Prognosis of chronic Chagas heart disease and other pending clinical challenges.

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Genetic characterization of residual Triatoma infestans populations from Brazil by microsatellite.

In spite of long-term efforts to eliminate Triatoma infestans (Klug 1834) from Brazil, residual foci still persist in the states of Bahia and Rio Grande do Sul. Data on the genetic variability and structuring of these populations are however lacking. Using nine microsatellite loci, we characterized one residual T. infestans population from Bahia and four from Rio Grande do Sul, and compared them with bugs originally from an older focus in São Paulo; 224 bugs were genotyped. The number of alleles per locus ranged from 5 to 11. Observed and expected heterozygosities per locus ranged, respectively, from 0 to 0.786 and from 0 to 0.764. Significant departures from Hardy-Weinberg equilibrium, mainly due to heterozygote deficits, were detected in all loci and in most populations. Global indices estimated by AMOVA were: Fis was 0.37; Fst was 0.28; and Fit was 0.55; overall indices with p = 0.00 indicated substantial differentiation. Inter-population Fst ranged from 0.118 to 0.562, suggesting strong genetic structuring and little to no gene flow among populations. Intra-population Fis ranged from 0.301 to 0.307. Inbreeding was apparent in all populations except that from Bahia-which might be either linked by gene flow to nearby unsampled populations or part of a relatively large local population. The overall pattern of strong genetic structuring among pyrethroid-susceptible residual T. infestans populations suggests that their persistence is probably due to operational control failures. Detection and elimination of such residual foci is technically feasible and must become a public health priority in Brazil.

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

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.

A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention.

The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.

First report of Panstrongylus megistus sylvatic focus in municipality of Bambuí, state of Minas Gerais, Brazil.

In 1943, the Center for the Study and Prophylaxis of Chagas Disease, Oswaldo Cruz Foundation, state of Minas Gerais (MG), was created in the municipality of Bambuí to carry out studies related to Chagas disease in the mid-western region of MG. Since that time, several investigations have been conducted to determine the natural habitat of triatomines, but Panstrongylus megistus colonies have never been found in this region. This paper records the first finding of a P. megistus sylvatic colony in 69 years of research. The characteristics of this ecotope and its implications for the epidemiology of Chagas disease are discussed.

Susceptibility of Triatoma brasiliensis from state of Ceará, Northeastern Brazil, to the pyrethroid deltamethrin.

After controlling Triatoma infestans in Brazil, other species of triatomine that were considered minor in the transmission of Chagas disease became important. The persistence of Triatoma brasiliensis in Northeastern Brazil, associated with reinfection of domestic environments recently sprayed with pyrethroids, may be a signal of susceptibility alteration of this species to this insecticide. Specimens of T. brasiliensis from the municipality of Tauá, state of Ceará, were captured before and one year after spraying. They were submitted to bioassays using deltamethrin. The LD50 ranged from 0.19-0.33 ng of deltamethrin/nymph. The resistance ratio among samples from Tauá varied from 1.16-1.79 in the samples captured before the spraying and 1.00-1.74 in the samples captured one year after spraying, demonstrating that the two populations were equally susceptible to deltamethrin. The small difference in susceptibility between the two captures suggests that T. brasiliensis obtained in the second capture are from new invasions of the domestic environment and that the insecticide did not select resistant individuals. Therefore, it is suggested that T. brasiliensis control be carried out supplementing the regular use of pyrethroids with complementary measures, such as improvement of the dwellings and health education.

Elimination of Chagas disease transmission: perspectives.

One hundred years after its discovery by Carlos Chagas, American trypanosomiasis, or Chagas disease, remains an epidemiologic challenge. Neither a vaccine nor an ideal specific treatment is available for most chronic cases. Therefore, the current strategy for countering Chagas disease consists of preventive actions against the vector and transfusion-transmitted disease. Here, the present challenges, including congenital and oral transmission of Trypanosoma cruzi infections, as well as the future potential for Chagas disease elimination are discussed in light of the current epidemiological picture. Finally, a list of challenging open questions is presented about Chagas disease control, patient management, programme planning and priority definitions faced by researchers and politicians.

Epidemiology, control and surveillance of Chagas disease: 100 years after its discovery.

Chagas disease originated millions of years ago as an enzootic infection of wild animals and began to be transmitted to humans as an anthropozoonosis when man invaded wild ecotopes. While evidence of human infection has been found in mummies up to 9,000 years old, endemic Chagas disease became established as a zoonosis only in the last 200-300 years, as triatomines adapted to domestic environments. It is estimated that 15-16 million people are infected with Trypanosoma cruzi in Latin America, and 75-90 million are exposed to infection. Control of Chagas disease must be undertaken by interrupting its transmission by vectors and blood transfusions, improving housing and areas surrounding dwellings, providing sanitation education for exposed populations and treating acute and recently infected chronic cases. These measures should be complemented by surveillance and primary, secondary and tertiary care.

Susceptibility of triatoma infestans to deltamethrin in Rio Grande do Sul, Brazil.

Strategies for controlling Chagas disease are based on spraying infested houses with pyrethroid insecticides. However, the intense use of these insecticides has promoted resistance of Triatoma infestans and, in Argentina, Bolivia and Southern Brazil, low levels of resistance have been reported. Due to the persistence of T. infestans in the state of Rio Grande do Sul (RS), we evaluated the occurrence of deltamethrin resistance in four strains from different municipalities in comparison to two susceptible strains from Brazil and one resistant strain from Bolivia. The results indicated the absence of resistance in T. infestansfrom RS.

[About an insecticidal paint for controlling Triatoma infestans, in Bolivia]. / Sobre uma pintura inseticida para o controle de Triatoma infestans, na Bolívia.

Preliminary evaluations of an insecticidal paint based on diazinon, chlorpyrifos and pyriproxyfen in a micro-encapsulated formulation (Inesfly 5A IGR) have shown that it has effective and persistent activity against Triatoma infestans inside homes and in areas surrounding homes, in a highly infested region of the Bolivian Chaco. Furthermore, the evaluations have highlighted that the product presents good handling characteristics and gives a good appearance to houses and outhouses that have been treated, and that its acceptance among the population and the local sanitary authorities is excellent. This encourages new investigations and the use of the product on a larger scale and against other vector species for Chagas disease.

Problems and perspectives for Chagas disease control: in search of a realistic analysis.

Chagas disease was an important medical and social problem in almost all of Latin America throughout the twentieth century. It has been combated over a broad swath of this continent over recent decades, with very satisfactory results in terms of vector and transfusional transmission. Today, a surveillance stage still remains to be consolidated, in parallel with appropriate care required for some millions of infected individuals who are today living in endemic and non-endemic areas. Contradictorily, the good results attained have generated excessive optimism and even disregard among health authorities, in relation to this disease and its control. The loss of visibility and priority may be a logical consequence, particularly in Latin American healthcare systems that are still disorganized and overburdened due to insufficiencies of financial and human resources. Consolidation of the victories against Chagas disease is attainable but depends on political will and continual attention from the most consequential protagonists in this struggle, especially the Latin American scientific community.

Chagas disease as a mechanistic model for testing a novel hypothesis.

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.

Conhecimentos sobre a doença de Chagas entre escolares de dois municípios de Minas Gerais, Brasil / Knowledge about Chagas disease among schoolchildren from two municipalities of Minas Gerais, Brazil

Resumo Introdução: No Brasil, a vigilância entomológica da doença de Chagas (DCh) é respaldada na participação comunitária, que notifica a presença dos vetores nas habitações. Assim, a sustentabilidade desta medida de controle depende do conhecimento da população sobre os vetores. Objetivo: Avaliar o conhecimento de escolares sobre a doença de Chagas nos municípios mineiros de Itatiaiuçu (vigilância ativa) e Sabará (vigilância inativa). Método: Questionário semiestruturado foi aplicado para alunos matriculados no ensino médio em duas escolas de Sabará (rural e urbana) e uma em Itatiaiuçu (urbana). Resultados: Em geral, os alunos residentes em Sabará demonstraram conhecimento limitado acerca dos vetores, patógeno, transmissão e doença (sem diferenças relevantes quanto à localização entre área urbana e rural), quando comparados aos residentes em Itatiaiuçu, que apesar de ter uma vigilância mais atuante, também não apresentaram conhecimento totalmente satisfatório. Conclusões: Os resultados enfatizam a carência de informações sobre a DCh tanto em relação ao conhecimento acadêmico quanto às campanhas de educação firmadas pelo programa. Ações educativas para sensibilizar a comunidade e promover o conhecimento sobre esta doença mostram-se necessárias e fundamentais para a manutenção da vigilância ao longo do tempo e espaço.

Abstract Background: In Brazil, entomological surveillance of Chagas disease (ChD) is based on community participation, which notifies the presence of vectors inside their homes. Thus, the sustainability of this control measure depends on the knowledge of the population about the vectors. Objective: To evaluate the knowledge of schoolchildren about ChD in the municipalities of Itatiaiuçu (active surveillance) and Sabará (inactive surveillance). Method: A semi-structured questionnaire was given to students enrolled in two high schools in Sabará (rural and urban) and one in Itatiaiuçu (urban). Results: In general, students living in Sabará demonstrated only limited knowledge about vectors, pathogens, transmission, and disease (with no significant differences between the schools in urban and rural areas). Similarly, the schoolchildren in Itatiaiuçu, despite living in an area of active surveillance, also did not have a fully satisfactory knowledge of ChD. Conclusions: The results emphasize the lack of information about ChD, both in relation to academic knowledge and the education campaigns established by the program. Improvements in educational interventions to raise community awareness and promote knowledge about ChD are necessary and vital for maintaining vigilance against ChD over space and time.

Non-conventional flow cytometry approaches to detect anti-Trypanosoma cruzi immunoglobulin G in the clinical laboratory.

We have recently developed a flow cytometric approach to detect anti-live trypomastigote and anti-fixed epimastigote IgG antibodies (FC-ALTA and FC-AFEA) in sera from individuals infected by Trypanosoma cruzi. Here, we present the first evaluation of the applicability of FC-AFEA-IgG as a diagnostic tool for Chagas disease. Performance analysis demonstrated that FC-AFEA-IgG has a sensitivity of 82% and a specificity of 100%. The assessment for prognosis performed by FC-ALTA-IgG1 and FC-AFEA-IgG, after classification of chagasic patients as belonging to indeterminate (IND), cardiac (CARD) or digestive (DIG) clinical forms, showed that most of IND have higher amounts of IgG than individuals' carrying CARD or DIG Chagas disease. FC-AFEA-IgG was also evaluated as a method to monitor chemotherapy efficacy in individuals classified into three distinct categories: not treated (NT), treated but not cured (TNC), and treated and cured (TC). Performance analysis demonstrated that FC-AFEA-IgG has an extraordinary capacity as a serological criterion to assess cure after therapeutic intervention in Chagas disease. These results represent a great advance in the application of serological techniques for clinical investigations on Chagas disease, and they clearly define new directions and perspectives. We intend to continue this field research focusing our attention on the influence of the degree of clinical damage on the FC-ALTA-IgG1 and FC-AFEA-IgG reactivity.

[Globalization, inequity and Chagas disease]. / Globalização, iniqüidade e doença de Chagas.

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.

[Chagas disease epidemiological surveillance in a decentralized program: evaluation of practice and knowledge among municipal health agents in an endemic region of Minas Gerais State, Brazil]. / Vigilância epidemiológica da doença de Chagas em programa descentralizado: avaliação de conhecimentos e práticas de agentes municipais em região endêmica de Minas Gerais, Brasil.

This study aimed to evaluate the epidemiological surveillance of Chagas disease in the central-western region of Minas Gerais State, Brazil, based on knowledge and practice among municipal health agents working in the Chagas Disease Control Program. Thirty-five municipalities (counties) were visited, with meetings and application of a questionnaire on knowledge, practice, and difficulties in conducting the surveillance work. Twenty-six agents were on temporary (annual) contracts, and only two had job stability. 77.1% of the agents commented that the local population had difficulty identifying the vector insects (triatomines). Twenty-three employees stated that the municipal governments provided adequate conditions for conducting the surveillance program, although 27 made suggestions, particularly requesting more educational materials, better wages, and greater appreciation of their work by the municipal governments. Such suggestions are crucial to the consolidation of the program's results.

Prognosis of chronic Chagas heart disease and other pending clinical challenges

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Seroprevalence of Chagas disease in schoolchildren from two municipalities of Jequitinhonha Valley, Minas Gerais, Brazil; six years following the onset of epidemiological surveillance.

Six years after the beginning of the epidemiological surveillance of Chagas disease in Berilo and José Gonçalves de Minas, Jequitinhonha Valley, MG, Brazil, a serological inquiry was performed to observe whether the transmission of this endemy was occurring in this area. A randomized sample of 1,412 children seven to 14 years old, was screened. Six asymptomatic children were found to be positive, leading to 0.4% of prevalence. Hemoculture confirmed infection in five out of the six positive cases. Additional epidemiological investigation revealed important antecedents, such as disease reports in relatives and predisposing ecological and housing conditions. Our results demonstrated similar seroprevalence (0.4%) in schoolchildren, ranging from seven to 14 years old, and that were observed six years ago (0.2%) for children 0-9 year-old. Thus, considering the constant presence of Panstrogylus megistus in the peridomicile these findings emphasize the need of continuous improved epidemiological surveillance of Chagas disease in this region.

[Notes about of Trypanosoma cruzi and yours bio-ecology characteristics with agents of the transmission by meals]. / Notas sobre o Trypanosoma cruzi e suas características bio-ecológicas, como agente de enfermidades transmitidas por alimentos.

Experimental evidence and field observations concerning the oral transmission of Trypanosoma cruzi to human beings and mammalian species are reviewed, confirming its unquestionable occurrence, mainly in the enzootic cycle of the parasite. Several types of foods and carriers of the flagellate have been involved in this transmission route, where the human cases are generally related to infected triatomines and/or natural reservoirs in the proximities of the event. The penetration points of the parasite (mouth, esophagus, stomach and intestinal mucosae) are reviewed, as well as the general anatomic and pathological processes, such as hemorrhagic phenomena, mesenteritis and interstitial hepatitis. In particular, different aspects of the biology and biochemistry of the parasite are analyzed, especially in terms of its epidemiology and the possibilities of the prevention of the oral transmission of Chagas' disease.

[Integral insecticide spraying followed by immediate triatomine research, as an additional strategy for the epidemiological surveillance of Chagas' disease, in areas of residual persisting foci]. / Nota sobre borrifação integral seguida de pesquisa, como estratégia de vigilância epidemiológica da doença de Chagas, em áreas de recrudescência de focos domiciliares de triatomíneos.

The locality of Altolândia (Tapiraí Municipality, Minas Gerais, Brazil), frequently presents Panstrongylus megistus infestation in the domiciliary environment. In order to improve epidemiological surveillance in this area, a strategy of domiciliary pyrethroid spraying with high flushing-out effect followed by immediate triatomine research, was implemented in all the existing dwellings. The main objectives were the detection and elimination of cryptic foci, thus reducing the opportunities for new infestations.