Tetanus, diphtheria, and acellular pertussis vaccine coverage in adults with chronic respiratory conditions.

BACKGROUND: Pertussis is a highly contagious respiratory disease, and those with chronic respiratory illnesses may be at higher risk of infection and severe pertussis. Acellular pertussis-containing vaccines (Tdap) are recommended in the United States for those with risk factors, such as asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine Tdap vaccination rates among people with asthma or COPD compared with matched controls with type 2 diabetes and the general population. METHODS: This observational database study identified adults with asthma or COPD, and their matched controls, from a large US administrative health claims system between January 2008 and December 2014. Vaccination with Tdap was identified using current procedural terminology and national drug codes, and vaccination rates per 1000 patient-years and adjusted rate ratios (RR) were calculated using a generalized linear model with a Poisson distribution and 95% confidence intervals (CI). RESULTS: Vaccination rates were low overall; however, they were slightly higher in asthma than the general population cohort, with vaccination incidence RRs of 1.12 (95% CI, 1.08-1.17), 1.09 (95% CI, 1.06-1.11), and 1.11 (95% CI, 1.07-1.16) in those aged 18 to 44, 45 to 64, and 65 years and older, respectively. However, Tdap vaccination rates were lower in the COPD than in the general population cohort, with vaccination incidence RRs of 0.72 (95% CI, 0.60-0.86), 0.87 (95% CI, 0.83-0.91), and 0.94 (95% CI, 0.92-0.96), respectively. CONCLUSION: Pertussis vaccination rates were suboptimal among adults in general and adults with asthma or COPD. Work is needed to boost Tdap vaccination uptake among people with chronic respiratory conditions.

Increased Burden of Pertussis Among Adolescents and Adults With Asthma or COPD in the United States, 2007 to 2019.

BACKGROUND: Individuals with chronic respiratory illnesses may be at higher risk of pertussis infection and severe pertussis than those without. RESEARCH QUESTION: What is the incidence of pertussis and pertussis complications in cohorts with preexisting asthma or COPD vs age- and sex-matched control patients from the general population in the United States? STUDY DESIGN AND METHODS: This observational, retrospective study included individuals aged ≥ 10 years from an administrative health claims system between 2007 and 2019. Individuals with preexisting asthma or COPD were matched with control patients from the general population. The incidence of pertussis infections and pertussis-related complications were assessed overall and by age. The incidence of asthma or COPD exacerbations was also assessed before and after diagnosis of pertussis. RESULTS: In the general population, incidence per 100,000 person-years of pertussis infection ranged from 5.33 in 2007 to 13.04 in 2012, with highest (all years) in those aged 10 to 17 years. The risk of pertussis was higher for the asthma (rate ratio, 3.57; 95% CI, 3.25-3.92) and COPD cohorts (rate ratio, 1.83; 95% CI, 1.57-2.12) than the general population. Those with asthma or COPD had a 4.12-fold (95% CI, 3.16-5.38) and 2.82-fold (95% CI, 2.14-3.27) increased risk of pertussis with complications than the general population, respectively. Exacerbations were most frequent 30 days before pertussis diagnosis (incidence rate [IR], 25%) in the asthma cohort and 30 days before (IR, 26%) and after (IR, 22%) pertussis diagnosis, remaining elevated for 180 days after diagnosis, in the COPD cohort. INTERPRETATION: Among these insured individuals, asthma or COPD increased the risk for pertussis disease and complications vs the general population. COPD and asthma exacerbations were observed most frequently within 30 days of receiving a pertussis diagnosis and remained elevated, suggesting a long-term effect of pertussis in the COPD cohort.

Prenatal tetanus-diphtheria-acellular pertussis vaccine effectiveness at preventing infant pertussis.

OBJECTIVE: To evaluate the effectiveness of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine containing five pertussis components (Tdap5; Adacel®, Sanofi) when given during pregnancy at preventing pertussis in infants less than 2 months of age. METHODS: The US Centers for Disease Control and Prevention (CDC), in collaboration with the Emerging Infections Program (EIP) Network, undertook a case-control study evaluating the effectiveness of Tdap vaccination in pregnancy against pertussis in infants less than 2 months of age based on data collected by the EIP Network from 2011 through 2014. The dataset from the CDC/EIP Network study was used to conduct this product-specific vaccine effectiveness analysis of Tdap5 vaccination in pregnancy to prevent disease in young infants. The main outcome of interest was vaccine effectiveness in infants whose pregnant parents were vaccinated with Tdap5 between 27 and 36 weeks' gestation, in accordance with the ideal timing for Tdap vaccination in pregnancy recommended by the US Advisory Committee on Immunization Practices. Odd ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression, and vaccine effectiveness was calculated as (1-OR) × 100 %. RESULTS: There were 160 infant pertussis cases and 302 matched controls included in this Tdap5-specific study. Tdap5 effectiveness in preventing pertussis in infants whose pregnant parents were vaccinated between 27 and 36 weeks' gestation was 92.5 % (95 % CI, 38.5 %-99.1 %). Effectiveness of Tdap5 against pertussis-related hospitalization in infants whose pregnant parents were vaccinated between 27 and 36 weeks' gestation could not be calculated due to lack of discordance among matched cases and controls. Vaccination of the parents after pregnancy or less than 14 days before delivery did not protect infants from pertussis. CONCLUSIONS: Tdap5 vaccination in pregnancy between 27 and 36 weeks' gestation is highly effective at protecting young infants from pertussis. STUDY REGISTRATION: ClinicalTrials.gov, NCT05040802.

DTaP combination vaccine use and adherence: A retrospective cohort study.

Despite universal recommendation of the 4-dose diphtheria, tetanus, and pertussis (DTaP) vaccine series, coverage and timeliness in the US remain suboptimal. DTaP-containing combination vaccines (i.e. quadrivalent and pentavalent) are presumed to improve vaccine coverage rates and timeliness, but research supporting this claim is limited. We sought to investigate the associations between DTaP-containing vaccine use and adherence to the recommended DTaP immunization schedule among children in the US. Using a large claims database, we identified privately insured children born between 2009 and 2016 that received ≥1 DTaP-containing vaccine and had ≥24 months of enrollment from birth, excluding those with DTaP vaccinations not aligned with approved dose indications. Children were classified by DTaP-containing vaccine receipt: combination vaccines only, stand-alone vaccines only, or a mixture of both. Outcome measures included: 1) completion of the 4-dose series and 2) timely receipt of doses. Outcomes were adjusted for gender, birth year, race, and socioeconomic status. The study cohort contained 412,441 children. Of these, 40.5% (167,084) received combination vaccines only, 14.9% (61,342) received stand-alone vaccines only, and 44.6% (184,015) received a mixture of both. Combination vaccine recipients were nearly 3 times as likely to complete the 4-dose series (OR 2.93 (95% CI: 2.88, 2.99)) and for all doses received, more than 4 times as likely to receive doses on time (OR 4.12 (4.04, 4.21), relative to stand-alone vaccine recipients. Significance disparities in adherence were also observed, where minorities were up to 30% less likely (OR 0.70 (0.68, 0.71)) to complete the 4-dose series and up to 27% less likely (OR 0.73 (0.72, 0.75)) to receive doses on time, relative to white children. Our findings demonstrated that adherence to the recommended DTaP immunization schedule was significantly greater among combination vaccine recipients, relative to stand-alone recipients. Further research is needed to investigate underlying causes of disparities in adherence.

Safety and use of tetanus-diphtheria-acellular pertussis-5 (Tdap5) vaccine during pregnancy: findings from 11 years of reporting to a pregnancy registry.

The "Adacel (Tdap5) Pregnancy Registry" was used to identify 1182 women who received the tetanus, diphtheria, acellular pertussis [5 components] (Tdap5) vaccine during pregnancy from 2005 to 2016. To evaluate the safety and use of prenatal Tdap5, we calculated the rate of maternal, obstetrical, pregnancy and neonatal outcomes following Tdap5 pregnancy exposure and assessed vaccine uptake by year and trimester of exposure. The most commonly reported maternal adverse events included injection site reactions (2.6%; 95% Confidence Interval 1.8%, 3.7%), nervous system events (1.3%; 0.8%, 2.1%) and musculoskeletal events (1.1%; 0.6%, 1.9%). The most commonly reported complications of pregnancy were hypertension/preeclampsia (5.5%; 3.3%, 8.9%) and gestational diabetes (2.5%; 1.1%, 5.3%), while those for labor and delivery were premature labor (2.9%; 1.4%, 5.7%) and premature membrane rupture (1.5%; 0.4%, 3.8%). These rates were similar to, or lower than those reported for the general population of pregnant women. Among pregnancies with known birth outcomes (N = 275), 90.4% (86.2%, 93.4%) resulted in a live birth, 5.9% (3.6%, 9.5%) in spontaneous abortion, 3.0% (1.4%, 5.8%) in stillbirth, and 0.7% (0.0%, 2.8%) in ectopic pregnancies. Most newborns had normal APGAR scores and birth weights (98.1% and 93.0%, respectively), and only two reported a congenital anomaly (0.7%; 0.0%, 2.8%). An influx of reports in 2012 with third trimester Tdap5 exposure coincided with the 2012 updated Advisory Committee on Immunization Practices recommendations. This analysis did not identify any safety concerns across the continuum of maternal, obstetrical, pregnancy, and neonatal outcomes in women who received Tdap5 vaccination during pregnancy.

Hypotonic-hyporesponsive Episodes After Diphtheria, Tetanus and Acellular Pertussis Vaccination.

BACKGROUND: Hypotonic-hyporesponsive episode (HHE) after whole cell pertussis vaccination is a known adverse event. Less is known about the risk of HHE after administration of acellular pertussis vaccines. METHODS: Using parental interviews, this study actively surveyed for HHE among infants after doses 1 and 2 of acellular pertussis vaccine. RESULTS: We interviewed the parents of 52,531 infants. HHE was reported at a rate of 22.8 per 100,000 doses (95% CI: 11.8-39.9) of acellular pertussis vaccine, approximately 45 episodes per 100,000 children. CONCLUSIONS: These rates are lower than HHE rates reported after whole cell pertussis vaccines and within the range of HHE rates reported in other studies of acellular pertussis vaccines.

Arthus Reaction as an Adverse Event Following Tdap Vaccination.

Repeat administration of tetanus toxoid-containing vaccines has rarely been associated with Arthus phenomenon, an immune-complex reaction. In the US, since 2013, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines (Tdap) have been recommended for administration during each pregnancy. Separately, in 2019, one Tdap was approved for repeat administration in adults in the US. We aimed to describe trends in spontaneously reported Arthus reactions following Tdap in the US and to assess the risk of this phenomenon in persons receiving Tdap repeatedly. We reviewed Arthus reports in the Vaccine Adverse Events Reporting System (VAERS), 1990-2018. Reporting rates were estimated using Tdap doses distributed data. A systematic literature review was conducted in MEDLINE for any Arthus cases reported in Tdap clinical trials and observational studies published between 2000 and 2019. We found 192 Arthus reports in VAERS after any vaccine, of which 36 occurred after Tdap and none were reported during pregnancy. The Arthus reporting rate was estimated at 0.1 per million doses distributed. We identified eight published studies of Tdap administration within five years after a previous dose of tetanus toxoid-containing vaccine; no Arthus cases were reported. We conclude that Arthus reaction following Tdap is extremely rare. Increasing frequency of repeat Tdap administration in adults in the US did not result in a detectable increase in reporting rates of this phenomenon, confirming the favorable safety profile of Tdap.

Brand-specific rates of pertussis disease among Wisconsin children given 1-4 doses of pertussis Vaccine, 2010-2014.

BACKGROUND: Acellular pertussis vaccines were initially licensed based on placebo-controlled efficacy trials, but such trials are no longer ethical. The effectiveness of current pertussis vaccines among properly vaccinated children <5 years is so high that a randomized trial is infeasible. Fluctuations in pertussis incidence and characteristics of the US vaccine marketplace make selection of suitable controls for a case-control study problematic. To satisfy an FDA requirement to evaluate rates of pertussis following licensure of Pentacel® vaccine, we used a case-cohort study design with a novel method for characterizing the cohort population. METHODS: This prospective, observational study was conducted in Wisconsin from 2010 to 2014 among Wisconsin residents <60 months of age who received ≤four doses of pertussis vaccine (surveillance population). Cases were identified by the Wisconsin Division of Public Health. Characteristics and pertussis vaccinations of the surveillance population were estimated by ongoing random telephonic survey. The primary objective was to determine rates of pertussis disease among those who received only Pentacel vaccine (Group 1) vs those who received a single brand of vaccine other than Pentacel vaccine (Group 2). RESULTS: 1195 pertussis cases were identified. It was estimated that the surveillance population accrued a total of 1,133,403 person-years (Group 1, 39%; Group 2, 41%; Group 3 [those not in Group 1 or Group 2], 20%). Pertussis rates were similar in Group 1 (98.9/100,000) and Group 2 (96.2/100,000); rate ratios were 1.03 (unadjusted; 90% CI, 0.92-1.15) and 0.99 (adjusted; 90% CI, 0.89-1.12). Persons with one or more delayed vaccinations had a 66% higher risk of pertussis (90% CI, 39-96%). DISCUSSION: Pertussis protection was not found to differ for recipients of the newly licensed vs other available pertussis vaccines. Delayed vaccination substantially increased risk of pertussis. Sample survey methodology was able to characterize the study cohort and enable an otherwise-infeasible study. Clinical Trial Registry number: ClinicalTrials.gov, NCT01129362.

Randomized study of immune responses to two Tdap vaccines among adolescents primed with DTaP and comparison with results among adolescents primed with DTwP.

BACKGROUND: It has been reported that persons primed with acellular (DTaP) pertussis vaccines have reduced duration of pertussis protection compared with those primed with whole-cell (DTwP) vaccines. However, due to the rapid transition to acellular vaccines, studies attempting directly to compare protection among DTaP-primed vs DTwP-primed individuals are subject to confounding by age and other limitations of ecological studies. Using validated assay results and stored sera from multiple Tdap studies, we evaluated two licensed Tdap vaccines among DTaP-primed adolescents to allow comparison with results obtained in the same laboratory from earlier studies involving DTwP-primed adolescents. METHODS: Participants 11-12 years of age who had received exactly 5 doses of DTaP vaccine prior to 7 years of age were randomly assigned in 2012 to receive one of two licensed Tdap vaccines. Serum specimens obtained pre- and post-vaccination were assayed for responses to the vaccines. Current results were then compared to results obtained in the same laboratory from prior randomized Tdap studies conducted among adolescents primed with DTwP or DTaP. RESULTS: Both Tdap vaccines produced strong antibody responses to diphtheria and tetanus; responses to contained pertussis antigens were consistent with the differing levels of those antigens in each Tdap vaccine. However, postvaccination pertussis antibody responses were as much as 71% lower in these DTaP-primed adolescents compared with responses among DTwP-primed adolescents in a prior study of the same two Tdap vaccines. In contrast, results from the present study were similar to those seen in another study of Tdap among DTaP-primed adolescents. DISCUSSION: Taken together, these results from randomized clinical trials provide direct evidence of reduced antibody responses to both licensed Tdap vaccines among adolescents primed with DTaP vaccine, compared with adolescents primed with DTwP vaccine. Clinical trial registry number: ClinicalTrials.gov, NCT01629589.

Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose.

BACKGROUND: Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. METHODS: We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. RESULTS: A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups. CONCLUSIONS: A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.

Preventable mix-ups of tuberculin and vaccines: reports to the US Vaccine and Drug Safety Reporting Systems.

BACKGROUND: Errors involving the mix-up of tuberculin purified protein derivative (PPD) and vaccines leading to adverse reactions and unnecessary medical management have been reported previously. OBJECTIVES: To determine the frequency of PPD-vaccine mix-ups reported to the US Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS), characterize adverse events and clusters involving mix-ups and describe reported contributory factors. METHODS: We reviewed AERS reports from 1969 to 2005 and VAERS reports from 1990 to 2005. We defined a mix-up error event as an incident in which a single patient or a cluster of patients inadvertently received vaccine instead of a PPD product or received a PPD product instead of vaccine. We defined a cluster as inadvertent administration of PPD or vaccine products to more than one patient in the same facility within 1 month. RESULTS: Of 115 mix-up events identified, 101 involved inadvertent administration of vaccines instead of PPD. Product confusion involved PPD and multiple vaccines. The annual number of reported mix-ups increased from an average of one event per year in the early 1990s to an average of ten events per year in the early part of this decade. More than 240 adults and children were affected and the majority reported local injection site reactions. Four individuals were hospitalized (all recovered) after receiving the wrong products. Several patients were inappropriately started on tuberculosis prophylaxis as a result of a vaccine local reaction being interpreted as a positive tuberculin skin test. Reported potential contributory factors involved both system factors (e.g. similar packaging) and human errors (e.g. failure to read label before product administration). CONCLUSIONS: To prevent PPD-vaccine mix-ups, proper storage, handling and administration of vaccine and PPD products is necessary.

Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine in the USA.

BACKGROUND: In a prospective, randomized pivotal phase III clinical trial, the immunogenicity and reactogenicity of a tetanus-diphtheria-acellular pertussis vaccine (Tdap) and a tetanus-diphtheria vaccine (Td) vaccine were studied in participants aged 11-64 years. Here we report antibody persistence through 10 years after vaccination. METHODS: Participants who received Tdap or Td in the original phase III trial and provided pre- and post-vaccination serum samples were recruited to donate sera at 1, 3, 5 and 10 years post-vaccination. Antibody concentrations were measured using standard assay techniques. RESULTS: Initially, 1457 Tdap and 1152 Td recipients were included; of these, 175 persons from Tdap group were available at the final study bleed point. Nearly all adolescents in both groups had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥95% of vaccinees at 5 and 10 years. Among adults, ≥94% had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥80% at 5 and 10 years. Nearly all participants had tetanus antibodies ≥0.1 IU/mL throughout the study. PT antibodies declined to pre-vaccination levels approximately 5 years post-vaccination; FHA, PRN and FIM antibodies waned at 5 and 10 years but remained several-fold higher than pre-vaccination levels. CONCLUSIONS: Tdap and Td provide long-lasting protective immune responses against diphtheria and tetanus. Pertussis antibodies following Tdap generally exceeded pre-vaccination levels throughout the study, but showed substantial waning. These data may inform discussion of the need for repeat Tdap booster vaccinations among adults. TRIAL REGISTRATION: The original phase III clinical trial, as well as the 1-, 3-, and 5-year serology follow-up studies were conducted prior to mandatory registration. The 10-year serology follow-up data collection was performed as part of a repeat Tdap administration clinical trial that was registered under clinicaltrials.gov number NCT01439165.

Data mining in the US using the Vaccine Adverse Event Reporting System.

The US Vaccine Adverse Event Reporting System (VAERS), which is charged with vigilance for detecting vaccine-related safety issues, faces an increasingly complex immunisation environment. Since 1990, steady increases in vaccine licensing and distribution have resulted in increasing numbers of reports to VAERS. Prominent features of current reports include more routine vaccine co-administration and frequent reports of new postvaccination clinical syndromes. Data-mining methods, based on disproportionality analyses, are one strategy being pursued by VAERS researchers to increase the utility of its complex database. The types of analyses used include proportional reporting ratios, association rule discovery, and various 'historic limits' methods that compare observed versus expected event counts. The use of such strategies in VAERS has been primarily supplemental and retrospective. Signals for inactivated influenza, typhoid and tetanus toxoid-containing vaccines have been successfully identified. Concerns flagged through data mining should always be subject to clinical case review as a first evaluation step. Persistent issues should be subject to formal hypothesis testing in large linked databases or other controlled-study settings. Automated data-mining techniques for prospective use are currently undergoing development and evaluation within VAERS. Their use (as one signal-detection tool among many) by trained medical evaluators who are aware of system limitations is one legitimate approach to improving the ability of VAERS to generate vaccine-safety hypotheses. Such approaches are needed as more new vaccines continue to be licensed.

Safety of DTaP-IPV/Hib vaccine administered routinely to infants and toddlers.

BACKGROUND: The combination DTaP-IPV/Hib vaccine was licensed in the United States in 2008 for children ages 6weeks through 4years with doses administered at 2, 4, 6, and 15-18months of age. The aim of this study was to assess the safety of DTaP-IPV/Hib vaccine routinely administered as part of clinical care to infants at Kaiser Permanente Northern California. METHODS: This was an observational, retrospective study that included all 2-month-old infants vaccinated with either DTaP-IPV/Hib or another DTaP-containing vaccine. We monitored all subjects for non-elective hospitalizations, emergency department visits and selected outpatient outcomes (seizures, Guillain-Barré Syndrome, encephalopathy, encephalitis, alteration of consciousness, meningitis, hypersensitivity reactions, immune thrombocytopenic purpura, hemolytic anemia, type 1 diabetes, and Kawasaki disease) beginning with their first dose through 6months after a 4th dose or until 24months of age. We calculated incidence rate ratios (IRRs) in the primary analysis by comparing rates of outcomes during the post-vaccination risk interval with rates during a comparison interval more remote from vaccination. Secondary analyses compared outcomes after DTaP-IPV/Hib with those after other DTaP-containing vaccines. We reviewed the medical records of selected outcomes. RESULTS: From October 1, 2008 through July 31, 2010, 14,042 subjects received a first dose of DTaP-IPV/Hib, 13,194 received 2 doses, 12,548 received 3 doses and 6702 received 4 doses. Overall, there were 166 comparisons with significantly elevated IRRs and 165 comparisons with significantly reduced IRRs. Medical record review of outcomes with significantly elevated IRRs in both the primary and secondary analyses did not suggest any relationship with DTaP-IPV/Hib. CONCLUSIONS: This study did not detect any safety concerns following DTaP-IPV/Hib and provides reassurance that DTaP-IPV/Hib administered as part of routine care was not associated with unexpected safety risks. ClinicalTrials.gov Identifier: NCT00804284.

Post-licensure safety surveillance study of routine use of tetanus toxoid, reduced diphtheria toxoid and 5-component acellular pertussis vaccine.

An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults.

Neonatal death: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data.

More than 40% of all deaths in children under 5 years of age occur during the neonatal period: the first month of life. Immunization of pregnant women has proven beneficial to both mother and infant by decreasing morbidity and mortality. With an increasing number of immunization trials being conducted in pregnant women, as well as roll-out of recommended vaccines to pregnant women, there is a need to clarify details of a neonatal death. This manuscript defines levels of certainty of a neonatal death, related to the viability of the neonate, who confirmed the death, and the timing of the death during the neonatal period and in relation to immunization of the mother.

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.

Safety and immunogenicity of tetanus-diphtheria-acellular pertussis vaccine administered to children 10 or 11 years of age.

Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.).