Adverse events following yellow fever vaccination in immunocompromised persons

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

Campaign, counseling and compliance with influenza vaccine among older persons

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

Adverse events following Quadrivalent HPV vaccination reported in Sao Paulo State, Brazil, in the first three years after introducing the vaccine for routine immunization (March 2014 to December 2016)

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

Aconselhamento pré-viagem aos voluntários com destino ao Haiti. Relato da experiência do Ambulatório dos Viajantes do Hospital das Clínicas da FMUSP

INTRODUÇÃO: Desastres naturais representam ameaça à vida e às condições mínimas de sobrevivência de milhares de pessoas. Em 12 de janeiro de 2010 o Haiti foi assolado por um dos mais devastadores terremotos da história do país. Equipes de resgate do mundo inteiro chegaram ao país para ajuda humanitária. O Ambulatório dos Viajantes, da Divisão de Clínica de Moléstias Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) fez a orientação pré-viagem dos voluntários que foram encaminhados ao serviço. OBJETIVO: Enfatizar a importância da medicina de viagem em emergência de saúde pública e descrever a orientação pré-viagem fornecida aos viajantes. MATERIAL E MÉTODOS: Estudo descritivo de relato da experiência do Ambulatório dos Viajantes da Divisão de Clínica de Moléstias Infecciosas e Parasitárias da FMUSP, na orientação pré-viagem de viajantes com destino ao Haiti. Toda a equipe profissional do ambulatório foi informada da situação e uma estratégia foi criada para atender a demanda sem comprometer a rotina. Orientação sobre os riscos de adoecimento através de água e alimentos, vetores, poluição do ar, animais peçonhentos, choque elétricos foram discutidos além da informação sobre os aspectos geográficos, históricos, políticos e econômicos. RESULTADOS: Foram atendidos 98 viajantes. A média da idade foi 38,9 (23 a 66) anos e 79,6% eram do sexo masculino. Entre as ocupações referidas pelos viajantes atendidos foi possível observar: profissionais de saúde e bombeiros (52%), técnicos de telefonia (17,3%), policiais e militares (16,3%) e outros profissionais (14,2%). Vacinas indicadas e realizadas no serviço: febre tifóide (92%), hepatite A (87%), febre amarela (46%), tétano e difteria (dT) (36%), sarampo, caxumba e rubéola (28%), poliomielite (19%), vacina antimeningocócica conjugada C (6%),  influenza e raiva. Todas as medidas de prevenção para a malária foram recomendadas. Cloroquina foi a droga de escolha para a quimioprofilaxia da malária, e a ciprofloxacina para diarreia do viajante. Conclusão: A MV se faz presente a cada dia entre nós e ultrapassa barreiras em situações de emergências em saúde pública, como no caso de desastres naturais.Natural disasters represent a threat to life and the minimum conditions of survival for millions of people can be compromised. On January 12, 2010 Haiti was ravaged by one of the most devastating earthquakes throughout its history. Rescue teams from around the world arrived in the country for humanitarian aid. OBJECTIVE: To emphasize the importance of travel medicine in emergency situations in international public health care and to describe the pre-travel medical advice provided to the travelers. MATERIAL AND METHODS: Retrospective analysis of records of travellers who sought pretravel medical advice at Travellers’ Clinic of HCFMUSP in January, 2010 with travel to Haiti for Humanitarian Aid. All the professional staff of the clinic was informed about the action and in 24 hours the group created a strategy to address the cluster of fast and efficient way without compromising the routine of the clinic. General information about the aspects: cultural, historical, political and economic on Haiti were discussed with all volunteers. In the guidance on the prevention of infectious diseases, were emphasized: the risks of disease through food and water, vectors, animals and air pollution. RESULTS: 98 professionals were attended, 78 (79,6%) male, the median age was 38,9 years old. Professionals categories: healthcare workers (29,6%); military personal (38,7%); phone technician (17,3%) and others professionals (14,2%). Recommended vaccines: typhoid fever (92%), hepatitis A (87%), yellow fever (46%), dT (36%), hepatitis B (36%), SCR (28%), polio (19%), meningococcal vaccine, rabies and influenza. All preventive measures were recommended against malaria, chloroquine was the drug of choice for malaria chemoprophylaxis, and ciprofloxacin was the antibiotic of choice for travelers’ diarrhea. CONCLUSION: The travel medicine is present every day between us and transcends barriers in unexpected situations such as emergency and rapid response in public health, as in the case of natural disasters

Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults

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

Prospective cohort studies to evaluate the safety and immunogenicity of the 2013, 2014, and 2015 seasonal influenza vaccines produced by Instituto Butantan

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. Fortyseven 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)

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study

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

Human Papillomavirus (HPV) seroprevalence, cervical HPV prevalence, genotype distribution and cytological lesions in solid organ transplant recipients and immunocompetent women in Sao Paulo, Brazil

INTRODUCTION: Solid organ transplant (SOT) recipients are at increased risk of Human Papillomavirus (HPV) persistent infection and disease. This study aimed to evaluate HPV seroprevalence, cervical HPV prevalence, genotype distribution, and frequency of HPV-related cervical lesions in SOT recipients in comparison to immunocompetent women. METHODS: Cross-sectional study including SOT and immunocompetent women aged 18 to 45 years who denied previous HPV-related lesions. Cervical samples were screened for HPV-DNA by a polymerase chain reaction (PCR)-based DNA microarray system (PapilloCheck®) and squamous intraepithelial lesions (SIL) by liquid-based cytology. A multiplexed pseudovirion-based serology assay (PsV-Luminex) was used to measure HPV serum antibodies. RESULTS: 125 SOT and 132 immunocompetent women were enrolled. Cervical samples were collected from 113 SOT and 127 immunocompetent women who had initiated sexual activity. HPV-DNA prevalence was higher in SOT than in immunocompetent women (29.6% vs. 20.2%, p = 0.112), but this difference was not statistically significant. High-risk (HR)-HPV was significantly more frequent in SOT than in immunocompetent women (19.4% vs. 7.9%, p = 0.014). Simultaneous infection with ≥2 HR-HPV types was found in 3.1% of SOT and 0.9% of immunocompetent women. HPV seropositivity for at least one HPV type was high in both groups: 63.8% of 105 SOT and 69.7% of 119 immunocompetent women (p = 0.524). Low-grade (LSIL) and high-grade SIL (HSIL) were significantly more frequent in SOT (9.7% and 5.3%, respectively) than in immunocompetent women (1.6% and 0.8%, respectively) (p = 0.001). CONCLUSIONS: These results may reflect the increased risk of HPV persistent infection and disease progression in SOT women due to chronic immunosuppression

Persistence of neutralizing antibodies anti-yellow fever in persons aged 60 years and older previously vaccinated

INTRODUÇÃO: A Febre Amarela (FA) é uma doença viral aguda endêmica em grande parte do Brasil. A principal medida de prevenção é a vacinação. O presente estudo avaliou a prevalência e os títulos de anticorpos neutralizantes em pessoas com 60 anos ou mais que haviam recebido anteriormente a vacina de FA 17DD, em comparação a adultos saudáveis com 18 a 59 anos. Além disso, foram avaliadas a correlação entre os títulos de anticorpos e o tempo decorrido desde a vacinação, nos participantes que receberam apenas uma dose da vacina, e a prevalência de anticorpos nos vacinados há menos e há mais de dez anos. MÉTODOS: Os participantes foram recrutados entre pessoas que procuraram o Centro de Referência para Imunobiológicos Especiais (CRIE) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) para receber diferentes vacinas e que referiam ter recebido a vacina de FA anteriormente. Os seguintes dados foram coletados: idade, etnia, sexo, número de doses da vacina de FA recebidas, data da última vacinação de FA. Foi realizada contagem de linfócitos TCD4+ usando citometria de fluxo. Os anticorpos neutralizantes contra FA foram dosados pelo teste de neutralização por redução de 50% das placas de lise (PRNT50). RESULTADOS: Foram incluídos 94 indivíduos, 46 com idade de 60 anos ou mais (Grupo 1) e 48 com 18 a 59 anos (Grupo 2). Não houve diferença significativa entre os dois grupos na distribuição de gênero, etnia, número de doses de vacina de FA recebidas anteriormente, tempo desde a última dose e contagem de linfócitos TCD4+. Não houve diferença na prevalência de anticorpos neutralizantes anti-FA entre os dois grupos (87% e 93,8% nos Grupos 1 e 2, respectivamente, p=0,263). O título médio geométrico (GMT) dos anticorpos neutralizantes foi maior no grupo mais jovem (3,77 log10mUI/mL) comparado ao grupo mais velho (3,64 log10mUI/mL) e essa diferença foi estatisticamente significante (p=0,022). Não foi encontrada correlação entre os títulos de anticorpos neutralizantes e o tempo decorrido desde a vacinação entre os participantes que receberam apenas uma dose de vacina, tendo sido analisados os dois grupos conjuntamente. Também não foi encontrada diferença estatisticamente significativa na prevalência de anticorpos neutralizantes entre os participantes que receberam apenas uma dose da vacina de FA há mais de 10 anos ou há menos de 10 anos. CONCLUSÕES: São necessários outros estudos de persistência de anticorpos na população idosa devido à possibilidade de resposta vacinal alterada pela imunosenescênciaINTRODUCTION. Yellow Fever (YF) is an acute viral disease endemic in large parts of Brazil. The main preventive measure is vaccination. This study aimed to assess the prevalence and titers of neutralizing antibodies in persons aged 60 years and older who had previously received YF 17DD vaccine, in comparison to healthy adults aged 18 to 59 years. The study also evaluated the correlation between the antibodies titers and the time elapsed since vaccination, in participants who had received a single dose of the vaccine, and the prevalence of antibodies in participants vaccinated within ten years and more than ten years before enrollment. METHODS. Participants were recruited among persons who came to the Reference Center for Special Immunobiologicals (Centro de Referência para Imunobiológcos Especiais, CRIE) of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) to receive any vaccine and who had previously received the YF vaccine. The following data were collected: age, ethnicity, gender, number of YF vaccine doses taken and date of last YF vaccination. CD4 T cells counts were performed using flow cytometry. YF neutralizing antibodies were measured using test of neutralization by 50% reduction of lysis plaques (PRNT50). RESULTS. Ninety-four subjects were enrolled: 46 persons aged 60 years and older (Group 1) and 48 persons aged 18 to 59 years (Group 2). There was no significant difference between the groups regarding gender, ethnicity, number of YF vaccine doses previously received, time since the last dose and CD4+T cells count. There was no difference in the prevalence of YF neutralizing antibodies between the groups (87% and 93.8% in Groups 1 and 2, respectively, p=0.263). The log-transformed Geometric Mean Titer (GMT) of YF neutralizing antibodies was higher in the younger group (3.77 log10mUI/mL) in comparison to the older group (3.64 log10mUI/mL), and this difference was statistically significant (p=0.022). There was no correlation between YF neutralizing antibodies titers and time elapsed since vaccination among the participants who had previously received a single dose of YF vaccine, with the two groups analyzed together. There was no significant difference in the prevalence of neutralizing antibodies among participants who received a single dose of YF vaccine within ten years or more than 10 years before enrollment. CONCLUSIONS. Further studies on antibodies persistence in the elderly are necessary, considering the possibility of compromised immune response to vaccines due to immunosenescenc