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BACKGROUND: Chagas cardiomyopathy (CCM) is increasingly prevalent in developed countries due to migration from endemic areas. Accurate risk stratification is crucial due to the variable clinical course of CCM. OBJECTIVE: To analyze the association between Rassi score progression and electrophysiology study (EPS) changes in CCM patients. METHODS: This prospective, observational cohort study involved CCM patients from two tertiary hospitals. Patients were classified as low, intermediate, or high risk based on the Rassi score. Data collected included demographics, clinical history, and diagnostic tests. EPS assessed AH, HH, and HV intervals, and inducibility of ventricular arrhythmias. Follow-ups were at 30 days and six-month intervals, with individualized discussions for cardiac implantable electric devices (CIED) based on EPS results. RESULTS: Of 67 screened CCM patients, 59 underwent EPS. The mean Rassi score was 8.7 ±â€¯4.5 points, with 33.8 % low, 38.9 % intermediate, and 27.1 % high risk. EPS abnormalities were found in 57.6 % of patients, mainly VT/VF (52.5 %). Most induced ventricular arrhythmias were monomorphic VT (80.7 %). A significant association was found between Rassi score risk classification and EPS changes (OR = 1.88 95 %CI: 1.15-3.06 p = 0.02). Higher Rassi scores correlated with VT presence on EPS (p = 0.0036). Syncope/pre-syncope had an OR 2.45 95 %CI:1.21-4.94; p = 0.012, independent of Rassi risk. Decreased ejection fraction was linked to EPS changes (p = 0.04). CONCLUSION: EPS changes among CCM was associated with progression of the Rassi score, indicating its utility as a stratification tool. Factors such as the presence of syncope/pre-syncope, decreased LVEF and wall motion abnormalities emerged as independent predictors within Rassi scores for changes in EPS.

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Resumo:A incorporação das demandas de conferências de saúde em seus respectivos planos tem se mostrado um desafio para a efetiva participação da comunidade no planejamento do Sistema Único de Saúde. Assim, este estudo teve por objetivo analisar tal processo de formulação de política pública a partir de uma abordagem qualitativa com base documental, em nível estadual. Para fins comparativos, as propostas do Relatório Consolidado da 8ª Conferência Estadual de Saúde do Rio Grande do Sul e as metas do Plano Estadual de Saúde correspondente foram sistematizadas em seis macro categorias, subdivididas em 20 categorias operacionais, de acordo com políticas, ações e serviços de saúde, verificando-se em que medida as demandas das propostas foram contempladas pelas metas do PES. Constatou-se que somente 20% das propostas foram inseridas no Plano correspondente. Inúmeros fatores podem contribuir para esse distanciamento entre os documentos analisados, tais como o elevado número de propostas, expressivo percentual de propostas intersetoriais, questões de redação, entre outros. Além disso, sugere-se que uma etapa intermediária, entre a conferência e o Plano, poderia representar uma oportunidade de melhoria para o processamento técnico das propostas, a fim de torná-las exequíveis e passíveis de incorporação.

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Resumo Este estudo teve como objetivo caracterizar as regiões de saúde do estado do Rio Grande do Sul (RS) quanto ao uso de agrotóxicos e à mortalidade por câncer de próstata, linfoma não Hodgkin (LNH) e leucemias. Para cada região de saúde foram estimados o volume total de agrotóxicos utilizado, o volume usado por área plantada, a proporção de lavouras com uso, a proporção de agricultura familiar e o grau de desigualdade na distribuição das terras. A mortalidade pelos três tipos de câncer foi descrita com base na mortalidade proporcional e na taxa de mortalidade ajustada por idade. A associação entre as variáveis foi estimada pelo coeficiente de correlação de Spearman. A mortalidade por câncer de próstata mostrou-se relacionada à produção agrícola intensa, utilização de elevado volume de agrotóxicos e menor proporção de agricultura familiar. Já a mortalidade por linfoma não Hodgkin e leucemias esteve associada positivamente à proporção de agricultura familiar. Mortalidade proporcional e taxa de mortalidade ajustada por idade mostraram-se positivamente correlacionadas para os três tipos de câncer. Este estudo demonstrou que, nas regiões de saúde do RS, a mortalidade pelos três tipos de câncer investigados está vinculada, em diferentes intensidades, ao uso de agrotóxicos e a características da agricultura praticada.

Abstract This study characterizes the health regions of the Rio Grande do Sul State regarding pesticide use and mortality by prostate cancer, Non-Hodgkin's Lymphoma and leukemias. Total volume of pesticide used, volume used per planted area, the proportion of crops using pesticides, the proportion of family farming and the degree of inequality in land distribution were estimated for each region. Mortality from the three types of cancer was described by proportional mortality and age-adjusted mortality rate. Association between variables was estimated using Spearman's correlation coefficient. Prostate cancer mortality was associated with intense agricultural production, high volume of pesticide use and a lower proportion of family farming. Mortality from Non-Hodgkin's Lymphoma and leukemias, in turn, was positively associated with the proportion of family farming. Proportional mortality and age-adjusted mortality rate were positively correlated for the three types of cancer. In conclusion, in the health regions of Rio Grande do Sul, mortality by the three types of cancer investigated is associated, albeit at different intensities, with pesticide use and the type of agriculture practiced.

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[This corrects the article DOI: 10.3389/fimmu.2019.01211.].

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RESUMEN Fundamento: las enfermedades cerebrovasculares constituyen la tercera causa de muerte en el mundo y una de las principales responsables de discapacidad y minusvalía en el adulto. Objetivo: describir las principales características clínicas en fallecidos por enfermedad cerebrovascular en el Hospital General Universitario Dr. Gustavo Aldereguía Lima de Cienfuegos. Métodos: se realizó un estudio descriptivo, transversal. El universo estuvo conformado por 517 pacientes fallecidos con diagnóstico de enfermedad cerebrovascular en el período comprendido entre el 1 de enero 2014 y el 31 de diciembre 2016 en Hospital General Universitario Dr. Gustavo Aldereguía Lima de Cienfuegos. Se consideraron como variables: edad, sexo, tipo y forma de presentación de la enfermedad cerebrovascular focal, estadía hospitalaria, patologías asociadas y año de defunción. Se obtuvieron los resultados en frecuencias absolutas y porcientos. Resultados: el 31,1 % de los fallecidos se halló entre los 80-89 años. Predominó el sexo masculino en un 55,3 %. El ictus de tipo isquémico representó el 62,5 %, fue la forma aterotrombótica la más frecuente con un 31,9 %. El 2015 fue el año con mayor número de defunciones con 186. El 75,2 % de las muertes se registró en los primeros 7 días de estadía hospitalaria. La principal patología asociada fue la hipertensión arterial (34,6 %). Conclusiones: la mortalidad por enfermedad cerebrovascular se presentó principalmente en pacientes de edades avanzadas, varones e hipertensos. Predominó la etiología isquémica. La mayoría de los pacientes que fallecieron lo hicieron en la primera semana de estadía hospitalaria.

ABSTRACT Foundation: cerebrovascular diseases are the third cause of death in the world and one of the main causes of disability in the adult. Objective: to describe the main clinical characteristics of deceased patients due to cerebrovascular disease at the Dr. Gustavo Aldereguía Lima General Hospital in Cienfuegos. Methods: a descriptive, cross-sectional study was conducted between January 1, 2014 and December 31, 2016 in the General University Hospital Gustavo Aldereguía Lima de Cienfuegos. The universe consisted of 517 deceased patients with a diagnosis of cerebrovascular disease in the period and the variables considered were: age, sex, type and form of presentation of focal cerebrovascular disease, hospital stay, associated pathologies and year of death. The results were obtained in absolute and percent frequencies. Results: from the deceased 31.1 % of were between 80-89 years old. Male sex predominated in 55.3 %. Stroke of the ischemic type represented 62.5 %, the athero-thrombotic form was the most frequent with 31.9 %. The year 2015 had the highest number of deaths with 186. The first 7 days of hospital stay recorded 75.2 % of deaths. The main associated pathology was hypertension (34.6 %). Conclusions: mortality from cerebrovascular disease. Most patients who died did so in the first week of hospital stay.

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The present study intends to assess the metal pollution of a eutrophic coastal lagoon, analyzing the long-term and actual metal content in surface sediments, suspended particles, aquatic macrophyte and fish species, and the loads emitted from natural processes and anthropogenic sources, including the relative emission of domestic untreated sewage. Distribution indicated contamination of suspended particles with Cd and the predominance of Pb in the bioavailable form in surface sediments which may explain Cd and Pb contamination in fish. Domestic untreated sewage was an important source of Cu and due to the lagoon's management, this source may be increasing the metal content in the lagoon's surface sediments. Soil loss, atmospheric deposition and solid waste disposal also contributed to metal inputs to the lagoon. Extensive contamination has been prevented by the lagoon's management such as sandbar opening. Metal retention within the watershed soils reduce the effective metal transference and lagoon pollution.

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RESUMEN Fundamento: La neumonía asociada a la ventilación mecánica se asocia a una elevada morbimortalidad, y su manejo integral es complejo. Objetivo: describir las características clínicas y microbiológicas en pacientes con neumonía asociada a la ventilación mecánica. Métodos: se realizó un estudio observacional, descriptivo, transversal. Fueron analizados 174 pacientes con diagnóstico de neumonía asociada a la ventilación mecánica, en el periodo comprendido entre el enero de 2015 y diciembre de 2017, en el Hospital Provincial de Cienfuegos. Se consideraron las variables: edad, sexo, servicio de procedencia, año, causa de ingreso, estado al egreso, resultado del cultivo bacteriológico, microorganismos aislados y resistencia in vitro. Resultados: el 26,4 % de los pacientes se halló entre los 70-79 años, con predominio del sexo masculino (52,3 %). El 71,3 % de las muestras tuvo resultados de cultivos monomicrobianos. El microorganismo más frecuente fue Acinetobacter baumannii, con un 50,5 %. La enfermedad cerebrovascular fue la causa de ingreso que más se presentó (28,7 %). El 47,7 % de los pacientes falleció. Existió una elevada resistencia in vitro en la mayoría de los microorganismos aislados. Conclusión: la enfermedad se presentó principalmente en pacientes de edades avanzadas, del sexo masculino. En correspondencia con estudios previos en la provincia, Acinetobacter baumannii se manifestó como el agente causal más frecuente, con una elevada resistencia in vitro. La enfermedad cerebrovascular fue la principal causa de ingreso.

ABSTRACT Foundation: Pneumonia associated with mechanical ventilation is associated with high morbidity and mortality, and its integral management is complex. Objective: to describe the clinical and microbiological characteristics in patients with pneumonia associated with mechanical ventilation. Methods: an observational, descriptive, cross-sectional study was conducted. A total of 174 patients diagnosed with pneumonia associated with mechanical ventilation were analyzed in the period between January 2015 and December 2017, at the Provincial Hospital of Cienfuegos. The variables were considered: age, sex, service of origin, year and cause of admission, state at discharge, result of bacteriological culture, isolated microorganisms and resistance in vitro. Results: 26.4% of the patients were between 70-79 years old, with a predominance of males (52.3%). Monomicrobial cultures were present in 71.3% of the samples. The most frequent microorganism was Acinetobacter baumannii, with 50.5%. Cerebrovascular disease was the most frequent cause of admission (28.7%). 47.7% of patients died. There was a high resistance in vitro in most of the isolated microorganisms. Conclusion: the disease appeared mainly in elderly male patients. In correspondence with previous studies in the province, Acinetobacter baumannii was manifested as the most frequent causative agent, with high resistance in vitro. Cerebrovascular disease was the main cause of admission.

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The present study aims to determine whether 17DD-YF-specific humoral and cellular immunological memory is maintained 8-years after primary vaccination with subdoses (10,447IU;3,013IU;587IU;158IU;31IU). For this purpose, this follow-up study was carried out in a subset of volunteers (n = 98) originally enrolled in the dose-response study in 2009 and 46 non-vaccinated controls. Our results demonstrated that vaccinees, who had seroconverted following primary vaccination and had not been revaccinated, present similar neutralizing antibodies levels and YF-specific cellular memory, particularly CMCD4 and EMCD8 as compared to the reference full dose (27,476IU). Although, PRNT seropositivity rates were similar across subgroups (94, 82, 83, 94, 80, and 91%, correspondingly), only doses above 587IU elicited similar iterative proportion of seropositivity rates, calculated as a progressive decrease on seropositivity rates along time (89, 80, 80, and 91%, respectively) as compared to 158IU and 31IU (68 and 46%, respectively). Noteworthy were the strong positive correlations ("EMCD4,EMCD8" and "TNFCD8,IFNCD8") observed in most subdoses, except for 31IU. Major similarities underscored the preserved antibody titers and the outstanding levels of EMCD8, relevant correlates of protection for YF-specific immunity. These findings provide evidences to support the regular use of dose sparing strategy for YF vaccine in adults.

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In this investigation, machine-enhanced techniques were applied to bring about scientific insights to identify a minimum set of phenotypic/functional memory-related biomarkers for post-vaccination follow-up upon yellow fever (YF) vaccination. For this purpose, memory status of circulating T-cells (Naïve/early-effector/Central-Memory/Effector-Memory) and B-cells (Naïve/non-Classical-Memory/Classical-Memory) along with the cytokine profile (IFN/TNF/IL-5/IL-10) were monitored before-NV(day0) and at distinct time-points after 17DD-YF primary vaccination-PV(day30-45); PV(year1-9) and PV(year10-11). A set of biomarkers (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) were observed in PV(day30-45), but not in NV(day0), with most of them still observed in PV(year1-9). Deficiencies of phenotypic/functional biomarkers were observed in NV(day0), while total lack of memory-related attributes was observed in PV(year10-11), regardless of the age at primary vaccination. Venn-diagram analysis pre-selected 10 attributes (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 and IL-5CD4), of which the overall mean presented moderate accuracy to discriminate PV(day30-45)&PV(year1-9) from NV(day0)&PV(year10-11). Multi-parameter approaches and decision-tree algorithms defined the EMCD8 and IL-5CD4 attributes as the top-two predictors with moderated performance. Together with the PRNT titers, the top-two biomarkers led to a resultant memory status observed in 80% and 51% of volunteers in PV(day30-45) and PV(year1-9), contrasting with 0% and 29% found in NV(day0) and PV(year10-11), respectively. The deficiency of memory-related attributes observed at PV(year10-11) underscores the conspicuous time-dependent decrease of resultant memory following17DD-YF primary vaccination that could be useful to monitor potential correlates of protection in areas under risk of YF transmission.

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In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether yellow fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study's results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the yellow fever vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT 03338231.

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En los últimos años Acinetobacter baumannii se ha convertido en uno de los gérmenes de mayor relevancia clínica, lo cual le convierte en un verdadero paradigma de las infecciones nosocomiales multirresistentes. El presente trabajo tuvo como objetivo describir los mecanismos de resistencia de Acinetobacter baumannii frente a múltiples fármacos, así como explicar las estrategias terapéuticas actuales en cepas multirresistentes; para ello fueron consultadas 37 fuentes bibliográficas. Los mecanismos implicados en la resistencia del microorganismo comprenden la inhibición del antibiótico por β-lactamasas, disminución de la permeabilidad de los antibióticos por pérdida de porinas, presencia de bombas de expulsión y la alteración del sitio de acción del fármaco. Se recomienda que el tratamiento de elección en cepas multirresistentes sea la colistina y la tigeciclina, aunque se pueden utilizar otros fármacos y combinaciones entre estos.

In the last years Acinetobacter baumannii has become one of the germs of higher clinical relevance, which really turns it into a paradigm in the nosocomial multi-drug resistant infections. The present work had the objective of describing the resistance mechanisms of Acinetobacter baumannii to multiple drugs, so as to explain current therapeutic strategies in multidrug-resistant strains; for that 37 bibliographic resources were consulted. The mechanisms involved in the micro-organism resistance include inhibition to the antibiotic by β-lactamases, decreasing of antibiotic permeability due to porin loses, presence of efflux pumps and drug action site disturbances. It is recommended that the treatment of choice in multi-drug resistant strains is colistin and tigecycline, though other drugs may be used so as their combination.

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La hipertensión intra-abdominal y el síndrome compartimental abdominal son entidades frecuentes en los pacientes graves, las cuales cursan con una alta mortalidad. El presente trabajo tuvo como objetivo explicar la etiopatogenia del síndrome compartimental abdominal, así como describir los mecanismos fisiopatológicos involucrados en dicha patología. Para ello se consultó un total de 25 fuentes bibliográficas, entre ellas artículos de revistas, libros y otras, accedidas por medio de los principales gestores de la información. Se concluyó que el síndrome compartimental abdominal es propiciado por la disminución de la distensibilidad de la pared abdominal, el aumento del volumen intra-abdominal o una combinación de ambas, y que además se produce compresión directa de los órganos por la hipertensión intra-abdominal, el edema, isquemia secundaria al descenso del flujo sanguíneo, alteración de la función y composición de la microbiota intestinal, llegando a causar tardíamente el síndrome de disfunción múltiple orgánica.

Intra-abdominal hypertension and compartment syndrome are frequent entities in severely ill patients and result in a high mortality. This work is aimed at explaining the ethiopathogenesis of compartment abdominal syndrome, so as describing pathophysilogical mechanisms involved in this pathology. For that, a total of 25 bibliographic resources were reviewed, among them journals, books and others, consulted through the main information agents. It was concluded that the compartment syndrome is caused by the decrease of the abdominal wall distensibility and the increase of intraabdominal volumen or a combination of both. In addition it is produced by the direct organ compression by intra-abdominal hypertension, edema, ischemia secundary to blood flow decreasing, disturbances of the function and composition of the intestinal microbiota, all which later causes a multiple organ disfunction.

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ABSTRACT The aim of the present study was to describe the clinical manifestation, treatment and outcome of a case of co- infection by Sarcoptes scabiei and Microsporum gypseum in Cerdocyon thous (crab-eating fox) from Northeastern Brazil.

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ABSTRACT: This paper described a case of a capuchin monkey (Sapajus libidinosus) with non-pruritic skin lesions. During the physical examination, multifocal areas of alopecia with crusts, erythema and scaling compatible with dermatophytosis were reported on the right fore and hind limbs and on tail. Fungal culture findings revealed a diagnosis of dermatophytosis due to Microsporum canis. The animal was successfully treated with itraconazole. This is the first report of a dermatophytosis case in S. libidinosus and the first description of an effective treatment in this species.

RESUMO: O presente trabalho relata o caso de um macaco capuchinho (Sapajus libidinosus) com lesões de pele não-pruriginosas. Durante o exame físico foram encontradas lesões multifocais com crostas, eritema e descamação compatíveis com dermatofitose, nos membros anterior e posterior direitos, bem como na cauda. O animal não tinha outras alterações. O diagnóstico de dermatofitose por Microsporum canis foi realizado através de cultura fúngica das lesões. O animal foi tratado com sucesso com itraconazol. Este é o primeiro relato de um caso de dermatofitose em S. libidinosus e a primeira descrição de um tratamento eficaz para esta espécie.

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A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.

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Objetivou-se analiar as potencialidades e fragilidades no conhecimento dos enfermeiros residentes acerca do cuidado ao cliente com estomia intestinal. Trata-se de uma pesquisa quantitativa e transversal, desenvolvida em hospital universitário no Município do Rio de Janeiro, no ano de 2012, com 35 residentes. Evidenciaram-se potencialidades (acertos) no conhecimento dos residentes de clínica cirúrgica, das quais se destacaram: localização e principais tipos de estomias (90%); troca do sistema coletor e higienização do estoma (66%); detecção de complicações e medidas preventivas (76%); orientação à família (27%). Ressaltaram-se fragilidades no conhecimento dos residentes de clínica médica para atuarem junto a estes clientes, tais como dificuldades em relação à orientação para o autocuidado (87%) e detecção de complicações e medidas preventivas (87%). Conclui-se que os residentes da clínica médica revelaram mais fragilidades no conhecimento sobre o tema do que os da clínica cirúrgica.

This quantitative study aimed to examine the strengths and weaknesses in 35 resident nurses' knowledge of care for clients with ostomy was conducted at a university hospital in Rio de Janeiro city in 2012. Strengths (right answers) showed in the residents' surgical clinical knowledge, particularly of the location and main types of ostomy (90%), replacing the collector system and cleaning the ostomy (66%), detection of complications and preventive measures (76%), and family guidance (27%). Salient weaknesses in clinical medical residents' knowledge of working with these clients included difficulties regarding: selfcare guidance (87%), and detection of complications and preventive measures (87%). It was concluded that internal medicine residents displayed more weaknesses in knowledge of the subject than surgical clinical residents.

El objetivo del estudio fue analizar las potencialidades y debilidades en el conocimiento de los enfermeros residentes sobre la atención al cliente portador de ostomía intestinal. Se trata de una investigación cuantitativa y transversal, desarrollada en un hospital universitario en la ciudad de Rio de Janeiro, en 2012, junto a 35 residentes. Se han evidenciado potencialidades (aciertos) en el conocimiento de los residentes de clínica quirúrgica, de las que destacaron: ubicación y principales tipos de ostomías (90%); cambio del sistema colector e higienización del estoma (66); detección de complicaciones y medidas preventivas (76%); orientación a la familia (27%). Se resaltan debilidades en el conocimiento de los residentes de la clínica médica para trabajar junto a esos clientes, tales como dificultades en cuanto a ofrecer orientación para el autocuidado (87%) y detectar complicaciones y medidas preventivas (87%). Se concluye que los residentes de clínica médica revelaron más debilidades en el conocimiento sobre el tema que los de la clínica quirúrgica.

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BACKGROUND: The live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine. METHODS: Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees. RESULTS AND DISCUSSION: The results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10). CONCLUSIONS: The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.

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OBJECTIVE: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. RESULTS: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. METHODS: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. CONCLUSION: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

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BACKGROUND: This study aimed to compare the cytokine-mediated immune response in children submitted to primary vaccination with the YF-17D-213/77 or YF-17DD yellow fever (YF) substrains. METHODS: A non-probabilistic sample of eighty healthy primary vaccinated (PV) children was selected on the basis of their previously known humoral immune response to the YF vaccines. The selected children were categorized according to their YF-neutralizing antibody titers (PRNT) and referred to as seroconverters (PV-PRNT(+)) or nonseroconverters (PV-PRNT(-)). Following revaccination with the YF-17DD, the PV-PRNT(-) children (YF-17D-213/77 and YF-17DD groups) seroconverted and were referred as RV-PRNT(+). The cytokine-mediated immune response was investigated after short-term in vitro cultures of whole blood samples. The results are expressed as frequency of high cytokine producers, taking the global median of the cytokine index (YF-Ag/control) as the cut-off. RESULTS: The YF-17D-213/77 and the YF-17DD substrains triggered a balanced overall inflammatory/regulatory cytokine pattern in PV-PRNT(+), with a slight predominance of IL-12 in YF-17DD vaccinees and a modest prevalence of IL-10 in YF-17D-213/77. Prominent frequency of neutrophil-derived TNF-α and neutrophils and monocyte-producing IL-12 were the major features of PV-PRNT(+) in the YF-17DD, whereas relevant inflammatory response, mediated by IL-12(+)CD8(+) T cells, was the hallmark of the YF-17D-213/77 vaccinees. Both substrains were able to elicit particular but relevant inflammatory events, regardless of the anti-YF PRNT antibody levels. PV-PRNT(-) children belonging to the YF-17DD arm presented gaps in the inflammatory cytokine signature, especially in terms of the innate immunity, whereas in the YF-17D-213/77 arm the most relevant gap was the deficiency of IL-12-producing CD8(+)T cells. Revaccination with YF-17DD prompted a balanced cytokine profile in YF-17DD nonresponders and a robust inflammatory profile in YF-17D-213/77 nonresponders. CONCLUSION: Our findings demonstrated that, just like the YF-17DD reference vaccine, the YF-17D-213/77 seed lot induced a mixed pattern of inflammatory and regulatory cytokines, supporting its universal use for immunization.

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BACKGROUND: The live attenuated yellow fever (YF) vaccines have been available for decades and are considered highly effective and one of the safest vaccines worldwide. METHODS: The impact of YF-17DD-antigens recall on cytokine profiles of YF-17DD-vaccinated children were characterized using short-term cultures of whole blood samples and single-cell flow cytometry. This study enrolled seroconverters and nonseroconverters after primovaccination (PV-PRNT⁺ and PV-PRNT⁻), seroconverters after revaccination (RV-PRNT⁺), and unvaccinated volunteers (UV-PRNT⁻). RESULTS: The analysis demonstrated in the PV-PRNT⁺ group a balanced involvement of pro-inflammatory/regulatory adaptive immunity with a prominent participation of innate immunity pro-inflammatory events (IL-12⁺ and TNF-α⁺ NEU and MON). Using the PV-PRNT⁺ cytokine signature as a reference profile, PV-PRNT⁻ presented a striking lack of innate immunity proinflammatory response along with an increased adaptive regulatory profile (IL-4⁺CD4⁺ T cells and IL-10⁺ and IL-5⁺CD8⁺ T cells). Conversely, the RV-PRNT⁺ shifted the overall cytokine signatures toward an innate immunity pro-inflammatory profile and restored the adaptive regulatory response. CONCLUSIONS: The data demonstrated that the overall cytokine signature was associated with the levels of PRNT antibodies with a balanced innate/adaptive immunity with proinflammatory/regulatory profile as the hallmark of PV-PRNT(MEDIUM⁺), whereas a polarized regulatory response was observed in PV-PRNT⁻ and a prominent proinflammatory signature was the characteristic of PV-PRNT(HIGH⁺).

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