Overdiagnosis of vaccine allergy: Skin testing and challenge at a public specialized unit (CRIE) in Rio de Janeiro, Brazil.

Background: Vaccination is an extremely safe public health intervention, but rare IgE-mediated adverse events must be identified to avoid the risk of anaphylaxis in the event of reexposure. However, using only clinical history to diagnose previous allergic reactions may lead to overdiagnosis of vaccine allergy and even to the use of medical exemptions as a subterfuge to mandatory vaccination. Methods: We conducted a retrospective study to describe the outcomes of patients with a history of vaccine or vaccine component allergy who were evaluated at our unit from 2011 to 2017. Data on allergy history, skin test results, vaccines prescribed, and adverse events were retrieved from the medical records at the Centro de Referência para Imunobiológicos Especiais (Reference Center of Special Immunobiologicals)-Fiocruz, in Rio de Janeiro, Brazil. Results: Of 34 adults with history of allergy to vaccine or vaccine components, 32 (94.1%) were successfully vaccinated without serious adverse events after our evaluation. In 12 patients (35%), the time elapsed between the allergy symptoms and evaluation in the Centro de Referência para Imunobiológicos Especiais-Fiocruz was more than 10 years. Conclusion: Specialized care and use of skin tests allowed safe vaccination of the majority of patients. An objective, systematic evaluation of a history of vaccine allergy can prevent its improper use to avoid mandatory vaccination and reduce missed opportunities for immunization.

Events preceding death among chikungunya virus infected patients: a systematic review.

Since its re-emergence in the late 1990s, there have been reports of Chikungunya fever (CHIK-F) presenting with severe or atypical findings. There is little knowledge regarding the clinical events leading to the death of patients with CHIK-F. This study aimed to systematically review the literature regarding CHIK-F and identify clinical features preceding death. We searched PubMed, Scopus, Embase, Lilacs, and IsiWeb for case-reports, case-series, or cohorts of CHIK-F reporting at least one death, up to December 2019. Fifty-seven reports were analyzed, including 2140 deaths. Data about specific clinical events that precede death are scarce. The central tendency of time between disease onset and death ranged from 2 days to 150 days. The most common clinical findings among decedents were fever (22.0%), arthralgia (15.7%), myalgia (10.7%), and headache (8.2%). Excluding pediatric populations, the reported central tendency of age among the decedents was 53 or older, with a non-weighted median of 67, ranging up to 80 years old. Authors mentioned organic dysfunction in 91.2% reports. Among all the 2140 decedents, the most common dysfunctions were cardiovascular (7.2%), respiratory (6.4%), neurological (5.4%), renal (4.2%), liver (3.0%), and hematological (1.3%) dysfunction. Exacerbation of previous diabetes (5.6%) or hypertension (6.9%) was mentioned as conditions preceding death. Currently, older age, primary neurological, cardiovascular, or respiratory dysfunction and a previous diagnosis of diabetes or hypertension are the main clinical events preceding death.

Seroprevalence of varicella antibodies in adults without clinical history of disease.

Varicella in adults and immunocompromised patients can be severe. The clinical diagnosis of varicella has high accuracy and the history of disease has a high positive predictive value for protection. A significant portion of adults, however, cannot remember if they have had varicella, especially older individuals. We conducted a cross-sectional study to determine the seroprevalence of varicella protective antibodies titers in adults with no clinical history of disease, attended at a Reference Center for Special Immunobiologicals and Travel Medicine in Rio de Janeiro (Brazil). Titration of immunoglobulin G (IgG) antibodies to varicella-zoster was determined by chemiluminescence immunoassay. Among 140 adults without history of varicella, 92% had protective antibody titers. We concluded that seroprevalence of varicella-zoster protection was very high in adults with negative history of disease and the use of serology before vaccination reduced significantly unnecessary vaccine and immunoglobulin use.

Events preceding death among chikungunya virus infected patients: a systematic review

Abstract Since its re-emergence in the late 1990s, there have been reports of Chikungunya fever (CHIK-F) presenting with severe or atypical findings. There is little knowledge regarding the clinical events leading to the death of patients with CHIK-F. This study aimed to systematically review the literature regarding CHIK-F and identify clinical features preceding death. We searched PubMed, Scopus, Embase, Lilacs, and IsiWeb for case-reports, case-series, or cohorts of CHIK-F reporting at least one death, up to December 2019. Fifty-seven reports were analyzed, including 2140 deaths. Data about specific clinical events that precede death are scarce. The central tendency of time between disease onset and death ranged from 2 days to 150 days. The most common clinical findings among decedents were fever (22.0%), arthralgia (15.7%), myalgia (10.7%), and headache (8.2%). Excluding pediatric populations, the reported central tendency of age among the decedents was 53 or older, with a non-weighted median of 67, ranging up to 80 years old. Authors mentioned organic dysfunction in 91.2% reports. Among all the 2140 decedents, the most common dysfunctions were cardiovascular (7.2%), respiratory (6.4%), neurological (5.4%), renal (4.2%), liver (3.0%), and hematological (1.3%) dysfunction. Exacerbation of previous diabetes (5.6%) or hypertension (6.9%) was mentioned as conditions preceding death. Currently, older age, primary neurological, cardiovascular, or respiratory dysfunction and a previous diagnosis of diabetes or hypertension are the main clinical events preceding death.

Seroprevalence of varicella antibodies in adults without clinical history of disease / Soroprevalência de anticorpos antivaricela em adultos sem história clínica da doença / Seroprevalencia de anticuerpos frente a la varicela en adultos sin historial clínico de la enfermedad

Abstract: Varicella in adults and immunocompromised patients can be severe. The clinical diagnosis of varicella has high accuracy and the history of disease has a high positive predictive value for protection. A significant portion of adults, however, cannot remember if they have had varicella, especially older individuals. We conducted a cross-sectional study to determine the seroprevalence of varicella protective antibodies titers in adults with no clinical history of disease, attended at a Reference Center for Special Immunobiologicals and Travel Medicine in Rio de Janeiro (Brazil). Titration of immunoglobulin G (IgG) antibodies to varicella-zoster was determined by chemiluminescence immunoassay. Among 140 adults without history of varicella, 92% had protective antibody titers. We concluded that seroprevalence of varicella-zoster protection was very high in adults with negative history of disease and the use of serology before vaccination reduced significantly unnecessary vaccine and immunoglobulin use.

Resumo: A varicela é uma doença potencialmente grave em adultos e em pacientes imunocomprometidos. O diagnóstico clínico da varicela apresenta alta acurácia, e o relato da doença na história individual tem alto valor preditivo positivo para a proteção. Entretanto, uma proporção significativa de adultos, principalmente os mais idosos, não se lembra se já teve a doença. Realizamos um estudo transversal para determinar a soroprevalência de títulos protetores de anticorpos contra a varicela em adultos sem história clínica da doença, atendidos em um Centro de Referência para Imunobiológicos Especiais e Medicina de Viagem no Rio de Janeiro, Brasil. Os títulos da imunoglobulina G (IgG) contra varicela-zoster foram determinados por quimiluminescência. Entre 140 adultos sem história de varicela, 92% apresentaram títulos protetores de anticorpos. Concluímos que a soroprevalência de proteção contra varicela-zoster é muito alta em adultos sem história da doença, e que o uso de teste sorológico antes da vacinação reduziria significativamente a vacinação desnecessária e o uso de imunoglobulina.

Resumen: La varicela en adultos y pacientes inmunocomprometidos puede ser grave. El diagnóstico clínico de la varicela tiene una gran precisión y la historia de la enfermedad cuenta con un alto valor predictivo positivo para la protección contra ella. Sin embargo, un porcentaje significativo de adultos, no puede recordar si tuvieron varicela, especialmente las personas más viejas. Realizamos un estudio transversal para determinar la seroprevalencia de las concentraciones de anticuerpos protectores frente a la varicela, en adultos sin historia clínica de la enfermedad, que se llevó a cabo en un Centro de Referencia para Inmunobiología Especial y Medicina del Viajero en Río de Janeiro (Brasil). Se determinó la valoración de los anticuerpos de inmunoglobulina G (IgG) a la varicela-zoster mediante un ensayo inmunológico quimioluminiscente. Entre 140 adultos sin historial de varicela, un 92% tuvieron concentraciones de anticuerpos protectores. Concluimos que la seroprevalencia de la protección a la varicela-zoster fue muy alta en adultos con un historial negativo de la enfermedad y la utilización de la serología antes de la vacunación redujo de manera significativa la vacunación innecesaria y el uso de la inmunoglobulina.

Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care Unit: The ICU Visits Randomized Clinical Trial.

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain. Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation. Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium. Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.

Addressing travelers' perception of risk in pre-travel care: Reports from a travel clinic in Rio de Janeiro, Brazil.

INTRODUCTION: Travel medicine is aimed at promoting health risk reduction. However, travelers' perception of risk is subjective and may influence implementation of recommendations. This study reports on travelers' perception of risk, pre-travel characteristics, and recommended interventions. METHODS: This is a descriptive cross-sectional study. RESULTS: This study included 111 individuals. Most travelers (74%) perceived their risk as low. Significant differences in travel-related risk perception between practitioners and travelers were observed (Gwet's agreement coefficient [AC1] 0.23; standard error 0.10; 95% confidence interval 0.02-0.44). CONCLUSIONS: Future studies should investigate the relationship between travelers' perception of risk and implementation of recommendations.

Severe infection increases cardiovascular risk among HIV-infected individuals.

BACKGROUND: The identification and management of cardiovascular risk factors became a major clinical issue among HIV-infected individuals in the post-cART era. As in the past decades the link between acute infections and cardiovascular diseases became clear in the general population, we sorted to investigate the role of severe infections on incident cardiovascular diseases (CVDs) among HIV-infected individuals. METHODS: HIV-infected individuals aged ≥18 years, with no history of CVD were followed from January 2000 to December 2013 until the occurrence of the first CVD event, death or end of study, whichever occurred first. To explore the effect of severe infections on the incidence of CVD we used extended Cox regression models and stratified post-hospitalization follow-up time into three periods: < 3 months, 3-12 months and > 12 months post discharge. RESULTS: One hundred-eighty four persons from 3384 HIV-infected individuals developed incident CVD events during the follow-up (incidence rate = 11.10/1000 PY (95%CI: 9.60-12.82)). Risk of an incident CVD was 4-fold higher at < 3 months post-hospitalization for severe infections (adjusted hazard ratio [aHR], 4.52; 95% confidence interval [CI] 2.46-8.30), after adjusting for sociodemographic and clinical factors as well as comorbidities. This risk remained significant up to one year (3-12 months post hospital discharge aHR 2.39, 95% CI 1.30-4.38). Additionally, non-white race/ethnicity (aHR 1.49, 95% CI 1.10-2.02), age ≥ 60 years (aHR 2.01, 95% CI 1.01-3.97) and hypertension (aHR 1.90, 95% CI 1.38-2.60) were associated with an increased risk of CVD events. High CD4 (≥ 500 cells/mm3: aHR 0.41, 95% CI 0.27-0.62) and cART use (aHR 0.21, 95% CI 0.14-0.31) reduced the risk of CVD events. CONCLUSIONS: We provide evidence for a time-dependent association between severe infection and incident cardiovascular disease in HIV-infected individuals. cART use, and high CD4 count were significantly associated with reduced hazards of CVD.

Addressing travelers' perception of risk in pre-travel care: Reports from a travel clinic in Rio de Janeiro, Brazil

Abstract INTRODUCTION: Travel medicine is aimed at promoting health risk reduction. However, travelers' perception of risk is subjective and may influence implementation of recommendations. This study reports on travelers' perception of risk, pre-travel characteristics, and recommended interventions. METHODS: This is a descriptive cross-sectional study. RESULTS: This study included 111 individuals. Most travelers (74%) perceived their risk as low. Significant differences in travel-related risk perception between practitioners and travelers were observed (Gwet's agreement coefficient [AC1] 0.23; standard error 0.10; 95% confidence interval 0.02-0.44). CONCLUSIONS: Future studies should investigate the relationship between travelers' perception of risk and implementation of recommendations.

Infecções graves, risco cardiovascular e função plaquetária em indivíduos infectados pelo HIV-1 / Serious infections, cardiovascular risk and platelet function in HIV-1 infected individuals

Introdução: A infecção pelo HIV-1 se tornou uma doença crônica. Este novo cenário clínico está associado a um estado pró-inflamatório e a um aumento proporcional na incidência de doenças cardiovasculares (DCV). Este tema foi abordado e será exposto na forma de dois artigos originais. Artigo 1: "Infecções graves aumentam o risco cardiovascular em indivíduos infectados pelo HIV". Objetivo: Avaliar se a presença de infecções graves influencia a ocorrência de DCV em indivíduos infectados pelo HIV. Métodos: Indivíduos infectados pelo HIV incluídos na coorte do Instituto Nacional de Infectologia Evandro Chagas (INI/FIOCRUZ) entre 2000 e 2013 foram seguidos até a ocorrência do primeiro evento cardiovascular, morte ou fim do estudo. Infecção grave foi definida como hospitalização associada ao tratamento de infecção. Modelos de regressão de Cox, ajustados para potenciais confundidores, foram utilizados para avaliar o efeito de uma hospitalização por infecção no risco de ocorrência de DCV. Resultados: O risco de uma DCV foi 4 vezes maior no período de <3 meses pós-hospitalização (hazard ratio ajustada [aHR], 4,52; intervalo de confiança de 95% [CI] 2,46-8,30) e permaneceu elevado até um ano (3-12 meses após a alta hospitalar aHR 2.39, IC 95% 1.30-4.38)

Conclusão: Infecções graves aumentam o risco cardiovascular na população estudada. Um gradiente de efeito foi observado, sendo o risco maior nos primeiros meses após o evento infeccioso. Artigo 2: "Persistência da ativação plaquetária e apoptose em indivíduos infectados pelo HIV-1". Objetivo: Investigar marcadores de ativação plaquetária e apoptose em indivíduos infectados pelo HIV-1 e controlados virologicamente. Métodos: Citometria de fluxo e microscopia de fluorescência foram utilizadas para avaliar parâmetros de ativação, função mitocondrial e apoptose em plaquetas de indivíduos infectados pelo HIV- 1 da coorte do INI/FIOCRUZ, e controles. Resultados: Maior ativação (expressão de Pselectina), disfunção mitocondrial (despolarização mitocondrial e aumento da geração de espécies reativas de oxigênio) e apoptose (fosfatidilserina e caspase-9) foi evidenciada na plaqueta de indivíduos infectados pelo HIV-1, comparada com controles. Conclusões: Apesar do controle virológico, infecção pelo HIV-1 está associada a um fenótipo de ativação, apoptose e exaustão granular. (AU)

Avaliação da função plaquetária na infecção pelo HIV-1 / Platelet activation and cell death pathways in platelets isolated from HIV/AIDS patients

A terapia antirretroviral de alta potência (TARV) aumentou significativamente a sobrevida e a qualidade de vida dos pacientes portadores de HIV/AIDS, levando, por conseguinte, à cronificação da doença. Neste novo cenário epidemiológico, cresce a importância de complicações cardiovasculares como o infarto agudo do miocárdio e a trombose venosa profunda. A plaqueta tem papel central na gênese destas complicações e seu papel na infecção pelo HIV-1 começa a ser explorado na literatura. No presente trabalho objetivamos avaliar a função plaquetária durante a infecção pelo HIV-1, especificamente o grau de ativação, disfunção mitocondrial, morte celular, produção de óxido nítrico e resposta a estímulos agonistas. Para tal, avaliamos 30 voluntários saudáveis e 26 pacientes infectados pelo HIV- 1 em acompanhamento no Instituto de Pesquisa Clínica Evandro Chagas (IPEC) da Fundação Oswaldo Cruz (FIOCRUZ) de Janeiro de 2012 a Janeiro de 2013. Dentre os pacientes infectados avaliados, 17 apresentavam uso regular de TARV e tinham a carga viral para HIV-1 no sangue periférico indetectável (< 50 cópias/mm3 ) e 9 apresentavam carga viral para HIV-1 no sangue periférico detectável (> 50 cópias/mm3 ). Observamos que a plaqueta dos dois grupos de pacientes portadores de HIV/AIDS analisados exibe um aumento no perfil de ativação (expressão de P-selectina e exposição de fosfatidilserina), aumento na produção de óxido nítrico e menor indução da expressão de P-selectina após estímulo com trombina, quando comparada à resposta da plaqueta de indivíduos controles. Além disso, observamos sinais claros de ativação da via intrínseca de apoptose (diminuição do potencial de membrana mitocondrial, aumento na produção de superóxido mitocondrial, exposição de fosfatidilserina e ativação de caspase 9) mesmo com o controle da replicação viral, atingido com o uso regular de TARV...

The advent of highly active antiretroviral therapy (HAART) has increased life expectancy and the quality of life of patients living with HIV/AIDS. Now, new clinical data emphasizes long term complications of HIV-1 infection, such as cardiovascular diseases. Blood human platelets have a pivotal role in thrombus formation and their physiology during the course of HIV-1 infection has recently begun to be explored. The aim of the present study is to build up this literature by characterizing platelet activation, mitochondrial dysfunction, apoptosis and response to agonist stimulus in HIV/AIDS patients and control subjects. From January of 2012 to January of 2013 we included 30 healthy volunteers and 33 HIV-1 infected subjects from the outpatient clinic of Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ). Among the HIV-1 population, 18 patients were under HAART therapy and had achieved virological suppression (viral load in peripheral blood < 50 copies/mm3 ) and 9 patients had uncontrolled viral replication (viral load in peripheral blood > 50 copies /mm3 ). We noted that HIV-1 infected individuals exhibit increased platelet activation (P-selectin expression and fosfatidilserine exposition), enhanced nitric oxide (NO) production and abnormal response to agonistic stimulus (thrombin). Moreover, we noted marked sigs of intrinsic apoptotic pathway activation (decreased transmembrane mitochondrial potential, increased superoxide production, fosfatidilserine exposure and caspase 9 activation) in patients under virological suppression achieved through HAART...