Search

Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (PI) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and PI temporal clusters were identified using scan statistics. The association between PI and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly PI and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p0.0001). A significant (p=0.001) cluster of PI hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, PI hospitalization was significantly associated (p0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June. PI hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level.

Objective In response to widespread pertussis outbreaks and infant deaths, in 2010, the California Department of Health (CDPH) and in 2011 the Advisory Committee on Immunization Practices (ACIP) advised that the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine be administered during pregnancy. The goals of this study were to describe Tdap coverage among pregnant women following these recommendations. Methods In this observational cohort study, we utilized electronic medical record and claims data from seven Vaccine Safety Datalink sites to identify pregnancies and Tdap administrations. All Tdap doses were classified as pre-pregnancy, during pregnancy or post-pregnancy/postpartum. For pregnancies ending in a live birth, we evaluated factors associated with Tdap vaccination. Results Among 289,141 live births at the California VSD sites, receipt of Tdap during pregnancy increased substantially in the years 2010, 2011, and 2012, when coverage was 15.9, 30.0 and 19.5%, respectively. Among 82,398 women with live births at the Oregon, Washington, Colorado, Wisconsin and Minnesota VSD sites, receipt of Tdap during pregnancy first increased in 2012, at 16.0%. Women receiving early prenatal care and other vaccine(s) during pregnancy had higher Tdap coverage. Conclusion We observed substantial increases in Tdap coverage during pregnancy following CDPH and ACIP recommendations.

Background Hypersensitivity disorders following vaccinations are a cause for concern. Objective To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. Design A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. Setting/patients US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Measurements Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Results Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Limitations Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Conclusions Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity reactions.

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.

In immunization safety research, individuals are considered at risk for the development of certain adverse events following immunization (AEFI) within a specific period of time referred to as the risk interval. These intervals should ideally be determined based on biologic plausibility considering features of the AEFI, presumed or known pathologic mechanism, and the vaccine. Misspecification of the length and timing of these intervals may result in introducing bias in epidemiologic and clinical studies of immunization safety. To date, little work has been done to formally assess and determine biologically plausible and evidence-based risk intervals in immunization safety research. In this report, we present a systematic process to define biologically plausible and evidence-based risk interval estimates for two specific AEFIs, febrile seizures and acute disseminated encephalomyelitis. In addition, we review methodologic issues related to the determination of risk intervals for consideration in future studies of immunization safety.

In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit-risk framework to ensure that population health benefits are maximized.

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

From the Vanderbilt Vaccine Research Program, Vanderbilt University Medical Center, Nashville, TN; Kaiser Permanente Vaccine Study Center, Oakland, CA; Division of Pediatric Infectious Diseases, Columbia University, New York City, NY; Department of International Health, Disease Prevention and Control Program, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Division of Pediatric Infectious Diseases, Stanford University School of Medicine, M any events occurring after vaccination have been attributed to vaccines, when in fact the associationwas often due to chance. However, as with any medical intervention, there are times when adverse events are caused by immunizations. Distinguishing which events are causally related to vaccine, rather than coincidental events, is a challenge for the pediatrician and amajor focus of vaccine safety science. Consider a childwho presents with asepticmeningitis after immunization. Because of the temporal relationship, one may suspect the immunizations as the cause, yet subsequent isolation of enterovirus from cerebrospinal fluid implicates the enteroviral infection instead. The term adverse event following immunization (AEFI) is defined as any untoward event that occurs after immunization, regardless of causal association. AEFI is the preferred notation to describe such clinical events because the term is free from implications regarding causal relationship and favors an openmind about the role of immunizations.AEFIs are a commonpart of routine clinical practice. The Clinical Immunization Safety Assessment (CISA) network has reviewedmany individual cases of AEFIs and found that when a comprehensive investigation for alternative etiologies of the AEFI is completed, other causes for the event can often be identified. Yet, such comprehensive evaluations are rarely performed. We describe a stepwise approach to the comprehensive assessment of serious AEFIs by health care providers. The main objective is to highlight the important role that health care providers play in this effort by actively evaluating for the most likely causes of serious events when they occur after immunization.

The objective of the study was to evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, in pregnant women who received influenza A (H1N1) 2009 monovalent vaccine to assess for potential vaccine safety problems.We reviewed reports of adverse events (AEs) in pregnant women who received 2009-H1N1 vaccines from Oct. 1, 2009, through Feb. 28, 2010.VAERS received 294 reports of AEs in pregnant women who received 2009-H1N1 vaccine: 288 after inactivated and 6 after the live attenuated vaccines. Two maternal deaths were reported. Fifty-nine women (20.1%) were hospitalized. We verified 131 pregnancy-specific outcomes: 95 spontaneous abortions (20 weeks); 18 stillbirths (≥20 weeks); 7 preterm deliveries (37 weeks); 3 threatened abortions; 2 preterm labor; 2 preeclampsia; and 1 each of fetal hydronephrosis, fetal tachycardia, intrauterine growth retardation, and cleft lip.Review of reports to VAERS following H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes.

Objective The objective of the study was to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received seasonal influenza vaccines to assess for potential vaccine safety concerns. Study Design We searched VAERS for reports of adverse events (AEs) in pregnant women who received trivalent inactivated influenza vaccine (TIV) from July 1, 1990 through June 30, 2009, or live attenuated influenza vaccine (LAIV) from July 1, 2003, through June 30, 2009. Results A total of 148 reports after TIV and 27 reports after LAIV were identified. Twenty TIV (13.5%) and 1 LAIV (4%) reports were classified as serious. No specific AEs were reported in 30 TIV (20.3%) and 16 LAIV (59%) reports. The most common pregnancy-specific AE was spontaneous abortion: 17 after TIV (11.5%) and 3 after LAIV (11%). The reporting rate of spontaneous abortion was 1.9 per million pregnant women vaccinated. Conclusion No unusual patterns of pregnancy complications or fetal outcomes were observed in the VAERS reports of pregnant women after the administration of TIV or LAIV.