Scientometric review of research on Neglected Tropical Diseases: a 31-year perspective from the Journal of the Brazilian Society of Tropical Medicine

ABSTRACT Background: To analyze the temporal evolution of research on Neglected Tropical Diseases (NTDs) published by the Journal of the Brazilian Society of Tropical Medicine (JBSTM). Methods: We performed an analysis of the scientific production in JBSTM on NTDs using an advanced search, which included authors' descriptors, title, and abstract, and by combining specific terms for each NTDs from 1991 to 2021. Data related to authors, countries of origin, institutions, and descriptors, were evaluated and analyzed over time. Bibliographic networks were constructed using VOSviewer 1.6.16. Results: The JBSTM published 4,268 scientific papers during this period. Of these 1,849 (43.3%) were related to NTDs. The number of publications on NTDs increased by approximately 2.4-fold, from 352 (total 724) during 1991-2000 to 841 (total 2,128) during 2011-2021, despite the proportional reduction (48.6% versus 39.5%). The most common singular NTDs subject of publications included Chagas disease (31.4%; 581/1,849), leishmaniasis (25.5%, 411/1,849), dengue (9.4%, 174/1,849), schistosomiasis (9.0%; 166/1,849), and leprosy (6.5%, 120/1,849), with authorship mostly from Brazil's South and Southeast regions. Conclusions: Despite the proportional reduction in publications, JBSTM remains an important vehicle for disseminating research on NTDs during this period. There is a need to strengthen the research and subsequent publications on specific NTDs. Institutions working and publishing on NTDs in the country were concentrated in the South and Southeast regions, requiring additional investments in institutions in other regions of the country.

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.

Correlation between the cytokine profile and anticongestive medication in patients with chronic chagasic cardiopathy

Abstract INTRODUCTION: Chronic chagasic cardiopathy (CCC) is essentially a dilated cardiomyopathy in which a subacute, but constant chronic inflammatory process causes progressive destruction of the heart tissue. The action of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and anti-inflammatory cytokines, like interleukin IL-10 and IL-17, plays a fundamental role in the immunopathogenesis and evolution of disease. Early anti-congestive therapy, aimed at changing the morbidity and mortality rate, has been shown to reduce disease progression and to alter patients' immune response pattern. METHODS: This cross-sectional study aimed to evaluate the profile of Th1 and Th17 cytokines and IL-17, TNF-α, and IFN-γ expressions in different stages of CCC. Forty patients affected by chronic Chagas disease were divided into different groups according to the stage of the pathology. In agreement with the Brazilian consensus on Chagas disease, patients were classified as presenting an undetermined form, a cardiac form and a digestive form. Serum IFN-γ, TNF-α, IL-10, and IL-17 were evaluated. RESULTS: Lower serum IFN-γ concentrations were detected in patients receiving angiotensin-converting enzyme inhibitors (p = 0.0182), but not in those using angiotensin receptor blockers (p = 0.0783). Patients using amiodarone and aldosterone antagonist presented higher serum TNF-α concentrations (p = 0.0106 and 0.0187, respectively). IL-10 and IL-17 levels did not differ between the study groups (p = 0.7273 and p = 0.6697, respectively). CONCLUSIONS: These results suggest that the cytokine profile and disease progression are altered by anti-congestive medications commonly prescribed for CCC.

Clinical and epidemiological characteristics of Chagas disease in an endemic area of Sergipe State, Brazil

Abstract INTRODUCTION: We evaluated clinical and epidemiological characteristics of Trypanosoma cruzi infection in Sergipe. METHODS: In this cross-sectional study, we collected serum samples to identify serological markers of Chagas disease. A questionnaire was used, and electrocardiogram, echocardiogram, chest radiography, and contrast radiography of esophagus and colon were performed. RESULTS: T. cruzi infection seroprevalence was 12.1%, mean age of subjects was 55 years, 90% had an elementary school education, 78.6% were agriculture workers, and 60.5% had electrocardiographic abnormalities. CONCLUSIONS: A high prevalence of T. cruzi infection was observed in mostly elderly individuals.

Systematic neonatal screening for congenital Chagas disease in northeast Brazil: prevalence of trypanosoma cruzi infection in the southern region of Sergipe

Abstract INTRODUCTION: Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi, being one of the leading causes of morbidity and mortality in the Americas with an estimated six to seven million infected people worldwide. In Brazil, the improvement in vector control and blood donor screening has evidenced the important epidemiological role of congenital transmission of Chagas disease. METHODS: A serological survey for Chagas disease was performed in 3,952 newborns in the southern region of Sergipe using paper filter disks of dried blood samples. The newborns were screened using the Sergipe State Neonatal Screening Program between July 2015 and July 2016, and 3,749 and 750 blood samples were obtained for the IgG enzyme-linked immunosorbent assay and indirect immunofluorescence assay, respectively. In addition, mothers of the children who presented initial reagent serology were examined. RESULTS: Among 3,749 blood samples, samples of two children were positive for the enzyme-linked immunosorbent assay; however, their confirmation test results were negative, suggesting passive transfer of the mother's antibody. One puerpera was identified with Chagas disease, with a prevalence of 0.02%. CONCLUSIONS: Congenital Chagas disease was not observed in newborns in the Southern region of Sergipe. However, Chagas disease was observed in women of reproductive age. Therefore, effective measurements for monitoring and systematic evaluation should be conducted. The Neonatal Screening Program proved to be an effective public health strategy for the prevention and control of Chagas disease.

OCCURRENCE OF Blastocystis spp. IN UBERABA, MINAS GERAIS, BRAZIL / Ocorrência de Blastocystis spp. em Uberaba, Minas Gerais, Brasil

Intestinal parasites are a problem for public health all over the world. The infection with Blastocystis, a protozoan of controversial pathogenicity, is one of the most common among them all. In this study, the occurrence of intestinal parasites, with emphasis on Blastocystis, in patients at the Universidade Federal do Triângulo Mineiro was investigated in Uberaba (MG) through microscopy of direct smears and fecal concentrates using Ritchie’s method. Feces of 1,323 patients were examined from April 2011 to May 2012. In 28.7% of them at least one intestinal parasite was identified, and the most frequent organisms were Blastocystis spp. (17.8%) and Giardia intestinalis (7.4%). The occurrence of parasitism was higher in children aged 6 -10 years old, and the infection with Blastocystis spp. was higher above the age of six (p < 0.001). The exclusive presence of G. intestinalis and of Blastocystis spp. was observed in 5.4% and 12.2% of the patients, respectively. Regarding patients with diarrheic feces, 8% revealed unique parasitism of Blastocystis spp. Other intestinal parasites observed in children were Ascaris lumbricoides (0.3%) and Entamoeba histolytica/dispar/moshkovskii (1.4%). The Ritchie’s method was more sensitive (92.8%) when compared to direct microscopy (89.8%), with high agreement between them (97.7%, kappa = 0.92). In conclusion, the occurrence of Blastocystis spp. in Uberaba is high and the presence of diarrheic feces with exclusive presence of the parasite of Blastocystis spp. was observed.

Parasitos intestinais são um problema de saúde pública no mundo e a infecção por Blastocystis, protozoário de patogenicidade controversa, é uma das mais frequentes. Nesse estudo foi investigada a ocorrência de parasitos intestinais em pacientes atendidos na Universidade Federal do Triângulo Mineiro, em Uberaba (MG), com ênfase em Blastocystis, pelos métodos parasitológicos direto e de Ritchie. Foram examinadas fezes de 1.323 pacientes de abril/2011 a maio/2012. Em 28,7% deles foi identificado um parasito intestinal, sendo Blastocystis spp. (17,8%) e Giardia intestinalis (7,4%) os mais frequentes. A ocorrência de parasitismo foi maior em crianças de 6-10 anos e a infecção por Blastocystis spp. foi maior acima de seis anos (p < 0,001). Presença exclusiva de G. intestinalis e de Blastocystis spp. foi observada em 5,4% e 12,2% dos pacientes, respectivamente, sendo que dos pacientes com fezes diarreicas, 8% apresentavam parasitismo exclusivo por Blastocystis spp. Outros parasitos intestinais observados em crianças foram Ascaris lumbricoides (0,3%) e Entamoeba histolytica/dispar/moshkovskii (1,4%). O método de Ritchie foi mais sensível (92,8%) que o direto (89,8%), com alta concordância entre eles (97,7%, kappa = 0,92). Em conclusão, a ocorrência de Blastocystis spp. em Uberaba é elevada e foi observada a presença de fezes diarreicas com parasitismo exclusivo por Blastocystis spp.

High similarity of Trypanosoma cruzi kDNA genetic profiles detected by LSSP-PCR within family groups in an endemic area of Chagas disease in Brazil

Introduction Determining the genetic similarities among Trypanosoma cruzi populations isolated from different hosts and vectors is very important to clarify the epidemiology of Chagas disease. Methods An epidemiological study was conducted in a Brazilian endemic area for Chagas disease, including 76 chronic chagasic individuals (96.1% with an indeterminate form; 46.1% with positive hemoculture). Results T. cruzi I (TcI) was isolated from one child and TcII was found in the remaining (97.1%) subjects. Low-stringency single-specific-primer-polymerase chain reaction (LSSP-PCR) showed high heterogeneity among TcII populations (46% of shared bands); however, high similarities (80-100%) among pairs of mothers/children, siblings, or cousins were detected. Conclusions LSSP-PCR showed potential for identifying similar parasite populations among individuals with close kinship in epidemiological studies of Chagas disease. .

Length and caliber of the rectosigmoid colon among patients with Chagas disease and controls from areas at different altitudes

Introduction In this study, we investigated radiological changes in the sigmoid colon in chagasic patients by comparing their colon lengths and caliber with those of non-chagasic living in the same region and non-chagasic living at high altitudes. Methods A total of 317 individuals were evaluated using clinical, serological and radiological methods and divided into three groups: 1) one hundred and nine non-chagasic individuals from Uberaba, Brazil; 2) sixty-one non-chagasic from Puno, Peru; 3) one hundred forty-seven chagasics examined in Uberaba, being 62 without megacolon (3A), 72 with megacolon (3B) and 13 with doubtful diagnosis of megacolon (3C). Results In group 2, the sigmoid colon had a significantly larger caliber (p=0.001) and the rectosigmoid colon was longer (p<0.001) than group 1. In subgroup 3A, the sigmoid colon (p<0.001) and rectum (p<0.001) had a significantly larger caliber and the rectosigmoid was longer (p<0.001) than that of the non-chagasic individuals. In subgroup 3B, the rectosigmoid was longer in all patients, and the caliber of the sigmoid was significantly larger than that of subjects in subgroups 3A and 3C (p<0.001). Conclusions Morphometric analysis confirms that Chagas disease may increase the caliber and length of the rectosigmoid. Our results suggest that altitude, ethnicity and diet may have influenced the size and length of the rectosigmoid of andean patients. .

Prevalence and genetic characterization of Cryptosporidium spp. and Cystoisospora belli in HIV-infected patients / Prevalência e caracterização genética de Cryptosporidium spp. e Cystoisospora belli em pacientes infectados pelo HIV

Cryptosporidium spp. and Cystoisospora belli are monoxenic protozoa that have been recognized as the causative agents of chronic diarrhea in immunocompromised individuals, especially HIV-infected subjects. The objective of this study was to evaluate the frequency of these intestinal protozoa in HIV-positive patients in the Triângulo Mineiro region of Brazil and to correlate the presence of these infections with clinical, epidemiological and laboratory data of the patients. Oocysts were detected in stool samples of 10 (16.9%) of the 59 patients studied, while Cryptosporidium spp. were present in 10.1% (6/59) and C. belli in 6.7% (4/59). The frequency of these parasites was higher among patients with diarrheic syndrome and CD4+ T lymphocyte counts < 200 cells/mm 3 , demonstrating the opportunistic characteristic of these infections. A significant association was observed between the lack of adherence to antiretroviral therapy and the presence of Cryptosporidium spp. and/or C. belli. Parasitism with Cryptosporidium spp. was more frequent in February and April, the months following the period of high rainfall. The same was not observed for C. belli. Genetic characterization of two isolates led to the identification of Cryptosporidium parvum, one of the main species associated with the zoonotic transmission of cryptosporidiosis.

Cryptosporidium spp. e Cystoisospora belli são protozoários monoxenos reconhecidos como agentes causadores de diarréia crônica em indivíduos imunocomprometidos, especialmente aqueles infectados pelo HIV. Os objetivos deste estudo foram o de avaliar a frequência destes protozoários em pacientes HIV - positivos na região do Triângulo Mineiro, Brasil, e correlacionar a presença destas infecções com dados clínicos, epidemiológicos e laboratoriais dos pacientes. Oocistos foram detectados em amostras fecais de 10 (16,9%) dos 59 pacientes estudados, sendo 10.1% (6/59) das amostras positivas para Cryptosporidium spp. e 6,7% (4/59) das amostras positivas para C. belli. A frequência destes parasitos foi maior entre pacientes com síndrome diarreica e contagem de linfócitos T CD4+ < 200 cells/mm 3 , o que demonstra o caráter oportunista destas infecções. Foi observada uma associação significativa entre a falta de aderência à terapia antiretroviral e a presença de Cryptosporidium spp. e/ou C. belli. Parasitismo por Cryptosporidium spp. foi mais frequente em fevereiro e abril, meses subsequentes ao período chuvoso. O mesmo não foi observado para C. belli. A caracterização genética de dois isolados levou à identificação de Cryptosporidium parvum, uma das principais espécies associadas com a transmissão zoonótica da criptosporidiose.

One-year cardiac morphological and functional evolution following permanent pacemaker implantation in right ventricular septal position in chagasic patients / Evolução funcional e morfológica cardíaca um ano após o implante de marcapasso definitivo na posição ventricular direita septal em pacientes chagásicos

INTRODUCTION: The septal position is an alternative site for cardiac pacing (CP) that is potentially less harmful to cardiac function. METHODS: Patients with Chagas disease without heart failure submitted to permanent pacemaker (PP) implantation at the Clinics Hospital of the Triângulo Mineiro Federal University (UFTM), were selected from February 2009 to February 2010. The parameters analyzed were ventricular remodeling, the degree of electromechanical dyssynchrony (DEM), exercise time and VO2 max during exercise testing (ET) and functional class (NYHA). Echocardiography was performed 24 to 48h following implantation and after one year follow-up. The patients were submitted to ET one month postprocedure and at the end of one year. RESULTS: Thirty patients were included. Patient mean age was 59±13 years-old. Indication for PP implantation was complete atrioventricular (AV) block in 22 (73.3%) patients and 2nd degree AV block in the other eight (26.7%). All patients were in NYHA I and no changes occurred in the ET parameters. No variations were detected in echocardiographic remodeling measurements. Intraventricular dyssynchrony was observed in 46.6% of cases and interventricular dyssynchrony in 33.3% of patients after one year. CONCLUSIONS: The findings of this work suggest that there is not significant morphological and functional cardiac change following pacemaker implantation in septal position in chagasic patients with normal left ventricular function after one year follow-up. Thus, patients may remain asymptomatic, presenting maintenance of functional capacity and no left ventricular remodeling.

INTRODUÇÃO:A posição septal representa um sítio alternativo de estimulação cardíaca artificial (ECA) potencialmente menos deletério para a função cardíaca. M ÉTODOS: Pacientes chagásicos sem insuficiência cardíaca submetidos a implante de marcapasso definitivo (MP) no Hospital de Clínicas da Universidade Federal do Triângulo Mineiro (UFTM) foram selecionados no período de fevereiro de 2009 a fevereiro de 2010. Os parâmetros analisados foram o remodelamento ventricular, o grau de dessincronia eletromecânica (DEM), tempo de exercício e VO2 máximo no teste ergométrico (TE) e a classe funcional (NYHA). O ecocardiograma foi realizado 24 a 48h após o implante e após um ano de seguimento. Os pacientes foram submetidos ao TE um mês após o procedimento e ao final de um ano. RESULTADOS: Foram incluídos 30 pacientes. A idade média foi de 59±13 anos. A indicação do implante de MP foi bloqueio atrioventricular (BAV) total em 22 (73,3%) pacientes e BAV do 2º grau nos outros 8 (26,7%). Todos os pacientes permaneceram em NYHA I e não houve mudança nos parâmetros do TE. Não foram detectadas variações nas medidas ecocardiográficas de remodelamento. Foi observada DEM intraventricular em 46,6% dos casos e interventricular em 33,3% dos pacientes ao final de um ano. CONCLUSÕES: Os achados deste trabalho sugerem que não houve mudanças morfológicas ou funcionais cardíacas significativas após o implante de marcapasso na posição septal em pacientes chagásicos com função ventricular esquerda normal após um ano de seguimento. Desta forma, os pacientes podem permanecer assintomáticos, com a manutenção da capacidade funcional e sem remodelamento ventricular esquerdo.

Co-infection Trypanosoma cruzi/HIV: systematic review (1980 - 2010) / Coinfecção Trypanosoma cruzi/HIV: revisão sistemática (1980 - 2010)

INTRODUCTION: The co-infection Trypanosoma cruzi/HIV has been described as a clinical event of great relevance. The objective of this study wasto describe clinical and epidemiological aspects published in literature. METHODS: It is a systematic review of a descriptive nature from the databases Medline, Lilacs, SciELO, Scopus, from 1980 to 2010. RESULTS: There were 83 articles (2.8 articles/year) with a total of 291 cases. The co-infection was described in 1980 and this situation has become the defining AIDS clinical event in Brazil. This is the country with the highest number of publication (51.8 percent) followed by Argentina (27.7 percent). The majority of cases are amongst adult men (65.3 percent) native or from endemic regions with serological diagnosis in the chronic stage (97.9 percent) and indeterminate form (50.8 percent). Both diseases follow the normal course, but in 41 percent the reactivation of the Chagas disease occurs. The most severe form is the meningoencephalitis, with 100 percent of mortality without specific and early treatment of the T. cruzi. The medication of choice was the benznidazole on doses and duration normally used for the acute phase. The high parasitemia detected by direct or indirect quantitative methods indicated reactivation and its elevation is the most important predictive factor. The lower survival rate was related to the reactivation of the Chagas disease and the natural complications of both diseases. The role of the antiretroviral treatment on the co-infection cannot yet be defined by the knowledge currently existent. CONCLUSIONS: Despite the relevance of this clinical event there are still gaps to be filled.

INTRODUÇÃO: A coinfecção Trypanosoma cruzi/HIV vem sendo sistematicamente descrita como um evento clínico de grande relevância. O objetivo deste estudo foi descrever aspectos clínicos e epidemiológicos publicados na literatura científica. MÉTODOS: Trata-se de revisão sistemática, de natureza descritiva, a partir da busca nas bases Medline, Lilacs, SciELO, Scopus, de 1980 a 2010. RESULTADOS: Identificou-se 83 artigos (2,8 artigos/ano), com um total de 291 casos registrados. A coinfecção foi descrita em 1980 e, no Brasil, tornou-se evento clínico definidor de AIDS. Este é o país com maior número de publicações (51,8 por cento), seguido pela Argentina (27,7 por cento). A maioria dos casos é de homens adultos (65,3 por cento), naturais ou procedentes de regiões endêmicas, com diagnóstico sorológico, na fase crônica (97,9 por cento) e na forma indeterminada (50,8 por cento). As duas doenças evoluem naturalmente, mas em 41 por cento dos casos ocorreu reativação da doença de Chagas. A forma mais grave é a meningoencefalite, com 100 por cento de letalidade nos casos sem tratamento específico e precoce do T. cruzi. O medicamento indicado foi benznidazole, nas doses e duração utilizadas na fase aguda em imunocompetentes. O diagnóstico da reativação foi comprovado por alta parasitemia, detectada por métodos diretos ou indiretos quantitativos, sendo a sua elevação considerada fator preditivo para reativação. A menor sobrevida nacoinfecção esteve relacionada à reativação da doença de Chagas e às complicações naturais de ambas as doenças. O papel do tratamento antirretroviral sobre a evolução da coinfecção ainda não pode ser definido pelo conhecimento existente. CONCLUSÕES: Apesar da relevância deste evento clínico, ainda persistem lacunas a serem preenchidas.

Immunophenotyping of circulating T cells in a mucosal leishmaniasis patient coinfected with HIV / Immunofenotipagem de células T circulantes em um paciente com leishmaniose mucosa co-infectado com HIV

HIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2 pattern of cytokine production. However, little information is available regarding the lymphocytic response in untreated coinfected patients. This work presents the immunophenotyping of Leishmania-stimulated T cells from a treatment-naÏve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69 expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL-17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17 population may serve as parasitic evasion mechanisms in HIV/ML. Further studies are required to confirm these results.

A co-infecção por HIV modifica o curso clínico da leishmaniose ao promover aumento no perfil Th2 de produção de citocinas. No entanto, há pouca informação a respeito da resposta linfocitária em pacientes co-infectados sem tratamento. Neste trabalho, foi realizada a imunofenotipagem de células T estimuladas com antígenos de Leishmania braziliensis em paciente não tratado HIV+ e com leishmaniose mucosa. Os resultados mostraram aumento na expressão de CD69 em células CD3+CD4+ e CD3+CD8+. Além disso, foi observado aumento de IL-4 na população de linfócitos CD3+CD4+GATA3- e diminuição no percentual de células CD3+CD4+IL-17+. Estes resultados sugerem que a modulação da via IL-4R/STAT6 e da população de células Th17 funcione como mecanismo de evasão parasitária em HIV/LM. Estudos futuros são necessários para confirmar estes resultados.

Sítios endocárdicos alternativos na estimulação cardíaca artificial / Alternative endocardial sites for artificial cardiac stimulation / Sitios endocárdicos alternativos en la estimulación cardíaca artificial

A estimulação ventricular direita convencional pode estar associada a efeitos deletérios sobre a função cardíaca. A necessidade de uma estimulação cardíaca artificial mais fisiológica é, indiscutivelmente, um dos pontos mais importantes na área da eletroterapia cardíaca. Os algoritmos de programação para a manutenção da condução atrioventricular própria, a estimulação de sítios endocárdicos alternativos e a terapia de ressincronização cardíaca são utilizados com o intuito de alcançar este objetivo. A estimulação do feixe de His e a estimulação septal têm sido estudadas como sítios endocárdicos alternativos para o posicionamento do eletrodo no ventrículo direito. A estimulação septal representa uma alternativa simples, prática e sem custos adicionais e com potenciais benefícios na redução dos efeitos deletérios da estimulação do ventrículo direito. Entretanto, esse sítio alternativo envolve um grupo heterogêneo de pacientes e apresenta resultados conflitantes quanto ao seu benefício clínico a longo prazo. Este artigo faz uma revisão das evidências científicas sobre os sítios alternativos de estimulação ventricular direita, com ênfase na segurança do procedimento, na medida dos parâmetros eletrofisiológicos, na avaliação da função ventricular esquerda e no acompanhamento clínico dos pacientes.

The conventional right ventricular stimulation can be associated with deleterious effects on cardiac function. The need for a more physiological artificial cardiac stimulation is undoubtedly one of the most important points in the area of cardiac electrotherapy. The programming algorithms for the maintenance of adequate atrioventricular conduction, the stimulation of alternative endocardial sites and the cardiac resynchronization therapy are used with the objective of attaining these goals. The stimulation of the bundle of His and the septal stimulation have been studied as alternative endocardial sites for the positioning of the electrode on the right ventricle. The septal stimulation represents a simple and practical alternative, with no additional costs involved and with potential benefits in decreasing the deleterious effects of the right ventricular stimulation. However, this alternative site involves a heterogeneous group of patients and presents conflicting results regarding its long-term clinical benefit. This article reviews the scientific evidence on the alternative sites for right ventricular stimulation, with emphasis on the safety of the procedure, the measurement of the electrophysiological parameters, assessment of the left ventricular function and the clinical follow-up of patients.

La estimulación ventricular derecha convencional puede estar asociada a efectos deletéreos sobre la función cardíaca. La necesidad de una estimulación cardíaca artificial más fisiológica es, indiscutiblemente, uno de los puntos más importantes en el área de la electroterapia cardíaca. Los algoritmos de programación para la manutención de la conducción atrioventricular propia, la estimulación de sitios endocárdicos alternativos y la terapia de resincronización cardíaca son utilizados con el propósito de alcanzar este objetivo. La estimulación del haz de His y la estimulación septal han sido estudiadas como sitios endocárdicos alternativos para el posicionamiento del electrodo en el ventrículo derecho. La estimulación septal representa una alternativa simple, práctica y sin costos adicionales y con potenciales beneficios en la reducción de los efectos deletéreos de la estimulación del ventrículo derecho. Entre tanto, ese sitio alternativo envuelve un grupo heterogéneo de pacientes y presenta resultados conflictivos en cuanto a su beneficio clínico a largo plazo. Este artículo hace una revisión de las evidencias científicas sobre los sitios alternativos de estimulación ventricular derecha, con énfasis en la seguridad del procedimiento, en la medida de los parámetros electrofisiológicos, en la evaluación de la función ventricular izquierda y en el control clínico de los pacientes.

Associação entre os níveis plasmáticos de TNF-α, IFN-γ, IL-10, óxido nítrico e os isotipos de IgG específicos nas formas clínicas da doença de Chagas crônica / Association between the plasma levels of TNF-α, IFN-γ, IL-10, nitric oxide and specific IgG isotypes in the clinical forms of chronic Chagas disease

A doença de Chagas é uma importante doença parasitária crônica, que acomete cerca de 9-11 milhões de pessoas na América Latina. Provavelmente, uma combinação de fatores relacionados ao parasito e ao hospedeiro podem ser os responsáveis pela patogênese na fase crônica da doença. Dentre os fatores relacionados ao hospedeiro, a resposta imunológica é um parâmetro de especial interesse. Objetivamos avaliar os níveis plasmáticos das citocinas interferon gama, interleucina 10, fator de necrose tumoral alfa e das imunoglobulinas G total, 3 e 4, por ELISA e do óxido nítrico, pela reação de Griess, entre indivíduos soronegativos e soropositivos para Trypanosoma cruzi, com as formas clínicas cardíaca, indeterminada e digestiva. Os indivíduos soropositivos para Trypanosoma cruzi produziram níveis significativamente mais elevados de imunoglobulinas G total e G3. Indivíduos com a forma digestiva apresentam níveis mais elevados de imunoglobulina G4 e interleucina 10. Entretanto, tais indivíduos apresentaram menores níveis de óxido nítrico do que controles. Os resultados sugerem que os maiores níveis de IL-10 observados nos indivíduos com a forma digestiva poderiam contribuir com os maiores níveis de IgG4 específicos observados.

Chagas disease is an important chronic parasitic disease that affects around 9-11 million people in Latin America. A combination of parasite and host-related factors are probably responsible for pathogenesis in the chronic phase of the disease. Among the host-related factors, the immunological response is a parameter of special interest. Our aim here was to evaluate the plasma levels of the cytokines interferon gamma, interleukin 10 and tumor necrosis factor alpha and the immunoglobulins total IgG and its subclasses 3 and 4, by means of ELISA, and the levels of nitric oxide by means of the Griess reaction, among individuals who were seropositive for Trypanosoma cruzi, presenting the cardiac, indeterminate and digestive clinical forms of the disease, and among seronegative individuals. The seropositive individuals produced significantly higher levels of total IgG and IgG-3. Individuals with the digestive form presented higher levels of IgG-4 and interleukin 10. However, these individuals presented lower levels of nitric oxide than the controls did. The results suggest that the higher levels of interleukin 10 observed among individuals with the digestive form may contribute towards the higher levels of the specific IgG-4 that were seen.