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JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1). JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2). On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged18 years (3). During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States. CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged18 years vaccinated before August 9, 2022. The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies. Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.

Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population.Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination.From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54).Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.

The COVID-19 pandemic caused an abrupt drop in in-person health care (inpatient, Emergency Department, outpatient) and an increase in telehealth care, which poses challenges in vaccine safety studies that identify outcomes from in-person encounters. We examined the changes in incidence rates of selected encounter-based outcomes during the COVID-19 pandemic.We assembled a cohort of members from 8 Vaccine Safety Datalink sites from January 1, 2017 through December 31, 2020. Using ICD-10 diagnosis codes or laboratory criteria, we identified 21 incident outcomes in traditional in-person settings and all settings. We defined 4 periods in 2020: January-February (pre-pandemic), April-June (early pandemic), July-September (middle pandemic), and October-December (late pandemic). We defined four corresponding periods in each year during 2017-2019. We calculated incidence rates, conducted difference in difference (DiD) analyses, and reported ratios of incidence rate ratios (RRR) to examine changes in rates from pre-pandemic to early, middle, and late pandemic in 2020, after adjusting for changes across similar periods in 2017-2019.Among 10 million members, regardless of setting and after adjusting for changes during 2017-2019, we found that incidence rates of acute disseminated encephalomyelitis, encephalitis/myelitis/encephalomyelitis/meningoencephalitis, and thrombotic thrombocytopenic purpura did not significantly change from the pre-pandemic to early, middle or late pandemic periods (p-values ≥ 0.05). Incidence rates decreased from the pre-pandemic to early pandemic period during 2020 for acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, convulsions/seizures, Guillain-Barré syndrome, immune thrombocytopenia (ITP), narcolepsy/cataplexy, hemorrhagic stroke, ischemic stroke, and venous thromboembolism (p-values 0.05). Incidence rates of Bell's palsy, ITP, and narcolepsy/cataplexy were higher in all settings than in traditional in-person settings during the three pandemic periods (p-values 0.05).Rates of some clinical outcomes during the pandemic changed and should not be used as historical background rates in vaccine safety studies. Inclusion of telehealth visits should be considered for vaccine studies involving Bell's palsy, ITP, and narcolepsy/cataplexy.

To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD.The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions.The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD.Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

BACKGROUND Understanding the long-term impact of the COVID-19 pandemic on health care utilization is important to health care organizations and policy makers, as well for researchers when designing studies that use observational electronic health record data during the pandemic period. OBJECTIVE To evaluate changes in health care utilization across all care settings among a large diverse insured population in the United States during the COVID-19 pandemic. METHODS We conducted a retrospective cohort study within 8 health care organizations participating in the Vaccine Safety Datalink Project using electronic health record data from members of all ages during January 2017 - December 2021. The visit rates per person-year were calculated monthly during the study period for all health care settings combined as well as by inpatient, emergency department (ED), outpatient, and telehealth settings, both among all members and members without COVID-19. Difference-in-difference analysis and interrupted time series analysis were performed to assess the changes in visit rates from the pre-pandemic period (January 2017 to February 2020) to the early pandemic period (April 2020 to December 2020) and the later pandemic period (July 2021 to December 2021), respectively. RESULTS The study included more than 11 million members between 2017 and 2021. Compared with the pre-pandemic period, we found reductions in visit rates during the early pandemic period for all in-person care settings. During the later pandemic period, overall utilization exceeded pre-pandemic levels (adjusted percent change = 5.1%; 95% CI 0.6% to 9.9%); inpatient and ED visits returned to pre-pandemic levels, although they remained 7.5% and 8.0% lower among members without a documented history of COVID-19. Telehealth visits, which were approximately 42% of the volume of outpatient visits during the later pandemic period, were increased by 97.5% (95% CI 86.0% to 109.7%) from the pre-pandemic period. CONCLUSIONS Our findings provide valuable information for longer-term strategic resource allocation for patient care in the post-pandemic period and for designing observational studies involving the pandemic period.

BACKGROUND Temporal associations between Kawasaki disease (KD) and childhood vaccines have been reported. Limited data on KD following 13-valent pneumococcal conjugate (PCV13) and rotavirus vaccines are available. METHODS We conducted a self-controlled risk interval study using Vaccine Safety Datalink electronic health record data to investigate the risk of KD following PCV13 and rotavirus vaccines in children RESULTS During the study period, 655 cases of KD were identified by International Classification of Diseases codes. Of these, 97 chart-confirmed cases were within risk or control intervals. In analyses, the age-adjusted relative risk for KD following any dose of PCV13 was 0.75 (95% confidence interval, 0.47–1.21). Similarly, the age-adjusted relative risk for KD following any dose of rotavirus vaccine was 0.66 (95% CI, 0.40–1.09). Overall, there was no evidence of an elevated risk of KD following PCV13 or rotavirus vaccines by dose. In addition, no statistically significant temporal clustering of KD cases was identified during days 1 to 70 postvaccination. CONCLUSIONS PCV13 and rotavirus vaccination were not associated with an increased risk of KD in children

COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC's Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18-24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19.

COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination† and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.

Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years.To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines.This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022.Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021.GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day.From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66).In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

ImportancePost-authorization monitoring of vaccines in a large population can detect rare adverse events not identified in clinical trials including Guillain-Barré syndrome (GBS). GBS has a background rate of 1-2 per 100,000 person-years.ObjectiveTo 1) describe cases and incidence of GBS following COVID-19 vaccination, and 2) assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines.DesignInterim analysis of surveillance data from the Vaccine Safety Datalink.SettingEight participating integrated healthcare systems in the United States.Participants10,158,003 individuals aged ≥12 years.ExposuresReceipt of Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine.Main Outcomes and MeasuresGBS with symptom onset in the 1-84 days after vaccination as confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared to the background rate, rate ratios (RRs) comparing GBS incidence in the 1-21 vs. 22-42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs. mRNA vaccination, using Poisson regression adjusted for age, sex, race/ethnicity, site, and calendar day.ResultsFrom December 13, 2020 through November 13, 2021, 14,723,318 doses of COVID-19 vaccines were administered, including 467,126 Ad.26.COV2.S, 8,573,823 BNT162b2, and 5,682,369 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of confirmed cases of GBS per 100,000 person-years in the 1-21 days after Ad.26.COV2.S was 34.6 (95% confidence interval [CI]: 15.8-65.7), significantly higher than the background rate, and the adjusted RR in the 1-21 vs. 22-42 days following Ad.26.COV2.S was 6.03 (95% CI: 0.79-147.79). Thirty-four cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate of confirmed cases per 100,000 person-years in the 1-21 days after mRNA vaccines was 1.4 (95% CI: 0.7-2.5) and the adjusted RR in the 1-21 vs. 22-42 days following mRNA vaccines was 0.56 (95% CI: 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs. mRNA vaccines, the adjusted RR was 20.56 (95% CI: 6.94-64.66).Conclusions and RelevanceIn this interim analysis of surveillance data of COVID-19 vaccines, the incidence of GBS was elevated after Ad.26.COV2.S. Surveillance is ongoing.

The COVID-19 pandemic has affected routine vaccine delivery in the US and globally. The magnitude of these disruptions and their association with childhood vaccination coverage are unclear.To compare trends in pediatric vaccination before and during the pandemic and to evaluate the proportion of children up to date (UTD) with vaccinations by age, race, and ethnicity.This surveillance study used a prepandemic-postpandemic control design with data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Children from age groups younger than 24 months and 4 to 6, 11 to 13, and 16 to 18 years were included if they had at least 1 week of health system enrollment from January 5, 2020, through October 3, 2020, over periods before the US COVID-19 pandemic (January 5, 2020, through March 14, 2020), during age-limited preventive care (March 15, 2020, through May 16, 2020), and during expanded primary care (May 17, 2020, through October 3, 2020). These individuals were compared with those enrolled during analogous weeks in 2019.This study evaluated UTD status among children reaching specific ages in February, May, and September 2020, compared with those reaching these ages in 2019.Weekly vaccination rates for routine age-specific vaccines and the proportion of children UTD for all age-specific recommended vaccines.Of 1 399 708 children in 2019 and 1 402 227 in 2020, 1 371 718 were female (49.0%) and 1 429 979 were male (51.0%); 334 216 Asian individuals (11.9%), 900 226 were Hispanic individuals (32.1%), and 201 619 non-Hispanic Black individuals (7.2%). Compared with the prepandemic period and 2019, the age-limited preventive care period was associated with lower weekly vaccination rates, with ratios of rate ratios of 0.82 (95% CI, 0.80-0.85) among those younger than 24 months, 0.18 (95% CI, 0.16-0.20) among those aged 4 to 6 years, 0.16 (95% CI, 0.14-0.17) among those aged 11 to 13 years, and 0.10 (95% CI, 0.08-0.13) among those aged 16 to 18 years. Vaccination rates during expanded primary care remained lower for most ages (ratios of rate ratios:24 months, 0.96 [95% CI, 0.93-0.98]; 11-13 years, 0.81 [95% CI, 0.76-0.86]; 16-18 years, 0.57 [95% CI, 0.51-0.63]). In September 2020, 74% (95% CI, 73%-76%) of infants aged 7 months and 57% (95% CI, 56%-58%) of infants aged 18 months were UTD vs 81% (95% CI, 80%-82%) and 61% (95% CI, 60%-62%), respectively, in September 2019. The proportion UTD was lowest in non-Hispanic Black children across most age groups, both during and prior to the COVID-19 pandemic (eg, in May 2019, 70% [95% CI, 64%-75%] of non-Hispanic Black infants aged 7 months were UTD vs 82% [95% CI, 81%-83%] in all infants aged 7 months combined).As of September 2020, childhood vaccination rates and the proportion who were UTD remained lower than 2019 levels. Interventions are needed to promote catch-up vaccination, particularly in populations at risk for underimmunization.

OBJECTIVES: Influenza vaccination coverage among pregnant women in the United States is suboptimal. We surveyed women who were pregnant during the 2016–17 influenza season to assess knowledge and attitudes regarding influenza vaccination. METHODS: We identified and sampled pregnant women to include approximately equal numbers of vaccinated and unvaccinated women from strata defined by vaccination status and trimester from four integrated health systems in the Vaccine Safety Datalink (VSD). Potential participants were contacted via mail and telephone to complete a standardized survey. Characteristics and responses of women vaccinated and unvaccinated during pregnancy were compared. RESULTS: The survey was completed by 510 (48%) of 1062 contacted women; 500 were included in the analysis. Vaccine receipt while pregnant was associated with primigravida status (p = 0.02), college degree (p = 0.01), employment in health care (p < 0.01), and history of routine annual influenza vaccination (p < 0.01). Among 330 vaccinated women, the primary reasons for vaccination included protection of self and baby from influenza (n = 233, 71%), and medical professional recommendation (n = 46, 14%). Multiple reasons were given for nonvaccination, but concern about ‘negative effects’ was cited most often (n = 44, 29%). Vaccinated women were significantly more likely to believe that influenza vaccines are safe and effective, and to recognize the potential for harm from influenza infection. Nearly all women reported receiving at least one influenza vaccination recommendation from a healthcare provider. CONCLUSIONS: Vaccinated pregnant women were more likely to receive routine annual influenza vaccine compared to those not vaccinated. Recommendations by obstetric providers should be supplemented with efforts to encourage women of childbearing age to receive annual vaccination.

Introduction A recent study reported an association between inactivated influenza vaccine (IIV) and spontaneous abortion (SAB), but only among women who had also been vaccinated in the previous influenza season. We sought to estimate the association between IIV administered in three recent influenza seasons and SAB among women who were and were not vaccinated in the previous influenza season. Methods We conducted a case-control study over three influenza seasons (2012–13, 2013–14, 2014–15) in the Vaccine Safety Datalink (VSD). Cases (women with SAB) and controls (women with live births) were matched on VSD site, date of last menstrual period, age group, and influenza vaccination status in the previous influenza season. Of 1908 presumptive cases identified from the electronic record, 1236 were included in the main analysis. Administration of IIV was documented in several risk windows, including 1–28, 29–56, and >56 days before the SAB date. Results Among 627 matched pairs vaccinated in the previous season, no association was found between vaccination in the 1–28 day risk window and SAB (adjusted odds ratio (aOR) 0.9; 95% confidence interval (CI) 0.6–1.5). The season-specific aOR ranged from 0.5 to 1.7 with all CIs including the null value of 1.0. Similarly, no association was found among women who were not vaccinated in the previous season; the season-specific aOR in the 1–28 day risk window ranged from 0.6 to 0.7 and the 95% CI included 1.0 in each season. There was no association found between SAB and influenza vaccination in the other risk windows, or when vaccine receipt was analyzed relative to date of conception. Conclusion During these seasons we found no association between IIV and SAB, including among women vaccinated in the previous season. These findings lend support to current recommendations for influenza vaccination at any time during pregnancy, including the first trimester.

Background Between May 2005 and March 2007, three vaccines were recommended by the Advisory Committee on Immunization Practices for routine use in adolescents in the United States: quadrivalent meningococcal conjugate vaccine (MenACWY), tetanus, diphtheria and acellular pertussis vaccine (Tdap), and human papillomavirus vaccine (HPV). Understanding historical adolescent vaccination patterns may inform future vaccination coverage efforts for these and emerging adolescent vaccines, including COVID-19 vaccines. Methods This was a descriptive, retrospective cohort study. All vaccines administered to adolescents aged 11 through 18 years in the Vaccine Safety Datalink population between January 1, 2007 and December 31, 2016 were examined. Vaccination coverage was assessed by study year for ≥1 dose Tdap or Td, ≥1 dose Tdap, ≥1 dose MenACWY, ≥1 dose HPV, and ≥3 dose HPV. The proportion of vaccine visits with concurrent vaccination (≥2 vaccines administered at the same visit) was calculated by sex and study year. The most common vaccine combinations administered in the study population were described by sex for two time periods: 2007–2010 and 2011–2016. Results The number of 11–18-year-olds in the study population averaged 522,565 males and 503,112 females per study year. Between January 2007 and December 2016 there were 4,884,553 vaccine visits in this population (45% among males). The overall proportion of concurrent vaccine visits among males was 43% (33–61% by study year). Among females, 39% of all vaccine visits included concurrent vaccination (32–48% by study year). Vaccine coverage for Tdap, MenACWY, and 1- and 3-dose HPV increased across the study period. A wide variety of vaccine combinations were administered among both sexes and in both time periods. Conclusions The high vaccine uptake and multitude of vaccine combinations administered concurrently in the adolescent population of the Vaccine Safety Datalink provide historical patterns with which to compare future adolescent vaccination campaigns.

Background The Vaccine Safety Datalink (VSD) uses vaccination data from electronic health records (EHR) at eight integrated health systems to monitor vaccine safety. Accurate capture of data from vaccines administered outside of the health system is critical for vaccine safety research, especially for COVID-19 vaccines, where many are administered in non-traditional settings. However, timely access and inclusion of data from Immunization Information Systems (IIS) into VSD safety assessments is not well understood. Methods We surveyed the eight data-contributing VSD sites to assess: 1) status of sending data to IIS; 2) status of receiving data from IIS; and 3) integration of IIS data into the site EHR. Sites reported separately for COVID-19 vaccination to capture any differences in capacity to receive and integrate data on COVID-19 vaccines versus other vaccines. Results All VSD sites send data to and receive data from their state IIS. All eight sites (100%) routinely integrate IIS data for COVID-19 vaccines into VSD research studies. Six sites (75%) also routinely integrate all other vaccination data; two sites integrate data from IIS following a reconciliation process, which can result in delays to integration into VSD datasets. Conclusions COVID-19 vaccines are being administered in a variety of non-traditional settings, where IIS are commonly used as centralized reporting systems. All eight VSD sites receive and integrate COVID-19 vaccine data from IIS, which positions the VSD well for conducting quality assessments of vaccine safety. Efforts to improve the timely receipt of all vaccination data will improve capacity to conduct vaccine safety assessments within the VSD.

This cohort study examines the risks for spontaneous abortion, preterm birth, small-for-gestational age birth, and major structural birth defects among female teenagers and adults who received the human papillomavirus vaccine., Key Points Question Is exposure to the 9-valent human papillomavirus (9vHPV) vaccine in pregnancy associated with adverse pregnancy or birth outcomes? Findings In this cohort study of 1493 pregnancies, in adjusted analyses, during-pregnancy or peripregnancy exposures to 9vHPV vaccine were not associated with spontaneous abortion. Among live births, 9vHPV vaccine exposures during or around the time of pregnancy were not associated with adverse birth outcomes. Meaning Results of this study suggest that, in an insured population, adverse events after exposure to 9vHPV vaccine during or around the time of pregnancy were uncommon; these findings can inform counseling after inadvertent 9vHPV vaccine exposures., Importance The 9-valent human papillomavirus (9vHPV) vaccine is recommended for individuals through age 26 years and may be administered to women up to age 45 years. Data on 9vHPV vaccine exposures during pregnancy are limited. Objective To evaluate the associations between 9vHPV vaccine exposures during pregnancy or peripregnancy and selected pregnancy and birth outcomes (spontaneous abortion [SAB], preterm birth, small-for-gestational age [SGA] birth, and major structural birth defect). Design, Setting, and Participants This cohort study analyzed data from 7 participating health systems in the Vaccine Safety Datalink. The cohort comprised pregnancies among girls and women aged 12 to 28 years that ended between October 26, 2015, and November 15, 2018. Singleton pregnancies that ended in a live birth, stillbirth, or SAB were included. Exposures Vaccine exposure windows were distal (9vHPV or 4vHPV vaccine administered from 22 to 16 weeks before last menstrual period [LMP]), peripregnancy (9vHPV vaccine administered from 42 days before LMP until LMP), and during pregnancy (9vHPV vaccine administered from LMP to 19 completed weeks’ gestation). Primary comparisons were (1) girls and women with 9vHPV vaccine exposures during pregnancy vs those with 4vHPV or 9vHPV distal vaccine exposures, (2) girls and women with vaccine exposures peripregnancy vs those with 4vHPV or 9vHPV distal vaccine exposures, and (3) girls and women with 9vHPV vaccine exposures during pregnancy or peripregnancy vs those with 4vHPV or 9vHPV distal vaccine exposure. Main Outcomes and Measures Spontaneous abortions were confirmed based on medical record review and adjudication. Preterm and SGA births were identified from electronic health record and birth data. Major structural birth defects were based on diagnostic codes using a validated algorithm. Inverse probability weighting was used to balance the covariates. Time-dependent covariate Cox proportional hazards regression models and Poisson regression were used to estimate the associations between 9vHPV vaccine exposures and pregnancy and birth outcomes. Results The final cohort included 1493 pregnancies among girls and women with a mean (SD) maternal age of 23.9 (2.9) years. Of these pregnancies, 445 (29.8%) had exposures to the 9vHPV vaccine during pregnancy, 496 (33.2%) had exposures to the 9vHPV vaccine peripregnancy, and 552 (37.0%) had 4vHPV or 9vHPV distal vaccine exposures. The 9vHPV vaccine administered during pregnancy was not associated with increased risk for SAB (hazard ratio, 1.12; 95% CI, 0.66-1.93) compared with distal vaccine exposures. Findings were similar for 9vHPV vaccine exposures peripregnancy (relative risk [RR], 0.72; 95% CI, 0.42-1.24). Among live births (n = 1409), 9vHPV vaccine exposures during pregnancy were not associated with increased risks for preterm birth (RR, 0.73; 95% CI, 0.44-1.20) or SGA birth (RR, 1.31; 95% CI, 0.78-2.20). Results were similar regarding the association between 9vHPV vaccine exposures peripregnancy and preterm birth (RR, 0.72; 95% CI, 0.45-1.17) and SGA birth (RR, 1.10; 95% CI, 0.65-1.88). Birth defects were rare in all exposure groups, occurring in about 1% of live births with available infant data. Conclusions and Relevance This study found that 9vHPV vaccine exposures during or around the time of pregnancy were uncommon and not associated with SABs or selected adverse birth outcomes. These findings can inform counseling for inadvertent 9vHPV vaccine exposures.

Seven to ten days after a first dose of a measles-containing vaccine (MCV; i.e., MMR or MMRV), children have elevated fever risk which can be associated with febrile seizures. This study investigated individual and familial factors associated with fever 7-10days after MCV.Retrospective cohort study among children who were36months of age at receipt of MCV in six sites of the Vaccine Safety Datalink from 1/1/2000 to 12/31/2012. We evaluated medically-attended clinic or emergency department visits with a code for fever 7-10days after any MCV ("MCV- associated"). We evaluated factors associated with MCV-associated fever using χAmong 946,806 children vaccinated with MCV, we identified 7480 (0.8%) MCV-associated fever visits. Compared with children without fever after MCV, children with MCV-associated fever were more likely to have received MMRV than MMR (OR 1.3 95% CI 1.2, 1.5), have had medically attended fever both following previous vaccines (OR 1.3 95% CI 1.1, 1.6) and at any other previous time (OR 1.7 95% CI 1.6, 1.8), have had at least 1 prior seizure (OR 2.2 95% CI 1.7, 2.7), and have had3 medical visits within the 6months before MCV (OR 1.7 95% CI 1.6, 1.8). In families with multiple MCV-immunized children, after adjusting for healthcare seeking behavior care for fever, those whose siblings had MCV-associated fever were more likely to also have MCV-associated fever (OR 3.5 95% CI 2.5, 4.8).Children who received MMRV vaccine or who had prior medically-attended fevers and seizures during the first year of life had increased risk of fever after a first dose of measles vaccine. After adjusting for familial propensity to seek care, MCV-associated fever still clustered within families, suggesting a possible genetic basis for susceptibility to developing fever due to measles vaccines.

BACKGROUND AND OBJECTIVES: Human papillomavirus is the most common sexually transmitted infection in the United States and causes certain anogenital and oropharyngeal cancers. The 9-valent human papillomavirus vaccine (9vHPV) provides protection against additional types not included in the quadrivalent vaccine. We conducted near real-time vaccine safety surveillance for 24 months after the vaccine became available in the Vaccine Safety Datalink. METHODS: Immunizations and adverse events were extracted weekly from October 2015 to October 2017 from standardized data files for persons 9 to 26 years old at 6 Vaccine Safety Datalink sites. Prespecified adverse events included anaphylaxis, allergic reaction, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, injection site reaction, pancreatitis, seizure, stroke, syncope, and venous thromboembolism. The observed and expected numbers of events after 9vHPV were compared weekly by using sequential methods. Both historical and concurrent comparison groups were used to identify statistical signals for adverse events. Unexpected signals were investigated by medical record review and/or additional analyses. RESULTS: During 105 weeks of surveillance, 838 991 doses of 9vHPV were administered. We identified unexpected statistical signals for 4 adverse events: appendicitis among boys 9 to 17 years old after dose 3; pancreatitis among men 18 to 26 years old; and allergic reactions among girls 9 to 17 years old and women 18 to 26 years old after dose 2. On further evaluation, which included medical record review, temporal scan analysis, and additional epidemiological analyses, we did not confirm signals for any adverse events. CONCLUSIONS: After 2 years of near real-time surveillance of 9vHPV and several prespecified adverse events, no new safety concerns were identified.

Background Some parents, especially those of children with autism spectrum disorders (ASD), are uncertain about the safety of childhood immunization. We compared rates of fever, febrile seizure and emergency room (ER) visits following measles and pertussis-containing vaccines recommended between ages 4–6 years among children with and without ASD. Methods The study included children who were born between 1995–2012, aged 4–7 years at vaccination, and members of six integrated healthcare delivery systems within the Vaccine Safety Datalink. Children with ASD were defined based on receipt of two separate International Classification of Diseases (ICD)-9 or 10 codes. Outcomes (fever, febrile seizures, and ER visits) were identified in electronic health records. To minimize confounding by unmeasured factors related both to avoidance of vaccination and to outcomes of interest, we compared rates of each outcome between children with and without ASD, in risk and control intervals, by estimating the difference-in-differences on a log scale (i.e. the ratio of rate ratios) using logistic regressions. We also conducted risk interval analyses comparing rates of outcomes in risk intervals and control intervals within each group. Results The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles or pertussis-containing vaccination, there were no differences in association between the two groups for fever or ER visits (Table). There were no febrile seizures identified among children with ASD. Within the ASD group, rates of fever, seizure or ER visits did not differ significantly between the risk and control intervals after vaccination. However, among the non-ASD group, measles and pertussis-containing vaccines were associated with higher rates of fever and seizure in risk intervals compared to controls intervals. Pertussis-containing vaccines were associated with increased risk of ER visits in risk interval compared to control interval (Table). Conclusion We found no difference in the risk of fever, and ER visits comparing children with autism to children without autism after measles or pertussis-containing vaccines. The study provides some reassurance that these vaccines are not less safe in children with ASD. Disclosures Lei Qian, PhD, GlaxoSmithKlein (Research Grant or Support) Nicola P. Klein, MD, PhD, GSK group of companies (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Protein Science (now SP) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)

OBJECTIVE: To evaluate the risk of spontaneous abortion after quadrivalent human papillomavirus (4vHPV) vaccination before and during pregnancy across seven integrated health systems within the Vaccine Safety Datalink. METHODS: Within a retrospective observational cohort, we compared risks for spontaneous abortion after 4vHPV in three exposure windows: distal (16–22 weeks prior to last menstrual period (LMP)), peripregnancy (within 6 weeks prior to LMP) and during pregnancy (LMP through 19 weeks of gestation). Women 12–27 years of age with a pregnancy between 2008 and 2014, with continuous insurance enrollment 8 months prior to and through pregnancy end, and with a live birth, stillbirth, or spontaneous abortion were included. Pregnancies were identified through validated algorithms. Spontaneous abortions and stillbirths were verified via chart review, with spontaneous abortions adjudicated by clinical experts. We excluded multiple gestations, spontaneous abortions before 6 weeks of gestation, and women using medications increasing risk for spontaneous abortion. Spontaneous abortion risk after 4vHPV during pregnancy was compared to distal vaccination using time dependent covariate Cox models. Spontaneous abortion risk for peri-pregnancy versus distal vaccination was evaluated with standard Cox models. RESULTS: We identified 2,800 pregnancies with 4vHPV exposure in specified risk windows: 919 (33%) distal, 986 (35%) peripregnancy and 895 (32%) during pregnancy. Mean age was 22.4 years in distal and peripregnancy groups versus 21.4 years among women vaccinated during pregnancy. Among women with distal 4vHPV exposure, 96 (10.4%) experienced a spontaneous abortion. For peripregnancy and during pregnancy exposures, spontaneous abortions occurred in 110 (11.2%) and 77 (8.6%), respectively. The risk of spontaneous abortion was not increased among women who received 4vHPV during pregnancy (adjusted hazard ratio 1.10 (95% CI: 0.81–1.51)) or peripregnancy 1.07 (0.81–1.41). CONCLUSION: Inadvertent 4vHPV exposure during or peripregnancy was not significantly associated with an increased risk for spontaneous abortion.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Introduction Infection with hepatitis A virus (HAV) during pregnancy, although uncommon, is associated with gestational complications and pre-term labor. Hepatitis A vaccine (HepA) is recommended for anyone at increased risk for contracting hepatitis A, including women at risk who are also pregnant. Limited data are available on the safety of maternal HepA vaccination. Objectives Assess the frequency of maternal HepA receipt and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. Methods A retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live births from 2004 through 2015 was included. Pregnancies with HepA exposure were compared to those with other vaccine exposures, and to those with no vaccine exposures. Risk factors for contracting hepatitis A were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were evaluated according to maternal HepA exposure status. Adjusted odds ratio (OR) were used to describe the association. Results Among 666,233 pregnancies in the study period, HepA was administered at a rate of 1.7 per 1000 (n = 1140), most commonly within the first six weeks of pregnancy. Less than 3% of those exposed to HepA during pregnancy had an ICD-confirmed risk factor. There were no significant associations between HepA exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, and low birthweight. There was a statistically significant association between HepA exposure during pregnancy and small-for-gestational age (SGA) infants (aOR 1.32, [95% CI 1.09, 1.60], p = 0.004). Conclusions The rate of maternal HepA vaccination was low and rarely due to documented risk factors for vaccination. HepA vaccination during pregnancy was not associated with an increased risk for a range of adverse events examined among pregnancies resulting in live births, but an identified association between maternal HepA and SGA infant outcomes, while likely due to unmeasured confounding, warrants further exploration.

Objective To determine the risks associated with zoster vaccine when administered to patients taking immunosuppressant medications. Patients and Methods Patients enrolled in 1 of 7 managed care organizations affiliated with the Vaccine Safety Datalink between January 1, 2006, and December 31, 2009, were eligible. The exposure of interest was zoster vaccination in patients with current or remote immunosuppressant drug use. The primary outcomes were disseminated varicella zoster virus (VZV) and herpes zoster in the 42 days after vaccination. Automated data were collected on immunosuppressant drugs and baseline medical conditions. A logistic regression model using inverse probability treatment weights was used to estimate the odds of developing VZV or herpes zoster. Results A total of 14,554 individuals had an immunosuppressant medication dispensed around the time of vaccination, including 4826 with current use and 9728 with remote use. Most patients were taking low-dose corticosteroids. No cases of disseminated VZV were found in the current or remote users. The risk of herpes zoster was elevated in the 42 days after vaccination in current vs remote users (adjusted odds ratio, 2.99; 95% CI, 1.58-5.70). Conclusion We found that patients taking immunosuppressant medications at the time of vaccination had a modest increased risk of herpes zoster in the 42 days after vaccination. The development of herpes zoster within 42 days after vaccination suggests that this is more likely due to reactivation of latent zoster virus than dissemination of the vaccine-derived varicella virus. These findings support the current zoster vaccination guidelines.

The goal of this study was to compare and contrast the use of personal protective equipment (PPE) and the practice of handwashing among participants of four studies assessing poultry and swine farms in the midwestern United States and in Thailand. This largely descriptive exercise was designed to assess and compare the frequency of these protective practices among the study populations. There were a total of 1113 surveys analyzed across the four studies. The respondents included workers in direct contact with animals as well as flock owners and veterinarians tending to farms. Handwashing was the most common practice observed among all participants with 42% "always" and 35% "sometimes" washing their hands after contact with the animals. This practice was least common among Minnesota swine workers. Even Thai poultry farmers, who demonstrated the lowest overall PPE use, reported a higher frequency of handwashing. Mask use during animal farming activities ("always" or "sometimes") was least commonly practiced, ranging from 1% in Thailand to 26% among backyard poultry farmers in Minnesota. Minnesota poultry and swine farmers had similar frequencies of mask (26%) and glove use (51% and 49%). All other comparisons differed significantly across the four sites (p-values0.05). The use of PPE in animal farming differed by study location and is likely related to prevalent norms in the respective regions. Overall, the use of PPE did not appear to be influenced by the particular animal (poultry or swine) being farmed. These findings may prove useful to regulating bodies and farm owners in formulating policy or planning strategies for improving personal hygiene practices in animal farming and preparing for influenza and other potential zoonotic disease outbreaks.

Background The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was recommended for use in adolescents in 2005. Soon after, case reports of Guillain-Barre syndrome (GBS) following vaccination prompted subsequent studies, with a meta-analysis concluding that the attributable risk of GBS after MenACWY-D is unlikely to exceed 1 case per million vaccinations. We conducted a retrospective cohort study in the Vaccine Safety Datalink to assess the risk of 10 outcomes, including GBS, following MenACWY-D. Methods We included adolescents (aged 11–18 years) vaccinated with MenACWY-D during the years 2005–2014. We identified pre-specified outcomes using ICD-9 (International Classification of Disease, version 9) codes. We used automated data only for Bell’s palsy, fever, seizure and syncope, and we confirmed incident cases by medical record review for acute disseminated encephalomyelitis (ADEM), acute transverse myelitis (ATM), anaphylaxis, chronic inflammatory demyelinating polyneuropathy (CIDP), GBS and Henoch-Schönlein purpura (HSP). We used a self-controlled risk interval design to estimate relative risk (RR). Results Following 1.4 million doses of MenACWY-D, we detected increased risks for fever in the 1–6 days following vaccination (RR 1.5, 95% confidence interval [CI] 1.3–1.7) and syncope on the day of vaccination (RR 5.8, 95% CI 4.1–8.3), but not for seizures (RR 1.1, 95% CI 0.7–1.9) or Bell’s palsy (RR 1.1, 95% CI 0.8–1.5). We detected no cases in the post-vaccination risk intervals for CIDP, ADEM or ATM. We detected few cases of the other outcomes resulting in relatively unstable RR estimates: anaphylaxis (RR 1.9, 95% CI 0.5–7.1), GBS (RR 2.5, 95% CI 0.6–10.0) and HSP (RR 1.6, 95% CI 0.7–3.3). We estimated that the attributable risk of GBS was 1.5 cases per million vaccinations (upper bound of one-sided 95% CI, 4.9). Conclusion In a large retrospective cohort, we detected increased risks for syncope and fever, but not seizures or Bell’s palsy, following vaccination with MenACWY-D. Other outcomes were rare. Our findings, consistent with previous studies, suggest that the increased risk of GBS, if any, is likely small (

Introduction The Vaccine Safety Datalink (VSD) is a collaborative project whose infrastructure provides comprehensive medical and immunization histories for more than 9 million adults and children annually, a predominantly insured population. This study provides the coverage rates of recommended vaccines among children 19–35 months in the VSD from 2005 through 2010. We examine the consistency in vaccine coverage levels, detect possible trends, and evaluate any effect of vaccine shortages on coverage in the VSD. Methods We included data from all 10 VSD sites, and examined each year independently. Coverage rates were defined as the percentage of children in the VSD aged 19, 24, or 35 months in a given study year who had received the specified Advisory Committee on Immunization Practices (ACIP) recommended vaccine(s). Results We assessed coverage on 658,154 children. The overall coverage rate for children receiving all of the specified ACIP recommended vaccines was 73%, 80%, and 78% at ages 19, 24, and 35 months respectively. The range of coverage across all ages and years was 95–97% for polio vaccine, 91–97%, for MMR vaccine, 94–97% for HepB vaccine, 81–95% for DTaP vaccine, 90–95% for varicella vaccine, 66–91% for PCV, and 93–98% for Hib vaccine. Coverage rates of 4 or more doses of PCV were relatively low in 2005 possibly due to a vaccine shortage, and increased sharply in 2007. Hib vaccine coverage was relatively stable among all ages until 2009 when rates declined among children aged 19 and 24 months also during a vaccine shortage. Conclusions Vaccine coverage in the VSD is high, but there is a decline from 2005 to 2010. The results of this study provide benchmark data for future studies, and describe how vaccine supply shortages and resulting changes in ACIP recommendations may have affected vaccine coverage rates in the VSD.

Background Determining the baseline mortality rate in a vaccinated population is necessary to be able to identify any unusual increases in deaths following vaccine administration. Background rates are particularly useful during mass immunization campaigns and in the evaluation of new vaccines. Purpose Provide background mortality rates and describe causes of death following vaccination in the Vaccine Safety Datalink (VSD). Methods Analyses were conducted in 2012. Mortality rates were calculated at 0–1 day, 0–7 days, 0–30 days, and 0–60 days following vaccination for deaths occurring between January 1, 2005, and December 31, 2008. Analyses were stratified by age and gender. Causes of death were examined, and findings were compared to National Center for Health Statistics (NCHS) data. Results Among 13,033,274 vaccinated people, 15,455 deaths occurred between 0 and 60 days following vaccination. The mortality rate within 60 days of a vaccination visit was 442.5 deaths per 100,000 person-years. Rates were highest in the group aged ≥85 years, and increased from the 0–1-day to the 0–60-day interval following vaccination. Eleven of the 15 leading causes of death in the VSD and NCHS overlap in both systems, and the top four causes of death were the same in both systems. Conclusions VSD mortality rates demonstrate a healthy vaccinee effect, with rates lowest in the days immediately following vaccination, most apparent in the older age groups. The VSD mortality rate is lower than that in the general U.S. population, and the causes of death are similar.

Although no increased risk was detected for serious adverse events in the prelicensure trials for the 13-valent pneumococcal vaccine, Prevnar 13(®) (PCV13), continued monitoring of rare but serious adverse events is necessary. A surveillance system using cohort study design was set up to monitor safety of PCV13 immediately after it was included in the childhood immunization program in the United States. The exposed population included children of 1 month to 2 years old who received PCV13 from April, 2010 to January, 2012 from the eight managed care organizations participating in the Vaccine Safety Datalink Project in the United States. The historical unexposed population was children of the same age who received the 7-valent pneumococcal conjugate vaccine Prevnar 7(®) (PCV7) in 2007 (or 2005 depending on the outcome of interest) to 2009. The risk of pre-specified adverse events in the risk window following PCV13 was repeatedly compared to that in the historical comparison group. The number of doses included in the study was 599,229. No increased risk was found for febrile seizures, urticaria or angioneurotic edema, asthma, thrombocytopenia, or anaphylaxis. An increased risk for encephalopathy was not confirmed following the medical record review. The relative risk for Kawasaki disease in 0-28 days following vaccination was 1.94 (95% confidence interval: 0.79-4.86), comparing PCV13 to PCV7. Comparing to PCV7 vaccine, we identified no significant increased risk of pre-specified adverse events in the Vaccine Safety Datalink study cohort. The possible association between PCV13 and Kawasaki disease may deserve further investigation.

OBJECTIVE: Our objective was to assess whether the occurrence of medically attended local reactions to intramuscularly administered vaccines varies by injection site (arm versus thigh) in children 1 to 6 years of age. METHODS: This is a retrospective cohort study of children in the Vaccine Safety Datalink population from 2002 to 2009. Site of injection and the outcome of medically attended local reactions were identified from administrative data. RESULTS: The study cohort of 1.4 million children received 6.0 million intramuscular (IM) vaccines during the study period. The primary analyses evaluated the IM vaccines most commonly administered alone, which included inactivated influenza, hepatitis A, and diphtheria-tetanus-acellular pertussis (DTaP) vaccines. For inactivated influenza and hepatitis A vaccines, local reactions were relatively uncommon, and there was no difference in risk of these events with arm versus thigh injections. The rate of local reactions after DTaP vaccines was higher, and vaccination in the arm was associated with a significantly greater risk of this outcome compared with vaccination in the thigh, both for children 12 to 35 months (relative risk: 1.88 [95% confidence interval: 1.34–2.65]) and 3 to 6 years of age (relative risk: 1.41 [95% confidence interval: 0.84–2.34]), although this difference was not statistically significant in the older age group. CONCLUSIONS: Injection in the thigh is associated with a significantly lower risk of a medically attended local reaction to a DTaP vaccination among children 12 to 35 months of age, supporting current recommendations to administer IM vaccinations in the thigh for children younger than 3 years of age.

SUMMARYWe conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42–63] and 35% in Marshfield (95% CI 28–42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.

BACKGROUND Published data on the safety of tetanus-diphtheria-acellular pertussis vaccine (Tdap) in persons aged ≥65 years are limited. This study aims to examine a large cohort of Tdap users ≥65 years for evidence of increased risk of adverse events following vaccination. METHODS A matched cohort study design and a self-controlled case series (SCCS) design were used. The study population was adults aged ≥65 years who received the Tdap or tetanus and diphtheria (Td) vaccine during 1 January 2006-31 December 2010 at 7 health maintenance organizations in the United States. Seven major groups of prespecified events were identified electronically by diagnostic codes. RESULTS The study included 119 573 Tdap vaccinees and the same number of Td vaccinees. The results indicated that the risk of the prespecified events following Tdap was comparable to that following Td vaccination in this elderly population. There was a small increased rate of codes suggesting medically attended inflammatory or allergic events in 1-6 days following Tdap in the SCCS analysis (incidence rate ratio, 1.59 [95% confidence interval, 1.40-1.81]). CONCLUSION Although there is a small increased risk of medically attended inflammatory or allergic events in 1-6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences.

The continuing epizootic of H5N1 avian influenza (AI) in Asia and subsequent zoonotic transmission has led to heightened concerns about a pandemic and the demand for improved surveillance of poultry in all sectors, including backyard poultry. We conducted a 15-month prospective study to determine the prevalence of AI in backyard poultry and extent of transmission to flock handlers.Starting July 2007, registered poultry owners in six counties in central Wisconsin were mailed invitations to participate; household members with poultry exposure were also invited. Premises with1000 birds were eligible. Participants completed a baseline interview to characterize poultry exposures. Illness in flocks and flock handlers was monitored using semimonthly telephone interviews and self-report of acute influenza-like symptoms by flock handlers. Participants provided blood at baseline and at the end of the surveillance period for serology and, if ill, nasopharyngeal, eye, and throat swabs for viral testing. Blood was also collected at baseline from a convenience sample of adult poultry.We enrolled 87 flocks and 128 persons who had regular contact with poultry. Influenza-like symptoms were reported by 77 (65%) persons. Swabs were collected from 53 persons at 88 illness episodes. AI was not isolated, but five persons were positive for human influenza. Twenty-one participants (20%) seroconverted to at least one human influenza strain, but there were no seroconversions to AI. Blood samples from all 717 birds tested were seronegative for influenza.Despite limited biosecurity there was no evidence of AI infection in participating backyard flocks or flock handlers.

During the 2007-08 influenza season, we reported an interim vaccine effectiveness (VE) estimate of 44% for preventing medically attended influenza. In this analysis we report results for the entire season and compare them with the interim estimate.Patients with feverishness, chills, or cough8 days duration were prospectively recruited over 10 weeks and tested for influenza by real-time reverse transcriptase PCR (rRT-PCR). Case-control analyses were performed using data from patients with rRT-PCR confirmed influenza (cases) and ill patients without influenza (test-negative controls). VE was estimated as 100×(1-adjusted odds ratio) in a logistic regression model adjusting for age, week, and high risk medical condition. A sample of influenza isolates was antigenically characterized.Influenza was detected by rRT-PCR in 865 (44%) of 1972 patients; 73% were type A and 27% were type B. VE was 37% (95% CI, 22-49%) overall and 44% (95% CI, 27-58%) among participants tested 0-3 days after illness onset. VE was 39% (95% CI, 2-62%) in children 6-59 months old and 37% (95% CI, -2% to 61%) in adults ≥50 years old. VE was 41% (95% CI, 24-53%) for influenza A and 31% (95% CI, 3-51%) for influenza B. All 24 characterized influenza A viruses were antigenically matched to the H3N2 vaccine strain, although 14 viruses exhibited mild antigenic drift. There was a lineage mismatch with the vaccine strain for all 39 characterized influenza B viruses.The 2007-08 influenza vaccine provided modest protection against medically attended influenza in this population. The interim estimate of VE after 17 days closely approximated the final season VE, supporting the potential use of interim VE estimates while influenza seasons are still in progress.

Mass vaccination campaigns during which new vaccines may be administered to many millions of people in a short period of time call for timely and accurate post-licensure surveillance to monitor vaccine safety. To address the need for timely H1N1 influenza vaccine safety information during the 2009-2010 H1N1 influenza pandemic, the Vaccine Safety Datalink (VSD) project assessed the feasibility and potential mechanisms for utilizing data from state and local immunization registries to capture vaccinations that would not otherwise be captured by the data systems of the participating VSD managed care organizations (MCOs). Three of the eight VSD sites were able to capture H1N1 immunization data electronically from the state and local registries, and one site was able to capture the immunizations through a paper-based system; however, the remaining four sites encountered various obstacles that prevented capture of such data. Additional work will be required at these sites to overcome the barriers, which included privacy and confidentiality laws, time constraints brought on by the pandemic, as well as data quality concerns.

Please cite this paper as: Irving et al. (2012) Comparison of clinical features and outcomes of medically attended influenza A and influenza B in a defined population over four seasons: 2004–2005 through 2007–2008. Influenza and Other Respiratory Viruses 6(1), 37–43. Background There are few prospectively collected data comparing illnesses caused by different subtypes of influenza. We compared the clinical presentation and outcomes of subjects with primarily outpatient‐attended influenza A and B infections during four consecutive influenza seasons (2004–2005 through 2007–2008). Methods Patients were prospectively enrolled and tested for influenza following an encounter for acute respiratory illness. Influenza infections were confirmed by culture or reverse transcription polymerase chain reaction; subtype was determined for a sample of influenza A isolates each season. Clinical characteristics of influenza A and B infections were compared across and within individual seasons. Results We identified 901 cases of influenza A and 284 cases of influenza B; 98% of cases were identified through an outpatient medical encounter. Thirty‐six percent of patients with each strain had received seasonal influenza vaccine prior to illness onset. There were no consistent differences in symptoms associated with influenza A and B. Influenza A infection was associated with earlier care seeking compared with influenza B during the 2005–2006 and 2007–2008 seasons, when H3N2 was the dominant type A virus, and in a combined analysis that included all seasons. Twenty‐six (2·2%) of 1185 cases were diagnosed with radiographically confirmed pneumonia, and 59 (5%) of 1185 patients were hospitalized within 30 days of illness onset. Conclusions Over four influenza seasons, aside from shorter intervals from illness onset to clinical encounter for infections with the A(H3N2) subtype, clinical symptoms and outcomes were similar for patients with predominantly outpatient‐attended influenza A and B infections.

Objectives. We performed a case–control study to determine if participants with herpes zoster had fewer contacts with persons with varicella or zoster, and with young children, to explore the hypothesis that exposure to persons with varicella zoster virus (VZV) results in “immune boosting.” Methods. Participants were patients of the multispecialty Marshfield Clinic in Wisconsin. We identified patients aged 40 to 79 years with a new diagnosis of zoster from August 2000 to July 2005. We frequency matched control participants to case participants for age. We confirmed diagnoses by chart review and assessed exposures by interview. Results. Interviews were completed by 633 of 902 eligible case participants (70.2%) and 655 of 1149 control participants (57.0%). The number of varicella contacts was not associated with zoster; there was no trend even at the highest exposure level (3 or more contacts). Similarly, there was no association with exposure to persons with zoster or to children, or with workplace exposures. Conclusions. Although exposure to VZV in our study was relatively low, the absence of a relationship with zoster reflects the uncertain influence of varicella circulation on zoster epidemiology.

Importance In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. Objectives To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. Design, Setting, and Participants This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. Exposures Recommended childhood vaccines between ages 1 month and 12 years. Main Outcome and Measure The proportion of children who received all of their vaccine doses according to ACIP recommendations. Results The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child’s younger sibling and to limit the number of vaccines administered during the younger sibling’s first year of life. Conclusions and Relevance Children with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.

Several case reports have described immune hemolytic anemia (IHA) following vaccination in children. We examined the risk of IHA in the 42 days following vaccination exposure using a self-controlled case series study design. In our population-based cohort of nearly 4.5 million children in the Vaccine Safety Datalink, we identified 55 confirmed cases of new-onset IHA from 1991 through 2000. We found no association between IHA and diphtheria-pertussis-tetanus vaccination (incidence rate ratio (IRR)=0.65, 95% CI: 0.19-2.24), hepatitis B vaccination (IRR=1.73, 95% CI: 0.59-5.01), or any vaccination (IRR=1.04, 95% CI: 0.46-2.32).

We evaluated influenza vaccination status as determined by self-report and a regional, real-time immunization registry during two influenza seasons when subjects were enrolled in a study to estimate vaccine effectiveness. We enrolled 2907 patients during the two consecutive seasons. The sensitivity and specificity of self-reported influenza vaccination when compared to immunization registry records were 95% and 90%, respectively. The positive predictive value of self-reported vaccination was 89% and negative predictive value was 96%. In our study population, self-reported influenza vaccine status was a sensitive and fairly specific indicator of actual vaccine status. Misclassification was more common among young children.

Background We estimated the effectiveness of inactivated influenza vaccines for the prevention of laboratory-confirmed, medically attended influenza during 3 seasons with variable antigenic match between vaccine and patient strains. Methods Patients were enrolled during or after a clinical encounter for acute respiratory illness. Influenza infection was confirmed by culture or reverse-transcriptase polymerase chain reaction. Case-control analyses were performed that used data from patients who were ill without influenza (hereafter, "test-negative control subjects") and data from asymptomatic control subjects from the population (hereafter, "traditional control subjects"). Vaccine effectiveness (VE) was estimated as [100 x (1-adjusted odds ratio)]. Influenza isolates were antigenically characterized. Results Influenza was detected in 167 (20%) of 818 patients in 2004-2005, in 51 (14%) of 356 in 2005-2006, and in 102 (11%) of 932 in 2006-2007. Analyses that used data from test-negative control subjects showed that VE was 10% (95% confidence interval [CI], -36% to 40%) in 2004-2005, 21% (95% CI, -52% to 59%) in 2005-2006, and 52% (95% CI, 22% to 70%) in 2006-2007. Using data from traditional control subjects, VE for those seasons was estimated to be 5% (95% CI, -52% to 40%), 11% (95% CI, -96% to 59%), and 37% (95% CI, -10% to 64%), respectively; confidence intervals included 0. The percentage of viruses that were antigenically matched to vaccine strains was 5% (3 of 62) in 2004-2005, 5% (2 of 42) in 2005-2006, and 91% (85 of 93) in 2006-2007. Conclusions Influenza VE varied substantially across 3 seasons and was highest when antigenic match was optimal. VE estimates that used data from test-negative control subjects were consistently higher than those that used data from traditional control subjects.

Adamantane-resistant influenza A is an emerging problem, but infections caused by resistant and susceptible viruses have not been compared. We identified adamantane resistance in 47% of 152 influenza A virus (H3N2) isolates collected during 2005. Resistant and susceptible viruses caused similar symptoms and illness duration. The prevalence of resistance was highest in children.

Summary Objectives: To assess how well selected ICD-9-CM diagnosis codes predict adverse events; to model bias and power loss when vaccine safety analyses rely on unverified codes. Methods: We extracted chart verification data for ICD-9-CM diagnosis codes from six Vaccine Safety Datalink (VSD) publications and modeled biases and power losses using positive predictive value (PPV) estimates and ranges of code sensitivity. Results: Positive predictive values were high for type 1 diabetes (80%) in children, relative to WHO criteria, and intussusception (81%) in young children, relative to a standard published case definition. PPVs were moderate (65%) for inpatient and emergency department childhood seizures and low (21%) for outpatient childhood seizures, both relative to physician investigator judgment. Codes for incident central nervous system demyelinating disease in adults had high PPV for inpatient codes (80%) and low PPV for outpatient codes (42%) relative to physicians’ diagnoses. Modeled biases were modest, but large increases in frequencies of adverse events are required to achieve adequate power if unverified ICD-9-CM codes are used, especially when vaccine associations are weak. Conclusions: ICD-9-CM codes for type 1 diabetes in children, intussusception in young children, childhood seizures in inpatient and emergency care settings, and inpatient demyelinating disease in adults were sufficiently predictive for vaccine safety analyses to rely on unverified diagnosis codes. Adverse event misclassification should be accounted for in statistical power calculations.

To investigate concerns about a potential association between quadrivalent human papillomavirus vaccination (HPV4) and venous thromboembolism (VTE), we conducted a self-controlled case series study in adolescents and young adults 9-26 years of age in the Vaccine Safety Datalink.We identified potential VTE cases diagnosed in 2008 through 2011 who had also received at least one HPV4 dose during that period. We confirmed each presumptive diagnosis by medical record review. We calculated incidence rate ratios (IRRs) and 95% confidence intervals (CI) to estimate the risk in the 1-60 day period following HPV4 exposure and in subsets of that period. IRRs were stratified by age, gender, hormonal contraceptive use, and recent surgery or trauma.We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 (54%) cases. VTE was uncommon among males (n=3) and 9-12 year olds (n=4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1-60 days following HPV4 exposure. The risk of VTE varied from 1.47 (95% CI: 0.47-4.64) in the 1-7 days following HPV4 exposure to 0.92 (95% CI: 0.54-1.57) in the 1-60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure.The risk of developing VTE among 9- to 26-year-olds was not elevated following HPV4 exposure. Sample size limited our ability to rigorously evaluate potential effect modifiers, such as gender, through stratified analysis.

Bioterrorism surveillance systems can be assessed using modeling to simulate real-world attacks., We measured sensitivity and timeliness of a syndromic surveillance system to detect bioterrorism events. A hypothetical anthrax release was modeled by using zip code population data, mall customer surveys, and membership information from HealthPartners Medical Group, which covers 9% of a metropolitan area population in Minnesota. For each infection level, 1,000 releases were simulated. Timing of increases in use of medical care was based on data from the Sverdlovsk, Russia, anthrax release. Cases from the simulated outbreak were added to actual respiratory visits recorded for those dates in HealthPartners Medical Group data. Analysis was done by using the space-time scan statistic. We evaluated the proportion of attacks detected at different attack rates and timeliness to detection. Timeliness and completeness of detection of events varied by rate of infection. First detection of events ranged from days 3 to 6. Similar modeling may be possible with other surveillance systems and should be a part of their evaluation.

Objective—To identify factors significantly associated with an epidemic of fibrinous pericarditis during spring 2001 among horses in central Kentucky. Design—Case-control study. Animals—38 horses with fibrinous pericarditis and 30 control horses examined for other reasons. Procedure—A questionnaire was developed to solicit information regarding a wide range of management practices and environmental exposures from farm owners or managers. Results—The following factors were found in bivariate analyses to be significantly associated with an increased risk of pericarditis: being from a farm with mares and foals affected by mare reproductive loss syndrome, exposure to Eastern tent caterpillars in or around horse pastures, younger age, shorter duration of residence in Kentucky and at the farm of current residence, being fed hay grown outside Kentucky, a lack of access to pond water, access to orchard grass for grazing, and a lack of direct contact with cattle. In multivariate logistic regression analyses, only variables related to caterpillar exposure and age were significantly associated with fibrinous pericarditis. Conclusions and Clinical Relevance—Results suggest that fibrinous pericarditis in horses may be associated with mare reproductive loss syndrome. Exposure to Eastern tent caterpillars was the greatest risk factor for development of fibrinous pericarditis. The distribution of times of diagnosis of fibrinous pericarditis was consistent with a point-source epidemic. (J Am Vet Med Assoc 2003;223:832–838)