Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) - United States, October 2017-June 2018.

Recombinant zoster vaccine (RZV; Shingrix), an adjuvanted glycoprotein vaccine, was licensed by the Food and Drug Administration (FDA) and recommended by the Advisory Committee on Immunization Practices for adults aged ≥50 years in October 2017 (1). The previously licensed live-attenuated zoster vaccine (ZVL; Zostavax) is recommended for adults aged ≥60 years. RZV is administered intramuscularly as a 2-dose series, with an interval of 2-6 months between doses. In prelicensure clinical trials, 85% of 6,773 vaccinated study participants reported local or systemic reactions after receiving RZV, with approximately 17% experiencing a grade 3 reaction (erythema or induration >3.5 inches or systemic symptoms that interfere with normal activity). However, rates of serious adverse events (i.e., hospitalization, prolongation of existing hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death) were similar in the RZV and placebo groups (2). After licensure, CDC and FDA began safety monitoring of RZV in the Vaccine Adverse Event Reporting System (VAERS) (3). During the first 8 months of use, when approximately 3.2 million RZV doses were distributed (GlaxoSmithKline, personal communication, 2018), VAERS received a total of 4,381 reports of adverse events, 130 (3.0%) of which were classified as serious. Commonly reported signs and symptoms included pyrexia (fever) (1,034; 23.6%), injection site pain (985; 22.5%), and injection site erythema (880; 20.1%). No unexpected patterns were detected in reports of adverse events or serious adverse events. Findings from early monitoring of RZV are consistent with the safety profile observed in prelicensure clinical trials.

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, $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 $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.

Notes from the field: rotavirus vaccine administration errors--United States, 2006-2013.

Two live rotavirus oral vaccines, RotaTeq (RV5) (Merck & Co., Inc.) and Rotarix (RV1) (GlaxoSmithKline Biologicals), are approved for prevention of rotavirus gastroenteritis and recommended at ages 2, 4 (RV5/RV1), and 6 (RV5) months by the Advisory Committee on Immunization Practices. Because most childhood vaccines are injectable, vaccination providers might have less experience administering oral vaccines. To assess that hypothesis, CDC searched for reports to the Vaccine Adverse Event Reporting System (VAERS) of rotavirus vaccine administration errors involving injection and eye splashes in the United States during the period January 1, 2006-August 1, 2013. A total of 66 reports were found.

Notes from the field: reports of expired live attenuated influenza vaccine being administered--United States, 2007-2014.

Annual influenza vaccination is recommended for all persons aged ≥6 months. Two vaccine types are approved in the United States, injectable inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV), which is administered intranasally. Influenza vaccine typicaly becomes widely available beginning in late summer or early fall. IIV has a standard expiration date of June 30 for any given influenza season (July 1 through June 30 of the following year). In contrast, after release for distribution, LAIV generally has an 18-week shelf life (Christopher Ambrose, MedImmune, personal communication, 2014). Because of its relatively short shelf life, LAIV might be more likely than IIV to be administered after its expiration date. To assess that hypothesis, CDC analyzed reports to the Vaccine Adverse Event Reporting System (VAERS) of expired LAIV administered during July 1, 2007, through June 30, 2014.

Parental delay or refusal of vaccine doses, childhood vaccination coverage at 24 months of age, and the Health Belief Model.

OBJECTIVE: We evaluated the association between parents' beliefs about vaccines, their decision to delay or refuse vaccines for their children, and vaccination coverage of children at aged 24 months. METHODS: We used data from 11,206 parents of children aged 24-35 months at the time of the 2009 National Immunization Survey interview and determined their vaccination status at aged 24 months. Data included parents' reports of delay and/or refusal of vaccine doses, psychosocial factors suggested by the Health Belief Model, and provider-reported up-to-date vaccination status. RESULTS: In 2009, approximately 60.2% of parents with children aged 24-35 months neither delayed nor refused vaccines, 25.8% only delayed, 8.2% only refused, and 5.8% both delayed and refused vaccines. Compared with parents who neither delayed nor refused vaccines, parents who delayed and refused vaccines were significantly less likely to believe that vaccines are necessary to protect the health of children (70.1% vs. 96.2%), that their child might get a disease if they aren't vaccinated (71.0% vs. 90.0%), and that vaccines are safe (50.4% vs. 84.9%). Children of parents who delayed and refused also had significantly lower vaccination coverage for nine of the 10 recommended childhood vaccines including diphtheria-tetanus-acellular pertussis (65.3% vs. 85.2%), polio (76.9% vs. 93.8%), and measles-mumps-rubella (68.4% vs. 92.5%). After adjusting for sociodemographic differences, we found that parents who were less likely to agree that vaccines are necessary to protect the health of children, to believe that their child might get a disease if they aren't vaccinated, or to believe that vaccines are safe had significantly lower coverage for all 10 childhood vaccines. CONCLUSIONS: Parents who delayed and refused vaccine doses were more likely to have vaccine safety concerns and perceive fewer benefits associated with vaccines. Guidelines published by the American Academy of Pediatrics may assist providers in responding to parents who may delay or refuse vaccines.

Age inappropriate influenza vaccination in infants less than 6 months old, 2010-2018.

BACKGROUND: Annual influenza vaccination is recommended for persons 6 months or older and vaccination in infants less than 6 months old is a vaccine administration error. There are limited safety studies in this population, particularly among infants less than 6 weeks old. METHODS: We searched the U.S. Vaccine Adverse Event Reporting System (VAERS) database for reports of adverse events (AEs) following influenza vaccination in infants less than 6 months old for the 2010-2018 influenza seasons. We conducted a descriptive and qualitative analysis of reports to describe AEs and identify possible risk factors. RESULTS: In total, 114 reports were identified; only 21 reported a specific AE. Pyrexia, irritability, crying and diarrhea were the most common symptoms. There were 12 reports involving newborns; the most common circumstance cited was confusion with the birth dose of hepatitis B vaccine. The following risk factors were identified: (1) individuals getting vaccinated together resulting in patient mix-ups; (2) healthcare provider not verifying the patient's information; (3) individual provider confusion due to similarities in vaccines' packaging and names of vaccines that sound alike. CONCLUSIONS: Reports identified of influenza vaccination in infants less than 6 months old indicate that vaccination errors in this age group are occurring and healthcare providers who vaccinate infants should be aware of how to prevent such events. Our study adds to the existing literature by providing valuable information regarding the general absence of serious adverse events in the case of vaccination errors associated with inadvertent influenza vaccine within this population.

Shoulder Injury Related to Vaccine Administration (SIRVA): Petitioner claims to the National Vaccine Injury Compensation Program, 2010-2016.

BACKGROUND: Since 2010, petitioner claims of shoulder injury related to vaccine administration (SIRVA) to the National Vaccine Injury Compensation Program (VICP) have been increasing. OBJECTIVE: To conduct a scientific review of clinical characteristics of SIRVA petitions to the VICP. METHODS: We queried the VICP's Injury Compensation System database for medical reports of alleged SIRVA and SIRVA-like injuries. Medical reports are summaries of petitioner claims and supporting documentation along with a VICP clinician reviewer diagnosis and assessment of criteria for concession. We conducted a descriptive analysis of SIRVA petitioner claims recommended by the VICP for concession as SIRVA injuries. RESULTS: We identified 476 petitioner claims recommended for concession. Claims per year increased from two in 2011, the first full year in the analytic period, to 227 in 2016. Median age was 51 years, 82.8% were women, and median body mass index was 25.1 (range 17.0-48.9). Four hundred cases (84.0%) involved influenza vaccine. Pharmacy or store (n = 168; 35.3%) was the most common place of vaccination followed by doctor's office (n = 147; 30.9%). Fewer than half of cases reported a suspected administration error; 172 (36.1%) reported 'injection too high' on the arm. Shoulder pain, rotator cuff problems, and bursitis were common initial diagnoses. Most (80.0%) cases received physical or occupational therapy, 60.1% had at least one steroid injection, and 32.6% had surgery. Most (71.9%) healthcare providers who gave opinions on causality considered the injury was caused by vaccination. A minority (24.3%) of cases indicated that symptoms had resolved by the last visit available in medical records. CONCLUSIONS: Most conceded claims for SIRVA were in women and involved influenza vaccines. Injection too high on the arm could be a factor due to the risk of injecting into underlying non-muscular tissues. Healthcare providers should be aware of proper injection technique and anatomical landmarks when administering vaccines.

Reports of atypical shoulder pain and dysfunction following inactivated influenza vaccine, Vaccine Adverse Event Reporting System (VAERS), 2010-2017.

BACKGROUND: Vaccines administered into or too close to underlying joint structures have the potential to cause shoulder injuries. Limited data exist on the epidemiology of such events. OBJECTIVE: To describe case reports of atypical shoulder pain and dysfunction following injection of inactivated influenza vaccine (IIV). METHODS: We searched the Vaccine Adverse Event Reporting System (VAERS) database from July 2010 to June 2017 for reports of atypical shoulder pain and dysfunction following IIV. When identifying reports, we made no assumptions about true incident injury or causality with respect to vaccination. Pain had to begin <48 h after vaccination and signs and symptoms had to continue for >7 days to differentiate from self-limited local reactions. We conducted descriptive analysis. RESULTS: We identified 1220 reports that met our case definition (2.0% of all IIV reports, range 1.5%-2.5% across influenza seasons). Median age was 52 years (range 16-94) and most patients (82.6%) were female. Shoulder pain (44.1%), injected limb mobility decreased (40.8%), joint range of motion decreased (21.2%), rotator cuff syndrome (9.2%), and bursitis (9.0%) were frequently reported. In 86.6% of reports, signs and symptoms had not resolved by the time of report submission. In reports that included descriptions suggesting contributing factors (n = 266), vaccination given "too high" on the arm was cited in 81.2%. Nearly half (n = 605, 49.6%) of reports described a healthcare provider evaluation. Treatments included non-narcotic analgesics, physical therapy, and corticosteroid injection. Vaccinations were most commonly administered in a pharmacy or retail store (41.0%) or doctor's office or hospital (31.6%). CONCLUSIONS: Reports of atypical shoulder pain and dysfunction following IIV were uncommon, considering the amount of IIV use, and stable across influenza seasons. While specific etiology of cases is unknown, improperly administered vaccine, which is preventable, might be a factor. Prevention strategies include education, training, and adherence to best practices for vaccine administration.

Is there any harm in administering extra-doses of vaccine to a person? Excess doses of vaccine reported to the Vaccine Adverse Event Reporting System (VAERS), 2007-2017.

BACKGROUND: The administration of an extra dose of a vaccine may occur due to a programmatic error (e.g., vaccination error) when there is need to provide one of the antigens of a combination vaccine not readily available as a single antigen, or when there is need to provide immunization in a person with uncertain vaccination histories (e.g., refugees). There is little data available on the safety of an extra dose of vaccine. OBJECTIVE: To assess for the presence of adverse events (AEs) most commonly reported following the administration of excess doses of vaccine in the Vaccine Adverse Event Reporting System (VAERS). METHODS: We searched VAERS for US reports where an excess dose of vaccine was administered to a person received from 1/1/2007 through 1/26/2018. We reviewed medical records for all serious reports and a random sample of non-serious reports. The most common AEs among reports of excess dose of vaccine administered were compared with the corresponding AEs for all vaccines reported to VAERS during the same period. RESULTS: Out of 366,815 total VAERS reports received, 5067 (1.4%) reported an excess dose of vaccine was administered; 3898 (76.9%) did not describe an adverse health event (AHE). The most common vaccines reported were trivalent inactivated influenza (15.4%), varicella (13.9%), hepatitis A (11.4%), and measles, mumps, rubella, varicella (11.1%). Among reports where only AHEs were reported, the most common were pyrexia (12.8%), injection site erythema (9.7%), injection site pain (8.9%), and headache (6.6%). The percentage of AHEs among these reports was comparable to all reports submitted to VAERS during the same study period. CONCLUSION: More than three-fourths of reports of an excess dose of vaccine did not describe an AHE. Among reports where an AHE event was reported, we did not observe any unexpected conditions or clustering of AEs.

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.

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

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.

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.

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

INTRODUCTION: The Vaccine Adverse Event Reporting System (VAERS) is the spontaneous (passive) reporting system CDC and FDA use to monitor vaccine safety. We used cognitive testing to evaluate proposed revisions to the current VAERS form. METHODS: We conducted in-person cognitive interviews with 22 volunteers to evaluate proposed revisions in a prototype VAERS 2.0 form (new VAERS form). We analyzed data using thematic analysis. RESULTS: Repeating themes included preferences for: brevity, simplicity and clarity; features to minimize time requirements and facilitate ease of completion; logical ordering of questions by topic and importance; and visual cues like color-coded highlighting. Interviews identified instances of discordance between the intended meaning questions (from the perspective of CDC and FDA) and interpretation by volunteers. CONCLUSIONS: Cognitive testing yielded useful information to guide further revisions of the VAERS form. Cognitive testing can be an effective tool for public health programs interested in developing surveys and reporting forms.

Immunization attitudes and beliefs among parents: beyond a dichotomous perspective.

OBJECTIVE: To better understand differences among parents in their attitudes, beliefs, and behaviors regarding childhood immunizations and health-related issues. METHODS: Forty-four survey variables assessing attitudes and beliefs about immunizations and health were analyzed. The K-means clusters technique was used to identify homogeneous groups of parents based upon their responses to the questions. RESULTS: Five clusters were identified: Immunization Advocates (33.0%), Go Along to Get Alongs (26.4%), Health Advocates (24.8%), Fencesitters (13.2%), and Worrieds (2.6%). CONCLUSIONS: Although only a small percentage of parents are seriously concerned, other parents who are generally supportive of immunizations for their child are also affected by immunization safety issues.

Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS) United States, 2000-2013.

IMPORTANCE: Vaccination errors are preventable events. Errors can have impacts including inadequate immunological protection, possible injury, cost, inconvenience, and reduced confidence in the healthcare delivery system. OBJECTIVES: To describe vaccination error reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and identify opportunities for prevention. METHODS: We conducted descriptive analyses using data from VAERS, the U.S. spontaneous surveillance system for adverse events following immunization. The VAERS database was searched from 2000 through 2013 for U.S. reports describing vaccination errors and reports were categorized into 11 error groups. We analyzed numbers and types of vaccination error reports, vaccines involved, reporting trends over time, and descriptions of errors for selected reports. RESULTS: We identified 20,585 vaccination error reports documenting 21,843 errors. Annual reports increased from 10 in 2000 to 4324 in 2013. The most common error group was "Inappropriate Schedule" (5947; 27%); human papillomavirus (quadrivalent) (1516) and rotavirus (880) vaccines were most frequently involved. "Storage and Dispensing" errors (4983; 23%) included mostly expired vaccine administered (2746) and incorrect storage of vaccine (2202). "Wrong Vaccine Administered" errors (3372; 15%) included mix-ups between vaccines with similar antigens such as varicella/herpes zoster (shingles), DTaP/Tdap, and pneumococcal conjugate/polysaccharide. For error reports with an adverse health event (5204; 25% of total), 92% were classified as non-serious. We also identified 936 vaccination error clusters (i.e., same error, multiple patients, in a common setting) involving over 6141 patients. The most common error in clusters was incorrect storage of vaccine (582 clusters and more than 1715 patients). CONCLUSIONS: Vaccination error reports to VAERS have increased substantially. Contributing factors might include changes in reporting practices, increasing complexity of the immunization schedule, availability of products with similar sounding names or acronyms, and increased attention to storage and temperature lapses. Prevention strategies should be considered.

Parental vaccine safety concerns. The experiences of pediatricians and family physicians.

OBJECTIVES: Recently several concerns regarding vaccine safety have received significant media attention. Primary care physicians are the most common interface for parents with the immunization delivery system and are likely to have the greatest opportunity for exposure and experience with parental vaccine safety concerns. METHODS: Mail survey study of a national random sample of 750 pediatricians (PDs) and 750 family physicians (FPs) was conducted in 2000. Outcome variables of primary interest included the number of parental vaccine refusals in the past year, frequency of specific parent vaccine safety concerns, and actions taken by physicians when parents refused a vaccine. Chi-square analysis was used to determine the significance of the association of each outcome variable of interest with physician specialty, frequency of vaccine refusal, and the demographic variables. Multivariate analysis explored the potential for independent predictors of physicians who experienced increases in vaccine refusal. RESULTS: The response rate was 70%. Overall, 93% of PDs and 60% of FPs reported at least one parental vaccine refusal in their practice in the past year. PDs also were more likely than FPs to report an increase in the number of vaccine refusals over the past year (18% v 8%, p =0.01), while FPs were more likely to report a decrease in vaccine refusals over the same time period (18% v 11%; p <0.5). PDs were more likely than FPs to provide additional information regarding vaccines to parents who refused vaccines and/or to discuss the issue at later visits. The most common concerns of parents were related to short-term reactions and pain from multiple injections. CONCLUSIONS: While almost all PDs and most FPs experienced at least one vaccine refusal from parents in the past year, far fewer physicians of both specialties observed an increase in their occurrence. Physicians must work to be consistently well informed of both the benefits of immunization as well as the issues of parental concern regarding vaccine safety.