Ultracompact and fabrication-tolerant integrated polarization splitter.

Design and fabrication of a 2×2 two-mode interference (TMI) coupler based on-chip polarization splitter is presented. By changing the angle between the access waveguides, one can tune the effective TMI length for the mode with less optical confinement (transverse magnetic, TM) to coincide with the target TMI length for a desired transmission of the mode with higher optical confinement (transverse electric, TE). The fabricated 0.94 µm long 2×2 TMI splits the input power into TM (bar) and TE (cross) outputs with splitting ratio over 15 dB over 50 nm bandwidth. Fabrication tolerance analysis shows that the device is tolerant to fabrication errors as large as 60 nm.

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

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

The National Immunization Information Hotline.

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

Haemophilus influenzae type b meningitis with subdural effusion: a case report.

Haemophilus influenzae type b causes invasive infection in children under 2 years of age. The disease may be complicated with hearing impairment, lowered learning ability, and other neurologic sequelae. The incidence of invasive H. influenzae type b has declined dramatically after the introduction of routine administration of protein-conjugated H. influenzae type b vaccine in the United States and some other countries. Because of its low incidence in Taiwan, many clinicians are not familiar with the initial symptoms and management of H. influenzae type b. This case report describes a 7-month-old H. influenzae type b meningitis patient who had initial presentations of prolonged intermittent fever and vague neurologic signs. Left peripheral facial palsy with hearing loss in left ear and bilateral frontal subdural effusion developed during the first 5 days of cefotaxime therapy. Betamethasone was then given for 4 days to relieve the severe inflammation. Drug-induced fever was observed after 11 days of antibiotic use and subsided with prednisolone treatment. Left ear hearing impairment persisted during the follow-up period, but the children did not experience other significant development delay.

Combination vaccines: postlicensure safety evaluation.

The success of immunizations in nearly eliminating many vaccine-preventable diseases has resulted in an increase in the need to study risks from vaccines, combination or otherwise. The well-known limitations associated with prelicensure trials have led many to hope that postlicensure studies can address safety issues. This article reviews measures that have been or should be taken to meet this expectation: establishment of clinical immunization safety assessment centers, standardization of case definitions for vaccine adverse events, use of the Vaccine Identification Standards Initiative to improve the accuracy and efficiency with which vaccination records are transferred, integration of vaccine safety monitoring into immunization registries, establishment (and enlargement) of the Vaccine Safety Datalink project, use of innovative analytic tools for better signal detection, and implementation of various methods to overcome confounding by contraindication. Only by investing in vaccine safety infrastructure at a level commensurate with investments in vaccine development can we hope to retain the public's confidence in immunization.

Safety of neonatal hepatitis B vaccine administration.

OBJECTIVE: To determine whether hepatitis B vaccination of newborns increases the incidence of fever and/or suspected sepsis. METHODS: A prospective clinical study was undertaken at the Kaiser Permanente San Francisco Medical Center involving normal full term newborns born between November 1, 1991, and April 30, 1994. During this time 3302 infants were vaccinated within 21 days of birth with hepatitis B vaccine, and 2353 were not. Clinical and demographic data were collected from Kaiser Permanente's existing clinical information systems, and laboratory data for blood and cerebrospinal fluid (CSF) cultures were obtained from the comprehensive automated regional laboratory reporting system. RESULTS: There were no significant differences between vaccinated and unvaccinated newborns in the proportion of infants who received care for fever (0.8% vaccinated and 1.1% unvaccinated, P = 0.28), allergic reactions, seizures or other neurologic events in the first 21 days of life. Vaccinated newborns were significantly less likely to undergo microbiologic evaluation for possible sepsis. Among vaccinated newborns 4.0% had blood cultures and 1.6% had CSF cultures. Among infants who were not vaccinated 8.3% had blood cultures and 1.6% had CSF cultures (P <0.001 for both tests). CONCLUSION: This study found no evidence that newborn hepatitis B vaccination is associated with an increase in the number of febrile episodes, sepsis evaluations or allergic or neurologic events. In addition our data did not support any increase in medical procedures attributed to receipt of hepatitis B vaccine.

Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus.

OBJECTIVES: To evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenzae type b, and risk of developing type 1 diabetes; and to determine whether timing of vaccination influences risk. METHODS: We conducted a case-control study within 4 health maintenance organizations (HMOs) that participate in the Vaccine Safety Datalink project of the Centers for Disease Control and Prevention. Study eligibility was restricted to children who met the following criteria: 1) born during 1988 through 1997; 2) HMO member since birth; 3) continuously enrolled for first 6 months of life; and 4) at least 12 months of HMO membership before diabetes incidence date (or index date for controls) unless incidence date was before 12 months of age. All 4 HMOs maintain registries of their members who have diabetes, and we used the registries to identify potential cases of diabetes. We conducted chart reviews to verify that potential cases met the World Health Organization epidemiologic case definition for type 1 diabetes mellitus (ie, a physician's diagnosis of diabetes plus treatment with daily insulin injections). We defined the incidence date of diabetes as the first date that the child received a diagnosis of diabetes. We attempted to match 3 controls to each case. Controls had the same eligibility criteria as cases and were matched to individual cases on HMO, sex, date of birth (within 7 days), and length of health plan enrollment (up to the incidence or index date). The index date for controls was defined as the incidence date of the case to which the control was matched. Chart abstraction was performed by trained chart abstractors using standardized forms. In addition to complete vaccination histories, the chart abstraction forms for both cases and controls included information on sociodemographic characteristics, selected medical conditions, history of breastfeeding, and family medical history. We used conditional logistic regression to estimate the odds ratio (OR) of diabetes associated with vaccination, with vaccine exposure defined as before the diabetes incidence date (or index date for controls). RESULTS: Two hundred fifty-two confirmed cases of diabetes and 768 matched controls met the study eligibility criteria. The OR (95% confidence interval) for the association with type 1 diabetes was 0.28 (0.07-1.06) for whole cell pertussis vaccine (predominantly in combination as diphtheria, tetanus toxoids and pertussis vaccine), 1.36 (0.70-2.63) for measles-mumps-rubella, 1.14 (0.51-2.57) for Haemophilus influenzae type b, 0.81 (0.52-1.27) for hepatitis B vaccine, 1.16 (0.72-1.89) for varicella vaccine, and 0.92 (0.53-1.57) for acellular pertussis-containing vaccines. Compared with children who had not received hepatitis B vaccine, the OR of diabetes was 0.51 (0.23-1.15) for children vaccinated at birth and 0.86 (0.54-1.35) for those first vaccinated against hepatitis B at 2 months of age or later. Race and ethnicity and family history of diabetes were independently associated with risk of type 1 diabetes, but adjustment for these factors did not materially alter the ORs for any of the vaccines. CONCLUSIONS: In this large, population-based, case-control study, we did not find an increased risk of type 1 diabetes associated with any of the routinely recommended childhood vaccines. Our study adds to previous research by providing data on newer vaccines, including hepatitis B, acellular pertussis, and varicella vaccines. For the older vaccines, our results are generally in agreement with previous studies in not finding any increased risks. Ours is the first epidemiologic study to evaluate the possibility that timing of vaccination is related to risk of clinical diabetes in children. Our results on hepatitis B vaccine do not support the hypothesis; risk of type 1 diabetes was not different between infants vaccinated at birth and those who received their first vaccination later in life. The results of our study and the preponderance of epidemiologic evidence do not support an association between any of the recommended childhood vaccines and an increased risk of type 1 diabetes. Suggestions that diabetes risk in humans may be altered by changes in the timing of vaccinations also are unfounded.

Enhancing vaccine safety surveillance: a capture-recapture analysis of intussusception after rotavirus vaccination.

The Vaccine Adverse Event Reporting System (VAERS) is the passive reporting system for postmarketing surveillance of vaccine safety in the United States. The proportion of cases of an adverse event after vaccination that are reported to VAERS (i.e., VAERS reporting completeness) is mostly unknown. Therefore, the risk of such an event cannot be derived from VAERS only. To study whether its reporting sensitivity and risks could be estimated, VAERS was linked to data from a case-control and a retrospective cohort study in a capture-recapture analysis of intussusception after rotavirus vaccination (RV). Cases of intussusception after RV were selected from the common time frame (December 1998 through June 1999) and the common geographic area (19 states) of the three sources. Matching occurred on birth date, gender, state, date of vaccination, and date of diagnosis. Thirty-five matches were identified among a total of 84 cases. The estimated VAERS reporting completeness was 47%. The relative risks of intussusception in the periods 3-7 and 8-14 days after RV (relative risk = 22.7 and 4.4, respectively) were comparable with those reported in the two studies. Linkage of VAERS to complimentary data sources may permit more timely postmarketing assessment of vaccine safety.

Autism and measles-mumps-rubella vaccination: controversy laid to rest?

It has been suggested that vaccination, particularly with measles-mumps-rubella (MMR) vaccine, may be related to the development of autism. The main evidence for a possible association is that the prevalence of autism has been increasing at the same time that infant vaccination coverage has increased, and that in some cases there is an apparent temporal association in which autistic characteristics are first noted shortly after vaccination. Although the prevalence of autism and similar disorders appears to have increased recently, it is not clear if this is an actual increase or the result of increased recognition and changes in diagnostic criteria. The apparent onset of autism in close proximity to vaccination may be a coincidental temporal association. The clinical evidence in support of an association derives from a series of 12 patients with inflammatory bowel conditions and regressive developmental disorders, mostly autism. The possibility that measles vaccine may cause autism through a persistent bowel infection has generated much interest, since it provides a possible biological mechanism. Epidemiological studies, however, have not found an association between MMR vaccination and autism. The epidemiological findings are consistent with current understanding of the pathogenesis of autism, which has a strong genetic component and in which the neurological defects probably occur early in embryonic development. It seems unlikely that a vaccination that is given after birth could cause autism. A minority of cases of autism may have onset after 1 year of age (regressive autism), but the single epidemiological study that included such cases did not find an association with MMR vaccination. Currently, the weight of the available epidemiological and related evidence does not support a causal association between MMR vaccine, or any other vaccine or vaccine constituent, and autism.

Safety and immunogenicity of varying dosages of trivalent inactivated influenza vaccine administered by needle-free jet injectors.

To evaluate the perceived pain, other adverse events, and immunogenicity of influenza virus vaccine administered by needle-free jet injector (JI) compared with that of vaccine administered by needle and syringe (N&S), we randomly assigned 304 healthy young adults to receive one of three dosages (0.5, 0.3, or 0.2 ml) of the 1998-1999 season vaccine administered by either of two JI devices or by N&S. In multivariate analysis, female gender and JI administration were associated with higher levels of pain reported at the time of vaccination as well as with the occurrence of local injection site reactions following vaccination. Immune response did not vary significantly by dosage but administration by one JI device was associated with higher post-vaccination H1N1 antibody titers.

The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine.

BACKGROUND: The administration of the diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine has been associated with adverse neurologic events, including seizures. We studied the relation between these vaccinations and the risk of a first seizure, subsequent seizures, and neurodevelopmental disability in children. METHODS: This cohort study was conducted at four large health maintenance organizations and included reviews of the medical records of children with seizures. We calculated the relative risks of febrile and nonfebrile seizures among 679,942 children after 340,386 vaccinations with DTP vaccine, 137,457 vaccinations with MMR vaccine, or no recent vaccination. Children who had febrile seizures after vaccination were followed to identify the risk of subsequent seizures and other neurologic disabilities. RESULTS: Receipt of DTP vaccine was associated with an increased risk of febrile seizures only on the day of vaccination (adjusted relative risk, 5.70; 95 percent confidence interval, 1.98 to 16.42). Receipt of MMR vaccine was associated with an increased risk of febrile seizures 8 to 14 days after vaccination (relative risk, 2.83; 95 percent confidence interval, 1.44 to 5.55). Neither vaccination was associated with an increased risk of nonfebrile seizures. Analyses of automated data alone gave results similar to the analyses of the data from medical-record reviews. The number of febrile seizures attributable to the administration of DTP and MMR vaccines was estimated to be 6 to 9 and 25 to 34 per 100,000 children, respectively. As compared with other children with febrile seizures that were not associated with vaccination, the children who had febrile seizures after vaccination were not found to be at higher risk for subsequent seizures or neurodevelopmental disabilities. CONCLUSIONS: There are significantly elevated risks of febrile seizures on the day of receipt of DTP vaccine and 8 to 14 days after the receipt of MMR vaccine, but these risks do not appear to be associated with any long-term, adverse consequences.

Injection safety: a global challenge

This article summarizes the key injection safety issues and announces the launch of the Safe Injection Global Network (SIGN). Document in pdf format; Acrobat Reader required.

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.

Epidemiology of autoimmune reactions induced by vaccination.

In order for vaccinations to 'work', the immune system must be stimulated. The concern that immunizations may lead to the development of autoimmune disease (AID) has been questioned. Since AID occur in the absence of immunizations, it is unlikely that immunizations are a major cause of AID. Epidemiological studies are needed, however, to assess whether immunizations may increase the risk in some susceptible individuals. This paper discusses the evidence for and against vaccination as a risk factor for AID. Evidence for immunizations leading to AID come from several sources including animal studies, single and multiple case reports, and ecologic association. However more rigorous investigation has failed to confirm most of the allegations. Unfortunately the question remains difficult to address because for most AIDs, there is limited knowledge of the etiology, background incidence and other risk factors for their development. This information is necessary, in the absence of experimental evidence derived from controlled studies, for any sort of adequate causality assessment using the limited data that are available. Several illustrative examples are discussed to highlight what is known and what remains to be explored, and the type of epidemiological evidence that would be required to better address the issues. Examples include the possible association of immunization and multiple sclerosis (and other demyelinating diseases), type 1 diabetes mellitus, Guillain-Barre Syndrome, idiopathic thrombocytopenic purpura, and rheumatoid arthritis.

Population-based study of rotavirus vaccination and intussusception.

BACKGROUND: During the first year that the rhesus rotavirus tetravalent vaccine (RRV-TV) was licensed, the Vaccine Adverse Event Reporting System received several reports of intussusception after vaccination. To evaluate the risk of intussusception, we conducted a retrospective cohort study in ten managed care organizations. METHODS: Cases of intussusception were identified by searching electronic databases for diagnoses of intussusception (ICD-9 Code 560.0) in infants 1 to 11 months of age and confirmed by medical chart review. Vaccination and enrollment data were obtained from administrative databases. Incidence rate ratios (RR) of intussusception were computed by dividing incidence rates in prespecified risk intervals after vaccination by the background rate of intussusception and adjusted for age by Poisson regression. Cox proportional hazard regression was used to evaluate risk by vaccine dose. RESULTS: Of 463,277 children 56,253 had been vaccinated with a total of 91 371 doses of RRV-TV. The incidence rate of intussusception was 25/100,000 person years among unexposed infants and 340/100,000 person years 3 to 7 days postvaccination. In the interval 3 to 7 days after vaccination, the age-adjusted RR was 16.0 (95% confidence interval, 5.5 to 46.7) for all doses combined and 30.4 (95% confidence interval, 8.8 to 104.9) after the first dose. RRs for the 8- to 14- and 15- to 21-day risk intervals were >1.0, but the confidence intervals substantially overlapped 1.0. The attributable risk was one case of intussusception per 11 073 children vaccinated. CONCLUSIONS: RRV-TV is associated with an increased risk of intussusception. The risk is greatest 3 to 7 days after the first vaccination dose.

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.

Processes for obtaining nonmedical exemptions to state immunization laws.

OBJECTIVES: This study sought to determine the specific processes required for obtaining religious and philosophical exemptions to school immunization laws. METHODS: State health department immunization program managers in the 48 states that offer nonmedical exemptions were surveyed. Categories were assigned to reflect the complexity of the procedure within a state for obtaining an exemption. RESULTS: Sixteen of the states delegated sole authority for processing exemptions to school officials. Nine states had written policies informing parents who seek an exemption of the risks of not immunizing. The complexity of the exemption process, in terms of paperwork or effort required, was inversely associated with the proportion of exemptions field. CONCLUSIONS: In many states, the process of claiming a nonmedical exemption requires less effort than fulfilling immunization requirements.

Does influenza vaccination prevent asthma exacerbations in children?

OBJECTIVE: Influenza can exacerbate asthma, particularly in children. The effectiveness of influenza vaccine in preventing influenza-related asthma exacerbations, however, is not known. We evaluated influenza vaccine effectiveness in protecting children against influenza-related asthma exacerbations. STUDY DESIGN: We conducted a population-based retrospective cohort study with medical and vaccination records in 4 large health maintenance organizations in the United States during the 1993-1994, 1994-1995, and 1995-1996 influenza seasons. We studied children with asthma who were 1 through 6 years of age and who were identified by search of computerized databases of medical encounters and pharmacy dispensings. Main outcome measures were exacerbations of asthma evaluated in the emergency department or hospital. RESULTS: Unadjusted rates of asthma exacerbations were higher after influenza vaccination than before vaccination. After adjustment was done for asthma severity by means of a self-control method, however, the incidence rate ratios of asthma exacerbations after vaccination were 0.78 (95% CI: 0.55 to 1.10), 0.59 (0.43 to 0.81), and 0.65 (0.52 to 0.80) compared with the period before vaccination during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination protects against acute asthma exacerbations in children.

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.

The incidence of Kawasaki syndrome in West Coast health maintenance organizations.

BACKGROUND: Kawasaki syndrome (KS) causes an acute vasculitis of unknown etiology. It is a leading cause of acquired heart disease of children in Japan and the United States. METHODS: We examined the incidence of KS in a well-defined population group of children < or =6 years of age, using data collected through the Vaccine Safety Datalink (VSD) project. The VSD database contains information on >1 million children enrolled in four West Coast health maintenance organizations (HMOs). RESULTS: During 1993 through 1996 a total of 234 physician-diagnosed KS patients were reported in the 4 HMOs; 152 (65.0%) were boys and 195 (83.3%) were <5 years of age. The incidence of KS among children <5 years of age in the HMOs ranged from 9.0 to 19.1 per 100,000 person years. KS incidence was higher among boys in 3 of the sites. In the 2 sites with the highest number of KS patients, a seasonal occurrence of KS in winter and early spring was observed. Overall 226 (96.6%) of the KS patients were reported to have been hospitalized; hospitalization rates for children <5 years of age ranged from 9.0 to 16.8 per 100,000 person years. CONCLUSIONS: The incidence of KS in the HMOs was similar to that reported in other population-based studies in the United States and higher than estimates for Australia and several European countries.