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.

Postlicensure evaluation of the effectiveness of seven valent pneumococcal conjugate vaccine.

OBJECTIVE: To evaluate the impact of the introduction and routine use of seven valent pneumococcal conjugate vaccine on the epidemiology of invasive pneumococcal disease within the Northern California Kaiser Permanente (KP) population. METHODS: Surveillance for invasive pneumococcal disease has been in place within KP since 1995. Isolates from normally sterile sites in children are routinely sent for serotyping. Cases of invasive disease are identified through review of automated microbiology records within KP. Incidence rates of invasive disease were compared for the period before and after routine use of pneumococcal conjugate vaccine in children. RESULTS: The incidence of invasive pneumococcal disease caused by vaccine serotypes before the licensure and routine use of pneumococcal conjugate vaccine ranged between 51.52 and 98.15 cases per 100 000 person years in children <1 year of age and fell to 9.35 after introduction of vaccine. The incidence in children <2 years of age was 81.67 to 113.80 before introduction and 38.22 cases per 100 000 person years after introduction of the vaccine into the general population. These reductions in disease rates exceeded the average vaccine coverage substantially in each age group. No increase in disease incidence was observed for possibly cross-reacting serotypes or nonvaccine serotypes. CONCLUSION: The introduction and routine use of pneumococcal conjugate vaccine in our population have been associated with a substantial reduction in invasive disease incidence in children <5 years of age.

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.

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.

Impact of the change in polio vaccination schedule on immunization coverage rates: a study in two large health maintenance organizations.

OBJECTIVE: In January 1997, one of the most significant changes to United States vaccine policy occurred when polio immunization guidelines changed to recommend a schedule containing inactivated polio vaccine (IPV). There were concerns that parent or physician reluctance to accept IPV into the routine childhood immunization schedule would lead to lowered coverage. We determined whether adoption of an IPV schedule had a negative impact on immunization coverage. DESIGN: A cohort study of 2 large health maintenance organizations (HMOs), Group Health Cooperative and Kaiser Permanente Northern California, was conducted. For analysis at 12 months of age, children who were born between October 1, 1996, and December 31, 1997, and were commercially insured and covered by Medicaid were continuously enrolled; for analysis at 24 months of age, children who were born between October 1, 1996, and June 30, 1997, and were commercially insured and covered by Medicaid were continuously enrolled. The 3 measures of immunization status at 12 and 24 months of age were up-to-date status, cumulative time spent up-to-date, and the number of missed opportunity visits. RESULTS: At both HMOs, children who received IPV were as likely to be up to date at 12 months as were children who received oral poliovirus vaccine (OPV), whereas at Group Health, children who received IPV were slightly more likely to be up to date at 24 months (relative risk: 1.12; 95% confidence interval [CI]: 1.05, 1.19). These findings were consistent for children who were covered by Medicaid. At Kaiser Permanente, children who received IPV spent ~3 fewer days up to date in the first year of life, but this difference did not persist at 2 years of age. At Group Health, children who received IPV were no different from those who received OPV in terms of days spent up to date by 1 or 2 years of age. At Group Health, children who received IPV were less likely to have a missed opportunity by 12 months old (odds ratio [OR] 0.46; 95% CI: 0.31, 0.70), but this finding did not persist at 24 months of age. At Kaiser Permanente, children who received IPV were more likely to have a missed opportunity by 12 months (OR 2.06; 95% CI: 1.84, 2.30), and 24 months of age (OR 1.50; 95% CI: 1.36, 1.67). CONCLUSIONS: The changeover from an all-OPV schedule to one containing IPV had little if any negative impact on vaccine coverage. Use of IPV was associated with a small increase in the likelihood of being up to date at 2 years of age at one of the HMOs and conversely was associated with a small increase in the likelihood of having a missed-opportunity visit in the other HMO.polio, poliomyelitis, vaccination, immunization coverage.

Variation in clinician recommendations for multiple injections during adoption of inactivated polio vaccine.

OBJECTIVES: To describe variation in clinician recommendations for multiple injections during the adoption of inactivated poliovirus vaccine (IPV) in 2 large health maintenance organizations (HMOs), and to test the hypothesis that variation in recommendations would be associated with variation in immunization coverage rates. DESIGN: Cross-sectional study based on a survey of clinician practices 1 year after IPV was recommended and computerized immunization data from these clinicians' patients. STUDY SETTINGS: Two large West Coast HMOs: Kaiser Permanente in Northern California and Group Health Cooperative of Puget Sound. OUTCOME MEASURES: Immunization status of 8-month-olds and 24-month-olds cared for by the clinicians during the study. RESULTS: More clinicians at Group Health (82%), where a central guideline was issued, had adopted the IPV/oral poliovirus vaccine (OPV) sequential schedule than at Kaiser (65%), where no central guideline was issued. Clinicians at both HMOs said that if multiple injections fell due at a visit and they elected to defer some vaccines, they would be most likely to defer the hepatitis B vaccine (HBV) for infants (40%). At Kaiser, IPV users were more likely than OPV users to recommend the first HBV at birth (64% vs 28%) or if they did not, to defer the third HBV to 8 months or later (62% vs 39%). In multivariate analyses, patients whose clinicians used IPV were as likely to be fully immunized at 8 months old as those whose clinicians used all OPV. At Kaiser, where there was variability in the maximum number of injections clinicians recommended at infant visits, providers who routinely recommended 3 or 4 injections at a visit had similar immunization coverage rates as those who recommended 1 or 2. At both HMOs, clinicians who strongly recommended all possible injections at a visit had higher immunization coverage rates at 8 months than those who offered parents the choice of deferring some vaccines to a subsequent visit (at Kaiser, odds ratio [OR]: 1.2; 95% confidence interval [CI]: 1.0-1.5; at Group Health, OR: 1.8; 95% CI: 1.1-2.8). CONCLUSIONS: Neither IPV adoption nor the use of multiple injections at infant visits were associated with reductions in immunization coverage. However, at the HMO without centralized immunization guidelines, IPV adoption was associated with changes in the timing of the first and third HBV. Clinical policymakers should continue to monitor practice variation as future vaccines are added to the infant immunization schedule.

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.

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.

The hidden costs of infant vaccination.

Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1-8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infant's vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of $25 to reduce injections from 4 to 3, $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean costs of $42 in medical utilization and $192 in work-loss among the families who experienced those events (Ns=62 and 35, respectively). When averaged among all 1657 study infants, vaccine-associated symptoms after the index vaccination visit resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct nonmedical costs, yielding total financial costs of $7.70. Parents of infants who had vaccine-associated symptoms said they would have paid a median of $50 to avoid these symptoms. Fever and fussiness were associated in logistic regression analysis with a two-fold increase in the odds of medical utilization, and fever with more than a three-fold increase in work loss. We conclude that multiple injections during a single clinic visit entail psychological costs. The psychological costs of vaccine-associated symptoms, as measured by willingness-to-pay methods, are higher than those resulting from multiple injections. The financial costs of medical utilization and work-loss resulting from common vaccine-associated symptoms are non-negligible and should be incorporated in economic analyses.

Does influenza vaccination exacerbate asthma? Analysis of a large cohort of children with asthma. Vaccine Safety Datalink Team.

CONTEXT: Although influenza vaccination is recommended for children with asthma, only a minority are vaccinated. One reason for low influenza vaccine coverage among children with asthma may be concern that influenza vaccination may induce an exacerbation of asthma. OBJECTIVE: To evaluate the safety of influenza vaccination in children with asthma, we studied the incidence of hospitalizations and emergency department visits for asthma following influenza vaccination. DESIGN: Retrospective cohort study-analysis of population-based computerized medical and vaccination records. SETTING: : Four large health maintenance organizations on the West Coast of the United States. SUBJECTS: Children with asthma 1 through 6 years of age, identified by search of computerized databases of medical encounters and pharmacy prescriptions. MAIN OUTCOME MEASURES: Exacerbations of asthma. RESULTS: In unadjusted analyses vaccination was associated with high rates of asthma exacerbations. However, after adjusting for asthma severity using a self-control method, the incidence rate ratios of asthma exacerbations after vaccination were 0.58 (95% confidence interval, 0.36-0.95), 0.74 (95% confidence interval, 0.47-1.17), and 0.98 (95% confidence interval, 0.76-1.27) during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination does not result in acute asthma exacerbations in children. Concern about possible exacerbation of asthma is not a valid reason to not vaccinate children with asthma against influenza.

Efficacy of pneumococcal conjugate vaccines in large scale field trials.

BACKGROUND: Each year Streptococcus pneumoniae causes approximately 1.2 million deaths worldwide from pneumonia. In the United States S. pneumoniae is estimated to cause 500,000 cases of pneumonia and 7 million episodes of acute otitis media annually. CONJUGATE VACCINES: The current pneumococcal polysaccharide vaccine is ineffective in children <2 years old and may not produce an adequate antibody response until children reach the age of 5 years. Pneumococcal conjugate vaccines are immunogenic after primary and booster vaccination in young children and in children and adults with immunodeficiencies. Immunization with conjugate vaccines also induces a strong and rapid anamnestic response and enhanced functional activity of antibodies. Two large scale field trials of pneumococcal conjugate vaccines were initiated in 1995, 1 in California and 1 in Finland. The California trial, involving 37,868 children, evaluated the efficacy of a 7-valent conjugate for the prevention of invasive pneumococcal disease and secondarily evaluated its efficacy for acute otitis media and pneumonia. RESULTS: Preliminary results indicate 94% efficacy against invasive pneumococcal disease caused by serotypes included in the vaccine in fully or partially vaccinated children. Preliminary evidence from large scale field trials indicates that pneumococcal conjugate vaccines are effective in reducing invasive pneumococcal disease as well as acute otitis media and pneumonia in children and represents a significant advance in the prevention of childhood infectious diseases.

The Vaccine Safety Datalink: immunization research in health maintenance organizations in the USA.

The Vaccine Safety Datalink is a collaborative project involving the National Immunization Program of the Centers for Disease Control and Prevention and several large health maintenance organizations in the USA. The project began in 1990 with the primary purpose of rigorously evaluating concerns about the safety of vaccines. Computerized data on vaccination, medical outcome (e.g. outpatient visits, emergency room visits, hospitalizations, and deaths) and covariates (e.g. birth certificates, census data) are prospectively collected and linked under joint protocol at multiple health maintenance organizations for analysis. Approximately 6 million persons (2% of the population of the USA) are now members of health maintenance organizations participating in the Vaccine Safety Datalink, which has proved to be a valuable resource providing important information on a number of vaccine safety issues. The databases and infrastructure created for the Vaccine Safety Datalink have also provided opportunities to address vaccination coverage, cost-effectiveness and other matters connected with immunization as well as matters outside this field.

Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children.

CONTEXT: Pneumococcal conjugate vaccine for infants has recently been found effective against meningitis, bacteremia, pneumonia, and otitis media. OBJECTIVE: To evaluate the projected health and economic impact of pneumococcal conjugate vaccination of healthy US infants and young children. DESIGN: Cost-effectiveness analysis based on data from the Northern California Kaiser Permanente randomized trial and other published and unpublished sources. SETTING AND PATIENTS: A hypothetical US birth cohort of 3.8 million infants. INTERVENTIONS: Hypothetical comparisons of routine vaccination of healthy infants, requiring 4 doses of pneumococcal conjugate vaccine (at 2, 4, 6, and 12-15 months), and catch-up vaccination of children aged 2 to 4.9 years requiring 1 dose, with children receiving no intervention. MAIN OUTCOME MEASURES: Cost per life-year saved and cost per episode of meningitis, bacteremia, pneumonia, and otitis media prevented. RESULTS: Vaccination of healthy infants would prevent more than 12000 cases of meningitis and bacteremia, 53000 cases of pneumonia, 1 million episodes of otitis media, and 116 deaths due to pneumococcal infection. Before accounting for vaccine costs, the vaccination program would save $342 million in medical and $415 million in work-loss and other costs from averted pneumococcal disease. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose. At the manufacturer's list price of $58 per dose, infant vaccination would cost society $80000 per life-year saved or $160 per otitis media episode prevented (other estimated costs would be $3200 per pneumonia case prevented, $15000 for bacteremia, and $280000 for meningitis). The cost-effectiveness of an additional program to administer 1 dose of vaccine to children aged 2 to 4.9 years would vary depending on the children's ages, relative risks of pneumococcal disease, and vaccine cost. CONCLUSIONS: Pneumococcal conjugate vaccination of healthy US infants has the potential to be cost-effective. To achieve cost savings, its cost would need to be lower than the manufacturer's list price. In addition to tangible costs, the vaccine should be appraised based on the less tangible value of preventing mortality and morbidity from pneumococcal disease.

Parents' preferences for outcomes associated with childhood vaccinations.

BACKGROUND: The number of shots in the childhood immunization schedule has been increasing and is likely to continue to increase in the coming years. Consideration of the psychologic costs of multiple injections, adverse events and vaccine-preventable disease is therefore growing in importance. METHODS: We assessed parent preferences, using both the time tradeoff (i.e. amount of parent time willing to trade) and willingness-to-pay (i.e. dollars willing to pay) metrics, for possible outcomes of vaccination among 206 parents of infants receiving care at Kaiser, Northern California Region. We also explored the relationship between preferences and subject characteristics. RESULTS: In general the amount of time subjects were willing to give up and the quantity of money they were willing to spend to avoid an outcome increased with the severity of the outcome. Preferences for our six main outcomes of interest all differed from one another (P < 0.0001, Tukey's multiple comparisons procedure). Rank correlation coefficients between time tradeoff and willingness-to-pay values for the six main outcomes ranged from 0.42 to 0.52 (all P < 0.004). Subject characteristics, including education, income, race/ethnicity and the child's birth order, did not explain the variation in parent preferences. CONCLUSIONS: In general subjects were willing to give up more money or time to avoid less desired outcomes. They were willing to give up only very small amounts of their own life expectancy or money to avoid minor, temporary outcomes (e.g. moderate fussiness, fever and pain) whereas they were willing to forego substantial lengths of their life or amounts of money to avoid a major, permanent outcome (i.e. permanent disability). Nonetheless much variation surfaced in the amount of time (or money) subjects were willing to trade to avoid outcomes. If this variation represents true differences in preferences, guideline developers must consider the role of individual parent preferences in decisions concerning vaccination.

Assessing costs and cost effectiveness of pneumococcal disease and vaccination within Kaiser Permanente.

OBJECTIVE: To review studies of the costs of pneumococcal disease and the cost effectiveness of pneumococcal conjugate vaccination conducted in association with the Kaiser Permanente Pneumococcal conjugate Efficacy Trial. RESULTS: for each birth cohort of 3.8 million infants, routine pneumococcal conjugate vaccination program for healthy infants would prevent more than 12000 (78% of potential) meningitis and bacteremia cases, 53000 (69% of potential) pneumonia cases, and 1 million (8% of potential) otitis media episodes. Before accounting for vaccine costs, the vaccination program would reduce the costs of pneumococcal disease by $342 million in medical and $415 million in work-loss and other costs. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose.

Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers.

OBJECTIVES: The objectives of this study were (1) to determine the safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate (PNCRM7) vaccine in infants and (2) to determine the effect of concurrent hepatitis B immunization during the primary series and the effect of concurrent diphtheria and tetanus toxoid and acellular pertussis [DTaP (ACEL-IMUNE)] and conjugate CRM197 Haemophilus influenzae type b [HbOC (HibTITER) immunization at time of the booster dose on the safety and immunogenicity of PNCRM7and these other concurrently administered vaccines. METHODS: This was a randomized double-blinded study in 302 healthy infants in the Northern California Kaiser Permanente (NCKP) Health Plan. Infants received either PNCRM7 vaccine or meningococcal group C conjugate vaccine as a control at 2, 4 and 6 months of age and a booster at 12 to 15 months of age. Study design permitted the evaluation of immunology and safety of concurrent administration of routine vaccines. Antibody titers were determined on blood samples drawn before and 1 month after the primary series and the booster dose. RESULTS: After the third dose of PNCRM7 geometric mean concentrations (GMCs) ranged from 1.01 for serotype 9V to 3.72 microg/ml for serotype 14. More than 90% of all subjects had a post-third dose titer of > or =0.15 microg/ml for all serotypes, and the percentage of infants with a post-third dose titer of > or =1.0 microg/ml ranged from 51% for type 9V to 89% for type 14. After the PNCRM7 booster dose, the GMCs of all seven serotypes increased significantly over both post-Dose 3 and pre-Dose 4 antibody levels. In the primary series there were no significant differences in GMCs of pneumococcal antibodies between the subjects given PN-CRM7 alone or concurrently with hepatitis B vaccine. At the toddler dose concurrent administration of PNCRM7 and DTaP and HbOC resulted in a near conventional threshold for statistical significance of a post-Dose 4 GMC for serotype 23F [alone 6.75 mirog/ml vs. concurrent 4.11 microg/ml (P = 0.057)] as well as significantly lower antibody GMCs for H. influenza polyribosylribitol phosphate, diphtheria toxoid, pertussis toxin and filamentous hemagglutinin. For all antigens there were no differences between study groups in defined antibody titers that are considered protective. CONCLUSION: We conclude that PNCRM7 vaccine was safe and immunogenic. When this vaccine was administered concurrently at the booster dose with DTaP and HbOC vaccines, lower antibody titers were noted for some of the antigens when compared with the antibody response when PNCRM7 was given separately. Because the GMCs of the booster responses were all generally high and all subjects achieved similar percentages above predefined antibody titers, these differences are probably not clinically significant.

Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status. Centers for Disease Control and Prevention Vaccine Safety Datalink Group.

CONTEXT: Studies have noted that health care professionals may not conform to proper immunization schedules for premature and low-birth-weight infants in the United States. Little is known about the success of current efforts to immunize these high-risk infants. OBJECTIVE: To describe current immunization practices for premature and low-birth-weight infants and ascertain risk factors for poor immunization status, using large population-based data sources. DESIGN AND SETTING: Cohort and case-control analyses of immunization data tracked from March 1991 through March 1997 for 3 large health maintenance organizations (HMOs) participating in the Centers for Disease Control and Prevention's Vaccine Safety Datalink project. PARTICIPANTS: A total of 11580 low-birth-weight and premature infants were enrolled from birth to age 2 months; 6832 of these were continuously enrolled from birth to age 24 months. At age 2 months, there were 173373 full-term, normal-birth-weight infants enrolled as controls; at age 24 months, there were 103 324. MAIN OUTCOME MEASURES: Age-specific immunization status by prematurity and birth weight (<1500 g, 1500-2500 g, born at <38 weeks' gestation with birth weight of >2500 g, or full-term with normal birth weight) and patient characteristics associated with up-to-date status. RESULTS: At each age, infants weighing less than 1500 g at birth had lower up-to-date immunization levels than other infants. At age 6 months, 52% to 65% of infants weighing less than 1500 g were up-to-date at each of the 3 HMOs compared with 69% to 73% of those weighing 1500 to 2500 g, 66% to 80% of premature infants weighing more than 2500 g, and 65% to 76% of full-term, normal-birth-weight infants. By age 24 months, 78% to 86% of infants weighing less than 1500 g were up-to-date, significantly less than heavier infants, who had levels of 84% to 89%. Well-child preventive care strongly predicted immunization status, while concomitant pulmonary disease did not. CONCLUSIONS: Our data suggest that infants born prematurely are vaccinated at levels approaching that of the general population, but levels of vaccination for very low-birth-weight infants lag slightly behind.