Revisiting the History of Chagas Disease: "Live to tell"

Abstract In 1907, Carlos Chagas was designated to fight paludism in the Rio das Velhas region along the Central do Brasil railroad. During his field research, Chagas discovered a hematophagous insect ( Panstrongylus megitus ) carrying a new trypanosomatide, which he named Trypanosoma cruzi . On April 14th, 1909, he found the same parasite in the blood of a febrile child, submitting the announcement of his discoveries to the Brasil Médico scientific journal. Here, we discuss the early stages in the establishment of a new human morbid entity during the first decades after its discovery with a definite influence from its discoverer, Carlos Chagas, as well the first collaborators. Moreover, we cover the importance of the Center for the Study and Prophylaxis of Chagas Disease in Bambuí (MG), unraveling the most advanced developments in research within the disease's habitat and the widening perspectives for modern research that have emerged after the 1960s and continue to improve to this day. In this revisitation to the history of Chagas disease, we begin at Manguinhos (RJ ), making our way to Lassance (MG), where the discovery took place. Then, we travel back to Rio de Janeiro in the beginning of the twentieth century and Brazilian republic until the current day, revealing milestone publications that settled Chagas disease both as a source of pride for Brazilian medicine and as a challenge with important aspects that remain to be clarified. Any similarities to our country's politics and economy in the twentieth century are not mere coincidences.

Acometimento miocárdico na Doença de Chagas: uma perspectiva a partir da avaliação pela ressonância magnética cardiovascular / Myocardial involvement in Chagas Disease: from the perspective of cardiovascular magnetic ressonance assessment

A doença de Chagas representa um importante problema de saúde pública, sobretudo nos países endêmicos da América Latina. Dentre suas apresentações clínicas, a cardiomiopatia crônica é a mais frequente. De patogênese multifatorial, o acometimento miocárdico pode levar à insuficiência cardíaca, a eventos tromboembólicos, a arritmias e à morte súbita. Nesse contexto, a ressonância magnética cardiovascular é um excelente método não invasivo para a investigação do dano miocárdico e a compreensão dos mecanismos e consequências relacionados às essas lesões. Com elevada resolução espacial e capacidade de caracterização tecidual, a ressonância magnética cardiovascular proporciona análise morfofuncional altamente confiável e possibilita a identificação de marcadores de risco de eventos adversos em pacientes com doença de Chagas, sendo de grande utilidade para o diagnóstico e o acompanhamento desses indivíduos na rotina clínica. (AU)

Chagas disease represents an important public health problem, especially in endemic countries in Latin America. Chronic cardiomyopathy is its most frequent clinical presentation. Myocardial involvement has a multifactorial pathogenesis and can lead to heart failure, thromboembolic events, arrhythmias, and sudden death. In this context, cardiovascular magnetic resonance imaging (CMR) is an excellent noninvasive method for investigating myocardial damage and understanding the mechanisms and consequences of these injuries. CMR has high spatial resolution and tissue characterization capacity, enabling a highly reliable morphofunctional analysis and the identification of risk markers for adverse events in patients with Chagas disease. This exam is very useful for the diagnosis and follow-up of these patients in the routine clinical setting. (AU)

La justicia social en salud y su relación con la enfermedad de Chagas / Social Justice in Health and its Relationship with Chagas Disease

Introducción: El mal de Chagas es una de las enfermedades consideradas como desatendidas, según la Organización Mundial de la Salud, se encuentra dentro del conjunto de las 17 enfermedades que afectan especialmente a personas que viven en los trópicos. Objetivo: Describir el estado investigativo sobre la enfermedad de Chagas en entornos de la justicia social en salud. Métodos: Se realizó una revisión narrativa, que incluyó 21 estudios empíricos sobre justicia social, bioética y enfermedad de Chagas. La búsqueda se realizó en idioma español, inglés y portugués. El procedimiento se desarrolló en cuatro etapas: búsqueda bibliográfica, sistematización de datos, elección de artículos, evaluación final y análisis temático previa codificación abierta. Se excluyeron estudios clínicos y no se tuvo en cuenta la calidad de su metodología para su inclusión. Se revisaron 21 estudios empíricos de Latinoamérica, Estados Unidos y Europa con diferentes diseños cuantitativos, cualitativos y mixtos. La revisión fue realizada sin límite de tiempo, incluyó estudios hasta la fecha en que se realizó la investigación. Conclusiones: Los enfoques multidisciplinarios que incorporan las actividades de atención en salud, condiciones de vida de las poblaciones y estado de salud son herramientas para reducir la incidencia de la enfermedad de Chagas a largo plazo. Esta enfermedad se vincula con experiencias de marginación, pobreza rural con múltiples impedimentos para acceder al sistema de salud, aspectos que están relacionados con la justicia social en salud y la bioética, todos presentes en procesos socioculturales, políticos y económicos que pueden ser analizados desde la salud pública(AU)

Introduction: Chagas disease is one of the conditions considered as "neglected," according to the World Health Organization, is one of the 17 diseases that affect especially people living on the tropics. Objective: To describe the research status concerning Chagas disease in healthcare social justice settings. Methods: A narrative review was carried out, which included 21 empirical studies on social justice, bioethics and Chagas disease. The search was carried out in Spanish, English and Portuguese. The procedure was developed in four stages: bibliographic search, data systematization, article selection, final evaluation and thematic analysis after open coding. Clinical studies were excluded, while the quality of their methodology was not taken into account for their inclusion. Twenty-one empirical studies with different quantitative, qualitative and mixed designs were reviewed, from Latin America, the United States, and Europe. The review was conducted without a time limit and included studies up to the date the research was conducted. Conclusions: Multidisciplinary approaches that involve healthcare activities, population living conditions, and health status are tools for reducing the incidence of Chagas disease in the long term. This disease is associated with experiences of marginalization and rural poverty, with multiple impediments for healthcare access, aspects related to social justice in health and bioethics, all present in sociocultural, political and economic processes that can be analyzed from the field of public health(AU)

Spatial patterns and temporal tendency of mortality related to Chagas disease in an endemic area of northeastern Brazil.

OBJECTIVE: To analyse spatial patterns and the temporal tendency of mortality related to Chagas disease, in order to identify priority control areas in the state of Sergipe, Northeast Brazil. METHODS: We conducted an ecological and time-series study with spatial analysis techniques on deaths from Chagas disease in the state of Sergipe (1996-2016). We used data from the Mortality Information System (SIM). The temporal analysis was performed using a statistical technique capable of describing changes in the trend pattern for the period. Thematic maps were elaborated from point and polygonal analyses. RESULTS: There were 247 deaths related to Chagas disease, with a mean of 11.7 deaths/year, most of them male (64%), and aged 50-59 years (21%) and 60-69 years (26%). Two segments with increasing, non-constant and significant trends were identified: 1996-2005 (APC = 21.6%; P = 0.01) and 2005-2016 (APC = 4.4%; P = 0.01), with APPC = 11.8% (P = 0.01). A positive and significant spatial autocorrelation with areas of higher risk of death was found in the southern region of the state. CONCLUSIONS: The trend of mortality related to Chagas disease in the state of Sergipe was increasing during the period analysed, with a heterogeneous distribution of cases. A main risk area was identified in the southern region of the state.

OBJECTIF: Analyser les profils spatiaux et la tendance temporelle de la mortalité liée à la maladie de Chagas, afin d'identifier les domaines de priorité de lutte dans l'Etat de Sergipe, dans le nord-est du Brésil. MÉTHODES: Nous avons mené une étude écologique et de séries chronologiques avec des techniques d'analyse spatiale sur les décès dus à la maladie de Chagas dans l'état de Sergipe (1996-2016). Nous avons utilisé les données du système d'information sur la mortalité (SIM). L'analyse temporelle a été réalisée à l'aide d'une technique statistique capable de décrire les changements dans le profil de tendance pour la période. Des cartes thématiques ont été élaborées à partir d'analyses ponctuelles et polygonales. RÉSULTATS: Il y a eu 247 décès liés à la maladie de Chagas, avec une moyenne de 11,7 décès/an, pour la plupart de sexe masculin (64%), et âgés de 50 à 59 ans (21%) et de 60 à 69 ans (26%). Deux segments avec des tendances à la hausse, non constantes et significatives ont été identifiés: 1996-2005 (APC = 21,6%; p = 0,01) et 2005-2016 (APC = 4,4%; p = 0,01), avec APPC = 11,8% (p = 0,01). Une autocorrélation spatiale positive et significative avec des zones à haut risque de décès a été trouvée dans la région sud de l'Etat. CONCLUSIONS: La tendance de la mortalité liée à la maladie de Chagas dans l'état de Sergipe a augmenté au cours de la période analysée , avec une répartition hétérogène des cas. Une principale zone à risque a été identifiée dans la région sud de l'Etat.

Potential association of Trypanosoma cruzi DTUs TcV and TcVI with the digestive form of Chagas disease.

The relationship among genetic diversity of Trypanosoma cruzi and clinical forms of Chagas disease remain elusive. In order to assess the possible association between different T. cruzi Discrete Typing Units (DTUs) and the clinical pictures of the disease, 205 chronic patients from Salta province, Argentina, were analysed. One hundred and twenty-two of these patients were clinically categorized as: cardiac 38.5% (47/122), digestive 15% (18/122), cardio-digestive 16% (20/122) and asymptomatic 30% (37/122). From each patient, blood samples were taken for both, Polymerase Chain Reaction (PCR) targeting kDNA and blood culture analyses. The presence of T. cruzi kDNA was detected in 43% (88/205) of the patients. T. cruzi DTUs were identified in 74% (65/88) of the kDNA positive patients by PCR-hybridization using specific probes. We detected the presence of DTUs TcI, TcII, TcV and TcVI. Single infections (i.e. presence of only one DTU in the sample) were detected in 38.64% of the samples (34/88), while mixed infections were 35.23% (31/88). TcV was the most prevalent DTU (60.3%- 53/88). The association analyses showed, for the first time to the best of our knowledge, that TcV and TcVI were associated with the digestive form of Chagas Disease (Fisher p = .0001).

Genetic polymorphisms of IL17A associated with Chagas disease: results from a meta-analysis in Latin American populations.

Genetic factors and the immunologic response have been suggested to determine the susceptibility against the infection and the outcome of Chagas disease. In the present study, we analysed three IL17A genetic variants (rs4711998, rs8193036 and rs2275913) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC) in different Latin American populations. A total of 2,967 individuals from Colombia, Argentina, Bolivia and Brazil, were included in this study. The individuals were classified as seronegative and seropositive for T. cruzi antigens, and this last group were divided into asymptomatic and CCC. For T. cruzi infection susceptibility, the IL17A rs2275913*A showed a significant association in a fixed-effect meta-analysis after a Bonferroni correction (P = 0.016, OR = 1.21, 95%CI = 1.06-1.41). No evidence of association was detected when comparing CCC vs. asymptomatic patients. However, when CCC were compared with seronegative individuals, it showed a nominal association in the meta-analysis (P = 0.040, OR = 1.20, 95%CI = 1.01-1.45). For the IL17A rs4711998 and rs8193036, no association was observed. In conclusion, our results suggest that IL17A rs2275913 plays an important role in the susceptibility to T. cruzi infection and could also be implicated in the development of chronic cardiomyopathy in the studied Latin American population.

Fatal acute Chagas disease by Trypanosoma cruzi DTU TcI, Ecuador.

BACKGROUND: Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis. CASE PRESENTATION: A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died. CONCLUSIONS: This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.

Lizards and rabbits may increase Chagas infection risk in the Mediterranean-type ecosystem of South America.

Studies of host-parasite relationships largely benefit from adopting a multifactorial approach, including the complexity of multi-host systems and habitat features in their analyses. Some host species concentrate most infection and contribute disproportionately to parasite and vector population maintenance, and habitat feature variation creates important heterogeneity in host composition, influencing infection risk and the fate of disease dynamics. Here, we examine how the availability of specific groups of hosts and habitat features relate to vector abundance and infection risk in 18 vector populations along the Mediterranean-type ecosystem of South America, where the kissing bug Mepraia spinolai is the main wild vector of the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. For each population, data on vectors, vertebrate host availability, vegetation, precipitation, and temperature were collected and analyzed. Vector abundance was positively related to temperature, total vegetation, and European rabbit availability. Infection risk was positively related to temperature, bromeliad cover, and reptile availability; and negatively to the total domestic mammal availability. The invasive rabbit is suggested as a key species involved in the vector population maintenance. Interestingly, lizard species -a group completely neglected as a potential reservoir-, temperature, and bromeliads were relevant factors accounting for infection risk variation across populations.

Geographic distribution of Trypanosoma cruzi genotypes detected in chronic infected people from Argentina. Association with climatic variables and clinical manifestations of Chagas disease.

Chronic Chagas disease affects large number of people in Latin America where it remains one of the biggest public health problems. Trypanosoma cruzi is genetically divided into seven discrete typing units (DTUs), TcI-TcVI and Tcbat, and exhibits differential distribution across vectors, host and transmission cycles. Clinical manifestations (cardiac, digestive and / or neurological) vary according to the geographical region; and the DTUs more frequently found in any of the chronic form of the disease, indeterminate or clinical, are TcI, TcII, TcV and TcVI. However, why they have a particular geographical distribution and how they affect the development of Chagas disease is still unknown. In this study, we assessed the geographic distribution of T. cruzi genotypes detected in chronic infected people from 57 localities of endemic regions of Argentina and analyzed their association with climatic variables. The prevalent DTUs detected in the whole population were TcV (47.4%) and TcVI (66.0%). TcI and TcII were identified in 5.2% each. All DTUs were detected in single and mixed infections (78.4% and 21.6%, respectively). TcV was found in infected people from localities with significantly higher average annual temperature, seasonal temperature and annual temperature range than those infected with TcVI. When we evaluated the association of DTUs with clinical manifestations of Chagas disease, the probability of finding TcVI in subjects with chronic Chagas cardiomyopathy (CCC) was higher than other DTUs, but without reaching statistical significance. Moreover, the probability of finding TcV in those who have not developed the disease after 20 years of infection was significantly higher than in CCC, either if it was present as unique DTU (reciprocal OR=4.95 95%CI: 1.42 to 17.27) (p=0.0117) or if it was also part of mixed infections (reciprocal OR=3.375; 95%CI: 1.227 to 9.276) (p=0.0264). There was no difference in the distribution of TcI between asymptomatic people and those with clinical manifestations, while TcII appeared more frequently in CCC cases, but without statiscal significance.

[Estimates of the spatial distribution of the relative risk of mortality of the main zoonoses in Chile: Chagas disease, hydatidosis, Hantavirus cardiopulmonary syndrome and leptospirosis]. / Estimaciones de la distribución espacial del riesgo relativo de mortalidad por las principales zoonosis en Chile: enfermedad de Chagas, hidatidosis, síndrome cardiopulmonar por hantavirus y leptospirosis.

BACKGROUND: Zoonoses are infections caused by all types of etiological transmissible agents from vertebrate animals to humans. During the last decades, the risk to health caused by different zoonoses has been a consequence of the natural distribution of the different etiological agents and by the emergence and reemergence of these diseases. AIM: To study the distribution of the risk of mortality of the four main zoonoses in continental Chile, based on national mortality data, with the objective of visualizing geographically where to focus the control efforts of these diseases. METHODS: Relative risk was estimated by means of Bayesian Statistics. RESULTS: The distribution in Chile of the main zoonoses was obtained. DISCUSSION/CONCLUSION: The risk maps obtained show a parasitic disease transmitted by high-risk vectors in the north, Chagas disease; a parasitic disease of biological communities in which man is an accidental host, associated with livestock areas, more prevalent in the south, hydatidosis; a bacterial disease transmitted by vertebrates, especially by rodents, where water is an important vehicle, dominant in the center, leptospirosis; and a viral disease transmitted by rodents, very dominant in the south, the hantavirus infection.

Doença de chagas: uma atualização bibliográfica / Chagas disease: a bibliographic update

É uma doença infecciosa causada por um protozoário parasita chamado Trypanosoma cruzi,nome dado por seu descobridor, o cientista brasileiro Carlos Chagas, em homenagem a outro cientista, também brasileiro, Oswaldo Cruz. Essa doença é conhecida popularmente como doença do coração crescido, além disso, os locais com mais índices dessa doença são as regiões do Norte e Sudeste e tem como formas de diagnósticos exames de sorologiaparasitários e xenodiagnóstico. E uma das principais formas de prevenção da doença vem sendo o uso de telas e repelentes.

It is an infectious disease caused by a protozoan parasite calledTrypanosoma cruzi, named after its discoverer, the Brazilian scientistCarlos Chagas, in honor of another scientist, also, Brazilian, Oswaldo Cruz. This disease is popularly known as a disease of the heart grown, in addition, the sites with the most indexes of this disease are the regions of the North and southeast and have as diagnostic methods serologica tests parasitic and xenodiagnosis. And one of the main forms of prevention of the disease has been the use of screens and repellents.

Estimaciones de la distribución espacial del riesgo relativo de mortalidad por las principales zoonosis en Chile: enfermedad de Chagas, hidatidosis, síndrome cardiopulmonar por hantavirus y leptospirosis / Estimates of the spatial distribution of the relative risk of mortality of the main zoonoses in Chile: Chagas disease, hydatidosis, Hantavirus cardiopulmonary syndrome and leptospirosis

Resumen Introducción: Las zoonosis son enfermedades o infecciones causadas por todo tipo de agentes etiológicos transmisibles desde animales vertebrados a humanos. Durante las últimas décadas, el riesgo para la salud ocasionado por diferentes zoonosis, ha sido generado por la distribución natural de los distintos agentes etiológicos y por la emergencia y reemergencia de estas enfermedades. Objetivo: Estudiar la distribución del riesgo de mortalidad de las cuatro principales zoonosis en Chile continental, basados en datos nacionales de mortalidad, con el objetivo de visualizar geográficamente donde focalizar los esfuerzos de control de estas enfermedades. Metodología: Se estima el riesgo relativo de las principales zoonosis en Chile, mediante estadística Bayesiana. Resultados: Se obtuvo la distribución de las cuatro principales zoonosis de Chile. Discusión/Conclusión: Se obtuvo la distribución de las cuatro principales zoonosis de Chile. Los mapas de riesgo obtenidos muestran una enfermedad parasitaria transmitida por vectores de alto riesgo en el norte, la enfermedad de Chagas; una enfermedad parasitaria de comunidades biológicas en que el hombre es un hospedero accidental, asociada a zonas ganaderas, prevalente en el sur, la hidatidosis; una enfermedad bacteriana transmitida por vertebrados, especialmente por roedores, donde el agua es un vehículo importante, dominante en el centro, la leptospirosis; y una enfermedad viral transmitida por roedores, muy dominante en el sur, la infección por hantavirus.

Background: Zoonoses are infections caused by all types of etiological transmissible agents from vertebrate animals to humans. During the last decades, the risk to health caused by different zoonoses has been a consequence of the natural distribution of the different etiological agents and by the emergence and reemergence of these diseases. Aim: To study the distribution of the risk of mortality of the four main zoonoses in continental Chile, based on national mortality data, with the objective of visualizing geographically where to focus the control efforts of these diseases. Methods: Relative risk was estimated by means of Bayesian Statistics. Results: The distribution in Chile of the main zoonoses was obtained. Discussion/Conclusion: The risk maps obtained show a parasitic disease transmitted by high-risk vectors in the north, Chagas disease; a parasitic disease of biological communities in which man is an accidental host, associated with livestock areas, more prevalent in the south, hydatidosis; a bacterial disease transmitted by vertebrates, especially by rodents, where water is an important vehicle, dominant in the center, leptospirosis; and a viral disease transmitted by rodents, very dominant in the south, the hantavirus infection.

Herramientas farmacométricas para antichagásicos, aplicadas a estudios fármaco y toxicocinéticos en contexto pediátrico / Pharmacometric tools for antihagasics, applied to drug and toxicokinetic studies in a pediatric context

La enfermedad de Chagas afecta aproximadamente a 10 millones de personas en Sudamérica y 1,5 millones en la Argentina. La transmisión congénita es la más importante en áreas urbanas. Existen dos drogas aprobadas para el tratamiento: nifurtimox (Laboratorios Bayer) y benznidazol (BNZ) (Laboratorios Roche, LAFEPE y Elea) que fueron desarrolladas hace más de 40 años y cuya farmacología y metabolismo en humanos han sido poco estudiados. La información disponible es virtualmente inexistente en niños y mujeres embarazadas. Se busca aportar estudios sistemáticos hacia una farmacoterapéutica racional en niños ya que empíricamente ha demostrado gran efectividad. Se desarrollaron métodos bioanalíticos aplicables a matrices biológicas como plasma, orina y leche materna para las drogas madres y la identificación de metabolitos en muestras de pacientes bajo terapéutica. La farmacocinética poblacional pediátrica descripta aquí para BNZ es concluyente respecto de sus diferencias con la farmacocinética en adultos. Se identificaron tres compuestos presentados como metabolitos del BNZ. La transferencia de dicho fármaco a la leche materna no supone riesgo para el lactante. Estos resultados brindan información para mejorar los protocolos de tratamiento existentes buscando una farmacoterapéutica adaptada a la edad y un uso más seguro de los fármacos en niños y eventualmente en adultos.

Chagas disease affects approximately 10 million people in South America and 1.5 million in Argentina. Congenital transmission is most important in urban areas. There are two drugs approved for treatment: nifurtimox (Bayer) and benznidazole (BNZ) (Roche, LAFEPE, Elea),developed more than 40 years ago. Their pharmacology and metabolism in humans have been seldom studied. The information available on children and pregnant women is virtually non-existent. The aim of this study is to provide systematic studies towards a rational pharmacotherapeutic sin children, which has been empirically proven to be highly effective. Bioanalytical methods were developed for plasma, urine and breast milk for parent drugs and for the identification of their metabolites in samples of patients under treatment. The pediatric population pharmacokinetics described here for BNZ is conclusive about their differences from adult pharmacokinetics. Three compounds presented as BNZ metabolites were identified. The transfer of this drug to the breast milk does not present a risk to the infant. These evidences offer information to improve the existing treatment protocols, seeking a pharmacotherapy adapted to the age and a safer use of the drugs in children and eventually in adults.

A doença de Chagas afeta aproximadamente 10 milhões de pessoas na América do Sul e 1,5 milhão na Argentina. A transmissão congênita é a mais importante em áreas urbanas. Existem dois medicamentos aprovados para o tratamento: nifurtimox (Laboratórios Bayer) e benznidazol (BNZ) (Laboratórios Roche, LAFEPE e Elea), desenvolvidas há mais de 40 anos, e sua farmacologia e seu metabolismo em humanos têm sido pouco estudados. A informação disponível é praticamente inexistente em crianças e mulheres grávidas. O objetivo é fornecer estudos sistemáticos para uma farmacoterapêutica racional em crianças visto que foram comprovadas empiricamente como sendo altamente eficazes. Métodos bioanalíticos aplicáveis a matrizes biológicas como plasma, urina e leite materno para fármacos-mãe e para a identificação de metabólitos em amostras de pacientes em tratamento terapêutico foram desenvolvidos. A farmacocinética da população pediátrica aqui descrita para BNZ é conclusiva em relação às suas diferenças com a farmacocinética de adultos. Três compostos apresentados como metabólitos do BNZ foram identificados. A transferência do referido medicamento para o leite materno não representa risco para o lactente. Essas evidências oferecem informações para melhorar os protocolos de tratamento existentes, buscando uma farmacoterapia adaptada à idade e um uso mais seguro dos medicamentos em crianças e eventualmente em adultos.

Chagas disease reactivation: cutaneous manifestations in a transplanted patient

Abstract: Chagas disease is an endemic zoonosis caused by a protozoan agent called Trypanosoma cruzi. It is mainly transmitted by a hematophagous vector, and less frequently by blood transfusion, transplacental and solid organ transplant. In most cases, primary infection is not diagnosed and the disease progresses to a chronic phase. Immunosuppressed patients are a vulnerable population that may present an acute, atypical and severe reactivation of the chronic form of this disease. We hereby report a case of a female patient, who received a renal transplant with immunosuppressive treatment, who was diagnosed with a chagasic hypodermitis secondary to an acute reactivation of a chronic phase of this disease. We describe the clinical features, epidemiological and histopathological findings, treatment and course.

Chagas disease reactivation: cutaneous manifestations in a transplanted patient.

Chagas disease is an endemic zoonosis caused by a protozoan agent called Trypanosoma cruzi. It is mainly transmitted by a hematophagous vector, and less frequently by blood transfusion, transplacental and solid organ transplant. In most cases, primary infection is not diagnosed and the disease progresses to a chronic phase. Immunosuppressed patients are a vulnerable population that may present an acute, atypical and severe reactivation of the chronic form of this disease. We hereby report a case of a female patient, who received a renal transplant with immunosuppressive treatment, who was diagnosed with a chagasic hypodermitis secondary to an acute reactivation of a chronic phase of this disease. We describe the clinical features, epidemiological and histopathological findings, treatment and course.

Clinical and epidemiological features of chronic Trypanosoma cruzi infection in patients with HIV/AIDS in Buenos Aires, Argentina.

OBJECTIVES: Trypanosoma cruzi reactivation in HIV patients is considered an opportunistic infection, usually with a fatal outcome. The aim of this study was to describe the epidemiological and clinical features of T. cruzi infection in HIV patients and to compare these findings between patients with and without Chagas disease reactivation. METHODS: The medical records of T. cruzi-HIV co-infected patients treated at the Muñiz Infectious Diseases Hospital from January 2005 to December 2014 were reviewed retrospectively. Epidemiological and clinical features were assessed and compared between patients with and without Chagas disease reactivation. RESULTS: The medical records of 80 T. cruzi-HIV co-infected patients were reviewed. The most likely route of T. cruzi infection was vector-borne (32/80 patients), followed by intravenous drug use (12/80). Nine of 80 patients had reactivation. Patients without reactivation had a significantly higher CD4 T-cell count at diagnosis of T. cruzi infection (144 cells/µl vs. 30 cells/µl, p=0.026). Chagas disease serology was negative in two of nine patients with reactivation. CONCLUSIONS: Serological assays for T. cruzi infection may be negative in severely immunocompromised patients. Direct parasitological techniques should be performed in the diagnosis of patients for whom there is a suspicion of T. cruzi reactivation. HIV patients with a lower CD4 count are at higher risk of reactivation.

Cell therapies for Chagas disease.

In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy.

[Strategy to improve access to etiological treatment of Chagas disease at the first level of care in Argentina]. / Estrategia para mejorar el acceso al tratamiento etiológico para la enfermedad de Chagas en el primer nivel de atención en Argentina.

OBJECTIVE: Improve distribution of etiological treatment of Chagas disease by identifying barriers to the decentralization of treatment to the first level of care in Argentina. METHODS: A qualitative, exploratory, and descriptive study was conducted using semi-structured interviews of key actors belonging to the National Chagas Program and members of health teams at the first level of care, for the purpose of identifying barriers to diagnosis and treatment of Chagas disease at different levels (administrative, health agents, and community) that could affect a decentralized distribution strategy. Additionally, pilot decentralization was instituted in 10 primary health care centers in an Argentine province. RESULTS: Semi-structured interviews were conducted with 22 program heads and health professionals. Principal obstacles found were lack of systematic case-finding, poor coordination among levels of care and health system actors, lack of health team training on treatment, patient monitoring, and patient-related barriers. A pilot decentralization program was carried out and strategies were evaluated to optimize large-scale intervention. CONCLUSIONS: The results made it possible to improve implementation of the plan to decentralize treatment through better inter-program coordination, capitalization on existing monitoring and communication tools, and sensitization of health teams. Furthermore, recommendations were developed to improve diagnosis and treatment of Chagas disease.

Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy.

Chronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoan Trypanosoma cruzi; it is estimated that 10-30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein from T. cruzi named P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein's direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate that T. cruzi P21 is an attractive target for the development of innovative therapeutic agents against CCC.

Transplante cardíaco na Doença de Chagas / Heart transplantation in Chagas Disease

A doença de Chagas afeta 16 a 18 milhões de pessoas na América Latina. No Brasil, estima-se a existência de 5 a 7 milhões de chagásicos, encontrados em quase todos os estados brasileiros. Aproximadamente 30% dos infectados desenvolvem a forma crônica da doença, com elevadas taxas de morbidade e mortalidade pelo envolvimento cardíaco, e a miocardiopatia chagásica apresenta pior prognóstico quando comparada a outras etiologias da insuficiência cardíaca. Em nosso meio, aproximadamente 30% dos pacientes com insuficiência cardíaca crônica refratária ao tratamento clínico, encaminhados para transplante cardíaco têm como etiologia a doença de Chagas. A experiência acumulada no Brasil demonstra que, a despeito de elevadas taxas da reativação da infecção pelo T. cruzi em decorrência da imunossupressão, os resultados do transplante cardíaco na doença de Chagas são altamente satisfatórios e com evolução pós-transplante a médio e longo prazo semelhante aos resultados do transplante cardíaco em pacientes não chagásicos. Esses resultados colocam o transplante cardíaco como uma excelente opção terapêutica nos casos de pacientes chagásicos com grave comprometimento funcional ou com arritmias malignas.

Chagas disease affects 16 to 18 million people in Latin America. In Brazil, the estimate is that there are 5-7 million people infected, located in almost all Brazilian states. Approximately 30% of those infected develop the chronic form of the disease, with high morbidity and mortality rates due to cardiac involvement, and Chagas cardiomyopathy has worse prognosis when compared to other causes of heart failure. In Brazil, approximately 30% of patients with chronic heart failure refractory to medical treatment, referred for heart transplantation have Chagas disease as etiology. The cumulative experience in Brazil shows that despite high rates of reactivation of infection with T. cruzi due to immunosuppression, the results of heart transplantation in Chagas disease are highly satisfactory and the results post-transplant in medium and long-term are similar to those of heart transplantation in patients without Chagas disease. These results make heart transplantation an excellent therapeutic option in cases of patients with Chagas disease with severe functional impairment or malignant arrhythmias.