Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.191
Filtrar
1.
Sr Care Pharm ; 34(7): 432-438, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383053

RESUMO

OBJECTIVE: To describe an interdisciplinary academic detailing project implemented to address low pneumococcal immunization rates. SETTING: Two medical clinics and four community pharmacies in rural Washington state. PRACTICE DESCRIPTION: The two medical clinics and four community pharmacies were all located in two rural counties and serve geographically large rural areas. PRACTICE INNOVATION: Academic detailing is an evidence-based approach designed to change clinical practice and improve decision-making. Our team utilized the academic detailing model to provide educational outreach to local rural health care providers. The detailing team visited each clinic and pharmacy on a defined schedule and provided information to physicians, clinic administrators, nurses, pharmacists, pharmacy technicians, medical assistants, and clinic front-end staff. MAIN OUTCOME MEASUREMENTS: The project team maintained detailed field notes from each academic detailing the visit and met to debrief about each encounter. From the field notes, through the process of thematic analysis and analytic memoing, the project team produced a list of "lessons learned" that could be used to guide other interprofessional teams wishing to embark on an academic detailing project. RESULTS: We have identified four key "lessons learned": Interprofessional team members bring different strengths to the project; using same-discipline team members paved the way for success; involving students aids in educating future practitioners in interprofessional practice; and scheduling meetings in advance is important. CONCLUSION: We described an approach to enhanced academic detailing using interprofessional team delivery, bringing interprofessional practice into the real-world practice setting.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinação , Idoso , Assistência à Saúde , Humanos , Washington
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(8): 851-854, 2019 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-31378048

RESUMO

There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 µg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.


Assuntos
Imunogenicidade da Vacina , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Anticorpos Antibacterianos/sangue , Humanos , Vacinas Conjugadas/uso terapêutico
3.
J Med Microbiol ; 68(6): 903-909, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31090535

RESUMO

PURPOSE: To prevent severe invasive pneumococcal infection, pneumococcal conjugate vaccines (PCVs) were introduced in Japan in 2010, and in 2013 a pneumococcal 13-valent conjugate vaccine (PCV13) was included in the routine vaccination schedule for infants. In this study, we analysed the antimicrobial susceptibilities and capsular types of pneumococci isolated from non-invasive patient sites from 2007 to 2016 to assess the impact of the introduction of PCV13. METHODOLOGY: A total of 618 pneumococcal isolates collected at a teaching hospital from 2007 to 2016 were used. These isolates were characterized by capsular typing, multilocus sequence typing and antimicrobial susceptibility testing. RESULTS: Capsular typing indicated that, after the introduction of the PCV, the proportion of PCV13 serotypes decreased (P<0.01), while non-PCV13 serotypes became diverse. In particular, increases in 22 F, 15A and 23A were noted among non-PCV13 serotypes. Regarding antimicrobial susceptibility, the non-susceptibility rate to penicillin of pneumococci that showed higher minimum inhibitory concentrations (MICs) than the susceptibility breakpoint decreased, and pneumococci tended to become susceptible. However, all type 23A pneumococci and 77.8  % of type 15A pneumococci showed the reverse trend, with low susceptibility to penicillin. Furthermore, all 15A and 23A isolates had macrolide resistance genes. CONCLUSION: These data suggest that PCVs can prevent infections caused by PCV serotypes. However, since non-PCV13-type pneumococci, in particular 15A and 23A, which have acquired multidrug resistance, have already emerged over time, the development of a novel vaccine targeting a broader spectrum of pneumococci is warranted.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Antibacterianos/farmacologia , Cápsulas Bacterianas/imunologia , Técnicas de Tipagem Bacteriana , Portador Sadio , DNA Girase/genética , DNA Topoisomerase IV/genética , Hospitais de Ensino , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Penicilinas/farmacologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética , Vacinas Conjugadas/imunologia
4.
Harefuah ; 158(5): 316-320, 2019 May.
Artigo em Hebraico | MEDLINE | ID: mdl-31104393

RESUMO

INTRODUCTION: Pneumococcal infections are an important cause of morbidity and mortality among children and adults worldwide. Acquisition and carriage of pneumococci are essential for the development of pneumococcal invasive (bacteremia, meningitis) and non-invasive disease. Pneumococcal conjugate vaccines (PCV) differ from the polysaccharide vaccine (PPV23) in its enhanced immunity and ability to prevent carriage of pneumococci. With the implementation of PCV to pediatric vaccination programs in different countries, we witnessed a change in the patterns of pneumococcal carriage and illness. In this review the authors present some of the changes that were observed with the implantation of PCV in Israel and other countries regarding pneumococcal carriage and invasive disease, with emphasis on the direct and indirect effect of this vaccine.


Assuntos
Portador Sadio , Nasofaringe , Streptococcus pneumoniae , Vacinas Conjugadas , Adulto , Criança , Humanos , Israel , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Streptococcus pneumoniae/isolamento & purificação , Vacinação , Vacinas Conjugadas/uso terapêutico
5.
Methods Mol Biol ; 1968: 205-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30929217

RESUMO

Streptococcus pneumoniae is one of the commonest bacteria that cause morbidity and mortality in children and the elderly. The two extremes of age and individuals with underlying disease are particularly at risk of developing pneumococcal disease. The pneumococcus is responsible for a wide range of infectious diseases, ranging from mild, non-invasive infections such as otitis media and sinusitis, to more severe infections including pneumonia, septicemia, and meningitis. Despite the licensure of highly effective pneumococcal conjugate vaccines, the control of pneumococcal disease is still challenging. Here we describe the critical role of Streptococcus pneumoniae in public health.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Saúde Pública/métodos , Streptococcus pneumoniae/patogenicidade , Humanos , Otite Média/imunologia , Otite Média/microbiologia , Otite Média/prevenção & controle , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Pneumonia/imunologia , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/uso terapêutico
6.
Methods Mol Biol ; 1968: 215-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30929218

RESUMO

Invasive infections caused by Streptococcus pneumoniae, such as pneumonia, meningitis, and bacteremia, are a major cause of morbidity and mortality in young children and older adults worldwide. The introduction of pneumococcal conjugate vaccines into national childhood immunization programs has led to large and sustained reductions in the incidence of invasive pneumococcal disease across all age groups. Here we describe the epidemiology and biostatistics of pneumococcal disease as well as the impact of vaccination on the burden of pneumococcal disease globally.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae/patogenicidade , Bioestatística , Humanos , Programas de Imunização , Incidência , Vacinas Pneumocócicas/uso terapêutico , Saúde Pública , Vacinas Conjugadas/uso terapêutico
7.
Lancet ; 393(10186): 2146-2154, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31000194

RESUMO

BACKGROUND: Ten-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2-11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12-59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County. METHODS: This study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999-Dec 31, 2010) and postvaccine (Jan 1, 2012-Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016. FINDINGS: Surveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03-0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17-0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5-14 years [adjusted IRR 0·26, 95% CI 0·11-0·59], and ≥15 years [0·19, 0·07-0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19-0·35) and non-PCV10-type carriage increased (1·71, 1·47-1·99). INTERPRETATION: Introduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa. FUNDING: Gavi, The Vaccine Alliance and The Wellcome Trust of Great Britain.


Assuntos
Nasofaringe/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Quênia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/isolamento & purificação , Adulto Jovem
8.
Expert Opin Drug Saf ; 18(4): 253-259, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30907170

RESUMO

INTRODUCTION: The introduction of pneumococcal conjugate vaccines (PCVs) in the routine immunization program has resulted in a significant decline in invasive pneumococcal diseases (IPD) around the world. Preterm infants are a special group at a high risk of invasive infection by encapsulated bacteria. However, their slow growth accrual and prolonged hospital stay frequently lead to delays in immunization, which contributes to their risk for severe infections. Areas covered: Authors reviewed the published immunogenicity and safety of the use of PCVs in preterm infants. Expert opinion: PCVs are safe and effective for use in low birth weight and in-hospital preterm infants. Local and systemic reactions are similar for both term and preterm populations. Reports were inconsistent on the risk of apnea, therefore hospitalized extremely premature infants should be kept under observation for at least 48 h after immunization.


Assuntos
Recém-Nascido Prematuro , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Humanos , Imunização/métodos , Programas de Imunização , Imunogenicidade da Vacina , Recém-Nascido , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Vacinas Conjugadas/administração & dosagem
9.
BMC Infect Dis ; 19(1): 227, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30836941

RESUMO

BACKGROUND: There is great interest in the use of reduced dosing schedules for pneumococcal conjugate vaccines, a strategy premised on maintaining an acceptable level of protection against disease and carriage of the organism. We asked about the practicality of measuring differential effectiveness against carriage in a population with and without widespread use of the vaccine for infants. METHODS: We adapted an existing transmission-dynamic, individual-based stochastic model fitted to the prevaccine epidemiology of pneumococcal carriage in the United States, and compared the observed vaccine-type carriage prevalence in different arms of a simulated trial with one, two, or three infant doses plus a 12-month booster. Using these simulations, we calculated vaccine efficacy that would be estimated at different times post-enrollment in the trial and calculated required sample sizes to see a difference in carriage prevalence. RESULTS: In a pneumococcal conjugate vaccine (PCV)-naïve population, the difference in vaccine-type (VT) pneumococcal carriage prevalence between trial arms was less than 7% and varied with sampling time. In a population already receiving routine PCV administration, VT pneumococcal prevalence is nearly indistinguishable between trial arms. Relative efficacy of different dosing schedules was strongly dependent on the time between enrollment and sampling, with maximal prevalence differences reached 1-3 years post-enrollment. Moreover, vaccine efficacy estimates were typically slightly higher in trials in communities already receiving vaccination. Despite this, much larger sample sizes-by more than an order of magnitude-are required for a vaccine trial conducted in a population receiving routine PCV administration as compared to in a PCV-naïve population. CONCLUSIONS: These findings highlight some underappreciated aspects of clinical trials of pneumococcal conjugate vaccines with efficacy endpoints, such as the context- and time-dependence of efficacy estimates. They support the wisdom of conducting comparative dose schedule trials of conjugate vaccine effects on carriage in vaccine-naïve populations.


Assuntos
Portador Sadio/imunologia , Imunidade Coletiva , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Simulação por Computador , Relação Dose-Resposta Imunológica , Feminino , Humanos , Lactente , Modelos Imunológicos , Infecções Pneumocócicas/prevenção & controle , Prevalência , Tamanho da Amostra , Streptococcus pneumoniae , Vacinas Conjugadas/imunologia
10.
Eur J Clin Microbiol Infect Dis ; 38(4): 785-791, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30778705

RESUMO

Pneumococcal disease constitutes a major global health problem. Adults aged over 50 years and younger adults with specific chronic health conditions are at risk for invasive pneumococcal disease, associated with substantial morbidity and mortality. In Europe, two vaccine types are used in adults for pneumococcal immunization: pneumococcal polysaccharide vaccine (PPV23) and pneumococcal conjugate vaccine (PCV13). To provide an overview and to compare the national guidelines for pneumococcal immunization for adults in Europe. In November 2016, national guidelines on pneumococcal vaccination for adults of 31 European countries were obtained by Google search, the website of European Centre for Disease Prevention and Control, and contacting public health officials. In our analysis, we distinguished between age-based and risk-based guidelines. In October 2017, we used the same method to retrieve guideline updates. We observed great variability regarding age, risk groups, vaccine type, and use of boosters. In age-based guidelines, vaccination is mostly recommended in adults aged over 65 years using PPV23. Boosters are generally not recommended. An upper age limit for vaccination is reported in three countries. In the immunocompromised population, vaccination with both vaccines and administration of a booster is mostly recommended. In the population with chronic health conditions, there is more heterogeneity according vaccine type, sequence, and administration of boosters. Asplenia is the only comorbidity for which all countries recommend vaccination. The great variability in European pneumococcal vaccination guidelines warrants European unification of the guidelines for better control of pneumococcal disease.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Guias de Prática Clínica como Assunto , Vacinação/estatística & dados numéricos , Fatores Etários , Idoso , Europa (Continente)/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Fatores de Risco , Streptococcus pneumoniae/imunologia
11.
Med Microbiol Immunol ; 208(2): 215-226, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707297

RESUMO

Streptococcuspneumoniae, or pneumococcus, is a major respiratory-tract pathogen that causes high levels of mortality and morbidity in infants and elderly individuals. Despite the development of various capsular polysaccharide vaccines to prevent pneumococcal disease, it remains epidemic. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein existing in all strains of S. pneumoniae, and it can elicit immunizing protection against pneumococcal infection. In our previous studies, a fusion protein (PsaA-PspA23), consisting of PspA and pneumococcal surface antigen A (PsaA), displayed greater immunogenicity and provided better protection in mice against S. pneumoniae strains than either PsaA or PspA. In this study, the fusion protein PsaA-PspA23, together with PspA4, was formulated with four adjuvants Al(OH)3, MF59, AS03, and AS02, and subsequently subjected to dose optimization and immunological evaluation for determination of the antibody titers, bacterial burden, survival rates, and levels of cytokines in mice. All vaccines with high adjuvant doses displayed higher antigen-specific immunoglobulin G (IgG) titers. Bacterial burdens were notably decreased to different extents in the lungs and blood of mice immunized with the antigen and various adjuvants. Among these adjuvants, AS02 provided outstanding protection against challenge with pathogenic bacteria from different families and clades; it also induced high titers of IgG1 and IgG2a. Moreover, only AS02 elicited high levels of cytokines, such as TNF-α, IFN-γ, IL-2, and IL-4. These results suggest that PsaA-PspA23 and PspA4 formulated with AS02 may potentially be used as a subunit vaccine against deadly pneumococcal infection.


Assuntos
Adesinas Bacterianas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Adesinas Bacterianas/genética , Animais , Anticorpos Antibacterianos/sangue , Carga Bacteriana , Proteínas de Bactérias/genética , Citocinas/análise , Modelos Animais de Doenças , Feminino , Lipoproteínas/genética , Camundongos Endogâmicos BALB C , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Análise de Sobrevida , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
12.
Brasília; CONITEC; fev. 2019. ilus, tab.
Não convencional em Português | BRISA/RedTESA | ID: biblio-997237

RESUMO

INTRODUÇÃO: A doença pneumocócica (DP) é causada pela bactéria Streptococcus pneumoniae, conhecida como pneumococo, sendo esta a causadora de doenças que atingem o trato respiratório e o cérebro. A DP pode ser classificada em dois tipos: a doença pneumocócica invasiva (DPI) ­ nos casos em que a bactéria invade a corrente sanguínea, e a doença pneumocócica não invasiva, sendo esta de menor gravidade, mas com maior recorrência e consequentemente maior peso econômico para o sistema de saúde. A infecção causada pelo pneumococo é uma das principais causas de morbimortalidade no mundo. Em 2005 a Organização Mundial de Saúde estimou a ocorrência de 1,6 milhão de mortes por ano por doença pneumocócica. Outros agravantes da situação são o aumento da resistência aos antibióticos pela bactéria e facilidade com que os sorotipos resistentes se disseminaram progressivamente pelo mundo. Atualmente, existem dois tipos de vacinas pneumocócicas, disponíveis no Sistema Único de Saúde (SUS), para prevenção das DPs: a vacina polissacarídica 23-valente (VPP-23) para pacientes de alto risco e a vacina conjugada 10-valente (VPC-10) para crianças de risco até os 5 anos de idade. TECNOLOGIA: Vacina pneumocócica conjugada 13-valente (Prevenar 13®). PERGUNTA: O uso da vacina pneumocócica conjugada 13-valente em combinação com a vacina pneumocócica polissacarídica 23-valente (VPC-13 + VPP-23) é eficaz e segura na prevenção de doença pneumocócica em pacientes de risco, acima de cinco anos de idade, de acordo com os critérios do Programa Nacional de Imunizações do Ministério da Saúde? EVIDÊNCIAS CIENTÍFICAS: Análise baseada em ensaios clínicos randomizados que avaliaram a sua aplicação em adultos/idosos com condição crônica preexistente (doenças cardiovasculares, pulmonares, hepáticas, distúrbios renais ou diabetes mellitus) e adultos HIV positivos. Para adultos/idosos com condição crônica preexistente, os resultados encontrados, de modo geral, evidenciaram que as médias geométricas dos títulos (MGTs) de AOP (atividade opsonofagocítica) da vacinação sequencial (VPC-13+VPP-23) foram não inferiores e/ou maiores, com significância estatística, para alguns dos 13 sorotipos, quando comparadas com as respostas da VPP-23 sozinha, ou combinada com ela mesma, a depender do intervalo de tempo entre as doses. Observa-se a vantagem potencial da administração inicial da VPC-13, que permite o estabelecimento de um estado imunológico que resulta em respostas de memória apropriadas para sorotipos em comum após a imunização subsequente com VPP-23. Tal resposta geral é consistentemente ausente quando a VPP-23 é administrada antes da VPC-13. Em adultos HIV positivos, com contagem de CD4>200 células/mm3, a combinação da VPC-13 com a VPP-23 obteve uma maior magnitude da resposta imunológica de IgG e de títulos da AOP em comparação com a VPP-23 isolada. A informação de eficácia é limitada a dados imunológicos (média geométrica dos títulos de atividade opsonofagocítica-MGT de AOP), faltando informações sobre a redução nas taxas de pneumonia (DPI) e outros resultados clínicos. AVALIAÇÃO ECONÔMICA: O demandante apresentou uma análise de custo-efetividade utilizando parâmetros extraídos da literatura e dados dos sistemas de informação do SUS e do IBGE, de forma combinada. Os resultados demonstraram que a vacinação sequencial (VPC-13 + VPP-23) proporcionou redução de custos com ganho em efetividade (cenário dominante) quando comparada à imunização com a VPP-23 isoladamente. Além disso, tanto os resultados da análise de sensibilidade univariada quanto da probabilística ratificaram o cenário de dominância da vacinação sequencial frente à VPP-23 isolada. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário foi calculado para 5 anos, 2019 a 2013, na perspectiva do SUS, considerando dois cenários: Cenário 1 ­pessoas, que são tratadas no SUS, com pelo menos uma das 17 condições clínicas de risco para as doenças pneumocócicas; Cenário 2 ­pessoas, que são tratadas no SUS, com pelo menos uma das 17 condições clínicas de risco para as doenças pneumocócicas estratificada segundo gravidade da condição clínica de risco: a)risco gravíssimo e b) risco grave. CONSIDERAÇÕES: Os achados da literatura apoiam as recomendações atuais de vacinação contra pneumococos nos Estados Unidos e na Europa para indivíduos infectados pelo HIV. A introdução da VPC-13 no esquema sequencial com a VPP-23, para populações de risco (pacientes que vivem com HIV/Aids, pacientes oncológicos e para indivíduos submetidos a transplante de medula óssea), foi recomendada pelo Comitê Técnico Assessor de Imunizações (CTAI) do Programa Nacional de Imunizações (PNI). Considera-se que a expansão do uso da vacina conjugada, em maiores de cinco anos de idade, para outros grupos, será tema abordado em revisões futuras. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Plenário, na 72ª reunião ordinária, realizada no dia 07 de novembro de 2018, indicaram que o tema seja submetido à Consulta Pública com recomendação preliminar a favor da incorporação no SUS da vacina pneumocócica conjugada 13-valente para prevenção da doença pneumocócica em pacientes de risco gravíssimo, acima de cinco anos de idade. Considerou-se que a vacina apresenta eficácia, principalmente para o grupo de risco gravíssimo que apresenta maior vulnerabilidade, maior risco de adoecer e condições clínicas que, mesmo se houver imunidade de rebanho na população em geral, essa população mais vulnerável não seria beneficiada. Além disso, os pacientes de risco gravíssimo representam 75% da população de risco, o que já representa uma expansão importante para o PNI. CONSULTA PÚBLICA: Por meio da Consulta Pública nº 69/2018, realizada entre os dias 27/11/2018 e 17/11/2018, foram recebidas 100 contribuições, sendo 27 técnico-científicas e 73 de experiência ou opinião. A maioria das contribuições da incorporação da vacina pneumocócica conjugada 13-valente no SUS. Entre as contribuições técnico-científicas, a empresa fabricante solicitou a inclusão do transplante de órgãos sólidos como uma comorbidade elegível para imunização, que constava no dossiê inicial apresentado e que está inserido no atual Manual dos Centros de Referência para Imunobiológicos Especiais do PNI/MS. A referida alteração foi aceita pelos membros do plenário. A CONITEC entendeu que não houve argumentação suficiente para alterar sua recomendação preliminar, a favor da incorporação no SUS da vacina pneumocócica conjugada 13-valente para prevenção da doença pneumocócica em pacientes de risco gravíssimo, acima de cinco anos de idade. RECOMENDAÇÃO FINAL: Os membros da CONITEC em 07/02/2019 deliberaram por unanimidade recomendar a incorporação, no SUS, da vacina pneumocócica conjugada 13-valente contra doenças pneumocócicas em pacientes de risco gravíssimo acima de 5 anos de idade nos Centros de Referência para Imunobiológicos Especiais - CRIE (pacientes que vivem com HIV/Aids, pacientes oncológicos e para indivíduos submetidos a transplante de medula óssea e de órgãos sólidos).


Assuntos
Humanos , Infecções Pneumocócicas/prevenção & controle , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Avaliação da Tecnologia Biomédica , Análise Custo-Eficiência , Avaliação em Saúde/economia , Sistema Único de Saúde , Brasil
13.
Int J Pediatr Otorhinolaryngol ; 119: 123-130, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30703661

RESUMO

OBJECTIVES: To evaluate the epidemiology, microbiology, Streptococcus pneumoniae serotypes distribution and serious bacterial infections (SBIs) occurrence in infants <2 months of age with tympanocentesis-documented acute otitis media (AOM), before and after the introduction of pneumococcal conjugate vaccines (PCVs). METHODS: The medical records of all hospitalized infants with AOM who underwent tympanocentesis during 2005-2014 were reviewed. RESULTS: Of the 303 infants with AOM who were diagnosed by an ENT specialist, 182 underwent tympanocentesis, 92 during 2005-2009 (prevaccine period) and 90 during 2010-2014 (postvaccine period). Streptococcus pneumoniae and nontypeable Hemophilus influenzae were isolated in 46/92 (50%) and 37/92 (40.2%) patients during 2005-2009 and decreased to 27/90 (30%) and 21/90 (23.3%). Respectively, during 2010-2014 (P = 0.006 and P = 0.001). The proportion of culture-negative patients increased from 18/92 (19.6%) during 2005-2009 to 32/90 (35.6%) during 2010-2014 (P = 0.02). There were only 6 (3.3%) patients <2 weeks of age. The most common S. pneumoniae vaccine serotypes isolated during 2005-2009 were 5, 3, 1, 19F and 14 (15.2%, 13.0%, 10.9%, 6.5%, and 4.3%, respectively) and 3, 5, 1, 14 and 19A (22.2%, 11.1%, 7.4%, 7.4%, and 7.4%, respectively) during 2010-2014. The proportion of culture-positive patients decreased during 2013-2014 compared with 2011-2012 (7/18, 38.9% vs. 40/54, 74.1%, P = 0.007). Serotypes 1 and 5 were not isolated during 2013-2014 and serotype 19A was not isolated during 2011-2014. . SBIs were recorded in 23/182 (12.64%) patients and urinary tract infections represented 19/23 (82.61%) of them (Escherichia coli isolated in 12, 63.2%). CONCLUSIONS: The overall number of AOM cases needing tympanocentesis seen at the PER and the proportion of S. pneumoniae and nontypeable H. influenzae-AOM decreased while the proportion of culture-negative AOM increased following the introduction of PCVs. SBIs associated with AOM were frequent and were represented mostly by urinary tract infections caused by pathogens unrelated to the etiologic agents of AOM.


Assuntos
Infecções por Haemophilus/epidemiologia , Otite Média/epidemiologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/administração & dosagem , Antibacterianos/uso terapêutico , Feminino , Infecções por Haemophilus/tratamento farmacológico , Haemophilus influenzae/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Ventilação da Orelha Média , Otite Média/microbiologia , Otite Média/prevenção & controle , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/prevenção & controle , Prevalência , Estudos Retrospectivos , Sorogrupo , Streptococcus pneumoniae/isolamento & purificação , Timpanocentese/estatística & dados numéricos
14.
Microb Genom ; 5(2)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30777813

RESUMO

The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the United States in 2010. Using a large paediatric carriage sample collected from shortly after the introduction of PCV-7 to several years after the introduction of PCV-13, we investigate alterations in the composition of the pneumococcal population following the introduction of PCV-13, evaluating the extent to which the post-vaccination non-vaccine type (NVT) population mirrors that from prior to vaccine introduction and the effect of PCV-13 on vaccine type lineages. Draft genome assemblies from 736 newly sequenced and 616 previously published pneumococcal carriage isolates from children in Massachusetts between 2001 and 2014 were analysed. Isolates were classified into one of 22 sequence clusters (SCs) on the basis of their core genome sequence. We calculated the SC diversity for each sampling period as the probability that any two randomly drawn isolates from that period belong to different SCs. The sampling period immediately after the introduction of PCV-13 (2011) was found to have higher diversity than preceding (2007) or subsequent (2014) sampling periods {Simpson's D 2007: 0.915 [95 % confidence interval (CI) 0.901, 0.929]; 2011:  0.935 [0.927, 0.942]; 2014 :  0.912 [0.901, 0.923]}. Amongst NVT isolates, we found the distribution of SCs in 2011 to be significantly different from that in 2007 or 2014 (Fisher's exact test P=0.018, 0.0078), but did not find a difference comparing 2007 to 2014 (Fisher's exact test P=0.24), indicating greater similarity between samples separated by a longer time period than between samples from closer time periods. We also found changes in the accessory gene content of the NVT population between 2007 and 2011 to have been reduced by 2014. Amongst the new serotypes targeted by PCV-13, four were present in our sample. The proportion of our sample composed of PCV-13-only vaccine serotypes 19A, 6C and 7F decreased between 2007 and 2014, but no such reduction was seen for serotype 3. We did, however, observe differences in the genetic composition of the pre- and post-PCV-13 serotype 3 population. Our isolates were collected during discrete sampling periods from a small geographical area, which may limit the generalizability of our findings. Pneumococcal diversity increased immediately following the introduction of PCV-13, but subsequently returned to pre-vaccination levels. This is reflected in the distribution of NVT lineages, and, to a lesser extent, their accessory gene frequencies. As such, there may be a period during which the population is particularly disrupted by vaccination before returning to a more stable distribution. The persistence and shifting genetic composition of serotype 3 is a concern and warrants further investigation.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/genética , Criança , Pré-Escolar , Estudos de Coortes , Variação Genética , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Humanos , Lactente , Massachusetts , Infecções Pneumocócicas/microbiologia , Estudos Retrospectivos , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Vacinação , Vacinas Conjugadas/administração & dosagem
15.
Ann Hematol ; 98(3): 775-779, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30683996

RESUMO

Streptococcus pnemoniae is a major cause of morbidity and mortality among splenectomised patients with ß-thalassemia major. We have previously shown that a 13-valent pneumococcal conjugate vaccine (PCV13) induces robust early immune responses in such patients, while history of repeated immunisations with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) results in attenuation of the response to PCV13. However, the duration of vaccine-induced protection in splenectomised thalassemic patients and the associated need for booster immunisation remains unclear. In the current study, we enumerate antibody persistence 5 years post-PCV13 and investigate any correlation with early immune response and immunisation history. Pneumococcal serotype (PS)-specific antibodies against 5 vaccine antigens were measured 5 years post-PCV13 in 34 asplenic adults with ß-thalassemia. PS-specific antibodies against 5 vaccine serotypes had declined significantly at 5 years post-PCV13 (year 5).Year 5 antibody titres remained above baseline for PS9V, 19A and19F, returned to baseline for PS23F, and dropped below baseline for PS3 (p < 0.001).Year 5 antibodies were positively correlated with day 28 antibody titres, while no correlation was found with early memory B cell response. Previous PPSV23 history was correlated with impaired antibody persistence against serotype 19A. Antibody levels dropped significantly but remained at protective levels 5 years post-PCV13.We propose that asplenic patients with ß-thalassemia may benefit from measurement of antipneumococcal antibodies after 5 years post-PCV13 as they may eventually be in need for booster pneumococcal vaccination. Clinical Trials Registration ID: www.clinicaltrials.gov NCT01846923.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções Pneumocócicas , Vacinas Pneumocócicas/administração & dosagem , Esplenectomia , Streptococcus pneumoniae , Talassemia beta , Adulto , Feminino , Seguimentos , Humanos , Imunização Secundária , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/etiologia , Infecções Pneumocócicas/prevenção & controle , Fatores de Tempo , Talassemia beta/sangue , Talassemia beta/complicações , Talassemia beta/cirurgia
16.
Int J Pediatr Otorhinolaryngol ; 119: 96-102, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30690309

RESUMO

OBJECTIVE: The 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) were approved in the US in 2000 and 2010, respectively, for active immunization against invasive disease caused by all vaccine serotypes and otitis media (OM) caused by 7 serotypes common to both vaccines, starting at ∼6 weeks of age. This study assessed the impact of PCV13 on OM by evaluating changes in US ambulatory care visit rates between the period before PCV7 (1997-1999), during PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013) among US children <5 years old. METHODS: This ecological study used US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data. Trend analyses using weighted least-squares regression and mean visit rates were calculated for OM and two control endpoints not likely to be related to either vaccine (skin rash and trauma). RESULTS: Among children <5 and < 2 years old, the observed reduction in OM visit rates was 22% (95%CI: 12%-32%) and 24% (95%CI: 13%-35%) when comparing PCV13 to PCV7 periods, and 41% (95%CI: 30%-52%) and 48% (95%CI: 37%-59%) when comparing PCV13 to pre-PCV7 periods. Visit rates for skin rash and trauma remained stable. CONCLUSION: Significant reductions in US ambulatory care visit rates for OM were observed among children aged <5 years after introduction of PCV13 compared to the periods before and during PCV7; reductions were greatest among children <2 years old. The reductions beyond the PCV7 period support the effectiveness of the vaccine's 6 additional serotypes in preventing OM.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Visita a Consultório Médico/estatística & dados numéricos , Otite Média/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Vacinas Conjugadas , Assistência Ambulatorial/tendências , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Visita a Consultório Médico/tendências , Sorogrupo , Estados Unidos
17.
PLoS One ; 14(1): e0210081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629620

RESUMO

BACKGROUND: In February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study. METHODS: The study period was divided into pre- (2009-2011) and post-period (2013-2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5-49 and ≥50 years old. Additionally, for the 5-49 and ≥50 years old, and the 50-59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression. RESULTS: The PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5-49 years old. CONCLUSIONS: Our study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time.


Assuntos
Programas de Imunização/estatística & dados numéricos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Avaliação de Programas e Projetos de Saúde , Adolescente , Adulto , Fatores Etários , Áustria/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Esquemas de Imunização , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Cobertura Vacinal/estatística & dados numéricos , Vacinas Conjugadas , Adulto Jovem
18.
Vaccine ; 37(1): 176-186, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30054160

RESUMO

BACKGROUND: We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent). METHODS: In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 µg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed. RESULTS: 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded. CONCLUSION: Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Imunogenicidade da Vacina , Imunoglobulina D/imunologia , Lipoproteínas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Haemophilus influenzae , Vacinas contra Hepatite B/administração & dosagem , Humanos , Imunização Secundária , Imunoglobulina D/genética , Lactente , Lipoproteínas/genética , Masculino , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/efeitos adversos , Vacina Antipólio de Vírus Inativado/administração & dosagem , Sorogrupo , Streptococcus pneumoniae , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
19.
Lancet Glob Health ; 7(1): e58-e67, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30554762

RESUMO

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) has substantially reduced disease burden due to Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. However, PCVs are among the most expensive vaccines, hindering their introduction in some settings and threatening sustainability in others. We aimed to assess the effect and cost-effectiveness of introduction of 13-valent PCV (PCV13) vaccination globally. METHODS: We assessed the incremental cost-effectiveness ratio of PCV13 introduction by integrating two models: an ecological model (a parsimonious, mechanistic model validated with data from post-seven-valent PCV introduction in 13 high-income settings) to predict the effect of PCV on childhood invasive pneumococcal disease, and a decision-tree model to predict a range of clinical presentations and economic outcomes under vaccination and no-vaccination strategies. The models followed 30 birth cohorts up to age 5 years in 180 countries from 2015 to 2045. One-way scenario and probabilistic sensitivity analyses were done to explore model uncertainties. FINDINGS: We estimate that global PCV13 use could prevent 0·399 million child deaths (95% credible interval 0·208 million to 0·711 million) and 54·6 million disease episodes (51·8 million to 58·1 million) annually. Global vaccine costs (in 2015 international dollars) of $15·5 billion could be partially offset by health-care savings of $3·19 billion (2·62 billion to 3·92 billion) and societal cost savings of $2·64 billion (2·13 billion to 3·28 billion). PCV13 use is probably cost-effective in all six UN regions. The 71 countries eligible for support from Gavi, the Vaccine Alliance, account for 83% of PCV13-preventable deaths but only 18% of global vaccination costs. The expected cost of PCV vaccination globally is around $16 billion per year. INTERPRETATION: Our findings highlight the value of Gavi's support for PCV introduction in low-income countries and of efforts to improve the affordability of PCVs in countries not eligible for, or transitioning from, Gavi support. FUNDING: World Health Organization; Gavi, the Vaccine Alliance; and the Bill & Melinda Gates Foundation.


Assuntos
Saúde Global/economia , Saúde Global/estatística & dados numéricos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/economia , Mortalidade da Criança/tendências , Pré-Escolar , Análise Custo-Benefício , Humanos , Lactente , Modelos Teóricos , Vacinas Conjugadas
20.
Expert Rev Vaccines ; 18(1): 89-94, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30526145

RESUMO

BACKGROUND: Invasive pneumococcal disease (IPD) is a serious threat to children worldwide. This study reported the serotype distribution, antibiotic resistance pattern, and multilocus sequence types of 111 IPD strains isolated from children less than 14 years old in two tertiary pediatric centers in Beijing during the years 2012-2017. METHODS: Serotypes were determined using Quellung reaction. Antibiotic resistance was tested using the E-test or disc diffusion method. Sequence types (STs) were assigned via multilocus sequence typing. RESULTS: The most common serotypes of the IPD isolates were 19F, 19A, 14, 23F, and 6B, and the PCV13 coverage rate was 90.1%. For the meningitis isolates, the resistance rate to penicillin was 95.7%, and the non-susceptibility rate to ceftriaxone was 65.2%. All of the non-meningitis isolates were susceptible to penicillin, and the susceptibility rate to ceftriaxone was 89.8%. All but one of the isolates were highly resistant to erythromycin. The multidrug resistance rate of all isolates was 89.2%. The most common STs were ST320, ST271, ST876, and ST81, which belonged to serotype 19A, 19F, 14, and 23F, respectively. CONCLUSION: Given the high coverage rate of PCV13 and the worrisome non-susceptibility rate of IPD isolates to antibiotics, PCV13 use would be beneficial for Chinese children.


Assuntos
Antibacterianos/farmacologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Pequim/epidemiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA