Financing immunization of adults in the United States.

Immunization is one of the most effective and cost-effective prevention measures available. As a result of universal vaccination of children, polio has been eliminated in the United States and much of the world, measles and rubella are no longer endemic diseases in the United States, and most of the other vaccine-preventable diseases of childhood are at or near record lows. A recent review of clinical preventive services by Partnership for Prevention gave childhood immunization a perfect score of 10, based on clinically preventable burden and cost-effectiveness.

Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system.

BACKGROUND: Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants. To assess rare adverse events, postlicensure surveillance was conducted. OBJECTIVE: To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999. SETTING AND PARTICIPANTS: Infants vaccinated with rotavirus vaccine in the United States. OUTCOME MEASURES: Intussusception confirmed by radiology, surgery, or autopsy report with medical record documentation or confirmed by a primary health care provider. RESULTS: There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination. Based on calculations using vaccine distribution data and intussusception incidence rates from 2 separate databases, an estimated 7 to 16 cases would have been expected to occur in the week after vaccination by chance alone. CONCLUSION: Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine. Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception. In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn.

Surveillance for poliovirus vaccine adverse events, 1991 to 1998: impact of a sequential vaccination schedule of inactivated poliovirus vaccine followed by oral poliovirus vaccine.

BACKGROUND: The elimination of wild-virus-associated poliomyelitis in the Western Hemisphere in 1991 and rapid progress in global polio eradication efforts changed the risk-benefit ratio associated with the exclusive use of oral poliovirus vaccine (OPV) for routine immunization. These changes, plus the November 1987 development of an enhanced-potency inactivated poliovirus vaccine (IPV), which poses no risk of vaccine-associated paralytic poliomyelitis (VAPP), resulted in a change in polio immunization policy in the United States. In September 1996, the Centers for Disease Control and Prevention recommended that IPV replace OPV for the first 2 doses in a sequential poliovirus vaccine schedule. The Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system for adverse events after receipt of any US-licensed vaccine, is used to monitor postlicensure vaccine safety. Postlicensure surveillance of vaccines is important to identify new, rare, or delayed-onset adverse reactions not detected in prelicensure clinical trials or when new vaccine schedules are adopted. Through continual monitoring of adverse events and identification of potential vaccine risks, VAERS can serve as an important resource to ensure continued public acceptance of vaccines. We compared VAERS reports after the receipt of IPV to reports after OPV in infants from 1991 through 1998. Comparisons included reports listing IPV and OPV coadministered with other vaccines. METHODS: Annual reporting rates per 100 000 doses distributed within 3 severity categories (fatal, nonfatal serious, less serious) were examined. Distributions of severity categories by vaccine type, age, and time period (pre- and postrecommendation) were constructed. Safety profiles (distribution of 21 symptom groupings) for IPV and OPV reports were compared. Analysis was restricted to reports for infants 1 to 3 months old and 4 to 6 months old, corresponding generally to first- and second-dose recipients. Any notable increase in a severity or safety category for IPV compared with OPV was followed up by examining the frequency of specific symptoms, reporting source, and date of vaccination. An important limitation of VAERS is that reports do not necessarily represent adverse events caused by vaccines. In many cases, the events are temporal associations only. RESULTS: The annual rates of VAERS reports per 100 000 vaccine doses distributed by severity category, 1991 to 1998, were in general similar for reports after IPV compared with those after OPV. The reporting rates for poliovirus vaccine did not increase materially with the shift to IPV usage. The relative frequencies of symptoms in the fatal and nonfatal serious categories for 1998 vaccine administrations were similar to 1997 reports. Severity profiles for IPV and OPV reports in infants 1 to 3 months old and 4 to 6 months old, corresponding to first- and second-dose recipients, were remarkably similar. The frequency of symptoms listed on IPV reports categorized as fatal or serious was examined by age, vaccine combinations, and time period, and the distribution of symptoms was similar for ages 1 to 3 months and 4 to 6 months. In the postrecommendation period, the 10 most frequent symptoms reported with IPV were also reported with OPV in either similar or lower relative frequency. During the postrecommendation period, safety profiles for infants 4 to 6 months old showed a 2.5% higher proportion in the allergic reaction category for IPV than for OPV, but none of the allergic reaction reports indicated anaphylaxis. In general, the distribution of symptom groupings was not markedly different for IPV compared with OPV. No cases of VAPP were reported after the administration of IPV, whereas 5 VAPP cases were reported after the administration of OPV. CONCLUSIONS: Although VAERS is subject to the limitations of most passive surveillance systems, the large number of reports and national coverage provide a unique database for monitoring vaccine safety. There was a marked increase of IPV reports in VAERS after 1996, consistent with implementation of the Advisory Committee on Immunization Practices recommendation for the sequential IPV/OPV poliovirus vaccination schedule. Given the increased use of IPV, a review of potential adverse events in VAERS compared IPV with OPV reports both before and after the introduction of the sequential vaccination schedule. Vaccine safety surveillance indicated no adverse events patterns of potential concern following the use of IPV in infants after the introduction of the sequential vaccination schedule. Ongoing surveillance is documenting a decrease in VAPP. These findings provide useful information to support the Advisory Committee on Immunization Practices recommendation, made in 1999, to shift to an all-IPV schedule.

Challenges and controversies in immunization safety.

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

Safety data on meningococcal polysaccharide vaccine from the Vaccine Adverse Event Reporting System.

Recent recommendations by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices may lead to the increased use of the meningococcal polysaccharide vaccine. The Vaccine Adverse Event Reporting System (VAERS) is useful for the detection of previously unrecognized reactions and for the monitoring of known reactions. Limitations of VAERS include underreporting and the inability to establish a causal relationship between vaccination and adverse events in most cases. From July 1990 through 31 October 1999, 110 adverse events were reported after receipt of meningococcal vaccine alone. Thirteen (12%) were serious, including 6 injection site reactions, 3 allergic reactions, 1 case of Guillain-Barré syndrome, and 3 miscellaneous events. Fever (30%), headache (17%), dizziness (15%), injection site hypersensitivity (13%), urticaria (12%), and paresthesia (10%) were among the most common events reported. Fever and injection site and allergic reactions are most likely causally linked to the vaccine. That there were few reports of serious adverse events, with >6 million doses having been distributed, and no clear signal of a previously unrecognized serious reaction is reassuring with regard to the safety of meningococcal vaccine.

The epidemiology of fatalities reported to the vaccine adverse event reporting system 1990-1997.

PURPOSE: To examine the fatalities reported to the federally administered Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system, in its first 7 years. METHODS: The working data set included variables such as demographic information, dates of vaccination, adverse event onset and death, vaccines administered, and vaccination facility data. Frequencies for these data and state reporting rates were calculated. RESULTS: A total of 1266 fatalities were reported to VAERS during July 1990 through June 1997. The number of death reports peaked in 1992-1993 and then declined. The overall median age of cases was 0.4 years, with a range of 1 day to 104 years. Nearly half of the deaths were attributed to sudden infant death syndrome (SIDS). CONCLUSIONS: The trend of decreasing numbers of deaths reported to VAERS since 1992-1993 follows that observed for SIDS overall for the US general population following implementation of the 'Back to Sleep' program. These data may support findings of past controlled studies showing that the association between infant vaccination and SIDS is coincidental and not causal. VAERS reports of death after vaccination may be stimulated by the temporal association, rather than by any causal relationship.

Infant immunization with acellular pertussis vaccines in the United States: assessment of the first two years' data from the Vaccine Adverse Event Reporting System (VAERS).

OBJECTIVE: To evaluate the safety of infant immunization with acellular pertussis vaccines in the United States. BACKGROUND: The US Food and Drug Administration approved the first acellular pertussis vaccine for use in infants in the United States on July 31, 1996. OUTCOME MEASURES: Adverse events in the United States after infant immunization with pertussis-containing vaccines, representing temporal (but not necessarily causal) associations between vaccinations and adverse events. DATA SOURCE: Reports to the Vaccine Adverse Event Reporting System (VAERS), a passive national surveillance system. DESIGN: Reports concerning infant immunization against pertussis between January 1, 1995 (when whole-cell vaccine was in exclusive use) and June 30, 1998 (when acellular vaccine was in predominant use) were analyzed, if the reports were entered into the VAERS database by November 30, 1998. RESULTS: During the study, there were 285 reports involving death, 971 nonfatal serious reports, and 4514 less serious reports after immunization with any pertussis-containing vaccine. For 1995 there were 2071 reports; in 1996 there were 1894 reports; in 1997 there were 1314 reports, and in the first half of 1998 there were 491 reports. Diphtheria-tetanus-pertussis vaccine (DTP) was cited in 1939 reports, diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b vaccine (DTPH) in 2918 reports, and diphtheria-tetanus-acellular pertussis vaccine (DTaP) in 913 reports. The annual number of deaths during the study was 85 in 1995, 82 in 1996, 77 in 1997, and 41 in the first half of 1998. The annual number of reported events categorized as nonfatal serious (defined as events involving initial hospitalization, prolongation of hospitalization, life-threatening illness, or permanent disability) to VAERS for all pertussis-containing vaccines declined: 334 in 1995, 311 in 1996, 233 in 1997, and 93 in the first half of 1998. Similarly, the annual number of less serious reports to VAERS for pertussis-containing vaccines declined: 1652 in 1995, 1501 in 1996, 1004 in 1997, and 357 in the first half of 1998. A comparison of the adverse event profiles (proportional distributions) for DTaP, DTP, and DTPH, as well as an analysis of specific adverse events considered in a 1991 Institute of Medicine report on the safety of diphtheria-tetanus-pertussis vaccine, did not identify any new, clear safety concerns. CONCLUSIONS: These findings reflect the administration of millions of doses of acellular pertussis vaccine and are reassuring with regard to the safety of marketed acellular pertussis vaccines. VAERS data, although subject to the limitations of passive surveillance, support the prelicensure data with regard to the safety of the US-licensed acellular pertussis vaccines that we evaluated.

Postlicensure safety surveillance for varicella vaccine.

CONTEXT: Since its licensure in 1995, the extensive use of varicella vaccine and close surveillance of the associated anecdotal reports of suspected adverse effects provide the opportunity to detect potential risks not observed before licensure because of the relatively small sample size and other limitations of clinical trials. OBJECTIVES: To detect potential hazards, including rare events, associated with varicella vaccine, and to assess case reports for clinical and epidemiological implications. DESIGN AND SETTING: Postlicensure case-series study of suspected vaccine adverse events reported to the US Vaccine Adverse Event Reporting System (VAERS) from March 17, 1995, through July 25, 1998. MAIN OUTCOME MEASURES: Numbers of reported adverse events, proportions, and reporting rates (reports per 100,000 doses distributed). RESULTS: VAERS received 6574 case reports of adverse events in recipients of varicella vaccine, a rate of 67.5 reports per 100,000 doses sold. Approximately 4% of reports described serious adverse events, including 14 deaths. The most frequently reported adverse events were rashes, possible vaccine failures, and injection site reactions. Misinterpretation of varicella serology after vaccination appeared to account for 17% of reports of possible vaccine failures. Among 251 patients with herpes zoster, 14 had the vaccine strain of varicella zoster virus (VZV), while 12 had the wild-type virus. None of 30 anaphylaxis cases was fatal. An immunodeficient patient with pneumonia had the vaccine strain of VZV in a lung biopsy. Pregnant women occasionally received varicella vaccine through confusion with varicella zoster immunoglobulin. Although the role of varicella vaccine remained unproven in most serious adverse event reports, there were a few positive rechallenge reports and consistency of many cases with syndromes recognized as complications of natural varicella. CONCLUSION: Most of the reported adverse events associated with varicella vaccine are minor, and serious risks appear to be rare. We could not confirm a vaccine etiology for most of the reported serious events; several will require further study to clarify whether varicella vaccine plays a role. Education is needed to ensure appropriate use of varicella serologic assays and to eliminate confusion between varicella vaccine and varicella zoster immunoglobulin. JAMA. 2000;284:1271-1279

Safety of routine childhood vaccinations. An epidemiological review.

Immunisations have been one of the most cost-effective public health interventions in human history. Despite remarkable progress, several challenges face immunisation programs worldwide. Paradoxically, despite vaccines' clear effectiveness in reducing risks of diseases that were previously widely prevalent and caused substantial morbidity and mortality, current vaccination policies have become increasingly controversial due to concerns about vaccine safety. Vaccines, like other pharmaceutical products, are not entirely risk-free. While most known adverse effects are minor and self-limited, some vaccines have been associated with very rare but serious adverse effects. Because such rare effects are often not evident until vaccines come into widespread use, ongoing surveillance programs to monitor vaccine safety are needed. Such monitoring will be essential if the public is to accept the increasing number of new vaccines made possible by biotechnology. The interpretation of data from vaccine safety research is complex and is associated with some uncertainty. Effectively communicating this uncertainty and continuing to improve understanding of rare risks and risk factors are essential for "mature" immunisation programs to maintain public confidence in immunisations.

An overview of the vaccine adverse event reporting system (VAERS) as a surveillance system. VAERS Working Group.

We evaluated the Vaccine Adverse Event Reporting System (VAERS), the spontaneous reporting system for vaccine-associated adverse events in the United States, as a public health surveillance system, using evaluation guidelines from the Centers for Disease Control and Prevention. We found that VAERS is simple for reporters to use, flexible by design and its data are available in a timely fashion. The predictive value positive for one severe event is known to be high, but for most events is unknown. The acceptability, sensitivity and representativeness of VAERS are unknown. The study of vaccine safety is complicated by underreporting, erroneous reporting, frequent multiple exposures and multiple outcomes.

Anaphylaxis from yellow fever vaccine.

BACKGROUND: There are very few reports of anaphylactic reactions to yellow fever (YF) vaccine in the literature, and these date from the 1940s. OBJECTIVE: We sought to estimate the rate of YF vaccine-related anaphylaxis. METHODS: All reports of adverse reactions to YF vaccine submitted to the Vaccine Adverse Event Reporting System between 1990 and 1997 were reviewed for those meeting criteria for probable or possible anaphylactic reactions. RESULTS: Of 243 reports submitted, 40 describe probable or possible anaphylactic reactions. In 22 of these 40, YF vaccine was the only vaccine administered. There were 5,236,820 doses of YF vaccine distributed in the United States during this period. By using all 40 cases, the rate of YF vaccine-related anaphylaxis would be 40 in 5, 236,820 or about 1 in 131,000. In 35 of the reports, information was provided on whether previous doses of YF vaccine had been given. In 34 of these 35, the reaction occurred after the first dose of YF vaccine, suggesting that vaccine constituents other than the viral proteins may have been the allergens. The vaccine is grown in chicken embryos and contains gelatin as a stabilizer. CONCLUSION: YF vaccine can cause anaphylactic reactions. Persons presenting for YF vaccine should be asked if they have had adverse reactions to previous doses of this or other vaccines and if they are allergic to eggs, chicken, or gelatin. Health care workers administering YF vaccine should be prepared to recognize and treat anaphylactic reactions should they occur.