[Sequence of unusual Chagas infection transmissions in the same family: mother by blood transfusion and child congenitally, with a treatment-resistant strain of Trypanosoma cruzi]. / Seqüência de transmissões não habituais da infecção chagásica em uma mesma família: transfusional para a mãe e congênita para o filho, de cepa de Trypanosoma cruzi resistente ao tratamento.

The authors present two cases of unusual transmission of Chagas infection in the same family: the mother by blood transfusion and her second child across the placenta. The child was diagnosed by chance and etiological treatment for both the mother and the child was ineffective in eradicating the parasitemia. At present, they continue to present the indeterminate form of the disease.

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination.

INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.

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

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

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination

Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.

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

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

II Consenso Brasileiro em Doença de Chagas, 2015 / Brazilian Consensus on Chagas Disease, 2015

A doença de Chagas é uma condição crônica negligenciada com elevada carga de morbimortalidade e impacto dos pontos de vista psicológico, social e econômico. Representa um importante problema de saúde pública no Brasil, com diferentes cenários regionais. Este documento traduz a sistematização das evidências que compõe o Consenso Brasileiro de Doença de Chagas. O objetivo foi sistematizar estratégias de diagnóstico, tratamento, prevenção e controle da doença de Chagas no país, de modo a refletir as evidências científicas disponíveis. Sua construção fundamentou-se na articulação e contribuição estratégica de especialistas brasileiros com conhecimento, experiência e atualização sobre diferentes aspectos da doença. Representa o resultado da estreita colaboração entre a Sociedade Brasileira de Medicina Tropical e o Ministério da Saúde. Espera-se com este documento fortalecer o desenvolvimento de ações integradas para enfrentamento da doença no país com foco em epidemiologia, gestão, atenção integral (incluindo famílias e comunidades), comunicação, informação, educação e pesquisas.

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

Tratamento etiológico da doença de Chagas / Etiologic treatment of Chagas disease

O tratamento etiológico da doença de Chagas ainda é assunto controverso. De acordo com o Consenso Brasileiro em Doenças de Chagas da Sociedade Brasileira de Medicina Tropical, esse tratamento está indicado consensualmente em casos agudos, na transmissão congênita, em crianças e em casos de contaminação acidental. Não consensualmente, poderá ser prescrito a qualquer portador da enfermidade, por médico com experiência no manuseio da medicação e com condições para acompanhamento posterior. A única medicação disponível entre nós é o benzonidazol, usado nas doses de 10mg/kg/dia por 60 dias em crianças ou casos agudos e 5mg/kg/dia por 60 dias em adultos crônicos. Seus principais efeitos colaterais são a dermatite e a polineuropatia, usualmente bem tolerados. A indicação do tratamento parasiticida em adultos crônicos divide a opinião dos pesquisadores quanto a sua eficácia em modificar a história natural da enfermidade. O estudo BENEFIT, iniciado em 2004 visa a analisar se o tratamento parasiticida com benzonidazol, nas doses habituais, modifica ou não a evolução da cardiopatia chagásica crônica. Esse estudo randomizado duplo-cego e controlado por placebo envolve Brasil, Argentina e Colômbia, tendo previsão de acompanhamento de 3 mil pacientes chagásicos crônicos com cardiopatia instalada (grau funcional de I a III da NYHA) por cinco anos, quando será possível definir o real papel do tratamento parasiticida na doença de Chagas.

Enzyme-linked immunoassay using recombinant trans-sialidase of Trypanosoma cruzi can be employed for monitoring of patients with Chagas' disease after drug treatment.

trans-Sialidase is an enzyme present on the surface of Trypanosoma cruzi and is an important antigen recognized by sera from patients with Chagas' disease. In the present study we investigated whether the benznidazole treatment of patients with Chagas' disease induced changes in the reactivity of serum toward a recombinant form of trans-sialidase in order to develop an assay for monitoring of patients after treatment for Chagas' disease, which is needed at Chagas' disease control centers. By using an enzyme-linked immunosorbent assay containing a recombinant protein corresponding to the catalytic domain of trans-sialidase, we found that the antigen had a high specificity for sera from untreated patients with Chagas' disease. Sera from healthy individuals or patients with active visceral leishmaniasis minimally cross-reacted with the antigen. Anti-trans-sialidase immunoglobulin was detected in 98% of 151 untreated patients with Chagas' disease. Of these, 124 patients were treated for 60 days with benznidazole (5 mg/kg of body weight/day), and their sera were assayed for reactivity with the recombinant trans-sialidase. By using this methodology, three groups of patients could be established. The first group (60 patients), which was considered to have been successfully treated, showed no reactivity after treatment. The second group (46 patients) still showed signs of infection, and after treatment their sera recognized trans-sialidase, but with reduced titers. The third group (18 patients) was considered to be resistant to drug treatment, and their sera presented identical reactivities before and after treatment. These results suggest that determination of the absence of antibodies to recombinant trans-sialidase in treated patients by the present assay is indicative of treatment success, while the presence of antibodies may indicate the persistence of infection. Therefore, this method may be useful for the diagnosis and monitoring of patients undergoing benznidazole treatment.

Seqüência de transmissões não habituais da infecção chagásica em uma mesma família: transfusional para a mãe e congênita para o filho, de cepa de Trypanosoma cruzi resistente ao tratamento / Sequence of unusual Chagas infection transmissions in the same family: mother by blood transfusion and child congenitally, with a treatment-resistant strain of Trypanosoma cruzi

Os autores apresentam dois casos de transmissão não habitual da infecção chagásica em uma mesma família: a mãe, por transfusão sangüínea e seu segundo filho, via transplacentária. O diagnóstico da criança foi acidental e a resposta ao tratamento etiológico, em ambos, foi ineficaz em erradicar a parasitemia. Atualmente, mãe e filho permanecem em forma indeterminada da doença.

The authors present two cases of unusual transmission of Chagas infection in the same family: the mother by blood transfusion and her second child across the placenta. The child was diagnosed by chance and etiological treatment for both the mother and the child was ineffective in eradicating the parasitemia. At present, they continue to present the indeterminate form of the disease.

Ethiological treatment of acute and chronic Chagas' heart disease

The uncertainties in the ethiological treatment of Chagas' Disease are consequence of the lack of entire knowledge of its pathogeny and the non existence of a healing criterium. There is a consensus that antiparasite drugs should be used in the acute phase of the infection, regardless of the infection route, in new crisis, in patients under immunossuppression and in organs transplantation. There is still controversy regarding subacute, chronic or undetermined phase or cases with mild cardiac/digestive forms, not included in the situations listed above neither in a research protocol. The treatment includes oral benzonidazol 5 mg/kg/day, bid or tid for 60 days. In 71 patients monitored in this fashion, the authors have found 60 percent of negative xenodiagnostic at the end of treatment. It is still necessary, however, to continue to investigate and accomplishing more randomized trials to confirm the efficacy of such method, and also to try to obtain effective and less toxic agents. It is also fundamental to standardize a more reliable healing criterium.

Prevalência de insuficiência cardíaca congestiva após ventriculomiectomia em portadores da cardiomiopatia hipertrófica obstrutiva / Prevalence of congestive heart failure after ventriculomiectomy in patients with obstructive hypertrophyc cardiomyopathy

Objetivo - Avaliar a prevalência de insuficiência cardíaca congestiva (ICC) no pós-operatório tardio em portadores de cardiomipatia hipertrófica obstrutiva (CMHO) submetidos à ventriculomiectomia. Métodos - Trinta e seis pacientes portadores de CMHO, todos com gradiente sistólico basal intraventricular (GSBIV) * 50 mmHg foram estudados. Dezesseis deles (grupo I) foram submetidos a VM e 20 (grupo II) foram seguidos sob tratamento clínico. No grupo I, a idade variou de 2 meses a 61 anos (28,25 ñ 15,39), 10 masculino; o GSBIV variou de 50 a 192 mmHg (98,09 ñ 42,76) com um tempo médio de seguimento de 13,06 ñ 7,19 anos. No grupo II a idade variou de 2 meses a 58 anos (31,01) ñ 18,61), 12 masculinos (60%); o GSBIV variou de 52 a 185 mmHg (83,47 ñ 3508) com tempo médio de seguimento de 9,6 ñ 4,93 anos. Resultados - No grupo I, a evoluçäo foi boa em 4 pacientes (25%), estável em 2 (12,5%) e má em 3 (18%). Sete pacientes (43,75%) desenvolveram ICC em um tempo médio de 7,53 ñ 8,44 anos. Houve um óbito operatório e perdeu-se o seguimento em sete pacientes. No grupo II, a evoluçäo foi boa em 3 pacientes (15%), estável em 6(30%) e má em 9(45%). Näo registraram-se óbitos. Dois pacientes desenvolveram ICC em prazo médio de 3 anos após o aparecimento da doença e em 8 pacientes (40%) perdeu-se o controle evolutivo. Conclusäo - 1) A ICC foi mais freqüente em pacientes submetidos a VM que naqueles näo operados (p 0,05); 2) a evoluçäo a curto prazo foi melhor nos operados dos que nos näo operados

Purpose - To assess the prevalence of congestive heart failure in the late post-operative follow-up in patients with hypertrophic obstructive cardiomyophaty (HOCM) submitted to ventriculomectomy (VM). Methods - Thirty six patients with HOCM, all of them with basal intraventricular sistolic pressure gradient (BPG)³50 mmHg, were studied. Sixteen (group I) were submitted to VM and 20 (group II) remained under clinical treatment. At group I the ages were 1 month to 61 years (28.25±15.39), 10 mule (62.5%); BPG rangedirom 50 to 192 mmHg (98.09±42.76) with mean follow-up of 13.06±7.19 years. At group II the age rangedirom 2 months to 58 years (31.01±18.61); 12 male (60%); BPG rangedirom 52 to 185 mmHg (83.47±35.08) with mean follow-up of 9.6±4.93 years. Results - At group I the follow-up was good in 4 patients (25%), stable in 2 (12.5%) and poor in 3 (18%). Seven patients (43.75%) developed congestive heart failare at mean time of 7.53±8.44 years; there was one operative death and the follow-up control was lost in 7 patients. In group II, the follow-up was good in 3 patients (15%), stable in a 6 (30%) and poor in a 9 (45%); no deaths occurred. Two patients had hear failure within 3 years after the onset of the disease. The follow-up control was lost in 8 patients (40%). Conclusion - 1) congestive heart failure was more frequent in patients submitted to VM rather than the nonoperated ones (p < 0.05); 2) the short-term followup was better in operated patients rather than in nonoperated ones

Aspectos clínicos e evolutivos da miocardiopatia dilatada nos lactentes e na infância / Clinical and evolutive aspects of dilated cardiomyopathy in infants and in childhood

Avaliar os aspectos clínicos, evolutivos e de prognóstico, em lactentes e crianças com miocardiopatia dilatada (MCPD). Trinta e oito pacientes divididos em grupos: A) lactentes até 23 (11,60 ñ 6,50) meses, 15 femininos, e B) 15 crianças de 2 a 12 (5,23 ñ 3,12) anos, a maioria (10) masculinos. O estudo foi retrospectivo, através de avaliaçäo clínica, eletrocardiográfica, radiológica e ecocardiográfica. A dispnéia aos esforços (inclusive às mamadas) foi sintoma predominante, observada em 15 (65,22%) pacientes do grupo A e 10 (66,6%) do B, seguida da cianose perilabial, em 7 (30,43%) e 6 (40%) pacientes respectivamente. No grupo A, a hipótese clínica foi de miocardite inespecífica (MI) em 8 (34,79%), e de MCPD "idiopática" em 3 (13,04%). No grupo B diagnosticou-se miocardite em 10 (66,67%) - sendo 5 inespecíficos - FEM em 3 (20%) e MCPD "idiopática" em 2 (13,33%). O tempo médio de evoluçäo foi de 5,48 meses no grupo A e 18,56 no B. No grupo A a evloluçäo foi ótima em 3 (13,04%), boa em 10 (43,46%), estável em 2 (8,70%) e má em 1 (4,35%), e no B: ótima em 8 (53,33%), boa em 3 (20%) e estável em 1 (6,67%), em nenhum má evoluçäo. Houve um óbito do grupo A (4,34%) e 6 pacientes deste grupo (26,09%) e 3 (20%) do B interromperam o controle evolutivo. 1) o prognóstico dos lactentes com MCPD, inclusive com hipótese diagnóstica de FEM parece ser menos sombrio do que habitualmente se supöe; 2) o prognóstico de crianças nas quais a MCPD é diagnosticada acima de 2 anos parece ser boa; ...

Pericardite tuberculosa / Tuberculous pericarditis

A pericardite tuberculosa é uma entidade freqüente, devendo ser lembrada em todos os casos de pericardite aguda. Seu diagnóstico deve basear-se na epidemiologia, na presença de intradermo-reação (PPD) positiva para tuberculose, nas características macroscópicas e histológicas do líquido pericárdico obtido por toracotomia subxifóidea (Marfan), em associação com os dados da biópsia de pericárdio. O tratamento específico deve ser orientado, sendo discutível o benefício da associação desse tratamento à corticoterapia, em decorrência da falta de evidências. Na identificação de tamponamento cardíaco, o esvaziamento do saco pericárdico deve ser prontamente indicado, e esses casos mais freqüentemente evoluem para a constrição. Na presença de pericardite constritiva, o tratamento cirúrgico está indicado precocemente, face à possibilidade de evolução para deterioração da função miocárdica.

Miocardiopatias dilatadas / Dilated myocardiopathies

A miocardiopatia (MCP) dilatada, entidade sobejamente conhecida, caracteriza-se hemodinamicamente por predominío inconteste da hipossistolia uni ou biventricular, muito embora o componente de hipodiastolia seja hoje indiscutivelmente admitido. Sua etiologia é muito diversificada, permanecendo, contudo, a maioria dos casos sob a denominaçäo de primária ou idiopática, fruto da falta de conhecimento atual. Dentre as de causa identificável, destacam-se as inflamatórias, as tóxicas, as metabólicas e as de caráter familiar. As manifestaçöes clínicas na MCP dilatada estäo relacionadas à hipossistolia e ao aumento de câmaras cardíacas, com o predomínio da insuficiência cardíaca, pelo comprometimento ventricular direito e/ou esquerdo, geralmente concomitante e näo conseqüente. As arritmias (ventriculares ou supraventriculares) säo freqüentes, bem como os distúrbios de conduçäo, das mais variadas formas. Como conseqüência da cardiomegalia pode ocorrer a formaçäo de trombos intracavitários, com fenômenos tromboembólicos, para a circulaçäo pulmonar ou sistêmica. O diagnóstico baseia-se näo só nas manifestaçöes clínicas que usualmente säo inespecíficas, como tambén, principalmente, na propedêutica armada invasiva ou näo, destacando-se mais recentemente o diagnóstico por imagens e a biópsia endomiocárdica. O tratamento da MCP dilatada inclui fundamentalmente o controle da insuficiência cardíaca e suas implicaçöes: arritmias, fenômenos tromboembólicos e a refratariedade. O prognóstico está intimamente relacionado ao grau de severidade da disfunçäo ventricular, sendo a mortalidade estimada em 50% em cinco anos, em grupos etiologicamente diversos e relacionada, entre outras coisas, ao grau funcional, à pressäo arterial e os níveis de sódio sérico e de catecolaminas circulantes. Cerca de 50% das mortes ocorrem subitamente, admitindo-se que näo só as taquiarritmias ventriculares (como a fibrilaçäo ventricular) sejam as responsáveis pelo evento fatal, mas também as bradiarritmias com os bloqueios e as assitolías. Assim sendo, as MCP dilatadas, que säo as mais freqüentes formas de apresentaçäo das MCP, ainda necessitam de grande desenvolvimento nos estudos diagnósticos e de tratamento, visando ao seu melhor entendimento e melhoria do prognóstico, hoje ainda muito sombrio

Tratamento etiológico da doença de Chagas nas fases aguda e crônica / Ethiological treatment of acute and chronic Chagas'disease

As dúvidas acerca da terapêutica etiológica da doença de Chagas derivam de incertezas quanto à patogenia, associadas à inexistência de critério de cura satisfatório. Ainda assim, é consensual a indicaçäo da terapêutica parasiticida na fase aguda da doença, independentemente da forma de transmissäo, nas reagudizaçöes em pacientes sob imunossupressäo, em crianças e nos procedimentos de transplantes de órgäos. É polêmica a indicaçäo, excetuando-se os protocolos de investigaçäo, nas formas crônicas indeterminadas, cardíaca leve e/ou digestiva, näo enquadradas nas situaçöes acima. O tratamento consiste no uso de benzonidazol por via oral 5 mg/kg/dia em 2 ou 3 tomadas, por 60 dias. Em 71 pacientes tratados com esse esquema, os autores obtiveram 61 por cento de negativaçào do xenodiagnóstico. É necessário o prosseguimento das pesquisas e a realizaçäo de estudos multicêntricos randomizados para confirmar-se o benefício da terapêutica, obter-se droga parasiticida mais eficaz e menos tóxica e estabelecer-se critério de cura confiável.