Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine and Guidance for Use as a Booster Dose.

On March 24, 2015, the Food and Drug Administration licensed an additional combined diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP) and inactivated poliovirus (IPV) vaccine (DTaP-IPV) (Quadracel, Sanofi Pasteur Inc.). Quadracel is the second DTaP-IPV vaccine to be licensed for use among children aged 4 through 6 years in the United States (1). Quadracel is approved for administration as a fifth dose in the DTaP series and as a fourth or fifth dose in the IPV series in children aged 4 through 6 years who have received 4 doses of DTaP-IPV-Hib (Pentacel, Sanofi Pasteur) and/or DTaP (Daptacel, Sanofi Pasteur) vaccine (2,3). This report summarizes the indications for Quadracel vaccine and provides guidance from the Advisory Committee on Immunization Practices (ACIP) for its use.

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.

Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

This report updates the 2008 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2008;57[No. RR-7]). Information on vaccination issues related to the recently identified novel influenza A H1N1 virus will be published later in 2009. The 2009 seasonal influenza recommendations include new and updated information. Highlights of the 2009 recommendations include 1) a recommendation that annual vaccination be administered to all children aged 6 months-18 years for the 2009-10 influenza season; 2) a recommendation that vaccines containing the 2009-10 trivalent vaccine virus strains A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; and 3) a notice that recommendations for influenza diagnosis and antiviral use will be published before the start of the 2009-10 influenza season. Vaccination efforts should begin as soon as vaccine is available and continue through the influenza season. Approximately 83% of the United States population is specifically recommended for annual vaccination against seasonal influenza; however, <40% of the U.S. population received the 2008-09 influenza vaccine. These recommendations also include a summary of safety data for U.S. licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2009-10 influenza season also can be found at this website. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008.

This report updates the 2007 recommendations by CDC's 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 2007;56[No. RR-6]). The 2008 recommendations include new and updated information. Principal updates and changes include 1) a new recommendation that annual vaccination be administered to all children aged 5--18 years, beginning in the 2008--09 influenza season, if feasible, but no later than the 2009--10 influenza season; 2) a recommendation that annual vaccination of all children aged 6 months through 4 years (59 months) continue to be a primary focus of vaccination efforts because these children are at higher risk for influenza complications compared with older children; 3) a new recommendation that either trivalent inactivated influenza vaccine or live, attenuated influenza vaccine (LAIV) be used when vaccinating healthy persons aged 2 through 49 years (the previous recommendation was to administer LAIV to person aged 5--49 years); 4) a recommendation that vaccines containing the 2008--09 trivalent vaccine virus strains A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Florida/4/2006-like antigens be used; and, 5) new information on antiviral resistance among influenza viruses in the United States. Persons for whom vaccination is recommended are listed in boxes 1 and 2. These recommendations also include a summary of safety data for U.S. licensed influenza vaccines. This report and other information are available at CDC's influenza website (http://www.cdc.gov/flu), including any updates or supplements to these recommendations that might be required during the 2008--09 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

Introduction: vaccination against smallpox in the posteradication era.

The following introduction describes the context in which the national smallpox vaccination program was implemented and highlights the significance of the key policy, programmatic, or scientific challenges, observations, and lessons learned that are presented in the articles that follow within this supplement to Clinical Infectious Diseases. Although the execution of this national program posed multiple complex and varied challenges, the focus of this supplement is on vaccine-associated adverse events and vaccine safety.

Economics of cardiac adverse events after smallpox vaccination: lessons from the 2003 US Vaccination Program.

Of >39,000 civilian public health responders vaccinated against smallpox in 2003, 203 reported cardiovascular adverse events (CAEs). An association exists between the US vaccinia strain and myocarditis and/or pericarditis ("myo/pericarditis" [MP]). Other associations are inconclusive. We used surveillance and follow-up survey data of CAE case patients to estimate the resources used during the 2003 smallpox vaccination program and used a probabilistic model to estimate the potential costs of CAEs in a mass vaccination campaign. For every million adult vaccinees, 3001 CAEs (including 351 MP cases) would occur, with >92% in revaccinees. CAEs would require a median of 5934 outpatient visits, 1786 emergency department visits, 533 days in general wards, 132 days in intensive care units, 5484 cardiac enzymes tests, 3504 electrocardiograms, 3049 chemistry tests, 2828 complete blood counts, and 1444 transthoracic echocardiograms, among other procedures. CAEs would reduce productivity (15,969 work days lost) and cost $11 per vaccinee. In a mass vaccination campaign, the care of a sizable number of CAEs would be resource intensive.

A review of the smallpox vaccine adverse events active surveillance system.

In response to concern about smallpox possibly being used as a biological weapon, the President of the United States launched the National Smallpox Pre-Event Vaccination Program on 13 December 2002. Given safety concerns, identifying potentially serious adverse events (SAEs) was an essential tool of the program. To monitor for SAEs, both enhanced passive surveillance and active surveillance systems were used. The enhanced passive system was built, in part, on the existing Vaccine Adverse Event Reporting System; the active system was implemented 24 January 2003. During January 2003-May 2005, the active system detected only 1 SAE in addition to those reported through the enhanced passive system. Furthermore, the active system was not universally used by states. With the enhancements to passive surveillance, the performance of enhanced passive surveillance was comparable to that of active surveillance. However, an active surveillance system may be important when there is no enhanced passive surveillance system available.

Follow-up of cardiovascular adverse events after smallpox vaccination among civilians in the United States, 2003.

Limited information exists regarding intermediate or long-term consequences of cardiac adverse events (CAEs) after smallpox vaccination. We conducted follow up at 5-12 months after vaccination of 203 US civilian vaccinees who reported a possible CAE. Among 31 of the 33 with confirmed CAEs, at least 1 health-related quality-of-life change persisted for approximately 48%; approximately 87% missed work (average, 11.5 days). Among 168 of the 170 case patients with other reported cardiovascular conditions, at least 1 health-related quality-of-life change persisted for approximately 40%; almost 49% missed work (average, 10.2 days). Almost all vaccinees with possible CAEs were working the same number of hours at follow-up compared with before vaccination. Although intermediate-term consequences among possible postvaccination CAEs were not considered serious, lost days of work and a decline in health-related quality of life at the time of follow-up were common, resulting in personal economic and quality-of-life burden.

Ischemic cardiac events during the Department of Health and Human Services Smallpox Vaccination Program, 2003.

Ten ischemic cardiac events (ICEs) were reported among 37,901 initial US Department of Health and Human Services (DHHS) smallpox vaccinees. Symptoms developed a median of 10 days after vaccination (range, 0-28 days). The median age of case patients was 56 years (range, 42-65 years), and 60% were male. Seven (70%) of the case patients had >/=3 cardiac risk factors or probable coronary artery disease before vaccination. Two women, 55 and 57 years of age, experienced acute myocardial infarction and fatal cardiac arrests. Background rates of ICEs during a 3-week period for civilian populations that were age and sex matched to DHHS vaccinees were estimated. The observed number of myocardial infarctions exceeded estimated expectations (5 vs. 2) but remained within the 95% predictive interval (PI) (0.6-5.4). New onset angina was observed significantly less frequently than estimated expectations (1 vs. 10; 95% PI, 3.5-15.7). After persons with >/=3 cardiac risk factors or known heart disease were deferred from vaccination, no ICEs were reported among an additional 6638 vaccinees.

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.

Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007.

This report updates the 2006 recommendations by CDC's 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 2006;55[No. RR-10]). The groups of persons for whom vaccination is recommended and the antiviral medications recommended for chemoprophylaxis or treatment (oseltamivir or zanamivir) have not changed. Estimated vaccination coverage remains <50% among certain groups for whom routine annual vaccination is recommended, including young children and adults with risk factors for influenza complications, health-care personnel (HCP), and pregnant women. Strategies to improve vaccination coverage, including use of reminder/recall systems and standing orders programs, should be implemented or expanded. The 2007 recommendations include new and updated information. Principal updates and changes include 1) reemphasizing the importance of administering 2 doses of vaccine to all children aged 6 months--8 years if they have not been vaccinated previously at any time with either live, attenuated influenza vaccine (doses separated by > or =6 weeks) or trivalent inactivated influenza vaccine (doses separated by > or =4 weeks), with single annual doses in subsequent years; 2) recommending that children aged 6 months--8 years who received only 1 dose in their first year of vaccination receive 2 doses the following year, with single annual doses in subsequent years; 3) highlighting a previous recommendation that all persons, including school-aged children, who want to reduce the risk of becoming ill with influenza or of transmitting influenza to others should be vaccinated; 4) emphasizing that immunization providers should offer influenza vaccine and schedule immunization clinics throughout the influenza season; 5) recommending that health-care facilities consider the level of vaccination coverage among HCP to be one measure of a patient safety quality program and implement policies to encourage HCP vaccination (e.g., obtaining signed statements from HCP who decline influenza vaccination); and 6) using the 2007--2008 trivalent vaccine virus strains A/Solomon Islands/3/2006 (H1N1)-like (new for this season), A/Wisconsin/67/2005 (H3N2)-like, and B/Malaysia/2506/2004-like antigens. This report and other information are available at CDC's influenza website (http://www.cdc.gov/flu). Updates or supplements to these recommendations (e.g., expanded age or risk group indications for currently licensed vaccines) might be required. Immunization providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.

CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. 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 biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case definitions presented in the report can be used in future vaccination programs to ensure uniform reporting guidelines and case classification.

Safety profile of smallpox vaccine: insights from the laboratory worker smallpox vaccination program.

BACKGROUND: The frequency of mild-to-moderate adverse events following smallpox vaccination was not well documented or reported during the pre-eradication era. This report describes the frequency of such symptoms among 936 adult smallpox vaccinees with and without a history of prior smallpox vaccination. METHODS: Diary cards were distributed to 1006 laboratory workers and members of the Centers for Disease Control and Prevention (CDC) smallpox response team who received smallpox vaccination under an investigational new drug protocol during 2001-2002. Vaccinees were requested to complete the diary card daily and return it to the CDC 28 days after vaccination. The proportion of vaccinees reporting symptoms was determined and compared among subgroups. RESULTS: Ninety-three percent of the diary cards were returned. The most common symptom reported was "itching at vaccination site." Primary vaccines reported statistically higher proportions of the following 11 symptoms: joint pain (25% vs. 11%; P=.0011), muscle pain (46% vs. 19%; P<.0001), fatigue (43% vs. 29%; P=.0161), swelling at vaccination site (58% vs. 33%; P<.0001), itching on the body (31% vs. 17%; P=.0048), abdominal pain (11% vs. 2%; P=.0012), swollen or tender lymph nodes (71% vs. 33%; P<.0001), pain at injection site (48% vs. 30%; P=.0018), headache (40% vs. 25%; P=.0088), backache (17% vs. 7%; P=.0090), and fever (temperature, >or=100 degrees F [37.7 degrees C]; 20% vs. 9%; P=.0047). CONCLUSIONS: This analysis suggests that previously unvaccinated persons aged <30 years experienced more symptoms than did previously vaccinated persons. The findings of increased proportions with joint pain, abdominal pain, backache, and difficulty breathing were unexpected. As with recently described cardiac adverse events, these symptoms are suggestive of systemic involvement and warrant further study.

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.

Surveillance for safety after immunization: Vaccine Adverse Event Reporting System (VAERS)--United States, 1991-2001.

PROBLEM/CONDITION: Vaccines are usually administered to healthy persons who have substantial expectations for the safety of the vaccines. Adverse events after vaccinations occur but are generally rare. Some adverse events are unlikely to be detected in prelicensure clinical trials because of their low frequency, the limited numbers of enrolled subjects, and other study limitations. Therefore, postmarketing monitoring of adverse events after vaccinations is essential. The cornerstone of monitoring safety is review and analysis of spontaneously reported adverse events. REPORTING PERIOD COVERED: This report summarizes the adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) from January 1, 1991, through December 31, 2001. DESCRIPTION OF SYSTEMS: VAERS was established in 1990 under the joint administration of CDC and the Food and Drug Administration (FDA) to accept reports of suspected adverse events after administration of any vaccine licensed in the United States. VAERS is a passive surveillance system: reports of events are voluntarily submitted by those who experience them, their caregivers, or others. Passive surveillance systems (e.g., VAERS) are subject to multiple limitations, including underreporting, reporting of temporal associations or unconfirmed diagnoses, and lack of denominator data and unbiased comparison groups. Because of these limitations, determining causal associations between vaccines and adverse events from VAERS reports is usually not possible. Vaccine safety concerns identified through adverse event monitoring nearly always require confirmation using an epidemiologic or other (e.g., laboratory) study. Reports may be submitted by anyone suspecting that an adverse event might have been caused by vaccination and are usually submitted by mail or fax. A web-based electronic reporting system has recently become available. Information from the reports is entered into the VAERS database, and new reports are analyzed weekly. VAERS data stripped of personal identifiers can be reviewed by the public by accessing http://www.vaers.org. The objectives of VAERS are to 1) detect new, unusual, or rare vaccine adverse events; 2) monitor increases in known adverse events; 3) determine patient risk factors for particular types of adverse events; 4) identify vaccine lots with increased numbers or types of reported adverse events; and 5) assess the safety of newly licensed vaccines. RESULTS: During 1991-2001, VAERS received 128,717 reports, whereas >1.9 billion net doses of human vaccines were distributed. The overall dose-based reporting rate for the 27 frequently reported vaccine types was 11.4 reports per 100,000 net doses distributed. The proportions of reports in the age groups <1 year, 1-6 years, 7-17 years, 18-64 years, and >/= years were 18.1%, 26.7%, 8.0%, 32.6%, and 4.9%, respectively. In all of the adult age groups, a predominance among the number of women reporting was observed, but the difference in sex was minimal among children. Overall, the most commonly reported adverse event was fever, which appeared in 25.8% of all reports, followed by injection-site hypersensitivity (15.8%), rash (unspecified) (11.0%), injection-site edema (10.8%), and vasodilatation (10.8%). A total of 14.2% of all reports described serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability. Examples of the uses of VAERS data for vaccine safety surveillance are included in this report. INTERPRETATION: As a national public health surveillance system, VAERS is a key component in ensuring the safety of vaccines. VAERS data are used by CDC, FDA, and other organizations to monitor and study vaccine safety. CDC and FDA use VAERS data to respond to public inquiries regarding vaccine safety, and both organizations have published and presented vaccine safety studies based on VAERS data. VAERS data are also used by the Advisory Committee on Immunization Practices and the Vaccine and Related Biological Products Advisory Committee to evaluate possible adverse events after vaccinations and to develop recommendations for precautions and contraindications to vaccinations. Reviews of VAERS reports and the studies based on VAERS reports during 1991-2001 have demonstrated that vaccines are usually safe and that serious adverse events occur but are rare. PUBLIC HEALTH ACTIONS: Through continued reporting of adverse events after vaccination to VAERS by health-care providers, public health professionals, and the public and monitoring of reported events by the VAERS working group, the public health system will continue to be able to detect rare but potentially serious consequences of vaccination. This knowledge facilitates improvement in the safety of vaccines and the vaccination process.

Behavior and beliefs about influenza vaccine among adults aged 50-64 years.

OBJECTIVE: To examine demographics and beliefs about influenza disease and vaccine that may be associated with influenza vaccination among 50- to 64-year-olds. METHODS: A national sample of adults aged 50-64 years surveyed by telephone. RESULTS: Variables associated with receiving influenza vaccination included age, education level, recent doctor visit, and beliefs about vaccine effectiveness and vaccine safety. Beliefs about influenza vaccination varied by race/ethnicity, age, education, and gender. CONCLUSION: The finding of demographic differences in beliefs suggests that segmented communication messages designed for specific demographic subgroups may help to increase influenza vaccination coverage.

An analysis of rotavirus vaccine reports to the vaccine adverse event reporting system: more than intussusception alone?

BACKGROUND: The rhesus-human rotavirus reassortant-tetravalent vaccine (RRV-TV) was licensed on August, 31, 1998, and subsequently recommended for routine infant immunizations in the United States. After approximately 1 million doses had been administered, an increase in acute risk of intussusception in vaccinees led to the suspension of the use of RRV-TV and its withdrawal from the market. These postmarketing safety studies focused on a single adverse event (intussusception) and, to minimize the risk of a false-positive finding, accepted only cases that met a strict case definition. Safer rotavirus vaccines are needed to prevent the substantial global morbidity and mortality caused by rotavirus infections; their development and future use may benefit from a better understanding of the postmarketing safety profile of RRV-TV beyond intussusception. OBJECTIVE: To characterize more completely the postmarketing surveillance safety profile of RRV-TV more completely by review and analysis of Vaccine Adverse Event Reporting System (VAERS) case reports to better understand 1) whether severe adverse events other than intussusception may have occurred after RRV-TV and 2) the likely scope of gastrointestinal illnesses, of which the previously identified, highly specific intussusception cases may account for just a fraction. SETTING AND PARTICIPANTS: Infants vaccinated with RRV-TV and other vaccines in the United States and for whom a report was submitted to VAERS during September 1, 1998, to December 31, 1999. METHODOLOGY: To detect adverse events of interest other than intussusception, we used proportional morbidity analysis to compare the adverse event profile of VAERS reports among infants who received routine vaccines including RRV-TV (after excluding confirmed and suspected intussusception reports) with infants who received identical vaccine combinations but without RRV-TV. Next, to better capture all described diagnoses, signs, and symptoms associated with the suspected adverse events, a set of new codes was developed and assigned to each VAERS report. All 448 nonfatal RRV-TV-associated reports (including intussusception) were recoded manually from the clinical description on the VAERS report and categorized into clinical groups to better describe a spectrum of reported illnesses after the vaccine. Each report was assigned to one of the following hierarchical and mutually exclusive clinical groups: 1) diagnosed intussusception; 2) suspected intussusception; 3) illness consistent with either gastroenteritis or intussusception; 4) gastroenteritis; 5) other gastrointestinal diagnoses (ie, not consistent with intussusception or rotavirus-like gastroenteritis); and 6) nongastrointestinal diagnoses. RESULTS: Even after excluding intussusception cases, a higher proportion of RRV-TV reports than non-RRV-TV reports included fever and various gastrointestinal symptoms, most notably bloody stool but also vomiting, diarrhea, abdominal pain, gastroenteritis, abnormal stool, and dehydration. Distribution of RRV-TV reports by clinical groups was as follows: diagnosed intussusception (109 [24%], suspected intussusception (36 [8%]), and illness consistent with gastroenteritis or intussusception (33 [7%]), gastroenteritis (101 [22%]), other gastrointestinal diagnoses (10 [2%]), and nongastrointestinal outcomes (159 [35%]). The median time interval between vaccination and illness onset decreased incrementally among the first 4 clinical groups: from 7 days for diagnosed intussusceptions to 3 days for gastroenteritis. CONCLUSIONS: Intussusception and gastroenteritis were the most commonly reported outcomes; however, a substantial number of reports indicate signs and symptoms consistent with either illness, possibly suggestive of a spectrum of gastrointestinal illness(es) related to RRV-TV. Although VAERS data have recognized limitations such as underreporting (that may differ by vaccine) and are nearly always insufficient to prove causality between a vaccine and an adverse event, this safety profile of RRV-TV may aid better understanding of the pathophysiology of intussusception as well as development of future safer rotavirus vaccines.

Adverse event reporting rates following tetanus-diphtheria and tetanus toxoid vaccinations: data from the Vaccine Adverse Event Reporting System (VAERS), 1991-1997.

Since 1966, the Advisory Committee on Immunization Practices (ACIP) has recommended tetanus-diphtheria toxoid (Td) be used instead of single antigen tetanus toxoid (TT) because, while both vaccines protect against tetanus, only Td protects against diphtheria. Despite this recommendation, approximately 2.5 million doses of TT were distributed annually from 1991 to 1997. One possible explanation for the continued use of TT is concern about the relative safety of Td. Small clinical trials found Td to be associated with a higher rate of local vaccine-associated adverse events (VAEs) than TT. To determine if the findings from the trials would hold up on a larger scale, we compared the rate of reporting to the Vaccine Adverse Event Reporting System (VAERS), a passive reporting system, after either vaccine from 1991 to 1997. There were 40 reports per million doses of Td, and 27 reports per million doses of TT, for a reporting rate ratio of 1.4. Reporting rates to VAERS are lower than the rates of VAEs identified in the clinical trials, but the magnitude of the difference in VAEs following TT versus Td is similar. While reporting rates are lower after TT than Td, rates of reported VAEs after both vaccines are low.

Adverse event reports following vaccination for Lyme disease: December 1998-July 2000.

CONTEXT: The vaccine adverse event reporting system (VAERS) monitors vaccine safety post-licensure. Although events reported to VAERS are not necessarily causally associated with vaccination, VAERS reports can be used to identify possible safety concerns that occur at too low a rate to have been identified prior to licensure. OBJECTIVE: To evaluate adverse events following Lyme disease vaccination reported to VAERS during the first 19 months of the vaccine's licensure. DESIGN, SETTING, AND PARTICIPANTS: Analysis of all VAERS reports of adverse events following vaccination for Lyme disease in the US from 28 December 1998 to 31 July 2000. MAIN OUTCOME MEASURE: We evaluated reported adverse events for unexpected patterns in age, gender, time to onset, dose number, and clinical characteristics and compared them to adverse events observed in clinical trials of this vaccine. RESULTS: Over 1,400,000 doses were distributed and 905 adverse events were reported to VAERS, 440 in men and 404 in women, with ages ranging from 10 to 82 years. The majority (56%) of adverse events occurred after administration of the first dose. The most frequently reported adverse events were arthralgia (250), myalgia (195), and pain (157). There were 59 reports coded as arthritis, 34 as arthrosis, 9 as rheumatoid arthritis, and 12 as facial paralysis. Sixty-six (7.4%) events were classified as serious, involving life-threatening illness, hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, or death. Twenty-two hypersensitivity reactions were reported. CONCLUSION: Based on reporting to VAERS, we did not detect unexpected or unusual patterns of reported adverse events following Lyme disease vaccine administration, other than hypersensitivity reactions, compared with adverse events observed in clinical trials.

Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States.

OBJECTIVE: Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions. METHODS: We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events. RESULTS: Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the United States between 1991 and 1997 is 1.8 per 1 million doses distributed. No substantial increase in the number of reported allergic events after frequently used gelatin containing MMR and varicella vaccines could be observed during the first 4 years (1997-2000) since the introduction of diphtheria-tetanus-acellular pertussis vaccines for use in infancy. CONCLUSION: Anaphylactic reactions to MMR in the United States are rare. The reporting rate has the same order of magnitude as estimates from other countries. Almost one fourth of patients with reported anaphylaxis after MMR seem to have hypersensitivity to gelatin in the vaccine. They may be at higher risk of developing anaphylaxis to subsequent doses of other gelatin-containing vaccines. These people should seek an allergy evaluation before such immunization.