Beth Hibbs

Vaccine safety: current and future challenges.

Immunizations are responsible for preventing death and disability from disease and are among the most cost-effective and widely used public health interventions. However, it is also recognized that no vaccine is perfectly safe or effective. Some people will experience side effects from vaccines, and a few may not experience a complete immunologic response to a vaccine, leaving them susceptible to disease. Sustaining high vaccine coverage rates may become more of a challenge as people question the limitations of vaccines and new parents no longer see or hear about the diseases from which vaccines protect them. In the future, maintaining public support for immunizations will be critical for preventing outbreaks of vaccine preventable diseases. In this chapter, we will focus on the importance of vaccine safety research; current gaps and limitations in knowledge in the field of vaccine safety; how vaccine safety is monitored; the vaccine injury compensation program; vaccine risk communication, and helpful resources for specific questions about vaccine safety.

Challenges and controversies in immunization safety.

No vaccine is perfectly safe or effective. As diseases such as diphtheria and polio fade, vaccine safety concerns, especially alleged links between vaccinations and several chronic illnesses, have become increasingly prominent in the media and to the public. This article reviews the current scientific evidence on several recent vaccine safety controversies. It also provides information on how various safety research is conducted, some of the concurrent challenges, and finally, some guidance on communicating with patients on vaccine risks.

Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January-October 2003

Myocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians.

National Immunization Information Hotline: Calls concerning adverse events, 1998-2000.

Data from the National Immunization Information Hotline(NIIH)concerning vaccine adverse event inquiries were analyzed from 1998 to 2000(totaln = 23,841[publicn = 14,330; health care professionalsn = 9,511]). Approximately 20%of calls from the public from 1998 to 2000 concerned vaccine adverse events. These calls increased 199.5%from 1998(n = 422)to 1999(n = 1,264), then declined 12.4%from 1999 to 2000(n = 1,107). A Lexus Nexus search showed that the number of news stories mentioning vaccine safety showed a similar pattern. Women were more likely to call the NIIH concerning vaccine adverse events than men, and persons 40–59 years old and persons 60 years old and over were less likely to call about vaccine adverse events than those 20–39 years. The parallel trends in news stories mentioning vaccine safety and calls to the NIIH concerning adverse events suggests that news stories may stimulate questions about vaccine safety. Understanding that news stories may elicit questions about vaccine adverse events and examining the characteristics of persons who ask vaccine adverse event questions may guide future informational interventions toward those most in need.

The National Immunization Information Hotline

The National Immunization Information Hotline (NIIH) has been providing information regarding immunizations to the public and to health care professionals since March 1997. We describe the operations of the NIIH, its experience over the first two and a half years of operation and lessons learned for other immunization hotlines. From 1998–2000, the hotline answered 246,859 calls. Calls concerning immunization information requests totaled 175,367; data about the calls were collected from 35,102. Approximately a third of the 35,102 calls were from health care providers. Of the remaining calls from the public, the greatest number of calls concerned childhood immunizations. Immunization schedule queries from the public increased 323.0% from 1998 to 2000. While the major goal of the NIIH is to provide accurate and reliable information to the public and to health care providers, data from the hotline can be used to monitor changes over time in calls concerning inquires about the immunization schedule in addition to other variables of interest.

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005–2015

INTRODUCTION Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. METHODS We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. RESULTS VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) in persons >18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1 month, were nervous system disorders (15) among children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. CONCLUSIONS Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations.

Frequency and Cost of Vaccinations Administered Outside Minimum and Maximum Recommended Ages—2014 Data From 6 Sentinel Sites of Immunization Information Systems

Objective To quantify vaccinations administered outside minimum and maximum recommended ages and to determine attendant costs of revaccination by analyzing immunization information system (IIS) records. Study design We analyzed deidentified records of doses administered during 2014 to persons aged <18 years within 6 IIS sentinel sites (10% of the US population). We quantified doses administered outside of recommended ages according to the Advisory Committee on Immunization Practices childhood immunization schedule and prescribing information in package inserts, and calculated revaccination costs. To minimize misreporting bias, we analyzed publicly funded doses for which reported lot numbers and vaccine types were consistent. Results Among 3 394 047 doses with maximum age recommendations, 9755 (0.3%) were given after the maximum age. One type of maximum age violation required revaccination: 1344 (0.7%) of 194 934 doses of the 0.25‐mL prefilled syringe formulation of quadrivalent inactivated influenza vaccine (Fluzone Quadrivalent, Sanofi Pasteur, Swiftwater, PA) were administered at age ≥36 months (revaccination cost,

Safety of vaccines that have been kept outside of recommended temperatures: Reports to the Vaccine Adverse Event Reporting System (VAERS), 2008–2012

111 964). We identified a total of 7 529 165 childhood, adolescent, and lifespan doses with minimum age recommendations, 9542 of which (0.1%) were administered before the minimum age. The most common among these violations were quadrivalent injectable influenza vaccines (3835, or 0.7% of 526 110 doses administered before age 36 months) and Kinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium; DTaP‐IPV) (2509, or 1.2% of 208 218 doses administered before age 48 months). The cost of revaccination for minimum age violations (where recommended) was

Cognitive testing to evaluate revisions to the Vaccine Adverse Event Reporting System (VAERS) reporting form

179 179. Conclusion Administration of vaccines outside recommended minimum and maximum ages is rare, reflecting a general adherence to recommendations. Error rates were higher for several vaccines, some requiring revaccination. Vaccine schedule complexity and confusion among similar products might contribute to errors. Minimization of errors reduces wastage, excess cost, and inconvenience for parents and patients.

Vaccine Safety Resources for Nurses.

BACKGROUND Vaccines should be stored and handled according to manufacturer specifications. Inadequate cold chain management can affect potency; but, limited data exist on adverse events (AE) following administration of vaccines kept outside of recommended temperatures. OBJECTIVE To describe reports to the Vaccine Adverse Event Reporting System (VAERS) involving vaccines inappropriately stored outside of recommended temperatures and/or exposed to temperatures outside of manufacturer specifications for inappropriate amounts of time. METHODS We searched the VAERS database (analytic period 2008-2012) for reports describing vaccines kept outside of recommended temperatures. We analyzed reports by vaccine type, length outside of recommended temperature and type of temperature excursion, AE following receipt of potentially compromised vaccine, and reasons for cold chain breakdown. RESULTS We identified 476 reports of vaccines kept outside of recommended temperatures; 77% described cluster incidents involving multiple patients. The most commonly reported vaccines were quadrivalent human papillomavirus (n = 146, 30%), 23-valent pneumococcal polysaccharide (n = 51, 11%), and measles, mumps, and rubella (n = 45, 9%). Length of time vaccines were kept outside of recommended temperatures ranged from 15 mins to 6 months (median 51 h). Most (n = 458, 96%) reports involved patients who were administered potentially compromised vaccines; AE were reported in 32 (7%), with local reactions (n = 21) most frequent. Two reports described multiple patients contracting diseases they were vaccinated against, indicating possible influenza vaccine failure. Lack of vigilance, inadequate training, and equipment failure were reasons cited for cold chain management breakdowns. CONCLUSIONS Our review does not indicate any substantial direct health risk from administration of vaccines kept outside of recommended temperatures. However, there are potential costs and risks, including vaccine wastage, possible decreased protection, and patient and parent inconvenience related to revaccination. Maintaining high vigilance, proper staff training, regular equipment maintenance, and having adequate auxiliary power are important components of comprehensive vaccine cold chain management.