Bruce G. Gellin

Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis

BACKGROUND The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a persons own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome. METHODS Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barré syndrome per million vaccinations. We used a self-controlled risk-interval design. FINDINGS Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barré syndrome (incidence rate ratio 2·35, 95% CI 1·42-4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barré syndrome per million people vaccinated. INTERPRETATION The modest risk of Guillain-Barré syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks. FUNDING US Federal Government.

Recommendations from the national vaccine advisory committee: Standards for adult immunization practice

National Vaccine Advisory Committee The Advisory Committee on Immunization Practices (ACIP) makes recommendations for routine vaccination of adults in the United States.1 Standards for implementing the ACIP recommendations for adults were published by the National Vaccine Advisory Committee (NVAC) in 20032 and by the Infectious Diseases Society of America in 2009.3 In addition, NVAC published a report in 2012 outlining a pathway for improving adult immunization rates.4 While most of these documents included guidelines for immunization practice, recent changes in the practice climate for adult immunization necessitated an update of existing adult immunization standards. Some of these changes include expansion of vaccination services offered by pharmacists and other community immunization providers both during and since the 2009 H1N1 influenza pandemic; vaccination at the workplace; increased vaccination by providers who care for pregnant women; and changes in the health-care system, including the Affordable Care Act (ACA), which requires first-dollar coverage of ACIP-recommended vaccines for people with certain private insurance plans, or those who are beneficiaries of expanded Medicaid plans.5 The ACA first-dollar provision is expected to increase the number of adults who will be insured for vaccines. Other changes include expanding the inclusion of adults in state immunization information systems (IISs) (i.e., registries) and the Centers for Medicare & Medicaid Services Meaningful Use Stage 2 requirements, which mandate provider reporting of immunizations to registries, including reporting of adult vaccination in states where such reporting is allowed.6 For the purposes of this report, provider refers to any individual who provides health-care services to adult patients, including physicians, physician assistants, nurse practitioners, nurses, pharmacists, and other health-care professionals. While previous versions of the adult immunization standards have been published, recommendations for adult vaccination are published annually, and many health-care organizations have endorsed routine assessment and vaccination of adults, vaccination among adults continues to be low.7–15 Several barriers to adult vaccination include:

Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines.

Addressing vaccine hesitancy: The potential value of commercial and social marketing principles and practices.

Many countries and communities are dealing with groups and growing numbers of individuals who are delaying or refusing recommended vaccinations for themselves or their children. This has created a need for immunization programs to find approaches and strategies to address vaccine hesitancy. An important source of useful approaches and strategies is found in the frameworks, practices, and principles used by commercial and social marketers, many of which have been used by immunization programs. This review examines how social and commercial marketing principles and practices can be used to help address vaccine hesitancy. It provides an introduction to key marketing and social marketing concepts, identifies some of the major challenges to applying commercial and social marketing approaches to immunization programs, illustrates how immunization advocates and programs can use marketing and social marketing approaches to address vaccine hesitancy, and identifies some of the lessons that commercial and non-immunization sectors have learned that may have relevance for immunization. While the use of commercial and social marketing practices and principles does not guarantee success, the evidence, lessons learned, and applications to date indicate that they have considerable value in fostering vaccine acceptance.

Translating vaccine policy into action: a report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings.

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life. In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success. We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant women during the 2009 influenza pandemic. We conclude with an analysis of data gaps and necessary activities to facilitate implementation of maternal influenza immunization programs in resource-limited settings.

Annual Universal Influenza Vaccination: Ready or Not?

Influenza causes annual worldwide epidemics of respiratory disease. Currently, the United States and many other countries recommend influenza vaccination for persons who are at high risk for influenza-related complications. This commentary explores the potential benefits of a policy advocating universal annual influenza vaccination and outlines obstacles that need to be overcome to make such a recommendation feasible. The 5-year experience of a free influenza vaccination program for everyone > or =6 months of age in the Canadian province of Ontario is reviewed.

Success Of Program Linking Data Sources To Monitor H1N1 Vaccine Safety Points To Potential For Even Broader Safety Surveillance

In response to the 2009 H1N1 pandemic and subsequent vaccination program, the Department of Health and Human Services and collaborators developed the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) Program as a demonstration project to detect rare adverse events rapidly. The program monitored three million people who had received the H1N1 vaccine by linking data from large private health plans and from public immunization registries that had originally not been designed to share data, and on a larger scale than had been previously attempted. The program generated safety data in two weeks rather than three to six monty 10ths-the standard time frame achievable using health plan data. PRISM substantially contributed to the understanding of the safety of H1N1 vaccines. Its use in the case of H1N1 highlights the necessity of proactive planning, scalable infrastructure, and public-private partnerships in tracking adverse events after vaccination in epidemics. It also illustrates how data could be integrated to produce policy-relevant information for other medical products.

Editors' Introduction: Vaccine Safety Throughout the Product Life Cycle

The development and widespread use, in the United States and globally, of safe and effective vaccines has been one of the greatest achievements in science, medicine, and public health—saving lives, preventing disabilities, contributing to improvements in life expectancy, and reducing health care costs. Serious and once common childhood infections are increasingly joining the ranks of “vaccine-preventable diseases.” The number of childhood and adolescent diseases prevented by vaccines has increased from 10 to 16 in just the last 10 years. Moreover, we now have vaccines that can prevent the infections that can lead to cervical and liver cancer. Ironically, as the threat of disease has been diminished by vaccines, there has been increasing attention on the risks, both real and perceived, from vaccines. When vaccines are used effectively, the incidence of vaccine-preventable diseases declines, and over time, the diseases that vaccines have prevented are less common. The result is that there is a subtle shift in the benefit/risk ratio. With the recent addition of new vaccines to the recommended childhood immunization schedule, an increasing number of parents have raised concerns that their children are receiving more vaccines than they need. Changes in information technology, such as the Internet, provide more access to information, both accurate and inaccurate. The safety standards for vaccines are arguably higher than those of any other medical product because vaccines are given to healthy persons to prevent disease, are recommended for near-universal use, and are often required by state laws for school entrance. Nevertheless, no medical product, including vaccines, is risk free. Similar to other infrastructures, the components of the US vaccine-safety system may not be familiar to many people. Because the quality and transparency of this system are critical to maintaining public confidence in our immunization program, this supplement to Pediatrics has been assembled to help … Address correspondence to Daniel Salmon, PhD, MPH, National Vaccine Program Office, Office of Public Health and Science, Office of the Secretary, Department of Health and Human Services, 200 Independence Ave SW, Room 715H, Washington, DC 20201. E-mail: daniel.salmon{at}hhs.gov

Overcoming Barriers to Low HPV Vaccine Uptake in the United States: Recommendations from the National Vaccine Advisory Committee: Approved by the National Vaccine Advisory Committee on June 9, 2015

An average of 25,900 cases of human papillomavirus (HPV)-associated cancers are newly diagnosed in the United States each year.1,2 An estimated 14 million people are newly infected with HPV each year, and nearly half of these infections occur in people aged 14–25 years.3 Although most infections resolve over time, persistent infection with oncogenic HPV types is associated with a variety of cancers. Virtually all cervical cancers are caused by HPV, along with 90% of anal, 69% of vaginal, 60% of oropharyngeal, 51% of vulvar, and 40% of penile cancers.1 Furthermore, 87% of anal, 76% of cervical, 60% of oropharyngeal, 55% of vaginal, 44% of vulva, and 29% of penile cancers are caused by oncogenic HPV type 16 or 18.4 Of the 35,000 HPV cancers reported in 2009 in the United States, 39% occurred in males.1 Three HPV vaccines are currently available in the United States. One is a bivalent vaccine (designated as HPV2) designed to protect against HPV types 16 and 18, which are responsible for the most HPV-associated cancers. One is a quadrivalent vaccine (HPV4), which protects against HPV types 16 and 18 and two additional types, 6 and 11, that are the most common causes of genital warts. One is a nonavalent vaccine (HPV9) that protects against HPV types 6, 11, 16, and 18, and offers additional protection against five oncogenic HPV types, 31, 33, 45, 52, and 58. To prevent cancers associated with HPV infections, the Advisory Committee on Immunization Practices (ACIP) recommends HPV immunization for all children aged 11 or 12 years with the licensed three-doses series. The ACIP has recommended routine HPV immunization for girls since 2006 and for boys since 2011.2 Despite ACIP’s recommendations, rates of vaccination have remained low. In 2013, initiation rates for the HPV vaccine series were just 57.3% for girls and 34.6% for boys, and completion rates were ,40% for girls and 15% for boys.2 These completion rates are well below the national Healthy People 2020 target of 80%.

Strengthening the U.S. Vaccine and Immunization Enterprise: The Role of the National Vaccine Advisory Committee

Address correspondence to: Angela K. Shen, MPH, National Vaccine Program Office, Department of Health and Human Services, 200 Independence Ave. SW, 717H, Washington, DC 20201-0004; tel. 202-690-5566; fax 202-690-4631; e-mail . The National Vaccine Advisory Committee (NVAC) is a federal advisory committee that provides vaccine and immunization policy recommendations to the U.S. Department of Health and Human Services (HHS). The NVAC’s diversity of professional and stakeholder perspectives enables the committee to play a role in strengthening the U.S. vaccine and immunization system, as well as inform vaccine policy. This article details the NVAC’s contribution, focusing on its recent response to the 2009 H1N1 pandemic, and reveals opportunities for the NVAC to further shape this public health sector in the future.