ABSTRACT Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.

ABSTRACT This observational retrospective study conducted during an yellow fever (YF) outbreak in Sao Paulo, Brazil, in 2017-2018, describes adverse events (AE) following YF vaccination of immunocompromised persons. Risks and benefits of vaccination were individually evaluated by physicians. AE were assessed by phone call or electronic mail, 14 to 90 days after vaccination. Three hundred and eighty one immunocompromised persons received a full-dose of YF vaccine. Their age ranged from 1.4 to 89.3 years (median 50.8 years); 53% were women; 178 (46.7%) had chronic kidney disease, 78 (20.5%) had immune-mediated inflammatory diseases; 94 (24.7%) were using or had recently used immunosuppressive/ immunomodulatory drugs. All of them denied previous YF vaccination. We were able to contact 341 (89.5%) vaccinees: 233 (68.3%) of them received the YF vaccine from BioManguinhos and 108 (31.7%) received the vaccine from Sanofi-Pasteur; 130 (38.1%) vaccinees received other vaccines (up to 4) simultaneously with the the YF vaccine, mostly hepatitis B (59 vaccinees), pneumococcal polysaccharide 23-valent (46), influenza (43) and diphtheria-tetanus (dT, 41). One hundred and eleven vaccinees (32.6%) reported at least one AE: 79 (23.2%) presented systemic AE, 44 (12.9%) had local AE and 12 had both, local and systemic AE. The most common AE was pain at the injection site (41 persons, 12%), myalgia (34; 10%), fever (25; 7.3%) and headache (16; 4.7%). There was no statistically significant difference on the AE frequency according to the vaccine producer. There were four severe AE: one hospitalization and three deaths, considered not related to the YF vaccine.

Abstract Introduction: Vaccination with tetanus-diphtheria-acellular pertussis (Tdap) has been recommended for healthcare workers (HCWs) by Brazilian Ministry of Health since November 2014. Objective: To describe the strategies implemented to improve Tdap uptake, cumulative vaccine coverage after each intervention, variables associated to Tdap vaccination, and reasons for non-vaccination among HCWs of the main building of a quaternary hospital attached to the Sao Paulo University Medical School. Methods: A list of HCWs eligible for pertussis vaccination was generated. From April to December 2015, the following interventions were implemented: note on intern journal reminding the importance of pertussis vaccination; email to the head nurses strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians of Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. Vaccine coverage was accessed at the end of each month. Multivariate Poisson regression model with a robust error variance was used to evaluate variables associated with Tdap vaccination. Reasons for non-vaccination were evaluated from January to May 2017 through phone calls for HCWs who had not received Tdap. Results: The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.8% to 41.2%. In the multivariate analysis, occupation (physician), working place (obstetrics or anesthesiology) and influenza vaccination in 2015 were independently associated to Tdap vaccination. The main reason for non-vaccination was unawareness of Tdap recommendations. Conclusions: Tdap uptake among HCWs was low in our hospital. Providing vaccination at convenient places/times for HCW seems to be the most efficient strategy to increase vaccine uptake.

ABSTRACT In March 2014, the Quadrivalent human papilloma virus vaccine (4vHPV) was introduced in the female adolescents vaccination schedule of the National Immunization Program (PNI). A school-based vaccination program was implemented. We conducted a retrospective, descriptive study of the adverse events that took place after HPV vaccination, reported to the Adverse Events Following Immunization (AEFI) Information System in Sao Paulo State, from March 2014 to December 2016. All reports that fit the definitions of the 2014 National Manual on AEFI surveillance were included. AEFI risk was estimated by dividing the number of reports by the number of vaccine doses administered in the period. In the three-year period, 3,390,376 HPV vaccine doses were administered and 465 AEFI reports were registered, with 1,378 signs and symptoms. The reporting rate was 13.72 per 100,000 vaccine doses administered. The reports peaked in the first year of the program. The most frequent AEFI was syncope, with 5.7 reports per 100,000 doses administered, followed by dizziness, malaise, headache and nausea. Overall, 39 AEFI cases (8.4%) were classified as severe , with a reporting rate of 1.15 per 100,000 vaccine doses administered. Most cases were classified as severe because of hospitalization. Among them, there were cases of Guillain-Barré Syndrome, deep vein thrombosis, seizures and miscarriage. All young women recovered without sequelae. We identified five clusters of AEFI reports in four cities; the larger AEFI cluster occurred in the city of Bertioga, in September 2014, involving 13 female adolescents. Our data are in accordance with those from other countries and corroborate the safety of HPV vaccines.

ABSTRACT Annual vaccination is the most effective way to prevent seasonal influenza illness. Instituto Butantan (IB) performed clinical studies with its 2013, 2014 and 2015 seasonal trivalent influenza vaccines (inactivated split-virion). Prospective cohort studies were carried out to describe the safety and immunogenicity of Instituto Butantan influenza vaccines, in healthy adults and elderly, from 2013 to 2015. Immediately after the informed consent was signed, participants underwent blood collection followed by vaccination. On study days 1, 2 and 3 post-vaccination participants were contacted by the staff to evaluate the occurrence of solicited (local and systemic) and non-solicited adverse reactions. On study day 21 (+7) subjects returned to the clinical site for final safety assessments and blood collection to evaluate post-vaccination immunogenicity. The immunogenicity analyses were performed by means of hemagglutination inhibition (HI) assay. The immunogenicity endpoints were: seroprotection (SPR) and seroconversion (SCR) rates and the geometric mean HI antibody titer ratio (GMTR). The 2013 study was conducted at the Centro de Referência para Imunobiológicos Especiais (CRIE) and at the Centro de Pesquisa Clínica do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo while the 2014 and 2015 studies were conducted at CRIE. The vaccine composition followed the WHO recommendation for the Southern hemisphere seasonal influenza vaccine. Forty-seven healthy adults and 13 elderly participated in the 2013 study, 60 healthy adults and 60 elderly in the 2014 study, and 62 healthy adults and 57 elderly in the 2015 study. In the 2013, 2014 and 2015 studies, pain was the most frequent local adverse reaction and headache the most frequent systemic adverse reaction. All observed adverse reactions were classified as mild or moderate and none as severe. SPR >70% and SPR >60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR >40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR >30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR >2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR >2.0 was observed among elderly, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. The 2013, 2014 and 2015 seasonal influenza vaccines produced by Instituto Butantan were safe and immunogenic according to the immunogenicity criteria defined by the European Medicines Agency (EMA).

ABSTRACT Introduction: The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged ≥ 60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. Methods: previously vaccinated healthy persons aged ≥ 18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. Results: 46 persons aged ≥ 60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. Conclusions: the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

Introduction This paper describes adverse events (AEs) temporally associated to the pandemic influenza A (H1N1) vaccine observed in a reference center in São Paulo, Brazil, during a 2010 mass vaccination campaign. Methods A retrospective study involving persons who sought medical care for AEs following influenza vaccination. Data were retrieved from medical records, vaccine AE notification forms, and a computerized system for immunobiological registration. Results Sixty-six vaccinees sought medical care for AEs after immunization. The most frequent AEs were fever, headache, myalgia, and pain at the injection site. No serious AEs were reported. Conclusions Few vaccinees spontaneously reported AEs to influenza A (H1N1) vaccine at this center.

OBJECTIVES: Population aging raises concerns regarding the increases in the rates of morbidity and mortality that result from influenza and its complications. Although vaccination is the most important tool for preventing influenza, vaccination program among high-risk groups has not reached its predetermined aims in several settings. This study aimed to evaluate the impacts of clinical and demographic factors on vaccine compliance among the elderly in a setting that includes a well-established annual national influenza vaccination campaign. METHODS: This cross-sectional study included 134 elderly patients who were regularly followed in an academic medical institution and who were evaluated for their influenza vaccination uptake within the last five years; in addition, the demographic and clinical characteristics and the reasons for compliance or noncompliance with the vaccination program were investigated. RESULTS: In total, 67.1% of the participants received the seasonal influenza vaccine in 2009. Within this vaccinationcompliant group, the most common reason for vaccine uptake was the annual nationwide campaign (52.2%; 95% CI: 41.4-62.9%); compared to the noncompliant group, a higher percentage of compliant patients had been advised by their physician to take the vaccine (58.9% vs. 34.1%; p,0.01). CONCLUSION: The education of patients and health care professionals along with the implementation of immunization campaigns should be evaluated and considered by health authorities as essential for increasing the success rate of influenza vaccination compliance among the elderly.

JUSTIFICATIVA E OBJETIVOS: O CO2 expirado (P ET CO2) reflete, além da ventilação pulmonar (eliminação), a produção de dióxido de carbono (metabolismo) e o fluxo sangüíneo pulmonar (circulação). Quando o metabolismo e a ventilação são constantes, o CO2 expirado reflete o fluxo sangüíneo pulmonar e, desta forma, o débito cardíaco (DC). Este estudo tem como objetivo a avaliação da correlação entre o dióxido de carbono expirado (P ET CO2) e o débito cardíaco em pacientes submetidos à cirurgia cardíaca com circulação extracorpórea (CEC). MÉTODO: Foram estudados 25 pacientes submetidos à cirurgia de revascularização miocárdica com CEC. Após a intubação traqueal iniciou-se a monitorização da P ET CO2. A determinação do débito cardíaco (DC) foi feita por método de termodiluição com o uso de cateter de Swan-Ganz e a PaCO2 foi avaliada através de gasometria arterial. Os parâmetros do estudo foram avaliados em quatro momentos: logo após a indução da anestesia geral; antes da circulação extracorpórea, ao término da circulação extracorpórea e ao final da cirurgia. RESULTADOS: O teste estatístico não demonstrou uma correlação entre o CO2 expirado e o DC, assim como o gradiente de dióxido de carbono arterial e expirado (Ga-eCO2) e o DC. Foi encontrada correlação entre a variação dos valores da P ET CO2, Ga-eCO2 e DC em relação ao basal antes da CEC com perda da correlação após a CEC até o final da cirurgia. CONCLUSÕES: Neste estudo, onde se avaliam pacientes submetidos à cirurgia cardíaca com CEC, as alterações de relação ventilação/perfusão ocorridas ao longo do procedimento são, provavelmente, os fatores determinantes da diminuição da correlação entre o débito cardíaco e o valor de dióxido de carbono expirado.

BACKGROUND AND OBJECTIVES: End-tidal carbon dioxide (P ET CO2) not only reflects pulmonary ventilation but also carbon dioxide production (metabolism) and pulmonary blood supply (circulation). During constant metabolism and ventilation, P ET CO2 reflects pulmonary blood perfusion, thus cardiac output (CO). This study aimed at evaluating the correlation between P ET CO2 levels and CO during cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Participated in this study 25 patients submitted to coronary artery bypass grafting (CABG) with CPB. End-tidal CO2 monitoring started after tracheal intubation. Cardiac output was determined by thermodilution with pulmonary artery catheter (Swan-Ganz). Carbon dioxide partial blood pressure (PaCO2) was obtained with arterial blood gases analysis. Studied parameters were evaluated in the following moments: immediately after general anesthesia induction, before cardiopulmonary bypass, at cardiopulmonary bypass completion and at surgery completion. RESULTS: Statistical analysis has not shown correlation between P ET CO2 and CO2, or between P ET CO2-PaCO2 gradient (Ga-eCO2) and CO. There has been correlation between P ET CO2, Ga-eCO2 and CO values variation as compared to baseline values before CPB, with loss of correlation after CPB until surgery completion. CONCLUSIONS: In this study, where patients submitted to cardiac surgery with CPB were evaluated, ventilation/perfusion changes throughout the procedure might have been the factors determining decreased correlation between cardiac output and end tidal CO2.

JUSTIFICATIVA Y OBJETIVOS: El CO2 expirado (P ET CO2) refleja, además de la ventilación pulmonar (eliminación), la producción de dióxido de carbono (metabolismo) y el flujo sanguíneo pulmonar (circulación). Cuando el metabolismo y la ventilación son constantes, el CO2 expirado refleja el flujo sanguíneo pulmonar y, de esta forma, el débito cardíaco (DC). Este estudio tiene como objetivo la evaluación de la correlación entre el dióxido de carbono expirado (P ET CO2) y el débito cardíaco en pacientes sometidos a la cirugía cardíaca con circulación extracorpórea (CEC). MÉTODO: Fueron estudiados 25 pacientes sometidos a la cirugía de revascularización miocárdica con CEC. Después de la intubación traqueal tuvo inicio la monitorización de la P ET CO2. La determinación del débito cardíaco (DC) fue hecha por método de termodiluición con el uso de catéter de Swan-Ganz y la PaCO2 fue evaluada a través de gasometría arterial. Los parámetros del estudio fueron evaluados en cuatro momentos: luego después de la inducción de la anestesia general; antes de la circulación extracorpórea, al término de la circulación extracorpórea y al final de la cirugía. RESULTADOS: El teste estadístico no demostró una correlación entre el CO2 expirado y el DC, así como el gradiente de dióxido de carbono arterial y expirado (Ga-eCO2) y el DC. Fue encontrada correlación entre la variación de los valores de la P ET CO2, Ga-eCO2 y DC en relación al basal antes de la CEC con pérdida de la correlación después de la CEC hasta el final de la cirugía. CONCLUSIONES: En este estudio, donde se evalúan pacientes sometidos a cirugía cardíaca con CEC, las alteraciones de relación ventilación/perfusión ocurridas a lo largo del procedimiento son, probablemente, los factores determinantes de la diminución de la correlación entre el débito cardíaco y el valor de dióxido de carbono expirado.