Immunogenicity and Reactogenicity of 2009 Influenza A (H1N1) Inactivated Monovalent Non-Adjuvanted Vaccine in Elderly and Immunocompromised Patients

Background\ud \ud Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them.\ud Methods\ud \ud This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination.\ud Results\ud \ud 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included.\ud \ud The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events.\ud Conclusions\ud \ud The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)Fundação Butantan funded the study, and employed several of the authors. The funder had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Profile of paediatric rheumatology specialists and services in the state of São Paulo

INTRODUCTION: Paediatric rheumatology (PR) is an emerging specialty, practised by a limited number of specialists. Currently, there is neither a record of the profile of rheumatology patients being treated in Brazil nor data on the training of qualified rheumatology professionals in the country. OBJECTIVE: To investigate the profile of PR specialists and services, as well as the characteristics of paediatric patients with rheumatic diseases, for estimating the current state of rheumatology in the state of São Paulo. PATIENTS AND METHODS: In 2010, the scientific department of PR of the Paediatric Society of São Paulo administered a questionnaire that was answered by 24/31 accredited specialists in PR practising in state of São Paulo and by 8/21 institutions that provide PR care. RESULTS: Most (91%) of the surveyed professionals practise in public institutions. Private clinics (28.6%) and public institutions (37.5%) reported not having access to nailfold capillaroscopy, and 50% of the private clinics reported not having access to acupuncture. The average duration of professional practise in PR was 9.4 years, and 67% of the physicians had attended postgraduate programmes. Seven (87.5%) public institutions perform teaching activities, in which new paediatric rheumatologists are trained, and five (62.5%) offer postgraduate programmes. Two-thirds of the surveyed specialists use immunosuppressants and biological agents classified as restricted use by the Health Secretariat. The disease most frequently reported was juvenile idiopathic arthritis (29.1-34.5%), followed by juvenile systemic lupus erythematosus (JSLE) (11.6-12.3%) and rheumatic fever (9.1-15.9%). The incidence of vasculitis (including Henoch-Schönlein purpura, Wegener's granulomatosis, and Takayasu's arteritis) and autoinflammatory syndromes was higher in public institutions compared to other institutions (P = 0.03, P = 0.04, P = 0.002, and P < 0.0001, respectively). Patients with JSLE had the highest mortality rate (68% of deaths), mainly due to infection. CONCLUSION: The field of PR in the state of São Paulo has a significant number of specialists with postgraduate degrees who mostly practise at teaching institutions with infrastructures appropriate for the care of high-complexity patients.INTRODUÇÃO: A reumatologia pediátrica (RP) é uma especialidade emergente, com número restrito de especialistas, e ainda não conta com uma casuística brasileira sobre o perfil dos pacientes atendidos e as informações sobre a formação de profissionais capacitados. OBJETIVO: Estudar o perfil dos especialistas e dos serviços em RP e as características dos pacientes com doenças reumáticas nessa faixa etária a fim de estimar a situação atual no estado de São Paulo (ESP). PACIENTES E MÉTODOS: No ano de 2010 o departamento científico de RP da Sociedade de Pediatria de São Paulo encaminhou um questionário respondido por 24/31 especialistas com título de especialização em RP que atuam no ESP e por 8/12 instituições com atendimento nesta especialidade. RESULTADOS: A maioria (91%) dos profissionais exerce suas atividades em instituições públicas. Clínicas privadas (28,6%) e instituições (37,5%) relataram não ter acesso ao exame de capilaroscopia e 50% das clínicas privadas não tem acesso à acupuntura. A média de tempo de prática profissional na especialidade foi de 9,4 anos, sendo 67% deles pós-graduados. Sete (87,5%) instituições públicas atuam na área de ensino, formando novos reumatologistas pediátricos. Cinco (62,5%) delas têm pós-graduação. Dois terços dos especialistas utilizam imunossupressores e agentes biológicos de uso restrito pela Secretaria da Saúde. A doença mais atendida foi artrite idiopática juvenil (29,1%-34,5%), seguida de lúpus eritematoso sistêmico juvenil (LESJ) (11,6%-12,3%) e febre reumática (9,1%-15,9%). Vasculites (púrpura de Henoch Schönlein, Wegener, Takayasu) e síndromes autoinflamatórias foram mais incidentes nas instituições públicas (P = 0,03; P = 0,04; P = 0,002 e P < 0,0001, respectivamente). O LESJ foi a doença com maior mortalidade (68% dos óbitos), principalmente por infecção. CONCLUSÃO: A RP no ESP conta com um número expressivo de especialistas pós-graduados, que atuam especialmente em instituições de ensino, com infraestrutura adequada ao atendimento de pacientes de alta complexidade.Universidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Setor de Reumatologia PediátricaUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasSanta Casa de Misericórdia de São Paulo Departamento de Pediatria Setor de ReumatologiaUniversidade Estadual de Campinas Unidade de Reumatologia PediátricaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Puericultura e PediatriaSanta Casa de Misericórdia de Santos Setor de Reumatologia PediátricaFaculdade de Medicina de Botucatu Hospital Estadual de Bauru Serviço de Reumatologia PediátricaFaculdade de Medicina de BotucatuUNIFESP, Depto. de Pediatria Setor de Reumatologia PediátricaSciEL

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems

Methods\ud \ud We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5.\ud Results\ud \ud A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene.\ud Conclusions\ud \ud Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.This study was funded by the Butantan Foundation

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems

Methods\ud \ud We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5.\ud Results\ud \ud A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene.\ud Conclusions\ud \ud Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.This study was funded by the Butantan Foundation