Dina Pfeifer

Influenza vaccination in pregnancy: current evidence and selected national policies

In several countries, pregnant women are recommended seasonal influenza vaccination and identified as a priority group for vaccination in the event of a pandemic. We review the evidence for the risks of influenza and the risks and benefits of seasonal influenza vaccination in pregnancy. Data on influenza vaccine safety in pregnancy are inadequate, but the few published studies report no serious side-effects in women or their infants, including no indication of harm from vaccination in the first trimester. National policies differ widely, mainly because of the limited data available, particularly on vaccination in the first trimester. The evidence of excess morbidity during seasonal influenza supports vaccinating healthy pregnant women in the second or third trimester and those with comorbidities in any trimester. The evidence of excess mortality in two previous influenza pandemics supports vaccinating in any trimester during a pandemic.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines.

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.

Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data

A 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) was licensed in the United States of America in 2000, but no comprehensive postmarketing review of safety has been carried out. We conducted a systematic review of the safety of PCV7 and other pneumococcal conjugate vaccines. A total of 42 studies were included in the review. Reactogenicity data from some randomized trials suggest that PCV7 may result in more local reactions and fever than certain comparison vaccines. However, the reactions were mild and self-limited, and PCV7 did not carry an increased risk of severe injection-site reactions or high fever. Some, although not all, of the randomized trials in children found that mild local and systemic reactions associated with PCV7 may increase with the number of doses, at least over the three-dose primary series. In addition, PCV7 and other pneumococcal conjugate vaccines were found to have tolerable reactogenicity in Native American and African populations and in medically high-risk groups for which pneumococcal vaccination is recommended. Two of the largest studies of PCVs, one involving PCV7 and the other, PCV9, found a statistically significant increased risk of hospitalization for reactive airway disease, including asthma. Another large trial of PCV9, however, did not find an increased risk of asthma. In conclusion, this review of the evidence did not identify any major safety problems with PCV7 or any other pneumococcal conjugate vaccine, with the possible exception of reactive airway disease, which may bear further scrutiny as additional data become available.

Global safety of vaccines: strengthening systems for monitoring, management and the role of GACVS.

Vaccines have contributed enormously in reducing the impact of many infectious diseases, and the expanded use of new and existing vaccines provides unprecedented potential for further reducing the global burden of infectious diseases. Yet, as with the deployment of other technologies, their use may also sometimes be associated with undesirable effects that need to be identified rapidly, understood and minimized. In this article, we review the models and systems that have been developed to monitor and respond to concerns regarding vaccine safety and we give illustrative examples of real or perceived vaccine safety issues. The Global Advisory Committee on Vaccine Safety (GACVS) was set up 10 years ago and charged to provide the WHO with independent advice on vaccine safety issues. The role of the GACVS is both to analyze and to interpret reports of the adverse effects of vaccines that impact on global vaccination programs and strategies, and to foster the development of improved surveillance systems to detect any adverse effects of vaccines, particularly in low- and middle-income countries. It also monitors the development of new vaccines during clinical testing and advises on the safe use of vaccines in immunization programs. As success is achieved with reducing the burden of vaccine-preventable diseases, there will be increasing attention focused on potential adverse effects, on the development of effective surveillance systems to detect adverse effects, and on improved methods to manage and control any harmful consequences of vaccination.

Effective vaccine safety systems in all countries: A challenge for more equitable access to immunization

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.

Defining the safety profile of pandemic influenza vaccines

www.thelancet.com Vol 375 January 2, 2010 9 10 Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with infl uenza A2 and B viruses. J Hyg (Lond) 1972; 70: 767–77. 11 Stephenson I, Heath A, Major D, et al. Reproducibility of serologic assays for infl uenza virus A (H5N1). Emerg Infect Dis 2009; 15: 1252–29. 12 Nauta JJ, Beyer WE, Osterhaus AD. On the relationship between mean antibody level, seroprotection and clinical protection from infl uenza. Biologicals 2009; 37: 216–21. 13 Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 infl uenza virus. N Engl J Med 2009; 361: 1945–52. 14 Greenbaum JA, Kotturi MF, Kim Y, et al. Pre-existing immunity against swine-origin H1N1 infl uenza viruses in the general human population. Proc Natl Acad Sci USA 2009; published online Nov 14. DOI:10.1073/ pnas.0911580106. 15 The ANZIC Infl uenza Investigators. Critical care services and 2009 H1N1 infl uenza in Australia and New Zealand. N Engl J Med 2009; 361: 1925–34. 16 Kelly HA, Grant KA, Williams S, Fielding J, Smith D. Epidemiological characteristics of pandemic infl uenza H1N1 2009 and seasonal infl uenza infection. Med J Aust 2009; 191: 146–69.

Challenges of Maintaining Polio-free Status of the European Region

BACKGROUND The European region, certified as polio free in 2002, had recent wild poliovirus (WPV) introductions, resulting in a major outbreak in Central Asian countries and Russia in 2010 and in current widespread WPV type 1 circulation in Israel, which endangered the polio-free status of the region. METHODS We assessed the data on the major determinants of poliovirus transmission risk (population immunity, surveillance, and outbreak preparedness) and reviewed current threats and measures implemented in response to recent WPV introductions. RESULTS Despite high regional vaccination coverage and functioning surveillance, several countries in the region are at high or intermediate risk of poliovirus transmission. Coverage remains suboptimal in some countries, subnational geographic areas, and population groups, and surveillance (acute flaccid paralysis, enterovirus, and environmental) needs further strengthening. Supplementary immunization activities, which were instrumental in the rapid interruption of WPV1 circulation in 2010, should be implemented in high-risk countries to close population immunity gaps. National polio outbreak preparedness plans need strengthening. Immunization efforts to interrupt WPV transmission in Israel should continue. CONCLUSIONS The European region has successfully maintained its polio-free status since 2002, but numerous challenges remain. Staying polio free will require continued coordinated efforts, political commitment and financial support from all countries.

Vaccine safety and adverse events: lessons learnt

The challenge for those who work in the field of vaccination is to collectively gather and present sound scientific evidence of the benefits and risks of vaccination, to recognise, understand and minimize the risks, and to define current vaccination policies as well as the future direction of vaccination. Convincing evidence needs to be presented to health professions, regulatory agencies, governments, and to parents who must decide whether their children should be vaccinated or not, despite uncertainties. There have been several examples of recently identified serious adverse events being linked to vaccination, some of which were identified after licensure of the product, such as the occurrence of Bell’s Palsy following vaccination with a new inactivated intranasal influenza vaccine [1, 2] and that of intussusception with rotavirus vaccination [3]. Some other purported claims of vaccine safety issues, such as that of a causal relationship between measles, mumps and rubella (MMR) vaccination and autism or inflammatory bowel disease or concerns about an “overload” effect of multiple childhood vaccinations on the immune system, have not been supported by scientific evidence but have had a major impact on vaccine acceptance and invited non-compliance [4–7]. These unsubstantiated threats to immunization programmes have had greatest impact in industrialized countries, due in part to a higher media coverage of claims of vaccination risks (whether or not such claims are correct), to the fact that many such claims involve medical conditions more prevalent or better recognized in industrialized countries (such as multiple sclerosis and autism), and to a lesser acceptance of small risks. As concerns in industrialized countries spread in the media or in the scientific literature, it is anticipated that they will have increasing impact in non-industrialized countries as well, potentially undermining vaccination coverage. Often an impact already exists in non-industrialized countries, albeit poorly quantified. Vaccine safety and adverse events: lessons learnt