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1.
Value Health ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977187

RESUMO

OBJECTIVES: The appraisal of vaccines in the European Union (EU) currently involves many different decision-making bodies and processes. The objective of this study was to help inform the development of standardized methodology and vaccine-specific processes for use in the EU Regulation on health technology assessment (HTA). METHODS: Literature reviews and expert consultation were conducted to identify current practices and gaps related to vaccine appraisals and to develop guiding principles for the joint clinical assessment of vaccines. RESULTS: We found that significant variation exists across the EU Member States in the decision-making processes when clinically evaluating vaccines. Three guiding principles consisting of 13 recommendations were developed to help inform the development of decision-making frameworks for the joint clinical assessment of vaccines in the EU: (1) Support the creation of appropriate terminology and measurements for clinical appraisals of vaccines; (2) Develop inclusive, timely, and transparent vaccine appraisal processes to support stronger evidence generation for vaccine decision-making and appraisal; and (3) Improve the collection and interoperability of real-world data, including robust surveillance, to foster evidence generation and support the standardization of vaccine clinical appraisals. CONCLUSIONS: Given the significance of vaccines for public health, there is an urgency to develop standardized and vaccine-specific methodologies and processes for use in the EU joint HTA framework. The proposed guiding principles could support the effective implementation of the EU Regulation on HTA for vaccines and have the potential to ensure consistent, transparent, and timely access to new vaccines in the EU.

2.
Expert Rev Vaccines ; 23(1): 324-335, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420698

RESUMO

BACKGROUND: The breadth of protection of National Immunisation Programmes (NIPs) across Europe varies, however, this has not been assessed within published literature. Therefore, a framework was developed to assess the comprehensiveness of pediatric NIPs in Europe. This study aimed to validate and further develop criteria used to cluster countries into three tiers. RESEARCH DESIGN AND METHODS: Independent Europe-based experts (n = 23) in the field of pediatric vaccination were invited to participate in a double-blinded modified Delphi panel, with two online survey rounds and a virtual consensus meeting. Consensus was defined as ≥ 80% of experts rating their agreement/disagreement on a 9-point Likert scale. RESULTS: The number of preventable diseases covered by an NIP, simplification of the vaccination calendar, strengthened protection by increasing serotype, degree of funding and epidemiological factors were considered key concepts for consideration of the comprehensiveness of pediatric NIPs in Europe. Experts highlighted that the framework should be extended to include adolescent vaccines and populations up to 18 years of age. Consensus regarding further amendments to the framework was also reached. CONCLUSIONS: This Delphi panel validated a framework to assess the comprehensiveness of European NIPs. The framework can be used to facilitate discussions to help countries improve and expand the breadth of protection provided by their NIP.


Assuntos
Vacinas , Humanos , Criança , Adolescente , Europa (Continente) , Consenso , Programas de Imunização
3.
Vaccine ; 41(22): 3399-3402, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37121805

RESUMO

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.


Assuntos
Vacinação , Vacinas , Humanos , Vacinação/efeitos adversos , Vacinas/efeitos adversos
4.
Vaccine ; 33(34): 4215-7, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-25896378

RESUMO

Based on the concerns about vaccine hesitancy and its impact on vaccine uptake rates and the performance of national immunization programmes, the Strategic Advisory Group of Experts (SAGE) on Immunization Working Group on Vaccine Hesitancy [1], carried out a review, and proposed a set of recommendations directed to the public health community, to WHO and its partners, and to the World Health Organization (WHO) member states. The final recommendations issued by SAGE in October 2014 fall into three categories: (1) those focused on the need to increase the understanding of vaccine hesitancy, its determinants and the rapidly changing challenges it entails; (2) those focused on dealing with the structures and organizational capacity to decrease hesitancy and increase acceptance of vaccines at the global, national and local levels; (3) and those focused on the sharing of lessons learnt and effective practices from various countries and settings as well as the development, validation and implementation of new tools to address hesitancy.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Programas de Imunização , Aceitação pelo Paciente de Cuidados de Saúde , Vacinas , Humanos , Cooperação do Paciente , Saúde Pública , Características de Residência , Recusa do Paciente ao Tratamento , Vacinação , Organização Mundial da Saúde
5.
Vaccine ; 33(34): 4157-60, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-25896380

RESUMO

Despite a wide array of safe and effective vaccines in use globally, with major impacts on health worldwide, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization has been repeatedly confronted with reports of hesitancy towards accepting specific vaccines or vaccination programmes. This paper summarizes the rationale for a SAGE review of the issue of vaccine hesitancy, its impact and ways to address it, and the convening of a Vaccine Hesitancy Working Group in March 2012 to prepare for the SAGE review. It describes the methods used and mode of operations, and advances in the relatively new field of research on vaccine hesitancy. It further elaborates and references the work conducted, including a series of products, conclusions and recommendations that emerged from the SAGE review in October 2014.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Programas de Imunização , Aceitação pelo Paciente de Cuidados de Saúde , Recusa do Paciente ao Tratamento , Educação , Humanos , Cooperação do Paciente , Vacinação/psicologia , Vacinas , Organização Mundial da Saúde
6.
Pathog Glob Health ; 108(1): 11-20, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24548156

RESUMO

A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs.


Assuntos
Programas de Imunização/organização & administração , Vacinação em Massa , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis , Feminino , Saúde Global , Humanos , Incidência , Masculino , Meningite Meningocócica/prevenção & controle , Infecções Meningocócicas/epidemiologia , Neisseria meningitidis/efeitos dos fármacos , Neisseria meningitidis/imunologia , Neisseria meningitidis/patogenicidade , Polissacarídeos/imunologia , Vacinas Conjugadas/administração & dosagem
7.
Popul Health Metr ; 11(1): 17, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24016339

RESUMO

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.

9.
Vaccine ; 31 Suppl 2: B108-14, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23598471

RESUMO

Serious vaccine-associated adverse events are rare. To further minimize their occurrence and to provide adequate care to those affected, careful monitoring of immunization programs and case management is required. Unfounded vaccine safety concerns have the potential of seriously derailing effective immunization activities. To address these issues, vaccine pharmacovigilance systems have been developed in many industrialized countries. As new vaccine products become available to prevent new diseases in various parts of the world, the demand for effective pharmacovigilance systems in low- and middle-income countries (LMIC) is increasing. To help establish such systems in all countries, WHO developed the Global Vaccine Safety Blueprint in 2011. This strategic plan is based on an in-depth analysis of the vaccine safety landscape that involved many stakeholders. This analysis reviewed existing systems and international vaccine safety activities and assessed the financial resources required to operate them. The Blueprint sets three main strategic goals to optimize the safety of vaccines through effective use of pharmacovigilance principles and methods: to ensure minimal vaccine safety capacity in all countries; to provide enhanced capacity for specific circumstances; and to establish a global support network to assist national authorities with capacity building and crisis management. In early 2012, the Global Vaccine Safety Initiative (GVSI) was launched to bring together and explore synergies among on-going vaccine safety activities. The Global Vaccine Action Plan has identified the Blueprint as its vaccine safety strategy. There is an enormous opportunity to raise awareness for vaccine safety in LMIC and to garner support from a large number of stakeholders for the GVSI between now and 2020. Synergies and resource mobilization opportunities presented by the Decade of Vaccines can enhance monitoring and response to vaccine safety issues, thereby leading to more equitable delivery of vaccines worldwide.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Farmacovigilância , Segurança , Vacinas/efeitos adversos , Países Desenvolvidos , Países em Desenvolvimento , Humanos , Imunização/efeitos adversos , Programas de Imunização , Cooperação Internacional , Organização Mundial da Saúde
10.
Duodecim ; 129(22): 2420-6, 2013.
Artigo em Finlandês | MEDLINE | ID: mdl-24397153

RESUMO

Globally 34 million children are born that do not receive the basic vaccines. Three million of them die of diseases, for which an effective vaccine exists. An effective vaccination program demands clear-cut objectives, righteous decision-making and an effective financing system. A vaccination program should strive for wide coverage globally, be credible in the citizens' view and flexible in situations of crisis. If the renewal plans for vaccination programs are actualized, 24 to 26 million unnecessary deaths can be prevented by the end of the decade.


Assuntos
Saúde Global , Política de Saúde , Vacinação/estatística & dados numéricos , Criança , Humanos
11.
Lancet ; 378(9790): 526-35, 2011 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-21664679

RESUMO

Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.


Assuntos
Saúde Global , Saúde Pública , Opinião Pública , Confiança , Vacinação/efeitos adversos , Vacinas/efeitos adversos , Transtorno Autístico/induzido quimicamente , Características Culturais , Surtos de Doenças , Medicina Baseada em Evidências , Haemophilus influenzae tipo b , Humanos , Esquemas de Imunização , Índia , Vacinas contra Influenza/administração & dosagem , Internacionalidade , Internet , Meios de Comunicação de Massa , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Vacinas contra Poliovirus/efeitos adversos , Política , Conservantes Farmacêuticos/efeitos adversos , Saúde Pública/tendências , Risco , Segurança , Fatores Socioeconômicos , Esterilização Reprodutiva , Toxoide Tetânico/efeitos adversos , Timerosal/efeitos adversos , Vacinas/administração & dosagem
13.
Duodecim ; 126(9): 1047-54, 2010.
Artigo em Finlandês | MEDLINE | ID: mdl-20593628

RESUMO

Global challenges of Haemophilus vaccinations quarter of a century after the Hib project In 2000, 8.13 million children contracted invasive Haemophilus infection globally, 0.37 million of which died. These were unnecessary disease cases and deaths that would have been preventable with the Hib vaccine. The vaccine was developed during the 1980's. During its application for more than twenty years, the vaccine has proven to be effective, safe and cost-effective. The wide application of the Hib vaccine has led to the eradication of life-threatening Haemophilus diseases from the industrialized countries, whereas in developing countries the vaccine should be permanently included in national vaccination programs.


Assuntos
Cápsulas Bacterianas/imunologia , Saúde Global , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Criança , Humanos
14.
PLoS One ; 5(12): e15885, 2010 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-21209964

RESUMO

BACKGROUND: Acute lower respiratory infection (ALRI) is a major cause of hospitalization for children in China, while the etiological diagnosis of ALRI remains a challenge. This study was performed to evaluate the utility of the blind Nasotracheal aspiration (NTA) in the pathogen detection in ALRI through an evaluation of the test's specificity. METHODOLOGY/PRINCIPAL FINDINGS: A hospital-based study of children ≤3 years was carried out from March 2006 through March 2007 in Suzhou University Affiliated Children's Hospital, including 379 cases with ALRI from the respiratory wards, and 394 controls receiving elective surgery. Nasopharyngeal swabs (NPS) and NTA specimens were taken on admission. S. pneumoniae was isolated from 10.3% of NTA samples from ALRI children, H. influenzae from 15.3%, and M. catarrhalis from 4.7%. The false positive rate--the strains from NTA in control group children--was 8.4% (95% CI: 5.8%-11.4%) for S. pneumoniae, 27.2% (95% CI: 22.7-31.5%) for H. influenzae, and 22.1% (95% CI: 18.0%-26.2%) for M. catarrhalis. The agreement between NPS and NTA in the control group was over 70%. CONCLUSION/SIGNIFICANCE: The blind NTA test is not a useful test for etiologic diagnosis of ALRI.


Assuntos
Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia/diagnóstico , Pneumonia/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Criança , Pré-Escolar , Reações Falso-Positivas , Feminino , Hospitais , Humanos , Masculino , Nasofaringe/microbiologia , Pneumologia/métodos , Respiração , Sucção/efeitos adversos
15.
Lancet ; 374(9707): 2115-2122, 2009 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-19880172

RESUMO

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/normas , Vacinação em Massa , Adolescente , Adulto , Pré-Escolar , Feminino , Síndrome de Guillain-Barré , Humanos , Vacinas contra Influenza/efeitos adversos , Masculino , Vacinação em Massa/efeitos adversos , Esclerose Múltipla/etiologia , Mielite Transversa/etiologia , Neurite (Inflamação)/etiologia , Trabalho de Parto Prematuro/etiologia , Neurite Óptica/etiologia , Gravidez
16.
Pediatr Infect Dis J ; 26(11): 979-84, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17984802

RESUMO

BACKGROUND: The large-scale implementation of human papilloma virus (HPV) immunization will be followed by cases of autoimmune diseases occurring in temporal association with immunizations. To anticipate events that might be mistakenly assumed to be caused by immunization, their prevalence was monitored before vaccine introduction. METHOD: Cohort study carried out within a database of female adolescents (n = 214,896) and young adults (n = 221,472) followed in the pre-HPV vaccine era (2005), computing rates of emergency consultations, hospitalizations and outpatient consultations, and estimation of risks of coincident associations. RESULTS: Immune-mediated conditions were a frequent cause (10.3%) of emergency room consultation by adolescent girls. Nonallergic immune-mediated conditions affected 86 per 100,000, diabetes ranking first. In 2005, 53 per 100,000 adolescents and 389 per 100,000 women were hospitalized for diseases of presumed autoimmune origin, thyroiditis being the most frequent diagnosis. If HPV immunization had been used with 80% coverage, 3 per 100,000 adolescents would have required emergency care for asthma/allergy within 24 hours and 2 per 100,000 for diabetes within 1 week of an injection. The risks of hospitalization in temporal association with immunization are 4 times higher for thyroiditis than for multiple sclerosis or Guillain-Barré's syndrome, and more than 20 times higher in young women than in adolescents. CONCLUSION: The distinction between HPV vaccine-caused adverse reactions and events only observed by chance in temporal association is difficult. The prior use of population-based data allows for identification of issues of potential concern, for monitoring the impact of large-scale interventions and for addressing rapidly vaccine-safety issues that may compromise vaccine programs.


Assuntos
Doenças Autoimunes/epidemiologia , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Autoimunidade , California , Criança , Estudos de Coortes , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Sistemas Pré-Pagos de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Imunização , Pacientes Ambulatoriais/estatística & dados numéricos , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Saúde Pública
17.
Duodecim ; 123(9): 1037-44, 2007.
Artigo em Finlandês | MEDLINE | ID: mdl-17612263
18.
Vaccine ; 23(46-47): 5328-32, 2005 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-16118028

RESUMO

Finnish and Israeli infants received an 11-valent mixed carrier pneumococcal conjugate vaccine (11PCV) with or without aluminum adjuvant at the age of 2, 4, 6, and 12 months. We measured opsonophagocytic activity (OPA) of antibodies to pneumococcal strains of serotypes 4, 6B, 14, 19F, and 23F. At 7 months, OPA was clearly detected for all the serotypes. At 13 months, OPAs increased further and the proportion of individuals with a positive OPA ranged between 81 and 100%. The adjuvant improved functional activity of antibodies to serotype 6B pneumococci. In conclusion, immunization of infants with the 11PCV induced functionally active antibodies.


Assuntos
Anticorpos Antibacterianos/imunologia , Vacinas Pneumocócicas/imunologia , Adjuvantes Imunológicos/farmacologia , Hidróxido de Alumínio/farmacologia , Anticorpos Antibacterianos/análise , Afinidade de Anticorpos , Finlândia , Humanos , Imunidade Celular/imunologia , Esquemas de Imunização , Técnicas Imunoenzimáticas , Imunoglobulina G/imunologia , Lactente , Recém-Nascido , Israel , Proteínas Opsonizantes , Fagocitose/imunologia , Polissacarídeos/imunologia , Vacinas Conjugadas/imunologia
20.
Infect Immun ; 72(9): 5383-91, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15322036

RESUMO

In pneumococcal conjugate vaccines (PCVs), polysaccharide antigens are often conjugated to protein carriers related to other common vaccines. It is therefore important to test PCV interaction with other pediatric vaccines when administered simultaneously. We assessed the immune response to an 11-valent PCV conjugated to diphtheria and tetanus carriers (PncD/T11), administered concomitantly, but in separate sites, with a combined vaccine containing epitopes related antigenically to the carriers: polyribosylribitol phosphate-tetanus tox oid (PRP-T), diphtheria toxoid (DT), and tetanus toxoid (TT). In addition, these combinations contained inactivated poliovirus vaccine (IPV) and either whole-cell pertussis (wP) or acellular pertussis (aP) components. After coadministration of PncD/T11 with the combined vaccine containing wP (DTwP/IPV/PRP-T), the responses to all polysaccharides in the PncD/T11 were satisfactory. In contrast, when coadministered with an aP-containing combination (DTaP/IPV/PRP-T), the response to all seven pneumococcal conjugates to TT was significantly reduced after primary and booster immunization. The pneumococcal conjugates to DT were not significantly reduced after the primary series, but were somewhat reduced after booster. It is likely that some suppression of the tetanus-mediated response occurred even when the PncD/T11 was coadministered with wP, but this suppression was masked by the adjuvant effect of wP. By replacing wP with aP, this adjuvant effect was removed, unmasking the suppression of the tetanus-mediated response. With the increasing use of multiple aP-containing vaccines in infancy, novel approaches to adjuvants and carrier protein technology are likely to be required.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacina contra Coqueluche/administração & dosagem , Vacinas Pneumocócicas/imunologia , Vacinas Combinadas/imunologia , Vacinas Conjugadas/imunologia , Toxoide Diftérico/administração & dosagem , Toxoide Diftérico/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Humanos , Imunização , Imunização Secundária , Lactente , Vacinas Pneumocócicas/administração & dosagem , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Polissacarídeos/administração & dosagem , Polissacarídeos/imunologia , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/administração & dosagem
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