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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., (© 2023 The Authors.)

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.

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.

Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2 , STAT1 , or STAT2 ). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT IFNAR1 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals., (© 2019 Hernandez et al.)

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.

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.

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/mm 3 : 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.

Cardiovascular diseases and thrombotic events became major clinical problems in the combined antiretroviral therapy (cART) era. Although the precise mechanisms behind these clinical problems have not been fully elucidated, a persistent pro-inflammatory state plays a central role. As platelets play important roles on both, thrombus formation and inflammatory/immune response, we aimed at investigating platelet function in HIV-infected subjects virologically controlled through cART. We evaluate parameters of activation, mitochondrial function and activation of apoptosis pathways in platelets from 30 HIV-infected individuals under stable cART and 36 healthy volunteers. Despite viral control achieved through cART, HIV-infected individuals exhibited increased platelet activation as indicated by P-selectin expression and platelet spreading when adhered on fibrinogen-coated surfaces. Platelets from HIV-infected subjects also exhibited mitochondrial dysfunction and activation of apoptosis pathways. Finally, thrombin stimuli induced lower levels of P-selectin translocation and RANTES secretion, but not TXA 2 synthesis, in platelets from HIV-infected individuals compared to control; and labeling of platelet alpha granules showed reduced granule content in platelets from HIV-infected individuals when compared to healthy subjects. In summary, platelets derived from HIV-infected individuals under stable cART exhibit a phenotype of increased activation, activation of the intrinsic pathway of apoptosis and undermined granule secretion in response to thrombin.

Background: Tuberculosis is one of the leading causes of death from infectious diseases worldwide, mainly after the human immunodeficiency virus (HIV) epidemics. Patient with HIV-related illness are more likely to present with severe TB due to immunosuppression. Very few studies have explored HIV/TB co-infection in critically ill patients. The goal of this study was to analyze factors associated with long-term mortality in critically ill patient with HIV-related disease coinfected with TB., Methods: We conducted a retrospective study in an infectious disease reference center in Brazil that included all patient with HIV-related illness admitted to the ICU with laboratory-confirmed tuberculosis from March 2007 until June 2012. Clinical and laboratory variables were analyzed based on six-month survival., Results: Forty-four patients with HIV-related illness with a confirmed diagnosis of tuberculosis were analyzed. The six-month mortality was 52 % (23 patients). The main causes of admission were respiratory failure (41 %), severe sepsis/septic shock (32 %) and coma/torpor (14 %). The median time between HIV diagnosis and ICU admission was 5 (1-60) months, and 41 % of patients received their HIV infection diagnosis ≤ 30 days before admission. The median CD4 count was 72 (IQR: 23-136) cells/mm(3). The clinical presentation was pulmonary tuberculosis in 22 patients (50 %) and disseminated TB in 20 patients (45.5 %). No aspect of TB diagnosis or treatment was different between survivors and nonsurvivors. Neurological dysfunction was more prevalent among nonsurvivors (43 % vs. 14 %, p = 0.04). The nadir CD4 cell count lower than 50 cells/mm(3) was independently associated with Six-month mortality (hazard ratio 4.58 [1.64-12.74], p < 0.01), while HIV diagnosis less than three months after positive serology was protective (hazard ratio 0.27, CI 95 % [0.10-0.72], p = 0.01)., Conclusion: The Six-month mortality of HIV critically ill patients with TB coinfection is high and strongly associated with the nadir CD4 cell count less than 50 cels/mm(3).

Introduction: In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients., Methods: We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients., Results: We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality., Conclusions: IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.

Introduction: New challenges have arisen for the management of critically ill HIV/AIDS patients. Severe sepsis has emerged as a common cause of intensive care unit (ICU) admission for those living with HIV/AIDS. Contrastingly, HIV/AIDS patients have been systematically excluded from sepsis studies, limiting the understanding of the impact of sepsis in this population. We prospectively followed up critically ill HIV/AIDS patients to evaluate the main risk factors for hospital mortality and the impact of severe sepsis on the short- and long-term survival., Methods: All consecutive HIV-infected patients admitted to the ICU of an infectious diseases research center, from June 2006 to May 2008, were included. Severity of illness, time since AIDS diagnosis, CD4 cell count, antiretroviral treatment, incidence of severe sepsis, and organ dysfunctions were registered. The 28-day, hospital, and 6-month outcomes were obtained for all patients. Cox proportional hazards regression analysis measured the effect of potential factors on 28-day and 6-month mortality., Results: During the 2-year study period, 88 HIV/AIDS critically ill patients were admitted to the ICU. Seventy percent of patients had opportunist infections, median CD4 count was 75 cells/mm3, and 45% were receiving antiretroviral therapy. Location on a ward before ICU admission, cardiovascular and respiratory dysfunctions on the first day after admission, and the presence of severe sepsis/septic shock were associated with reduced 28-day and 6-month survival on a univariate analysis. After a multivariate analysis, severe sepsis determined the highest hazard ratio (HR) for 28-day (adjusted HR, 3.13; 95% CI, 1.21-8.07) and 6-month (adjusted HR, 3.35; 95% CI, 1.42-7.86) mortality. Severe sepsis occurred in 44 (50%) patients, mainly because of lower respiratory tract infections. The survival of septic and nonseptic patients was significantly different at 28-day and 6-month follow-up times (log-rank and Peto test, P < 0.001)., Conclusions: Severe sepsis has emerged as a major cause of admission and mortality for hospitalized HIV/AIDS patients, significantly affecting short- and longer-term survival of critically ill HIV/AIDS patients.