First-in-human experience of preload regulation with percutaneous transluminal caval flow regulation in heart failure with reduced ejection fraction patients.

AIMS: This study aims to investigate the acute haemodynamic effects of percutaneous transluminal flow regulation (PTCR®) with an inferior vena cava regulator balloon in heart failure patients. Preload reduction in heart failure has been achieved with high potency diuretics. However, no study has been conducted in humans to assess the effect of inferior vena cava intermittent occlusion for preload reduction. METHODS AND RESULTS: Six patients were included in the study: four men (55 ± 6 years old) and two women (63 ± 4 years old). Baseline evaluations included Doppler echocardiogram, coronary angiogram, and right heart catheterization. Caval balloon was kept inflated for 30 min, and right catheterization and control echocardiogram were performed while the balloon was still inflated. The balloon was then deflated and removed. Right haemodynamic variables were evaluated before balloon insertion and with the inflated balloon. The mean right atrial pressure decreased by 42.59% (P = 0.005); systolic right ventricular pressure decreased by 30.19% (P < 0.003); mean pulmonary arterial pressure decreased by 25.33% (P < 0.043); mean pulmonary capillary wedge pressure decreased by 31.37% (P > 0.016); and cardiac output increased by 9.92% (P < 0.175). CONCLUSIONS: The haemodynamic and echocardiographic changes obtained in our study using PTCR® suggest that this innovative approach can play a beneficial role in the heart failure treatment.

Autoantibodies against the immunodominant sCha epitope discriminate the risk of sudden death in chronic Chagas cardiomyopathy.

In Chagas disease (ChD) caused by Trypanosoma cruzi, new biomarkers to predict chronic cardiac pathology are urgently needed. Previous studies in chagasic patients with mild symptomatology showed that antibodies against the immunodominant R3 epitope of sCha, a fragment of the human basic helix-loop-helix transcription factor like 5, correlated with cardiac pathology. To validate sCha as a biomarker and to understand the origin of anti-sCha antibodies, we conducted a multicenter study with several cohorts of chagasic patients with severe cardiac symptomatology. We found that levels of antibodies against sCha discriminated the high risk of sudden death, indicating they could be useful for ChD prognosis. We investigated the origin of the antibodies and performed an alanine scan of the R3 epitope. We identified a minimal epitope MRQLD, and a BLAST search retrieved several T. cruzi antigens. Five of the hits had known or putative functions, of which phosphonopyruvate decarboxylase showed the highest cross-reactivity with sCha, confirming the role of molecular mimicry in the development of anti-sCha antibodies. Altogether, we demonstrate that the development of antibodies against sCha, which originated by molecular mimicry with T. cruzi antigens, could discriminate electrocardiographic alterations associated with a high risk of sudden death.

Differential cytokine profiling in Chagasic patients according to their arrhythmogenic-status.

BACKGROUND: Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by heart failure and sudden death. Identifying which factors are involved in evolution and treatment response is actually challenging. Thus, the aim of this work was to determine the Th1/Th17 (IL-6, IL-2, TNF, IL-17 and IFN-γ) and Th2 (IL-4 and IL-10) serum profile in Venezuelan Chagasic patients stratified according amiodarone treatment, hypertension and arrhythmias. METHODS: Sera from 38 chagasic patients were analyzed to determine the level of cytokines by Multiplexed Bead-Based Immunoassays. ANOVA test was applied to determine differences for each group. Additionally, a Linear Discriminant Analysis (LDA) was applied to observe the accuracy of different cytokines to discriminate between the groups. RESULTS: The levels of several cytokines were significantly higher in the high-risk of sudden death and untreated group. LDA showed that IL-2, IFN-γ and IL-10 were the best cytokines for discriminating between high-risk of sudden death and untreated patients versus low-risk of sudden death, treated and control groups. CONCLUSIONS: High IL-2 levels seem to identify patients with high-risk of sudden death and seems adequate as treatment efficacy marker. To our knowledge, this is the first report about the anti-inflammatory role of the amiodarone in Chagas disease, suggesting an inmunomodulatory effect that may be exploited as coadjutant therapy in chronic Chagas disease.

Sudden death circadian rhythm in Chagasic patients compared to non-Chagasic patients.

Chagas disease (Ch) affects 8-10 million people in Latin America, most of them are poor. Sudden death (SD) is the major cause of death in patients with Ch. To the best of our knowledge, the present report covers the largest reported series comparing the SD of Ch versus non-Ch patients Objective: To compare the circadian rhythm of SD in Ch versus non-Ch patients. METHODS: Retrospective analysis of all the cases of SD recorded in our department, including autopsied patients from 1963 until 2011. The pattern of SD of 262 patients (116 Ch and 146 non-Ch), 56.7% men, average age 54, 6 years old, divided into four groups: Group A: Ch with SD (n = 38), Group B: non-Ch with SD (n = 58), Group C. Ch with non SD (n = 89), and Group D: non-Ch with non SD (n = 81). For the statistical analysis, proportion comparison was used. RESULTS: 44.7% (17/38) of SDs in Group A (Ch) occurred between 6 a.m. and 5:59 p.m., while for Group B (not Ch) 70.7% (41 /58) died in that time (p < 0.005). 55.3% (21/38) of the SD in Group A (Ch) occurred between 6 p.m. and 5:59 a.m. compared with 29.3% (17/58) in Group B (p < 0, 005). CONCLUSIONS: Circadian rhythm of SD in patient with Ch differs from those with non-Ch. In Ch patients, SD occurs predominantly during the night compared with non-Ch SD that occurs predominantly during the day especially during the morning.

Satisfação no trabalho hospitalar de técnicos de enfermagem com formação superior / Job satisfaction of nursing technicians with higher education in the hospital work / Satisfacción en el trabajo hospitalario de técnicos de enfermería con educación superior

O objetivo deste estudo foi compreender a satisfação no trabalho hospitalar de técnicos de enfermagem com formação superior. Optou-se por pesquisa descritiva, com abordagem qualitativa com 14 técnicos de enfermagem. Os cenários foram as unidades de terapia intensiva de um hospital universitário, localizado em um município do interior do estado do Rio Grande do Sul, Brasil. Para a coleta de dados foi utilizada a entrevista semiestruturada individual. Como resultado, emergiram duas categorias: "foi um divisor de águas" – satisfação no trabalho relacionada ao aprimoramento após o curso superior; e sentimentos de insatisfação: frustração e subutilização do conhecimento adquirido. Os trabalhadores percebem um posicionamento mais crítico e apresentam uma visão mais ampla na práxis laboral. Porém, diante de situações em que não podem intervir e da não valorização por atividades desempenhadas, surgem sentimentos de subutilização e frustração no contexto do trabalho. Concluiu-se que a realização de um curso superior para os trabalhadores técnicos de enfermagem nesse cenário hospitalar contribuiu para a qualificação do cuidado prestado, impelindo para sentimentos de satisfação. Porém, deve-se repensar, no âmbito das instituições de saúde, aspectos que possam almejar a participação mais ativa e o reconhecimento da qualificação desses trabalhadores.

The objective of this study was to understand the job satisfaction of nursing technicians with higher education. This is a descriptive research withqualitative approach with 14 nursing technicians. The scenarios were the intensive care units of a university hospital, located in a municipalityin the State of Rio Grande do Sul, Brazil. For the data collection, a semi-structured interview was used. As a result, two categories emerged:"It was a watershed": job satisfaction related to improvement after attending higher education; and Feelings of dissatisfaction: frustration andunderutilization of the knowledge acquired. Workers perceive a more critical position and present a broader view in labor praxis. However, facedwith situations in which they cannot intervene and with non-appreciation for performed activities, feelings of frustration and underutilization arisein the labor context. It is concluded that the achievement of a higher education course by the nursing technicians working in hospitals contributedto the qualification of the care provided, thus impelling to feelings of satisfaction. However, it is necessary, in the scope of health institutions, torethink aspects that could target greater participation and appreciation of the qualification of these workers.

El objetivo de este estudio fue conocer la satisfacción laboral de los técnicos de enfermería con formación superior. Investigación descriptivacon enfoque cualitativo llevada a cabo con 14 técnicos de enfermería. Los escenarios fueron las unidades de terapia intensiva de un hospital universitario de un municipio del estado de Rio Grande do Sul, Brasil. Para la recogida de datos se utilizó la entrevista semiestructurada individual. Como resultado surgieron dos categorías: "fue un punto de inflexión": satisfacción laboral relacionada con la propia superación después del curso y sentimientos de insatisfacción: frustración y subutilización del conocimiento adquirido. Los trabajadores perciben que asumen una postura más crítica y que tienen una visión más amplia para ejercer sus labores. Sin embargo, ante situaciones donde no pueden intervenir y cuando no se les reconoce la importancia de sus tareas, surgen sentimientos de subutilización y frustración. Se concluye que el curso superior contribuye a la calificación de los cuidados brindados por los enfermeros en el ambiente hospitalario y que genera sentimientos desatisfacción. Sin embargo, habría que repensar, en el ámbito de las instituciones de salud, en los aspectos que incentivan la participación más activa y el reconocimiento de la cualificación profesional.

Intranasal administration of a polyvalent bacterial lysate induces self-restricted inflammation in the lungs and a Th1/Th17 memory signature.

Respiratory tract infections are among the most frequent infections in humans causing millions of deaths especially in children and the elderly. Antibiotics and vaccines are the main available tools of control, but resistant strains are continuously arising and available vaccines only account for few of many pathogens involved. Non-specific immunotherapies are an emerging alternative to induce protective immunity at the airways. Mucosally administered polyvalent bacterial lysates (PBLs) have been widely used for decades for prevention of respiratory diseases, but the bases of their proposed therapeutic effectiveness are still controversial. Here, we show that PBL engages a pro-inflammatory gene expression program in macrophages and epithelial cells, induces an acute lung inflammatory response and elicits full protection against pneumococcal pneumonia. Chronic lung inflammation may have pathological consequences, so the capacity to regain local homeostasis after treatment is central. We found that local inflammation is fully resolved and 30 days after treatment lungs become undistinguishable from naïve mice. Nevertheless, this process leaves an immunological imprinting with a Th1/Th17 memory phenotype that may be a marker of the protective immunity elicited. Increasing our understanding of the mechanism of action of PBLs may improve the efficiency of these immunotherapies and expand their range of action.

Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE: The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS: We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS: These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

Salmonella enterica serovar Typhimurium immunotherapy for B-cell lymphoma induces broad anti-tumour immunity with therapeutic effect.

Despite the efficacy of current immune-chemotherapy for treatment of B-cell non-Hodgkin lymphoma, a substantial proportion of patients relapse, highlighting the need for new therapeutic modalities. The use of live microorganisms to develop anti-tumoural therapies has evolved since Coley's toxin and is now receiving renewed attention. Salmonella Typhimurium has been shown to be highly effective as an anti-tumour agent in many solid cancer models, but it has not been used in haemato-oncology. Here, we report that intra-tumoural administration of LVR01 (attenuated S. Typhimurium strain with safety profile) elicits local and systemic anti-tumour immunity, resulting in extended survival in a lymphoma model. LVR01 induces intra-tumoural recruitment of neutrophils and activated CD8(+) T cells, as well as increasing the natural killer cell activation status. Furthermore, a systemic specific anti-tumour response with a clear T helper type 1 profile was observed. This approach is an alternative therapeutic strategy for lymphoma patients that could be easily moved into clinical trials.

Usefulness of real-time PCR assay targeting lipL32 gene for diagnosis of human leptospirosis in Uruguay.

INTRODUCTION: Assays based on DNA amplification can provide information that contributes to the initial management of patients with leptospirosis. However, these have not been adopted in Uruguay. Our aim was to evaluate the performance of the lipL32 real-time PCR (qPCR) for diagnosis of leptospirosis. METHODOLOGY: We analyzed by microscopic agglutination test (MAT) and lipL32 qPCR serum samples from 183 patients with suspected leptospirosis. To establish the analytical sensitivity of the qPCR, experimentally spiked samples with known amounts of Leptospira interrogans were analyzed. RESULTS: The analytical sensitivity of the qPCR was 102 leptospires/mL. In 98 patients MAT results were negative meanwhile 85 showed positive reactions, revealing acute infections. Twenty six acute-phase sera of these 85 patients showed a positive signal by qPCR (diagnostic sensitivity 30%). In these patients the average time between onset of symptoms and collection of the first sample was 8 days. In patients with negative results for qPCR and positive MAT results (n=59) the average interval between onset of symptoms and collection of the first sample was 13 days. The qPCR did not yield false positive results. CONCLUSIONS: The qPCR had a lower diagnostic sensitivity than MAT and a higher cost. However, it allowed to make an early diagnosis in 26 patients. In patients with confirmed acute infections and negative results by qPCR, more than 8 days had elapsed between the onset of the illness and extraction of the first serum sample. Our data support that the qPCR from sera have clinical utility within the first week of illness.

O etanercepte induz QRS de baixa tensão e disfunção autonômica em camundongos com doença de Chagas experimental / Etanercept induces low QRS voltage and autonomic dysfunction in mice with experimental Chagas disease

FUNDAMENTO: A doença de Chagas é uma doença parasitária tropical causada pelo protozoário flagelado Trypanosoma cruzi. A cardiomiopatia chagásica é caracterizada por distúrbios na regulação autonômica e na condução do potencial de ação nas fases aguda e crônica da infecção. Embora o fator de necrose tumoral alfa (TNF-α) tenha sido associadoà cardiomiopatia em modelos experimentais e em pacientes com doença de Chagas, outros relatos sugerem que o TNF-α pode exercer ações antiparasitárias durante a fase aguda da infecção. OBJETIVOS: Este estudo teve como objetivo determinar os efeitos de um blocker TNF-α solúvel, o etanercepte, em parâmetros eletrocardiográficos na fase aguda da infecção experimental com Trypanosoma cruzi. MÉTODOS: Foram feitos eletrocardiogramas em camundongos infectados não tratados e camundongos infectados que foram tratados com etanercepte 7 dias após a infecção. Os parâmetros de variabilidade onda do eletrocardiograma e frequência cardíaca foram determinados utilizando o Chart para Windows. RESULTADOS: O tratamento com etanercepte resultou em uma baixa tensão do complexo QRS e uma redução da variabilidade da frequência cardíaca em comparação com a ausência de tratamento. No entanto, os camundongos tratados apresentaram um atraso na queda da curva de sobrevivência durante a fase aguda. CONCLUSÃO: Os resultados deste estudo sugerem que, embora o tratamento com etanercepte promova a sobrevivência em camundongos infectados com uma linhagem virulenta de T. cruzi, o bloqueio do TNF-α gera um complexo de baixa tensão e disfunção autonômica durante a fase aguda da infecção. Esses resultados indicam que a mortalidade durante a fase aguda pode ser atribuída a uma resposta inflamatória sistêmica, em vez da disfunção cardíaca.

BACKGROUND: Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagasic cardiomyopathy is characterized by disorders of autonomic regulation and action potential conduction in the acute and chronic phases of infection. Although tumor necrosis factor alpha (TNF-α) has been linked to cardiomyopathy in experimental models and in patients with Chagas disease, other reports suggest that TNF-α may exert anti-parasitic actions during the acute phase of infection. OBJECTIVES: This study aimed to determine the effects of a soluble TNF-α agonist, etanercept, on electrocardiographic parameters in the acute phase of experimental infection with Trypanosoma cruzi. METHODS: Electrocardiograms were obtained from untreated infected mice and infected mice who were treated with etanercept 7 days after infection. ECG wave and heart rate variability parameters were determined using Chart for Windows. RESULTS: Etanercept treatment resulted in a low QRS voltage and decreased heart rate variability compared with no treatment. However, the treated mice exhibited a delay in the fall of the survival curve during the acute phase. CONCLUSION: The results of this study suggest that although etanercept treatment promotes survival in mice infected with a virulent T. cruzi strain, TNF-α blockade generates a low voltage complex and autonomic dysfunction during the acute phase of infection. These findings indicate that mortality during the acute phase can be attributed to a systemic inflammatory response rather than cardiac dysfunction.).

As manifestações de ECG do maior surto da doença de Chagas devido a infecção oral na América Latina / ECG manifestations of the biggest outbreak of Chagas disease due to oral Infection in Latin-America

FUNDAMENTO: A doença de Chagas afeta mais de 15 milhões de pessoas em todo o mundo. Embora a transmissão vetorial tenha diminuído, a transmissão oral tornou-se relevante. Recentemente, nosso grupo publicou as características clínicas e epidemiológicas do maior surto relatado até hoje da doença de Chagas transmitida oralmente. OBJETIVO: Descrever alterações eletrocardiográficas que ocorrem na população de estudo durante o surto causado pela ingestão de suco de goiaba contaminado. MÉTODOS: Avaliamos 103 casos positivos, dos quais 76 (74%) tinham <18 anos de idade (média das idades: 9,1 ± 3,1 anos) e 27 (26%) tinham >18 anos (média das idades: 46 ± 11,8 anos). Todos os pacientes foram submetidos a avaliações clínicas e ECG. Caso os pacientes apresentassem palpitações ou alterações evidentes do ritmo na linha basal, o monitoramento de ECG ambulatorial seria realizado. RESULTADOS: Um total de 68 casos(66%;53 crianças e15 adultos) apresentaram anormalidades no ECG. Além disso, 69,7% (53/76) daqueles com idade < 18anos e 56% (15/27) daqueles com idade >18 anos apresentaram alguma alteração no ECG(p = ns). Anormalidades de ST-T foram observadas em 37,86% casos (39/103) e arritmias foram evidente sem 28,16% casos(29/103). Alterações de ST ocorreram em 72% daqueles com idade < 18 anos em comparação aos de > 18 anos (p < 0,0001). CONCLUSÃO: Este estudo relata o maior número de casos no mesmo surto de doença de Chagas causada por contaminação oral, com ECGs relatados. As alterações no ECG que sugerem miocardite aguda e arritmias foram as anormalidades encontradas com maior frequência.

BACKGROUND: Chagas disease affects more than 15 million people worldwide. Although vector-borne transmission has decreased, oral transmission has become important. Recently, our group published the clinical and epidemiological characteristics of the largest outbreak of orally transmitted Chagas disease reported till date. OBJECTIVE: To describe electrocardiographic changes occurring in the study population during the outbreak caused by ingestion of contaminated guava juice. METHODS: We evaluated 103 positive cases, of which 76 (74%) were aged <18 years (average age: 9.1 ± 3.1 years) and 27 (26%) were aged > 18 years (average age: 46 ± 11.8 years). All patients underwent clinical evaluations and ECG. If the patients had palpitations or evident alterations of rhythm at baseline, ambulatory ECG monitoring was performed. RESULTS: A total of 68 cases (66%; 53 children and 15 adults) had ECG abnormalities. Further, 69.7% (53/76) of those aged < 18 years and 56% (15/27) of those aged >18 years showed some ECG alteration (p = ns). ST-T abnormalities were observed in 37.86% cases (39/103) and arrhythmias were evident in 28.16% cases (29/103). ST alterations occurred in 72% of those aged <18 years compared with 19% of those aged >18 years (p < 0.0001). CONCLUSIONS: This study reports the largest number of cases in the same outbreak of acute Chagas disease caused by oral contamination, with recorded ECGs. ECG changes suggestive of acute myocarditis and arrhythmias were the most frequent abnormalities found.

ECG manifestations of the biggest outbreak of Chagas disease due to oral infection in Latin-America.

BACKGROUND: Chagas disease affects more than 15 million people worldwide. Although vector-borne transmission has decreased, oral transmission has become important. Recently, our group published the clinical and epidemiological characteristics of the largest outbreak of orally transmitted Chagas disease reported till date. OBJECTIVE: To describe electrocardiographic changes occurring in the study population during the outbreak caused by ingestion of contaminated guava juice. METHODS: We evaluated 103 positive cases, of which 76 (74%) were aged ≤ 18 years (average age: 9.1 ± 3.1 years) and 27 (26%) were aged > 18 years (average age: 46 ± 11.8 years). All patients underwent clinical evaluations and ECG. If the patients had palpitations or evident alterations of rhythm at baseline, ambulatory ECG monitoring was performed. RESULTS: A total of 68 cases (66%; 53 children and 15 adults) had ECG abnormalities. Further, 69.7% (53/76) of those aged ≤ 18 years and 56% (15/27) of those aged >18 years showed some ECG alteration (p = ns). ST-T abnormalities were observed in 37.86% cases (39/103) and arrhythmias were evident in 28.16% cases (29/103). ST alterations occurred in 72% of those aged ≤ 18 years compared with 19% of those aged >18 years (p < 0.0001). CONCLUSIONS: This study reports the largest number of cases in the same outbreak of acute Chagas disease caused by oral contamination, with recorded ECGs. ECG changes suggestive of acute myocarditis and arrhythmias were the most frequent abnormalities found.

Etanercept induces low QRS voltage and autonomic dysfunction in mice with experimental Chagas disease.

BACKGROUND: Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagasic cardiomyopathy is characterized by disorders of autonomic regulation and action potential conduction in the acute and chronic phases of infection. Although tumor necrosis factor alpha (TNF-α) has been linked to cardiomyopathy in experimental models and in patients with Chagas disease, other reports suggest that TNF-α may exert anti-parasitic actions during the acute phase of infection. OBJECTIVES: This study aimed to determine the effects of a soluble TNF-α agonist, etanercept, on electrocardiographic parameters in the acute phase of experimental infection with Trypanosoma cruzi. METHODS: Electrocardiograms were obtained from untreated infected mice and infected mice who were treated with etanercept 7 days after infection. ECG wave and heart rate variability parameters were determined using Chart for Windows. RESULTS: Etanercept treatment resulted in a low QRS voltage and decreased heart rate variability compared with no treatment. However, the treated mice exhibited a delay in the fall of the survival curve during the acute phase. CONCLUSION: The results of this study suggest that although etanercept treatment promotes survival in mice infected with a virulent T. cruzi strain, TNF-α blockade generates a low voltage complex and autonomic dysfunction during the acute phase of infection. These findings indicate that mortality during the acute phase can be attributed to a systemic inflammatory response rather than cardiac dysfunction.

Innate immune responses to Proteus mirabilis flagellin in the urinary tract.

Flagella are bacterial virulence factors allowing microorganisms to move over surfaces. Flagellin, the structural component of flagella, is sensed by the host via Toll and NOD-like receptors and triggers pro-inflammatory responses. The use of Toll-like receptors agonists to modulate innate immune responses has aroused great interest as an alternative to improve the treatment of diverse infectious diseases. Proteus mirabilis is a Gram negative bacterium that causes urinary tract infections in humans. In the present work we used different approaches to study the ability of P. mirabilis flagellin to induce an innate immune response. We demonstrated that P. mirabilis flagellin has the ability to induce pro-inflammatory chemokines expression in T24 bladder cultures cells and in the mouse bladder after instillation. It was evidenced also that flagellin from different P. mirabilis strains differed in their capacity to induce an innate immune response in the CacoCCL20-Luc system. Also, flagellin elicited inflammation, with recruitment of leukocytes to the bladder epithelium. Flagellin instillation before an experimental P. mirabilis infection showed that the inflammatory response due to flagellin did not help to clear the infection but favored bacterial colonization. Thus, induction of inflammatory response in the bladder did not contribute to P. mirabilis infection neutralization.

Echinococcus granulosus: different cytokine profiles are induced by single versus multiple experimental infections in dogs.

Modulation of host responses is an important strategy by which parasites ensure successful establishment and persistence. Host counteraction against this modulation may be required for the host to develop resistance to infection. In this pilot study, experimental infection of dogs with Echinococcus granulosus induced a strong polarization of the cytokine response towards a Th2 phenotype. Consecutive rounds of infection and cure induced resistance to infection resulting in a dramatically lower parasite burden. Repeatedly-infected resistant dogs also lost immune polarization and developed a balanced Th1/Th2 response. No major differences were observed in the production of regulatory cytokines (IL-10, TGF-ß) between dogs with high parasite load and dogs with only few intestinal parasites. These results suggest that E. granulosus-driven immunomodulation contributes to successful infection in the definitive host. This information might be relevant for the development of more effective vaccines against this stage of the parasite.

Un aspecto crítico olvidado con frecuencia: la adherencia al tratamiento / A critical aspect often neglected: adherence

Aun cuando la importancia del tratamiento adecuado y de su cumplimento para alcanzar las metas en salud están claramente demostrados, la falla de adherencia al tratamiento en general supera el 50%. Este es un problema multidimensional donde el paciente es sólo uno de los factores involucrados. Comprender los diferentes factores involucrados así como el impacto de la no adherencia no solamente en la falla de eficacia, sino en el incremento de riesgo y de costos para el sistema de salud, es clave para poder generar acciones que lleven a mejorar la. En Estados Unidos solamente, los costos incrementales relacionados con la no adherencia se calculan por encima de los 300 millardos de dólares.

Although the importance of proper treatment and its compliance to achieve health goals is clearly demonstrated, the failure in treatment adherence generally exceeds 50%. The lack of treatment adherence is a multidimensional problem where the patient is just one of the factors involved. Understanding the different factors in question and the impact of failure in treatment adherence not only in the efficiency, but the increase in risk and cost in the health system, are key for generating actions that lead to improvement. In the U.S. alone incremental costs associated with non-adherence are calculated above 300 billion.

Early peritoneal immune response during Echinococcus granulosus establishment displays a biphasic behavior.

BACKGROUND: Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. PRINCIPAL FINDINGS: Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4(+) T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). CONCLUSIONS: Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies based on stimulation of effective responses and blockade of evasion mechanisms.