcarena and were confirmed by visualization of parasites on blood smears. Using cohort and case-control studies, we implicated oral transmission by consumption of açaí palm fruit. PMID:19331764

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results. PMID:27049698

  1. Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

    PubMed

    Vasconcelos, R H T; Azevedo, E de A N; Diniz, G T N; Cavalcanti, M da G A de M; de Oliveira, W; de Morais, C N L; Gomes, Y de M

    2015-07-01

    In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease. PMID:25728555

  2. Chagas Disease in 2 Geriatric Rhesus Macaques (Macaca mulatta) Housed in the Pacific Northwest

    PubMed Central

    Dickerson, Mary F; Astorga, Nestor Gerardo; Astorga, Nestor Rodrigo; Lewis, Anne D

    2014-01-01

    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission. PMID:25296019

  3. Congenital Chagas' disease transmission in the United States: Diagnosis in adulthood.

    PubMed

    Murillo, Jorge; Bofill, Lina M; Bolivar, Hector; Torres-Viera, Carlos; Urbina, Julio A; Benhayon, Daniel; Torres, Jaime R

    2016-01-01

    Two brothers with congenitally-acquired Chagas' disease (CD) diagnosed during adulthood are reported. The patients were born in the USA to a mother from Bolivia who on subsequent assessment was found to be serologically positive for Trypanosoma cruzi. Serologic screening of all pregnant women who migrated from countries with endemic CD is strongly recommended. PMID:27516969

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

    PubMed

    Bravo-Tobar, Iván Darío; Nello-Pérez, Carlota; Fernández, Alí; Mogollón, Nora; Pérez, Mary Carmen; Verde, Juan; Concepción, Juan Luis; Rodriguez-Bonfante, Claudina; Bonfante-Cabarcas, Rafael

    2015-01-01

    Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease. PMID:26603224

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

    BRAVO-TOBAR, Iván Darío; NELLO-PÉREZ, Carlota; FERNÁNDEZ, Alí; MOGOLLÓN, Nora; PÉREZ, Mary Carmen; VERDE, Juan; CONCEPCIÓN, Juan Luis; RODRIGUEZ-BONFANTE, Claudina; BONFANTE-CABARCAS, Rafael

    2015-01-01

    SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease. PMID:26603224

  7. Immunosuppression and Chagas disease; experience from a non-endemic country.

    PubMed

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality. PMID:26055418

  8. High resolution of Trypanosoma cruzi amastigote antigen in serodiagnosis of different clinical forms of Chagas' disease.

    PubMed Central

    Matsumoto, T K; Hoshino-Shimizu, S; Nakamura, P M; Andrade, H F; Umezawa, E S

    1993-01-01

    The serodiagnosis of Chagas' disease, a highly prevalent disorder in South American countries, is usually made by the detection of antibodies to Trypanosoma cruzi epimastigote antigen. In this study, we assess the diagnostic performance of the immunofluorescence test with T. cruzi (Y strain) amastigote antigen from an LLC-MK2-infected cell supernatant in comparison with a test with the conventional epimastigote antigen. A total of 238 serum samples from patients in the acute and chronic phases of the disease, with the chronic indeterminate, cardiac, and digestive forms, and from nonchagasic individuals were tested for the presence of immunoglobulin G (IgG), IgM, and IgA antibodies. The reactivity of the amastigote antigen in terms of geometric mean titers was 2 to 4 times higher than that of the epimastigote antigen. Clear-cut results were obtained with the amastigote antigen, with no overlapping of true and false positives. IgG antibodies to amastigotes were found in all patients with Chagas' disease, whereas all sera from nonchagasic patients were negative, except for those from patients with visceral leishmaniasis, in which 63% cross-reactivity was observed. IgM antibodies to amastigotes were detected in 100% of sera from patients with acute Chagas' disease and in 7.5% of sera from patients with chronic Chagas' disease, whereas IgA antibodies were found in 60% of sera from patients in the acute phase and in 33% of sera from patients in the chronic phase. Despite the cross-reactivity observed with sera from visceral leishmaniasis patients, the IgG immunofluorescence test with the amastigote antigen had the highest sensitivity, specificity, and efficiency. No relationship was observed between the class-specific antibodies or their titers and the clinical forms of patients in the chronic phase. Amastigotes from the cell culture supernatant proved to be useful as an alternative antigen to epimastigotes because of their high resolution in the serodiagnosis of Chagas

  9. Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.

    PubMed

    Pérez-Fuentes, Ricardo; Guégan, Jean-François; Barnabé, Christian; López-Colombo, Aurelio; Salgado-Rosas, Hilda; Torres-Rasgado, Enrique; Briones, Bernardo; Romero-Díaz, Mónica; Ramos-Jiménez, Judith; Sánchez-Guillén, María del Carmen

    2003-03-01

    Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease. PMID:12670514

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

    PubMed

    Soto, Hugo; Tibaduiza, Tania; Montilla, Marleny; Triana, Omar; Suárez, Diana Carolina; Torres Torres, Mariela; Arias, María Teresa; Lugo, Ligia

    2014-04-01

    Colombia recorded 11 cases of acute Chagas disease and 80 cases of oral contamination with Trypanosoma cruzi. The current study analyzes the entomological and parasitological characteristics of the outbreak in Aguachica, Cesar Department, in 2010. An interdisciplinary group of health professionals and regional university personnel conducted the laboratory tests in the patients and the investigation of the transmission focus. Eleven cases of acute Chagas diseases were detected in a single family in a dwelling with domiciliated triatomines and Rhodnius pallescens, Pantrongylus geniculatus, Eratyrus cuspidatus, and two Didelphis marsupialis opossums infected with T. cruzi in Attalea butyracea and Elaeis oleifera palm trees in the urban area of Aguachica. The study analyzes the role of R. pallescens and palm trees in the wild cycle of T. cruzi and in oral transmission of Chagas disease. Sporadic incursions by wild R. pallescens, P. geniculatus, and E. cuspidatus from the nearby palm trees into human dwellings may cause increasingly frequent outbreaks of oral Chagas disease. PMID:24896050

  11. Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells

    PubMed Central

    Youn, Myung-Ja; Kim, Jin-Kyung; Park, Seong-Yeol; Kim, Yunha; Kim, Se-Jin; Lee, Jin Seok; Chai, Kyu Yun; Kim, Hye-Jung; Cui, Ming-Xun; So, Hong Seob; Kim, Ki-Young; Park, Raekil

    2008-01-01

    AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines, HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, flow cytometry analysis, Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells, as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner, which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition, G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53, pRb, p27, cyclins D1, D2, E, cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option, as a potential anticancer agent, in the treatment of hepatoma. PMID:18203281

  12. Circadian entrainment by light and host in the Chagas disease vector, Triatoma infestans.

    PubMed

    Valentinuzzi, Verónica Sandra; Amelotti, Ivana; Gorla, David Eladio; Catalá, Silvia Susana; Ralph, Martin Roland

    2014-03-01

    Triatoma infestans (Reduviidae: Triatominae, "kissing bug") is the main insect vector of Trypanosoma cruzi, the causative agent of Chagas disease, a chronic trypanosomiasis infecting 10 million people world-wide. This hematophagous bug feeds on diurnal and nocturnal species during each host's quiescent time. As the hosts are also its major predators, kissing bugs are subjected to dual selective pressures from a single source. Therefore, synchronization of feeding with the host's behavior is critical to the insects' survival. We show that nonphotic signals linked to the host eclipse the role of light and dark as the primary circadian zeitgeber for these bugs, although light still strongly inhibits locomotor behavior directly. In nature, this combination provides the insect with great flexibility in organizing physiology and behavior: anticipating a quiescent host or avoiding its potential predation while remaining directly responsive to immediate environmental conditions. Manipulation of nonphotic entrainment could be a useful chronobiotic tool in the control of Chagas disease. PMID:24156522

  13. From ancient to contemporary molecular eco-epidemiology of Chagas disease in the Americas.

    PubMed

    Guhl, Felipe; Auderheide, Arthur; Ramírez, Juan David

    2014-08-01

    One of the best-studied populations with regard to Chagas disease is from the coastal area of northern Chile at the foot of the western Andean slopes. The extremely arid climate here generates rapid, spontaneous desiccation of buried bodies, arresting the decay process. The absence of rainfall then preserves these dried bodies (mummies) for millennia. The aim of the present study was to perform the first molecular paleoepidemiological study on a set of 43 mummified human remains from the Atacama Desert in Northern Chile in order to elucidate the transmission dynamics and determinants of ancient genotypes, to try to unravel the natural history of the Trypanosoma cruzi taxon and Chagas disease. Interestingly, TcBat, a recently described Discrete Taxonomic Unit, emerges as the plausible ancestor of T. cruzi. The findings herein presented allow us to present a plausible model of T. cruzi transmission in pre-Columbian civilisations. PMID:24675555

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

    PubMed

    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

  15. New approach towards the synthesis of selenosemicarbazones, useful compounds for Chagas' disease.

    PubMed

    Pizzo, Chiara; Faral-Tello, Paula; Yaluff, Gloria; Serna, Elva; Torres, Susana; Vera, Ninfa; Saiz, Cecilia; Robello, Carlos; Mahler, Graciela

    2016-02-15

    Herein, we describe a new approach towards the synthesis of selenosemicarbazones. The reaction involves an O-Se exchange of semicarbazones using Ishihara reagent. Eleven selenosemicarbazones were prepared using this methodology, with low to moderate yields. Among the prepared compounds the m-bromo phenyl methyl derivative 1b was selected to be evaluated in vivo, in a murine model of acute Chagas' disease. Compound 1b 10 mg/kg bw/day reduced 50% of parasitaemia profile compared with the control group, but was less effective than Benznidazole (50 mg/kg bw/day reduced 90%) and toxic. These studies are important to guide future Chagas drug design. PMID:26774036

  16. Radionuclide evaluation of left-ventricular function in chronic Chagas' cardiomyopathy

    SciTech Connect

    Arreaza, N.; Puigbo, J.J.; Acquatella, H. Casal, H.; Giordano, H.; Valecillos, R.; Mendoza, I.; Perez, J.F.; Hirschhaut, E.; Combellas, I.

    1983-07-01

    Left-ventricular ejection fraction (LVEF) and abnormalities of regional wall motion (WMA) were studied by means of radionuclide ventriculography in 41 patients prospectively diagnosed as having chronic Chagas' disease. Thirteen patients were asymptomatic (ASY), 16 were arrhythmic (ARR), and 12 had congestive heart failure (CHF). Mean LVEF was normal in ASY but markedly depressed in CHF. Regional WMAs were minimal in ASY and their severity increased in ARR. Most CHFs (75%) had diffuse hypokinesia of the left ventricle. Seven patients had a distinct apical aneurysm. Correlation between radionuclide and contrast ventriculography data was good in 17 patients. Selective coronary arteriography showed normal arteries in all patients. Therefore, chronic Chagas' heart disease joins ischemic heart disease as a cause of regional WMA.

  17. Sperm Morphological Features Associated with Chronic Chagas Disease in the Semen of Experimentally Infected Dogs

    PubMed Central

    Rodríguez-Morales, Olivia; Pedro-Martínez, Elvia; Hernández-Pichardo, José Ernesto; Alejandre-Aguilar, Ricardo; Aranda-Fraustro, Alberto; Graullera-Rivera, Verónica; Arce-Fonseca, Minerva

    2014-01-01

    The presence of trypanosomatids in the reproductive systems of different mammals (causing genital lesions in the acute stage of the disease) may predispose the animals to low semen quality. However, there are no studies examining the alterations in the sperm morphological features in the chronic stage of Trypanosoma cruzi infection. Knowledge of these aspects is important to understand the other ways of transmission of the Chagas disease. Progressive motility, mass motility, concentration, and sperm morphology of 84 ejaculates of dogs that were chronically infected with T. cruzi were evaluated. Most of the findings were consistent with the reference values and with those obtained from healthy control dogs. The scrotal circumference was not correlated with spermatozoa concentration in the infected animals. In conclusion, the T. cruzi Ninoa (MHOM/MX/1994/Ninoa) strain does not cause significant alterations in the semen quality of dogs experiencing chronic Chagas disease (at concentrations of 5 × 104 to 1 × 106 parasites per animal). PMID:25114010

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

    PubMed

    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

  19. The impact of Chagas disease control in Latin America: a review.

    PubMed

    Dias, J C P; Silveira, A C; Schofield, C J

    2002-07-01

    Discovered in 1909, Chagas disease was progressively shown to be widespread throughout Latin America, affecting millions of rural people with a high impact on morbidity and mortality. With no vaccine or specific treatment available for large-scale public health interventions, the main control strategy relies on prevention of transmission, principally by eliminating the domestic insect vectors and control of transmission by blood transfusion. Vector control activities began in the 1940s, initially by means of housing improvement and then through insecticide spraying following successful field trials in Brazil (Bambui Research Centre), with similar results soon reproduced in São Paulo, Argentina, Venezuela and Chile. But national control programmes only began to be implemented after the 1970s, when technical questions were overcome and the scientific demonstration of the high social impact of Chagas disease was used to encourage political determination in favour of national campaigns (mainly in Brazil). Similarly, large-scale screening of infected blood donors in Latin America only began in the 1980s following the emergence of AIDS. By the end of the last century it became clear that continuous control in contiguous endemic areas could lead to the elimination of the most highly domestic vector populations - especially Triatoma infestans and Rhodnius prolixus - as well as substantial reductions of other widespread species such as T. brasiliensis, T. sordida, and T. dimidiata, leading in turn to interruption of disease transmission to rural people. The social impact of Chagas disease control can now be readily demonstrated by the disappearance of acute cases and of new infections in younger age groups, as well as progressive reductions of mortality and morbidity rates in controlled areas. In economic terms, the cost-benefit relationship between intervention (insecticide spraying, serology in blood banks) and the reduction of Chagas disease (in terms of medical and

  20. Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease.

    PubMed

    Dandapani, Sivaraman; Germain, Andrew R; Jewett, Ivan; le Quement, Sebastian; Marie, Jean-Charles; Muncipinto, Giovanni; Duvall, Jeremy R; Carmody, Leigh C; Perez, Jose R; Engel, Juan C; Gut, Jiri; Kellar, Danielle; Siqueira-Neto, Jair Lage; McKerrow, James H; Kaiser, Marcel; Rodriguez, Ana; Palmer, Michelle A; Foley, Michael; Schreiber, Stuart L; Munoz, Benito

    2014-02-13

    A phenotypic high-throughput screen using ∼100,000 compounds prepared using Diversity-Oriented Synthesis yielded stereoisomeric compounds with nanomolar growth-inhibition activity against the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. After evaluating stereochemical dependence on solubility, plasma protein binding and microsomal stability, the SSS analogue (5) was chosen for structure-activity relationship studies. The p-phenoxy benzyl group appended to the secondary amine could be replaced with halobenzyl groups without loss in potency. The exocyclic primary alcohol is not needed for activity but the isonicotinamide substructure is required for activity. Most importantly, these compounds are trypanocidal and hence are attractive as drug leads for both acute and chronic stages of Chagas disease. Analogue (5) was nominated as the molecular libraries probe ML341 and is available through the Molecular Libraries Probe Production Centers Network. PMID:24900788

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

    PubMed

    Monsalve, Yoman; Panzera, Francisco; Herrera, Leidi; Triana-Chávez, Omar; Gómez-Palacio, Andrés

    2016-06-01

    The emerging vector of Chagas disease, Triatoma maculata (Hemiptera, Reduviidae), is one of the most widely distributed Triatoma species in northern South America. Despite its increasing relevance as a vector, no consistent picture of the magnitude of genetic and phenetic diversity has yet been developed. Here, several populations of T. maculata from eleven Colombia and Venezuela localities were analyzed based on the morphometry of wings and the mitochondrial NADH dehydrogenase subunit 4 (ND4) gene sequences. Our results showed clear morphometric and genetic differences among Colombian and Venezuelan populations, indicating high intraspecific diversity. Inter-population divergence is suggested related to East Cordillera in Colombia. Analyses of other populations from Colombia, Venezuela, and Brazil from distinct eco-geographic regions are still needed to understand its systematics and phylogeography as well as its actual role as a vector of Chagas disease. PMID:27232127

  2. Diversity-Oriented Synthesis Yields a New Drug Lead for Treatment of Chagas Disease

    PubMed Central

    2013-01-01

    A phenotypic high-throughput screen using ∼100,000 compounds prepared using Diversity-Oriented Synthesis yielded stereoisomeric compounds with nanomolar growth-inhibition activity against the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. After evaluating stereochemical dependence on solubility, plasma protein binding and microsomal stability, the SSS analogue (5) was chosen for structure–activity relationship studies. The p-phenoxy benzyl group appended to the secondary amine could be replaced with halobenzyl groups without loss in potency. The exocyclic primary alcohol is not needed for activity but the isonicotinamide substructure is required for activity. Most importantly, these compounds are trypanocidal and hence are attractive as drug leads for both acute and chronic stages of Chagas disease. Analogue (5) was nominated as the molecular libraries probe ML341 and is available through the Molecular Libraries Probe Production Centers Network. PMID:24900788

  3. [Carlos Chagas Filho: an articulator of the history of sciences in Brazil].

    PubMed

    Domingues, Heloisa Maria Bertol

    2012-06-01

    A letter sent in 1982 by a group of scientists to the president of Conselho Nacional de Desenvolvimento Científico e Tecnológico appealed for a policy of preservation of Brazilian scientific culture. The name of Carlos Chagas Filho topped the list of signatures thereby proving his commitment to that proposal, the ideological structure of which was part of his experience in scientific policy in Brazil and abroad. This document harks back to the practice of the history of the sciences in Brazil and the creation of places for the safeguard and organization of scientific memory, such as the Museu de Astronomia e Ciências Afins, Casa de Oswaldo Cruz and the Sociedade Brasileira de História da Ciência, of which Carlos Chagas Filho was an inaugural member of the board of directors. PMID:22473448

  4. Chagas Disease Vector Control in a Hyperendemic Setting: The First 11 Years of Intervention in Cochabamba, Bolivia

    PubMed Central

    Espinoza, Natalisisy; Borrás, Rafael; Abad-Franch, Fernando

    2014-01-01

    Background Chagas disease has historically been hyperendemic in the Bolivian Department of Cochabamba. In the early 2000s, an extensive vector control program was implemented; 1.34 million dwelling inspections were conducted to ascertain infestation (2000–2001/2003–2011), with blanket insecticide spraying in 2003–2005 and subsequent survey-spraying cycles targeting residual infestation foci. Here, we assess the effects of this program on dwelling infestation rates (DIRs). Methodology/Principal Findings Program records were used to calculate annual, municipality-level aggregate DIRs (39 municipalities); very high values in 2000–2001 (median: 0.77–0.69) dropped to ∼0.03 from 2004 on. A linear mixed model (with municipality as a random factor) suggested that infestation odds decreased, on average, by ∼28% (95% confidence interval [CI95] 6–44%) with each 10-fold increase in control effort. A second, better-fitting mixed model including year as an ordinal predictor disclosed large DIR reductions in 2001–2003 (odds ratio [OR] 0.11, CI95 0.06–0.19) and 2003–2004 (OR 0.22, CI95 0.14–0.34). Except for a moderate decrease in 2005–2006, no significant changes were detected afterwards. In both models, municipality-level DIRs correlated positively with previous-year DIRs and with the extent of municipal territory originally covered by montane dry forests. Conclusions/Significance Insecticide-spraying campaigns had very strong, long-lasting effects on DIRs in Cochabamba. However, post-intervention surveys consistently detected infestation in ∼3% of dwellings, underscoring the need for continuous surveillance; higher DIRs were recorded in the capital city and, more generally, in municipalities dominated by montane dry forest – an eco-region where wild Triatoma infestans are widespread. Traditional strategies combining insecticide spraying and longitudinal surveillance are thus confirmed as very effective means for area-wide Chagas disease vector

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

    SciTech Connect

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

    1987-06-01

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

  6. Geology of the platanares geothermal area, Departamento de Copán, Honduras

    NASA Astrophysics Data System (ADS)

    Heiken, Grant; Ramos, Napoleon; Duffield, Wendell; Musgrave, John; Wohletz, Kenneth; Priest, Sue; Aldrich, James; Flores, Wilmer; Ritchie, Alexander; Goff, Fraser; Eppler, Dean; Escobar, Carlos

    1991-03-01

    The Platanares geothermal area, Departamento de Copán, Honduras, is located within a graben that is complexly faulted. The graben is bounded on the north by a highland composed of Paleozoic (?) metamorphic rocks in contact with Cretaceous - Tertiary redbeds of unknown thickness. These are unconformably overlain by Tertiary andesitic lavas, rhyolitic ignimbrites, and associated sedimentary rocks. The volcanic rocks are mostly older than 14 Ma, and thus are too old to represent the surface expression of an active crustal magma body. Thermal fluids that discharge in the area are heated during deep circulation of meteoric water along faults in a region of somewhat elevated heat flow. Geothermometry based upon the chemical composition of thermal fluids from hot springs and from geothermal gradient coreholes suggests that the reservoir equilibrated at temperatures as high as 225 to 240°C, within the Cretaceous redbed sequence. Three continuously cored geothermal gradient holes have been drilled; fluids of about 165°C have been produced from two drilled along a NW-trending fault zone, from depths of 250 to 680 m. A conductive thermal gradient of 139°C/km, at a depth of 400 m, was determined from the third well, drilled 0.6 km west of that fault zone. These data indicate that the Platanares geothermal area holds considerable promise for electrical generation by moderate- to hightemperature geothermal fluids.

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

    PubMed

    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

  8. A Scientometric Evaluation of the Chagas Disease Implementation Research Programme of the PAHO and TDR

    PubMed Central

    Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E.

    2013-01-01

    The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

  9. Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease.

    PubMed Central

    Combellas, I; Puigbo, J J; Acquatella, H; Tortoledo, F; Gomez, J R

    1985-01-01

    To study left ventricular diastolic function in Chagas's disease, simultaneous echocardiograms, phonocardiograms, and apexcardiograms were recorded in 20 asymptomatic patients with positive Chagas's serology and no signs of heart disease (group 1), 12 with Chagas's heart disease and symptoms of ventricular arrhythmia but no heart failure (group 2), 20 normal subjects (group 3), and 12 patients with left ventricular hypertrophy (group 4). The recordings were digitised to determine left ventricular isovolumic relaxation time and the rate and duration of left ventricular cavity dimension increase and wall thinning. In groups 1 and 2 (a) aortic valve closure (A2) and mitral valve opening were significantly delayed relative to minimum dimension and were associated with prolonged isovolumic relaxation, (b) left ventricular cavity size was abnormally increased during isovolumic relaxation and abnormally reduced during isovolumic contraction, and (c) peak rate of posterior wall thinning and dimension increase were significantly reduced and duration of posterior wall thinning was significantly prolonged; both of these abnormalities occurred at the onset of diastolic filling. These abnormalities were more pronounced in group 2 and were accompanied by an increase in the height of the apexcardiogram "a" wave, an indication of pronounced atrial systole secondary to end diastolic filling impairment due to reduced left ventricular distensibility. Group 4, which had an established pattern of diastolic abnormalities, showed changes similar to those in group 2; however, the delay in aortic valve closure (A2) and in mitral valve opening and the degree of dimension change were greater in the latter group. Thus early isovolumic relaxation and left ventricular abnormalities were pronounced in the patients with Chagas's heart disease and may precede systolic compromise, which may become apparent in later stages of the disease. The digitised method is valuable in the early detection of

  10. Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease.

    PubMed

    Assíria Fontes Martins, Tassiane; de Figueiredo Diniz, Lívia; Mazzeti, Ana Lia; da Silva do Nascimento, Álvaro Fernando; Caldas, Sérgio; Caldas, Ivo Santana; de Andrade, Isabel Mayer; Ribeiro, Isabela; Bahia, Maria Terezinha

    2015-01-01

    The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease. PMID:26076455

  11. Association of Bartonella spp bacteremia with Chagas cardiomyopathy, endocarditis and arrhythmias in patients from South America.

    PubMed

    Corrêa, F G; Pontes, C L S; Verzola, R M M; Mateos, J C P; Velho, P E N F; Schijman, A G; Selistre-de-Araujo, H S

    2012-07-01

    Infection with Bartonella spp may cause cardiac arrhythmias, myocarditis and endocarditis in humans. The aim of the present study was to evaluate a possible association between Bartonella spp bacteremia and endocarditis, arrhythmia and Chagas cardiomyopathy in patients from Brazil and Argentina. We screened for the presence of bacterial 16S rRNA in human blood by PCR using oligonucleotides to amplify a 185-bp bacterial DNA fragment. Blood samples were taken from four groups of subjects in Brazil and Argentina: i) control patients without clinical disease, ii) patients with negative blood-culture endocarditis, iii) patients with arrhythmias, and iv) patients with chronic Chagas cardiomyopathy. PCR products were analyzed on 1.5% agarose gel to visualize the 185-bp fragment and then sequenced to confirm the identity of DNA. Sixty of 148 patients (40.5%) with cardiac disease and 1 of 56 subjects (1.8%) from the control group presented positive PCR amplification for Bartonella spp, suggesting a positive association of the bacteria with these diseases. Separate analysis of the four groups showed that the risk of a Brazilian patient with endocarditis being infected with Bartonella was 22 times higher than in the controls. In arrhythmic patients, the prevalence of infection was 45 times higher when compared to the same controls and 40 times higher for patients with Chagas cardiomyopathy. To the best of our knowledge this is the first report of the association between Bartonella spp bacteremia and Chagas disease. The present data may be useful for epidemiological and prevention studies in Brazil and Argentina. PMID:22584639

  12. Association of Bartonella spp bacteremia with Chagas cardiomyopathy, endocarditis and arrythmias in patients from South America

    PubMed Central

    Corrêa, F.G.; Pontes, C.L.S.; Verzola, R.M.M.; Mateos, J.C.P.; Velho, P.E.N.F.; Schijman, A.G.; Selistre-de-Araujo, H.S.

    2012-01-01

    Infection with Bartonella spp may cause cardiac arrhythmias, myocarditis and endocarditis in humans. The aim of the present study was to evaluate a possible association between Bartonella spp bacteremia and endocarditis, arrhythmia and Chagas cardiomyopathy in patients from Brazil and Argentina. We screened for the presence of bacterial 16S rRNA in human blood by PCR using oligonucleotides to amplify a 185-bp bacterial DNA fragment. Blood samples were taken from four groups of subjects in Brazil and Argentina: i) control patients without clinical disease, ii) patients with negative blood-culture endocarditis, iii) patients with arrhythmias, and iv) patients with chronic Chagas cardiomyopathy. PCR products were analyzed on 1.5% agarose gel to visualize the 185-bp fragment and then sequenced to confirm the identity of DNA. Sixty of 148 patients (40.5%) with cardiac disease and 1 of 56 subjects (1.8%) from the control group presented positive PCR amplification for Bartonella spp, suggesting a positive association of the bacteria with these diseases. Separate analysis of the four groups showed that the risk of a Brazilian patient with endocarditis being infected with Bartonella was 22 times higher than in the controls. In arrhythmic patients, the prevalence of infection was 45 times higher when compared to the same controls and 40 times higher for patients with Chagas cardiomyopathy. To the best of our knowledge this is the first report of the association between Bartonella spp bacteremia and Chagas disease. The present data may be useful for epidemiological and prevention studies in Brazil and Argentina. PMID:22584639

  13. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

    PubMed

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease. PMID:27324760

  14. High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross-Sectional Evaluation

    PubMed Central

    Sánchez-Montalvá, Adrián; Moris, María; Mego, Marianela; Salvador, Fernando; Accarino, Anna; Ramírez, Kathleen; Azpiroz, Fernando; Ruiz-de-Leon, Antonio; Molina, Israel

    2016-01-01

    Introduction Gastrointestinal involvement affects 30–40% of the patients with chronic Chagas disease. Esophageal symptoms appear once the structural damage is established. Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement. Method We performed a cross-sectional study at the Vall d’Hebron University Hospital (Barcelona, Spain) between May 2011 and April 2012. Consecutive patients diagnosed with Chagas disease in the chronic phase were offered to participate. All patients underwent a structured questionnaire about digestive symptoms, a barium esophagogram (Rezende classification) and an esophageal high resolution manometry (HRM). A control group of patients with heartburn who underwent an esophageal HRM in our hospital was selected. Results 62 out of 73 patients that were included in the study fulfilled the study protocol. The median age of the Chagas disease group (CG) was 37 (IQR 32–45) years, and 42 (67.7%) patients were female. Twenty-seven (43.5%) patients had esophageal symptoms, heartburn being the most frequent. Esophagogram was abnormal in 5 (8.77%). The esophageal HRM in the CG showed a pathological motility pattern in 14 patients (22.6%). All of them had minor disorders of the peristalsis (13 with ineffective esophageal motility and 1 with fragmented peristalsis). Hypotonic lower esophageal sphincter was found more frequently in the CG than in the control group (21% vs 3.3%; p<0.01). Upper esophageal sphincter was hypertonic in 22 (35.5%) and hypotonic in 1 patient. When comparing specific manometric parameters or patterns in the CG according to the presence of symptoms or esophagogram no statistically significant association were seen, except for distal latency. Conclusion The esophageal involvement measured by HRM in patients with chronic Chagas disease in our cohort is 22.6%. All the patients with esophageal alterations had minor disorders of the peristalsis. Symptoms and

  15. Human Chagas Disease and Migration in the Context of Globalization: Some Particular Aspects

    PubMed Central

    Pinto Dias, João Carlos

    2013-01-01

    Human Chagas disease originated in Latin America, being spread around the world in relation with multiple bioecological, sociocultural, and political factors. The process of the disease production and dispersion is discussed, emphasizing the human migration and correlated aspects, in the context of globalization. Positive and negative consequences concern the future of this trypanosomiasis, mainly in terms of the ecologic and sociopolitical characteristics of the endemic and nonendemic countries. PMID:23606862

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

    PubMed Central

    Nieto-Sanchez, Claudia; Baus, Esteban G; Guerrero, Darwin; Grijalva, Mario J

    2015-01-01

    Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region. PMID:25807468

  17. The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions - A comprehensive review

    PubMed Central

    Coura, José Rodrigues

    2015-01-01

    This review deals with transmission of Trypanosoma cruzi by the most important domestic vectors, blood transfusion and oral intake. Among the vectors, Triatoma infestans, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidiata, Triatoma brasiliensis, Triatoma pseudomaculata, Triatoma sordida, Triatoma maculata, Panstrongylus geniculatus, Rhodnius ecuadoriensis and Rhodnius pallescens can be highlighted. Transmission of Chagas infection, which has been brought under control in some countries in South and Central America, remains a great challenge, particularly considering that many endemic countries do not have control over blood donors. Even more concerning is the case of non-endemic countries that receive thousands of migrants from endemic areas that carry Chagas disease, such as the United States of America, in North America, Spain, in Europe, Japan, in Asia, and Australia, in Oceania. In the Brazilian Amazon Region, since Shaw et al. (1969) described the first acute cases of the disease caused by oral transmission, hundreds of acute cases of the disease due to oral transmission have been described in that region, which is today considered to be endemic for oral transmission. Several other outbreaks of acute Chagas disease by oral transmission have been described in different states of Brazil and in other South American countries. PMID:25466622

  18. A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors

    PubMed Central

    Farrow, Anitra L.; Peng, Binghao J.; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L.

    2016-01-01

    Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi’s amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the “Antigen Capsid-Incorporation” strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

  19. Modelling inter-human transmission dynamics of Chagas disease: analysis and application.

    PubMed

    Fabrizio, M C; Schweigmann, N J; Bartoloni, N J

    2014-05-01

    Transmission of Trypanosoma cruzi, the causal agent of Chagas disease, has expanded from rural endemic to urban areas due to migration. This so-called urban Chagas is an emerging health problem in American, European, Australian and Japanese cities. We present a mathematical model to analyse the dynamics of urban Chagas to better understand its epidemiology. The model considers the three clinical stages of the disease and the main routes of inter-human transmission. To overcome the complexities of the infection dynamics, the next-generation matrix method was developed. We deduced expressions which allowed estimating the number of new infections generated by an infected individual through each transmission route at each disease stage, the basic reproduction number and the number of individuals at each disease stage at the outbreak of the infection. The analysis was applied to Buenos Aires city (Argentina). We estimated that 94% of the new infections are generated by individuals in the chronic indeterminate stage. When migration was not considered, the infection disappeared slowly and R0 = 0.079, whereas when migration was considered, the number of individuals in each stage of the infection tended to stabilize. The expressions can be used to estimate different numbers of infected individuals in any place where only inter-human transmission is possible. PMID:24533945

  20. Oesophageal motility disorders in infected immigrants with Chagas disease in a non-endemic European area

    PubMed Central

    Valerio, Lluís; Vallès, Xavier; Morales, Betty; Garcia-Diaz, M Immaculada; Pedro-Botet, M Luisa; Serra, Jordi

    2016-01-01

    Background Immigration-related new diseases pose a growing challenge for healthcare services in receptor countries. Following Latin American migration, Chagas disease has inevitably appeared in Europe. Aim To determine the prevalence and characteristics of oesophageal motility disorders in immigrants infected with Trypanosoma cruzi, using high resolution oesophageal manometry (HREM). Methods In all newly-diagnosed cases with chronic Chagas infection referring upper digestive symptoms, a protocolized clinical evaluation and complementary tests including barium oesophagogram and HREM were carried out. As control group, 14 healthy subjects from the same endemic areas were studied with HREM. Results We included 61 patients (46 female, 15 male; age range 26–63 years). Only seven patients (11%) had a minor alteration on barium oesophagogram. By contrast, 23 (37%) patients showed an alteration in oesophageal manometry, mainly minor motility disorders (34%). Only one healthy control (7%) had a minor motility disorder at HREM (p = 0.029 vs. patients). Conclusions Oesophageal motor disorders in infected immigrants with Chagas disease are common, and mainly characterized by a minor motility disorder that is not detected by barium oesophagogram. Hence, as well as barium oesophagogram examination, HREM should be considered, to assess oesophageal damage in this specific group of patients. PMID:27536373

  1. Prevalence and Risk Factors for Chagas Disease in Pregnant Women in Casanare, Colombia

    PubMed Central

    Cucunubá, Zulma M.; Flórez, Astrid C.; Cárdenas, Ángela; Pavía, Paula; Montilla, Marleny; Aldana, Rodrigo; Villamizar, Katherine; Ríos, Lyda C.; Nicholls, Rubén S.; Puerta, Concepción J.

    2012-01-01

    Knowledge of the prevalence and risk factors associated with maternal infection is the first step to develop a surveillance system for congenital transmission of Chagas disease. We conducted a cross-sectional study in Casanare, a disease-endemic area in Colombia. A total of 982 patients were enrolled in the study. A global prevalence of Trypanosoma cruzi infection of 4.0% (95% confidence interval [CI] = 2.8–5.3%) was found. Multivariate analysis showed that the most important risk-associated factors were age > 29 years (adjusted odds ratio [aOR] = 3.4, 95% CI = 0.9–12.4), rural residency (aOR = 2.2, 95% CI = 1.0–4.6), low education level (aOR = 10.2, 95% CI = 1.6–82.7), and previous knowledge of the vector (aOR = 2.2, 95% CI = 1.0–4.9). Relatives and siblings of infected mothers showed a prevalence of 9.3%. These findings may help physicians to investigate congenital cases, screen Chagas disease in siblings and relatives, and provide early treatment to prevent the chronic complications of Chagas disease. PMID:23033397

  2. Evaluation of a Recombinant Trypanosoma cruzi Mucin-Like Antigen for Serodiagnosis of Chagas' Disease ▿

    PubMed Central

    De Marchi, Claudia R.; Di Noia, Javier M.; Frasch, Alberto C. C.; Amato Neto, Vicente; Almeida, Igor C.; Buscaglia, Carlos A.

    2011-01-01

    Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and is one of the most important endemic problems in Latin America. Lately, it has also become a health concern in the United States and Europe. Currently, a diagnosis of Chagas' disease and the screening of blood supplies for antiparasite antibodies are achieved by conventional serological tests that show substantial variation in the reproducibility and reliability of their results. In addition, the specificity of these assays is curtailed by antigenic cross-reactivity with sera from patients affected by other endemic diseases, such as leishmaniasis. Here we used a highly sensitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to evaluate a recombinant protein core of a mucin-like molecule (termed trypomastigote small surface antigen [TSSA]) for the detection of specific serum antibodies in a broad panel of human sera. The same samples were evaluated by CL-ELISA using as the antigen either a mixture of native T. cruzi trypomastigote mucins or an epimastigote extract and, for further comparison, by conventional serologic tests, such as an indirect hemagglutination assay and indirect immunofluorescence assay. TSSA showed ∼87% sensitivity among the seropositive Chagasic panel, a value which was increased up to >98% when only parasitologically positive samples were considered. More importantly, TSSA showed a significant increase in specificity (97.4%) compared to those of currently used assays, which averaged 80 to 90%. Overall, our data demonstrate that recombinant TSSA may be a useful antigen for the immunodiagnosis of Chagas' disease. PMID:21880857

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

    PubMed

    Duthie, Malcolm S; Guderian, Jeffery A; Vallur, Aarthy C; Misquith, Ayesha; Liang, Hong; Mohamath, Raodoh; Luquetti, Alejandro O; Carter, Darrick; Tavares, Suelene N B; Reed, Steven G

    2016-03-01

    We previously reported that tandem repeat (TR) proteins from Trypanosoma cruzi could serve as targets of the antibody response and be useful as diagnostic indicators. To optimize reagents for detecting T. cruzi infection we evaluated individual TR proteins and identified several that were recognized by the majority of Chagas patient's sera collected from individuals form Brazil. We then produced novel, recombinant fusion proteins to combine the reactive TR proteins into a single diagnostic product. Direct comparison of the antibody response of serum samples that were readily detected by the established fusion antigen used in commercial detection of Chagas disease, TcF, revealed strong responses to TcF43 and TcF26 proteins. While the TcF43 and TcF26 antigens enhanced detection and strength of signal, they did not compromise the specificity of detection compared to that obtained with TcF. Finally, it was apparent by testing against a panel of 84 serum samples assembled on the basis of moderate or weak reactivity against TcF (mostly signal:noise <5) that TcF43 and TcF26 could more strongly detected by many of the sera that had low TcF antibody levels. Taken together, these data indicate that TcF43 and TcF26 could be used to enhance the detection of T. cruzi infection as well as supporting a diagnosis of Chagas disease. PMID:26658314

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

    PubMed

    Lima, Marli M; Carvalho-Costa, Filipe A; Toma, Helena K; Borges-Pereira, José; de Oliveira, Tiago Guedes; Sarquis, Otília

    2015-05-01

    Chagas disease was investigated in two new settlements of landless rural workers inhabiting prefabricated, triatomine-proof houses and in four neighboring older communities where mud huts were still well suitable for vectors. Through a cross-sectional survey and entomological assessment, we surveyed 148 houses/families in the two new settlements and in 47 houses/families in the four older localities. We determined seroprevalence of Chagas disease through IFI and Elisa (eluates) assays and searched for vectors in the domestic and peridomestic environments. Seroprevalence reached 0.6% (3/466) in the new settlements and 0.8% (1/115) in the older communities. Triatomines were not found in the new settlements, while 7 Triatoma brasiliensis, 4 T. pseudomaculata, 1 Panstrongylus lutzi, and 145 Rhodnius nasutus were collected in the older localities. In addition, a colony of T. brasiliensis (n = 55) was encountered inside a school attended by children of the region. Parasite strains isolated from the insects were characterized as T. cruzi I. Despite the low prevalence of Chagas disease in both scenarios, entomological surveillance must be strengthened and housing improvement reinforced in order to control vector transmission. The risk of infection by the vectors was lower in the settlements of improved homes, where conditions for colonization of the peridomestic environment by transmitting insects were not observed. PMID:25673077

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

    PubMed

    Nieto-Sanchez, Claudia; Baus, Esteban G; Guerrero, Darwin; Grijalva, Mario J

    2015-05-01

    Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region. PMID:25807468

  6. A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors.

    PubMed

    Farrow, Anitra L; Peng, Binghao J; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L

    2016-03-01

    Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi's amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the "Antigen Capsid-Incorporation" strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

  7. Chagas disease in the 21st Century: a public health success or an emerging threat?

    PubMed Central

    Bonney, Kevin M.

    2014-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health burden in Latin America and a potentially serious emerging threat to a number of countries throughout the world. Although public health programs have significantly reduced the prevalence of Chagas disease in Latin America in recent decades, the number of infections in the United States and non-endemic countries in Europe and the Western Pacific Region continues to rise. Moreover, there is still no vaccine or highly effective cure available for the approximately 10 million people currently infected with T. cruzi, a third of which will develop potentially fatal cardiomyopathy and/or severe digestive tract disorders. As Chagas disease becomes an increasingly globalized public health issue in the twenty-first century, continued attentiveness from governmental and health organizations as well as improved diagnostic tools, expanded surveillance and increased research funding will be required to maintain existing public health successes and stymie the spread of the disease to new areas and populations. PMID:24626257

  8. Symbolic features and classification via support vector machine for predicting death in patients with Chagas disease.

    PubMed

    Sady, Cristina C R; Ribeiro, Antonio Luiz P

    2016-03-01

    This paper introduces a technique for predicting death in patients with Chagas disease using features extracted from symbolic series and time-frequency indices of heart rate variability (HRV). The study included 150 patients: 15 patients who died and 135 who did not. The HRV series were obtained from 24-h Holter monitoring. Sequences of symbols from 5-min epochs from series of RR intervals were generated using symbolic dynamics and ordinal pattern statistics. Fourteen features were extracted from symbolic series and four derived from clinical aspects of patients. For classification, the 18 features from each epoch were used as inputs in a support vector machine (SVM) with a radial basis function (RBF) kernel. The results showed that it is possible to distinguish between the two classes, patients with Chagas disease who did or did not die, with a 95% accuracy rate. Therefore, we suggest that the use of new features based on symbolic series, coupled with classic time-frequency and clinical indices, proves to be a good predictor of death in patients with Chagas disease. PMID:26851730

  9. Access to care for Chagas disease in the United States: a health systems analysis.

    PubMed

    Manne-Goehler, Jennifer; Reich, Michael R; Wirtz, Veronika J

    2015-07-01

    There are 300,000 estimated cases of Chagas disease in the United States but limited data on access to care. This study analyzed trends in access to care for Chagas disease in the United States and assessed the national and state barriers to access. Data on cases in blood donors and drug releases were obtained from the AABB (formerly American Association of Blood Banks) and U.S. Centers for Disease Control and Prevention (CDC), respectively. Semi-structured in-depth interviews were conducted with 30 key informants at the national level and in five states where treatment had been released. Interview responses were analyzed according to the health systems dimensions of regulation, financing, payment, organization, and persuasion. Data indicate that 1,908 cases were identified in the blood donation system from 2007 to 2013 and that CDC released 422 courses of benznidazole or nifurtimox during this period. The barriers to access at the national level include limited diagnostic and institutionalized referral and care processes, lack of financing for patient-care activities, and limited awareness and training among providers. This study demonstrates that access to treatment of Chagas disease in the United States is limited. The lack of licensing is only one of several barriers to access, highlighting the need for a health systems perspective when scaling up access to these essential medicines. PMID:25986581

  10. Prevalence of Chagas Disease in Latin-American Migrants Living in Europe: A Systematic Review and Meta-analysis

    PubMed Central

    Requena-Méndez, Ana; Aldasoro, Edelweiss; de Lazzari, Elisa; Sicuri, Elisa; Brown, Michael; Moore, David A. J.; Gascon, Joaquim; Muñoz, Jose

    2015-01-01

    Background Few studies have assessed the burden of Chagas disease in non-endemic countries and most of them are based on prevalence estimates from Latin American (LA) countries that likely differ from the prevalence in migrants living in Europe. The aim of this study was to systematically review the existing data informing current understanding of the prevalence of Chagas disease in LA migrants living in European countries. Methods We conducted a systematic review and meta-analysis of studies reporting prevalence of Chagas disease in European countries belonging to the European Union (EU) before 2004 in accordance with the MOOSE guidelines and based on the database sources MEDLINE and Global Health. No restrictions were placed on study date, study design or language of publication. The pooled prevalence was estimated using random effect models based on DerSimonian & Laird method. Results We identified 18 studies conducted in five European countries. The random effect pooled prevalence was 4.2% (95%CI:2.2-6.7%); and the heterogeneity of Chagas disease prevalence among studies was high (I2 = 97%,p<0.001). Migrants from Bolivia had the highest prevalence of Chagas disease (18.1%, 95%CI:13.9–22.7%). Conclusions Prevalence of Chagas in LA migrants living in Europe is high, particularly in migrants from Bolivia and Paraguay. Data are highly heterogeneous dependent upon country of origin and within studies of migrants from the same country of origin. Country-specific prevalence differs from the estimates available from LA countries. Our meta-analysis provides prevalence estimates of Chagas disease that should be used to estimate the burden of disease in European countries. PMID:25680190

  11. BNP, NTproBNP, CMBK, and MMP-2 predict mortality in severe Chagas cardiomyopathy

    PubMed Central

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

    2015-01-01

    Background Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival. Objectives Our study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital. Methods The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, ECG findings, medications, and serum cardiac biomarker levels (BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2) were ascertained. Echocardiograms were preferentially performed on those with cardiac symptoms or electrocardiogram abnormalities. Participants were contacted by phone approximately 1 year after initial evaluation; deaths were reported by family members. Receiver operating characteristic curves were used to optimize cut-off values for each marker. For markers with area under curve > 0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality. Results The median follow-up time was 14.1 months (interquartile range 12.5- 16.7 months). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy, 20 (40%) had died. Higher baseline levels of BNP (HR[95% CI]:3.1 [1.2, 8.4]), NTproBNP (4.4[1.8,11.0]), CKMB (3.3[1.3, 8.0]), and MMP-2 (4.2[1.5, 11.8]) were significantly associated with subsequent mortality. Conclusions Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NTproBNP, CKMB and MMP2 have added predictive value for mortality, even in the presence of

  12. alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation.

    PubMed

    Laucella, S A; Riarte, A; Prado, N; Zapata, J; Segura, E L

    2001-05-01

    We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease. PMID:11309161

  13. Clinical, electrocardiographic and echocardiographic abnormalities in Latin American migrants with newly diagnosed Chagas disease 2005-2009, Barcelona, Spain.

    PubMed

    Valerio, L; Roure, S; Sabria, M; Balanzo, X; Valles, X; Seres, L

    2011-01-01

    Following Latin American migration, Chagas disease has inevitably appeared in non-endemic countries in Europe and elsewhere. New policies are necessary to prevent transmission in those countries but the long, often undetected chronic period of the early stages of the disease also renders epidemiological studies important. The main objective of our study was to determine the presence of clinical, electrocardiogram (ECG) and echocardiographic abnormalities in a population of Latin American migrants infected with Trypanosoma cruzi at the moment of diagnosis. We performed a hospital-based observational study of 100 adult patients with newly diagnosed Chagas infection between January 2005 and December 2009. Thirty-seven patients were classified within the Brazilian Consensus on Chagas cardiomyopathy early cardiac stages (A or B1) and 49 presented pathological findings (stage B2) according to the Panamerican Health Organization Classification. Overall, 49 patients showed ECG and/or echocardiographic alterations. The presence of ECG and ecocardiographic alterations were significantly associated (p=0.038). The most frequent ECG and echocardiographic findings were right bundle branch block (12 cases) and impaired left ventricular wall relaxation (24 cases), respectively. In conclusion, ECG and echocardiographic alterations coherent with Chagas cardiomyopathy were found in a large proportion of newly diagnosed Latin American migrants infected with T. cruzi. In the mid-term, Chagas disease might become an important cause of chronic cadiomyopathy in our attendance area. PMID:21958530

  14. [The assessment process within science and the nomination of Carlos Chagas for the Nobel prize for Physiology or Medicine].

    PubMed

    Pittella, José Eymard Homem

    2009-01-01

    One of the greatest achievements in the history of medicine was the description of Chagas disease by the physician and scientist Carlos Chagas. A hundred years after the discovery of the disease, speculation still remains regarding the two official nominations of Carlos Chagas for the Nobel Prize, the biggest worldwide scientific award, in 1913 and in 1921. It has been accepted that the reason why the prize was not awarded to this brilliant scientist may have been the strong opposition that he faced in Brazil, from some physicians and researchers of that time. They went as far as questioning the existence of Chagas disease, thereby possibly influencing the decision of the Nobel Committee not to award the prize to him. Analysis of the database of the Nobel prize archives, with the revelation of the names of nominators, nominees and prizewinners spanning the years 1901-1951, brought information not only about what was considered to be a scientific achievement at that time, but also about who the important scientists were and what the relationships between them were. The non-recognition of Carlos Chagas' discoveries by the Nobel Committee appears to be more correctly explained by these factors than by the negative impact of the local opposition. PMID:19287939

  15. [A study of the antiherpetic activity of the chaga mushroom (Inonotus obliquus) extracts in the Vero cells infected with the herpes simplex virus].

    PubMed

    Polkovnikova, M V; Nosik, N N; Garaev, T M; Kondrashina, N G; Finogenova, M P; Shibnev, V A

    2014-01-01

    The chaga mushroom (Inonotus obliquus) contains a wide range of excellent bioactive compounds. However, limited information exists on the antiviral activity of the compounds extracted from chaga. A number of subfractions of chaga were obtained using different solvents and different procedures. The subfractions of chaga extracted with water, alcohol, alkali were tested for their toxicity for the Vero cell culture and antiviral effect in the Vero cells infected with the Herpes simplex virus (HSV), Type 1. It was shown that most of the subfractions were not toxic for the Vero cells and had protective effect on the Vero cells infected with HSV. The subfraction IV in the concentration 5 microg/ml protected the Vero cells from cytodestructive action of HSV and no viral DNA was detected in infected cells treated with chaga extracts. Best protective effect was observed when compound was added before or within one hour after the Vero cells were infected with HSV. PMID:25069286

  16. Coronary Microvascular Disease in Chronic Chagas Cardiomyopathy Including an Overview on History, Pathology, and Other Proposed Pathogenic Mechanisms

    PubMed Central

    Rossi, Marcos A.; Tanowitz, Herbert B.; Malvestio, Lygia M.; Celes, Mara R.; Campos, Erica C.; Blefari, Valdecir; Prado, Cibele M.

    2010-01-01

    This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease. PMID:20824217

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

    PubMed Central

    Salvador, Fernando; Sulleiro, Elena; Sánchez-Montalvá, Adrián; Martínez-Gallo, Mónica; Carrillo, Eugenia; Molina, Israel

    2016-01-01

    Abstract Background Helminth infections are highly prevalent in tropical and subtropical countries, coexisting in Chagas disease endemic areas. Helminth infections in humans may modulate the host immune system, changing the Th1/Th2 polarization. This immunological disturbance could modify the immune response to other infections. The aim of this study is to evaluate the relationship between clinical, microbiological and epidemiological characteristics of Chagas disease patients, with the presence of helminth infection. Methods A prospective observational study was conducted at Vall d’Hebron University Hospital (Barcelona, Spain). Inclusion criteria were: age over 18 years, diagnosis of Chagas disease, and not having received specific treatment for Chagas disease previously to the inclusion. The study protocol included Chagas disease assessment (cardiac and digestive evaluation, detection of T. cruzi DNA measured by PCR in peripheral blood), and helminth infection diagnosis (detection of IgG anti-Strongyloides stercoralis by ELISA, microscopic examination of stool samples from three different days, and specific faecal culture for S. stercoralis larvae). Results Overall, 65 patients were included, median age was 38 years, 75.4% were women and most of them came from Bolivia. Cardiac and digestive involvement was present in 18.5% and 27.7% of patients respectively. T. cruzi PCR was positive in 28 (43.1%) patients. Helminth infection was diagnosed in 12 (18.5%) patients. No differences were observed in clinical and epidemiological characteristics between patients with and without helminth infection. Nevertheless, the proportion of patients with positive T. cruzi PCR was higher among patients with helminth infection compared with patients without helminth infection (75% vs 35.8%, p = 0.021). Conclusions We observed a high prevalence of S. stercoralis infection among chronic Chagas disease patients attended in our tropical medicine unit. Strongyloidiasis was associated

  18. Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease

    PubMed Central

    Ayo, Christiane Maria; Reis, Pâmela Guimarães; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Oliveira, Camila de Freitas; de Araújo, Silvana Marques; de Oliveira Marques, Divina Seila; Sell, Ana Maria

    2015-01-01

    The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy—CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30–18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy. PMID:25978047

  19. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole.

    PubMed

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-03-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective. PMID:26982179

  20. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole

    PubMed Central

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-01-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective. PMID:26982179

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

    PubMed

    Moncayo, Alvaro; Silveira, Antonio Carlos

    2009-07-01

    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 worldwide network of

  2. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

    PubMed Central

    Khare, Shilpi; Roach, Steven L.; Barnes, S. Whitney; Hoepfner, Dominic; Walker, John R.; Chatterjee, Arnab K.; Neitz, R. Jeffrey; Arkin, Michelle R.; McNamara, Case W.; Ballard, Jaime; Lai, Yin; Fu, Yue; Molteni, Valentina; Yeh, Vince; McKerrow, James H.; Glynne, Richard J.; Supek, Frantisek

    2015-01-01

    Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease. PMID:26186534

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

    PubMed

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard; Supek, Frantisek

    2015-10-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates. PMID:26239982

  4. Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease

    PubMed Central

    da Mota, Fabio Faria; Marinho, Lourena Pinheiro; Moreira, Carlos José de Carvalho; Lima, Marli Maria; Mello, Cícero Brasileiro; Garcia, Eloi Souza; Carels, Nicolas; Azambuja, Patricia

    2012-01-01

    Background Chagas disease is a trypanosomiasis whose agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous bugs known as triatomines. Even though insecticide treatments allow effective control of these bugs in most Latin American countries where Chagas disease is endemic, the disease still affects a large proportion of the population of South America. The features of the disease in humans have been extensively studied, and the genome of the parasite has been sequenced, but no effective drug is yet available to treat Chagas disease. The digestive tract of the insect vectors in which T. cruzi develops has been much less well investigated than blood from its human hosts and constitutes a dynamic environment with very different conditions. Thus, we investigated the composition of the predominant bacterial species of the microbiota in insect vectors from Rhodnius, Triatoma, Panstrongylus and Dipetalogaster genera. Methodology/Principal Findings Microbiota of triatomine guts were investigated using cultivation-independent methods, i.e., phylogenetic analysis of 16s rDNA using denaturing gradient gel electrophoresis (DGGE) and cloned-based sequencing. The Chao index showed that the diversity of bacterial species in triatomine guts is low, comprising fewer than 20 predominant species, and that these species vary between insect species. The analyses showed that Serratia predominates in Rhodnius, Arsenophonus predominates in Triatoma and Panstrongylus, while Candidatus Rohrkolberia predominates in Dipetalogaster. Conclusions/Significance The microbiota of triatomine guts represents one of the factors that may interfere with T. cruzi transmission and virulence in humans. The knowledge of its composition according to insect species is important for designing measures of biological control for T. cruzi. We found that the predominant species of the bacterial microbiota in triatomines form a group of low complexity whose structure

  5. Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

    PubMed Central

    Silva, A. R.; Do Bem, V. A. L.; Bahia, M. T.; Martins-Filho, O. A.; Dias, J. C. P.; Albajar-Viñas, P.; Torres, R. M.; Lana, M.

    2012-01-01

    We performed a critical study of conventional serology, followed by supplementary serological, parasitological, and molecular tests, to assess the response to etiologic treatment of Chagas' disease. A group of 94 Chagas' disease patients treated with benznidazole at least 10 years earlier were evaluated from the laboratory and clinical points of view. When conventional serology (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IIF], and indirect hemagglutination [IHA]) and classic criteria (consistent results with any two of the three tests) or more rigorous criteria (consistent results from the three tests) were used, 10.6% and 8.5% of patients were considered treated and cured (TC) by classic and rigorous criteria, respectively. Patients were then evaluated using supplementary (recombinant ELISA and Trypanosoma cruzi excreted-secreted antigen blotting [TESA-blot]), parasitological (hemoculture), and molecular (PCR) tests. The results of recombinant ELISA were similar to those with the rigorous criterion (three consistent test results). The TESA-blot group showed a higher percentage (21.3%) of negative results than the groups defined by either cure criterion. Hemoculture and PCR gave negative results for all treated and cured (TC) patients, regardless of the criterion used. Recombinant ELISA and TESA-blot tests showed negative results for 70% and 87.5% of the patients categorized as TC by the classic and three-test criteria, respectively. For patients with discordant conventional serology, the supplementary serological and molecular tests were the decisive factor in determining therapeutic failure. Clinical evaluation showed that 62.5% of TC patients presented with the indeterminate form of the disease. Additionally, treated patients with negative TESA-blot results should be reevaluated later with all methodologies used here to verify whether TESA-blot is a reliable way to determine early parasitological cure of Chagas' disease. PMID

  6. Cancer cell cytotoxicity of extracts and small phenolic compounds from Chaga [Inonotus obliquus (persoon) Pilat].

    PubMed

    Nakajima, Yuki; Nishida, Hiroshi; Matsugo, Seiichi; Konishi, Tetsuya

    2009-06-01

    Previously, we studied the antioxidant potential of Chaga mushroom [Inonotus obliquus (persoon) Pilat] extracts and isolated several small (poly)phenolic compounds as the major antioxidant components in the 80% methanol (MeOH) extract. In the present study, these isolated phenolic ingredients together with several other types of Chaga extracts were examined for cytotoxic effects against normal (IMR90) and cancer (A549, PA-1, U937, and HL-60) cell lines. Results revealed decoctions from both the fruiting body (FB) and sclerotium (ST) parts of Chaga, especially the ST part, showed considerable cytotoxicity toward tumor cells, but the cytotoxicity appeared to be stronger against normal cells than cancer cells. The 80% MeOH ST extract also showed the same trend. On the other hand, the 80% MeOH extract of FB showed significant cytotoxicity towards tumor cell lines without affecting normal cells, for example, the 50% lethal dose was 49.4 +/- 2.9 microg/mL for PA-1 cells versus 123.6 +/- 13.8 microg/mL for normal cells. The phenolic components isolated from the 80% MeOH extracts had markedly greater cancer cell toxicity than the extracts themselves. In particular, two out of seven compounds showed strong cytotoxicity towards several tumor cell lines without giving rise to significant cell toxicity toward normal cells. For example, the 50% lethal dose for 3,4-dihydroxybenzalacetone was 12.2 micromol/L in PA-1 cells but was 272.8 micromol/L in IMR90 cells. Fluorescence-activated cell sorting analysis further revealed these phenolic ingredients have high potentiality for apoptosis induction in PA-1 cells. PMID:19627197

  7. Chagas' disease parasite-derived neurotrophic factor activates cholinergic gene expression in neuronal PC12 cells.

    PubMed

    Akpan, Nsikan; Caradonna, Kacey; Chuenkova, Marina V; PereiraPerrin, Mercio

    2008-06-27

    A parasite-derived neurotrophic factor (PDNF) produced by the Chagas' disease parasite Trypanosoma cruzi binds nerve growth factor (NGF) receptor TrkA, increasing receptor autophosphorylation, and activating phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK/Erk) pathways, and transcription factor CREB. The end-result is enhanced survival and neuritogenesis of various types of neurons. PDNF also enhances the expression and activity of tyrosine hydroxylase, a rate limiting enzyme in the synthesis of dopamine and other catecholamine neurotransmitters. It remains unknown, however, if PDNF alters expression and metabolism of acetylcholine (ACh), a neurotransmitter thought to play a role in Chagas' disease progression. Here we demonstrate that PDNF stimulates mRNA and protein expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are critical for synthesis and storage of ACh. Stimulation requires functional TrkA because it did not occur in cell mutants that lack the receptor and in TrkA-expressing wild-type cells treated with K252a, an inhibitor of TrkA kinase activity. It also requires TrkA-dependent PI3K and MAPK/Erk signaling pathways because PDNF stimulation of cholinergic transcripts is abolished by specific pharmacological inhibitors. Furthermore, the cholinergic actions of PDNF were reproduced by PDNF-expressing extracellular T. cruzi trypomastigotes at the start of host cell invasion. In contrast, host cells bearing intracellular T. cruzi showed decreased, rather than increased, cholinergic gene expression. These results suggest that T. cruzi invasion of the nervous system alters cholinergic gene expression and that could play a role in neuropathology, and/or lack thereof, in Chagas' disease patients. PMID:18502403

  8. Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

    PubMed Central

    Lepesheva, Galina I.

    2013-01-01

    Introduction Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14α-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. PMID:24079515

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

    PubMed

    Péneau, Julie; Nguyen, Anne; Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

    2016-02-01

    The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species. PMID:26867025

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

    PubMed Central

    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