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.

Advisory committee on immunization practices recommended immunization schedules for persons aged 0 through 18 years--United States, 2015.

Each year, the Advisory Committee on Immunization Practices (ACIP) reviews the recommended immunization schedules for persons aged 0 through 18 years to ensure that the schedules reflect current recommendations for Food and Drug Administration-licensed vaccines. In October 2014, ACIP approved the recommended immunization schedules for persons aged 0 through 18 years for 2015, which include several changes from the 2014 immunization schedules. For 2015, the figures, footnotes, and tables are being published on the CDC immunization schedule website (http://www.cdc.gov/vaccines/schedules/index.html). This provides readers electronic access to the most current version of the schedules and footnotes on the CDC website. Health care providers are advised to use figures, tables, and the combined footnotes together. Printable versions of the 2015 immunization schedules for persons aged 0 through 18 years also are available at the website in several formats, including portrait, landscape, and pocket-sized versions. Ordering instructions for laminated versions and "parent-friendly" schedules also are available at the immunization schedule website.

Vaccination policies among health professional schools: evidence of immunity and allowance of vaccination exemptions.

OBJECTIVE To characterize health professional schools by their vaccination policies for acceptable forms of evidence of immunity and exemptions permitted. METHODS Data were collected between September 2011 and April 2012 using an Internet-based survey e-mailed to selected types of accredited health professional programs. Schools were identified through accrediting associations for each type of health professional program. Analysis was limited to schools requiring ≥1 vaccine recommended by the Advisory Committee on Immunization Practices (ACIP): measles, mumps, rubella, hepatitis B, varicella, pertussis, and influenza. Weighted bivariate frequencies were generated using SAS 9.3. RESULTS Of 2,775 schools surveyed, 75% (n=2,077) responded; of responding schools, 93% (1947) required ≥1 ACIP-recommended vaccination. The proportion of schools accepting ≥1 non-ACIP-recommended form of evidence of immunity varied by vaccine: 42% for pertussis, 37% for influenza, 30% for rubella, 22% for hepatitis B, 18% for varicella, and 9% for measles and mumps. Among schools with ≥1 vaccination requirement, medical exemptions were permitted for ≥1 vaccine by 75% of schools; 54% permitted religious exemptions; 35% permitted personal belief exemptions; 58% permitted any nonmedical exemption. CONCLUSIONS Many schools accept non-ACIP-recommended forms of evidence of immunity which could lead some students to believe they are protected from vaccine preventable diseases when they may be susceptible. Additional efforts are needed to better educate school officials about current ACIP recommendations for acceptable forms of evidence of immunity so school policies can be revised as needed.

Influenza vaccination performance measurement among acute care hospital-based health care personnel--United States, 2013-14 influenza season.

Annual influenza vaccination is recommended for all health care personnel (HCP). In August 2011, the Centers for Medicare and Medicaid Services (CMS) published a final rule requiring acute care hospitals that participate in its Hospital Inpatient Quality Reporting Program to report HCP influenza vaccination data through the National Healthcare Safety Network (NHSN) beginning January 1, 2013. Data reported by 4,254 acute care hospitals, covering the period October 1, 2013, through March 31, 2014, were analyzed to collect estimates of the proportion of HCP vaccinated nationally and by state for three groups: (1) employees, (2) licensed independent practitioners (LIPs), and (3) adult students/trainees and volunteers. Overall in the United States, 81.8% of hospital-based HCP were reported vaccinated, with the highest proportion (86.1%) among employees and the lowest (61.9%) among LIPs. The proportion reported vaccinated varied widely by state, with ranges of 69.0%-97.6% for employees, 33.8%-93.6% for LIPs, and 50.3%-96.3% for adult students/trainees and volunteers. Public reporting of vaccination data has been shown to increase HCP influenza vaccination coverage. These new NHSN data provide a baseline for measuring changes in future hospital-based reporting of HCP influenza vaccination.

Student vaccination requirements of U.S. health professional schools: a national survey.

UNLABELLED: To help protect healthcare personnel (HCP) from infection and to prevent possible disease transmission to their patients, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination of all HCP, including students. We sought to gather information on the vaccination policies of U.S. health professional (i.e., non-physician HCP) programs and to compare those requirements to current ACIP recommendations. METHODS: A self-administered, internet-based survey sent to 2,779 U.S. health professional programs was used to collect data on program demographics; student vaccination requirements; deadlines for adherence, consequences for non-adherence, and permitted exemptions to these requirements; and factors influencing the program's vaccination policy. RESULT: The response rate was 75%. Among 2,077 responding programs, 19% required all ACIP-recommended vaccines for HCP--87% required measles, mumps, and rubella; 84% required hepatitis B; 75% required varicella; 48% required tetanus, diphtheria, and acellular pertussis (Tdap); and 32% required influenza. Programs reviewing requirements at least annually and those that reported the ACIP influenced requirements were significantly more likely to require varicella, Tdap, and influenza vaccine. During the 2009-2010 influenza season, only 59% of programs offered influenza vaccine to students. CONCLUSION: Health professional schools should update their vaccination requirements annually to be consistent with ACIP recommendations.

Pandemic influenza planning, United States, 1978-2008.

During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community's response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.

Adult immunization policies in advanced economies: vaccination recommendations, financing, and vaccination coverage.

OBJECTIVES: While many countries have robust child immunization programs and high child vaccination coverage, vaccination of adults has received less attention. The objective of this study was to describe the adult vaccination policies in developed countries. METHODS: From 2010 to 2011, we conducted a survey of 33 advanced economies as defined by the International Monetary Fund. The survey asked about national recommendations for adults for 16 vaccines or vaccine components, funding mechanisms for recommended adult vaccines, and the availability of adult vaccination coverage estimates. RESULTS: Thirty-one of 33 (93.9 %) advanced economies responded to the survey. Twelve of 31 (38.7 %) reported having a comprehensive adult immunization schedule. The total number of vaccines or vaccine components recommended for adults ranged from one to 15 with a median of 10. Seasonal influenza (n = 30), tetanus (n = 28), pneumococcal polysaccharide (n = 27), and hepatitis B (n = 27) were the most frequently recommended vaccines or components. CONCLUSIONS: Approximately two-thirds of survey respondents do not have a comprehensive adult vaccine schedule, and most do not measure vaccination coverage. We found that a funding mechanism is available for most recommended adult vaccines.

Variation in adult vaccination policies across Europe: an overview from VENICE network on vaccine recommendations, funding and coverage.

BACKGROUND: In 2010-2011, in the framework of the VENICE project, we surveyed European Union (EU) and Economic Area (EEA) countries to fill the gap of information regarding vaccination policies in adults. This project was carried out in collaboration with the United States National Vaccine Program Office, who conducted a similar survey in all developed countries. METHODS: VENICE representatives of all 29 EU/EEA-countries received an online questionnaire including vaccination schedule, recommendations, funding and coverage in adults for 17 vaccine-preventable diseases. RESULTS: The response rate was 100%. The definition of age threshold for adulthood for the purpose of vaccination ranged from 15 to 19 years (median=18 years). EU/EEA-countries recommend between 4 and 16 vaccines for adults (median=11 vaccines). Tetanus and diphtheria vaccines are recommended to all adults in 22 and 21 countries respectively. The other vaccines are mostly recommended to specific risk groups; recommendations for seasonal influenza and hepatitis B exist in all surveyed countries. Six countries have a comprehensive summary document or schedule describing all vaccines which are recommended for adults. None of the surveyed countries was able to provide coverage estimates for all the recommended adult vaccines. CONCLUSIONS: Vaccination policies for adults are not consistent across Europe, including the meaning of "recommended vaccine" which is not comparable among countries. Coverage data for adults should be collected routinely like for children vaccination.

Student vaccination requirements of U.S. health professional schools: a survey.

BACKGROUND: Unvaccinated health care personnel are at increased risk for transmitting vaccine-preventable diseases to their patients. The Advisory Committee on Immunization Practices (ACIP) recommends that health care personnel, including students, receive measles, mumps, rubella, hepatitis B, varicella, influenza, and pertussis vaccines. Prematriculation vaccination requirements of health professional schools represent an early opportunity to ensure that health care personnel receive recommended vaccines. OBJECTIVE: To examine prematriculation vaccination requirements and related policies at selected health professional schools in the United States and compare requirements with current ACIP recommendations. DESIGN: Cross-sectional study using an Internet-based survey. SETTING: Medical and baccalaureate nursing schools in the United States and its territories. PARTICIPANTS: Deans of accredited medical schools granting MD (n = 130) and DO (n = 26) degrees and of baccalaureate nursing programs (n = 603). MEASUREMENTS: Proportion of MD-granting and DO-granting schools and baccalaureate nursing programs that require that entering students receive vaccines recommended by the ACIP for health care personnel. RESULTS: 563 schools (75%) responded. More than 90% of all school types required measles, mumps, rubella, and hepatitis B vaccines for entering students; varicella vaccination also was commonly required. Tetanus, diphtheria, and acellular pertussis vaccination was required by 66%, 70%, and 75% of nursing, MD-granting, and DO-granting schools, respectively. Nursing and DO-granting schools (31% and 45%, respectively) were less likely than MD-granting schools (78%) to offer students influenza vaccines free of charge. LIMITATIONS: Estimates were conservative, because schools that reported that they did not require proof of immunity for a given vaccine were considered not to require that vaccine. Estimates also were restricted to schools that train physicians and nurses. CONCLUSION: The majority of schools now require most ACIP-recommended vaccines for students. Medical and nursing schools should adopt policies on student vaccination and serologic testing that conform to ACIP recommendations and should encourage annual influenza vaccination by offering influenza vaccination to students at no cost. PRIMARY FUNDING SOURCE: None.

Should health-care providers in the United States have access to influenza vaccines formulated for the southern hemisphere?

BACKGROUND: Influenza is the most common vaccine-preventable disease in travelers. It circulates year-round in the tropics, November to March in the northern hemisphere (NH), and April to October in the southern hemisphere (SH). In 2005, approximately 8.5 million US adults aged 18 years and older traveled to the Caribbean. A similar number traveled to the tropics and the SH. SH formulation of influenza vaccine is not available in the United States. We surveyed International Society of Travel Medicine (ISTM) members to ask if they would use SH influenza vaccine if available. METHODS: We electronically mailed a survey in December 2006 to 1,251 ISTM members in the United States. We asked if respondents would use SH vaccine for patients traveling to the SH or tropics, how many such patients per week they see, and their practice location. RESULTS: We received 157 responses for a response rate of 12.5%. Of these, 129 (82%) stated that they would be interested in having SH influenza vaccine available. Of those indicating interest, 73 (60%) reported seeing >10 patients traveling to the SH or tropics each week. Respondents reported practice settings in 34 states and the District of Columbia. Respondents requested more information about the likely cost of SH influenza vaccine, ordering conditions, vaccine use guidelines, comparability with NH vaccine, and approval of SH vaccine by the Food and Drug Administration. CONCLUSIONS: Many travelers to the SH are at risk for influenza infection. Although only a limited number of ISTM members responded, respondents indicated considerable interest in availability of SH influenza vaccine for their patients. More data from travel medicine and other practitioners are needed on this topic. Inquiries are being made of influenza vaccine manufacturers about licensing SH influenza vaccines in the United States. Adding SH influenza vaccine to the vaccines available to NH clinicians could help mitigate the morbidity of influenza in travelers.

US Civilian Smallpox Preparedness and Response Program, 2003.

Variola virus, the cause of smallpox disease, has been deemed a possible bioterrorism agent. Since November 2001, federal, state, and local public health partners implemented activities to prepare for a possible smallpox outbreak. The Centers for Disease Control and Prevention (CDC) produced and delivered training and educational materials for smallpox preparedness in many formats, developed detailed smallpox vaccine information statements about vaccine contraindications and vaccination site care, and established mechanisms to monitor and respond to adverse events after smallpox vaccination. The last included enhancements to the Vaccine Adverse Event Reporting System, a pregnancy registry for inadvertently vaccinated pregnant women, and a Clinician Telephone Information Line to collect reports about adverse events. The civilian responder vaccination program was conducted with rigorous safety procedures, and few historically recognized adverse events were observed. However, myocarditis and/or pericarditis was newly recognized as an adverse event caused by the New York City Board of Health vaccinia vaccine strain. This smallpox preparedness program put into place a number of measures to advance the United States' readiness for a smallpox outbreak that have assisted in preparedness for other threats.

Immunization information systems: National Vaccine Advisory Committee progress report, 2007.

This article summarizes principal findings and recommendations of the National Vaccine Advisory Committee 2007 Progress report on Immunization Information Systems (IIS). Considerable progress has been made in each of the four primary objectives of the IIS: ensure appropriate protections of privacy and confidentiality for individuals and security for information included in the registry; ensure participation of all immunization providers and recipients; ensure appropriate functioning of registries; and ensure sustainable funding for registries. In addition, IIS use has been extended to deal with adolescent/adult immunization, preparedness, vaccine shortages, health information exchanges, and electronic medical records. Notwithstanding the progress, several factors impede smooth achievement of the 2010 goal. The three most critical are difficulties in exchanging information among different information systems, difficulties in exchanging information across state lines, and ensuring sustainable funding for registries. The committee has made a number of recommendations to address these issues.

Influenza vaccine supply, 2005-2006: did we come up short?

BACKGROUND: Although total influenza vaccine doses available in the 2005/2006 influenza season were over 80 million, CDC received many reports of delayed and diminished vaccine shipments in October to November of 2005. To better understand the supply problems, CDC and partners surveyed several health care professional groups. METHODS: Surveys were sent to representative samples of influenza vaccine providers including pediatricians, internists, federally qualified health centers, visiting nurse organizations, and all 64 state and other health departments receiving federal immunization funds directly. In November and December, 2005, providers were asked questions about their experience in ordering influenza vaccine, sources where orders were placed, proportion of orders received, and referral of patients to other vaccination sites. RESULTS: The number of providers surveyed (median: 154; range: 64-308) and response rates (median: 62%; range: 51%-77%) varied among groups. Less than half of the providers in most groups placed a single order that was accepted (median: 31%; range: 8%-53%), and most placed multiple orders. Only 57% of federally qualified health centers and 60% of internists reported they received at least 40% of their orders by the middle of December; the other provider groups received a greater proportion of their orders. Most internists (80%) and federally qualified health centers (54%) reported that they had referred priority group patients to other locations to receive the influenza vaccine due to inadequate supplies. Vaccine providers who ordered only from Chiron received a lower proportion of their orders than providers that ordered from another source or ordered from multiple sources. CONCLUSION: Most of the providers surveyed received only part of their orders by the middle of December. Disruptions in receipt of influenza vaccine during the fall of 2005 were due primarily to shortfalls in vaccine from Chiron and also due to delays and partial shipments from other distributors.

Universal influenza vaccination in the United States: are we ready? Report of a meeting.

Universal influenza vaccination has been proposed as one strategy to improve vaccination coverage and disease prevention. In October 2005, influenza and vaccination experts, public health practitioners, representatives from medical professional societies, influenza vaccine manufacturers, and managed care organizations met to assess whether current data were sufficient to support an expansion of universal influenza vaccination and to define information gaps and potential barriers to implementation. Presenters at the meeting documented the substantial burden of influenza disease among all age groups, the major role of children in transmission, and the effectiveness of vaccine, especially in healthy children and adults. Observational studies and a mathematical model suggested that indirect protection, or "herd immunity," resulting from vaccination of school-age children would substantially reduce the incidence of disease in other age groups. Economic analyses generally showed that vaccination of healthy children and adults is cost-effective and is sensitive to vaccine cost, population group, and season. Influenza vaccination received annually over several years is safe and effective, but data on long-term use are limited. Challenges to expanded recommendations include maintenance of the vaccine supply, implementation of a feasible and effective strategy for vaccine delivery, the burden on the public health infrastructure, public acceptability, and financing. Overall, meeting attendees favored incremental expansion of recommendations, potentially toward universal influenza vaccination. They preferred to expand recommendations among children first, because children have a higher risk of illness, compared with healthy adults; because there is greater feasibility of implementation of the recommendations among children; and because of the potential for herd immunity decreasing morbidity and mortality among adults.

Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).

This report updates the 2005 recommendations by the Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine and antiviral agents (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54[No. RR-8]:1--44). The 2006 recommendations include new and updated information. Principal changes include 1) recommending vaccination of children aged 24-59 months and their household contacts and out-of-home caregivers against influenza; 2) highlighting the importance of administering 2 doses of influenza vaccine for children aged 6 months--<9 years who were previously unvaccinated; 3) advising health-care providers, those planning organized campaigns, and state and local public health agencies to a) develop plans for expanding outreach and infrastructure to vaccinate more persons than the previous year and b) develop contingency plans for the timing and prioritization of administering influenza vaccine, if the supply of vaccine is delayed and/or reduced; 4) reminding providers that they should routinely offer influenza vaccine to patients throughout the influenza season; 5) recommending that neither amantadine nor rimantadine be used for the treatment or chemoprophylaxis of influenza A in the United States until evidence of susceptibility to these antiviral medications has been re-established among circulating influenza A viruses; and 6) using the 2006-07 trivalent influenza vaccine virus strains: A/New Caledonia/20/1999 (H1N1)-like, A/Wisconsin/67/2005 (H3N2)-like, and B/Malaysia/2506/2004-like antigens. For the A/Wisconsin/67/2005 (H3N2)-like antigen, manufacturers may use the antigenically equivalent A/Hiroshima/52/2005 virus; for the B/Malaysia/2506/2004-like antigen, manufacturers may use the antigenically equivalent B/Ohio/1/2005 virus. A link to this report and other information can be accessed at http://www.cdc.gov/flu.

Influenza vaccination of healthcare workers in the United States, 1989-2002.

OBJECTIVES: We sought to estimate influenza vaccination coverage among healthcare workers (HCWs) in the United States during 1989-2002 and to identify factors associated with vaccination in this group. The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for HCWs to reduce transmission of influenza to patients at high risk for serious complications of influenza. DESIGN: Analysis of cross-sectional data from 1989-2002 surveys conducted by the National Health Interview Survey (NHIS). The outcome measure was self-reported influenza vaccination in the past 12 months. Bivariate and multivariate analysis of 2002 NHIS data. SETTING: Household interviews conducted during 1989-2002, weighted to reflect the noninstitutionalized, civilian US population. PARTICIPANTS: Adults aged 18 years or older participated in the study. A total of 2,089 were employed in healthcare occupations or settings in 2002, and 17,160 were employed in nonhealthcare occupations or settings. RESULTS: The influenza vaccination rate among US HCWs increased from 10.0% in 1989 to 38.4% in 2002, with no significant change since 1997. In a multivariate model that included data from the 2002 NHIS, factors associated with a higher rate of influenza vaccination among HCWs aged 18-64 years included age of 50 years or older (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.1), hospital employee status (OR, 1.5; 95% CI, 1.2-1.9), 1 or more visits to the office of a healthcare professional in the past 12 months (OR, 1.5; 95% CI, 1.1-2.2), receipt of employer-provided health insurance (OR, 1.5; 95% CI, 1.1-2.1), a history of pneumococcal vaccination (OR, 3.9; 95% CI, 2.5-6.1), and history of hepatitis B vaccination (OR, 1.9; 95% CI, 1.4-2.4). Non-Hispanic black persons were less likely to be vaccinated (OR, 0.6; 95% CI, 0.5-0.9) than non-Hispanic white persons. There were no significant differences in vaccination levels according to HCW occupation category. CONCLUSIONS: Influenza immunization among HCWs reached a plateau during 1997-2002. New strategies are needed to encourage US HCWs to receive influenza vaccination to prevent influenza illness in themselves and transmission of influenza to vulnerable patients.

Adverse events associated with smallpox vaccination in the United States, January-October 2003.

CONTEXT: On January 24, 2003, the US Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a bioterrorism event. OBJECTIVE: To describe results from the comprehensive DHHS smallpox vaccine safety monitoring and response system. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of adverse event reports from the DHHS smallpox vaccine safety monitoring and response system received between January 24 and October 31, 2003, through the Vaccine Adverse Event Reporting System (VAERS) and the Centers for Disease Control and Prevention. A total of 37,901 volunteers in 55 jurisdictions received at least 1 dose of smallpox vaccine. MAIN OUTCOME MEASURES: Number of vaccinations administered and description of adverse events and reporting rates. RESULTS: A total of 38,885 smallpox vaccinations were administered, with a take rate of 92%. VAERS received 822 reports of adverse events following smallpox vaccination (overall reporting rate, 217 per 10,000 vaccinees). A total of 590 adverse events (72%) were reported within 14 days of vaccination. Nonserious adverse events (n = 722) included multiple signs and symptoms of mild and self-limited local reactions. One hundred adverse events (12%) were designated as serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the serious adverse events, 21 cases were classified as myocarditis and/or pericarditis and 10 as ischemic cardiac events that were not anticipated based on historical data. Two cases of generalized vaccinia and 1 case of postvaccinial encephalitis were detected. No preventable life-threatening adverse reactions, contact transmissions, or adverse reactions that required treatment with vaccinia immune globulin were identified. Serious adverse events were more common among older revaccinees than younger first-time vaccinees. CONCLUSIONS: Rigorous smallpox vaccine safety screening, educational programs, and older vaccinees may have contributed to low rates of preventable life-threatening adverse reactions. Other rare, clinically significant, or unexpected cardiac adverse events were detected by timely review of VAERS data and intensive clinical case investigation.