OBJECTIVES:(1) Characterize the initial clinical characteristics and long-term outcomes of smallpox vaccine-associated hypersensitivity myocarditis and pericarditis (MP) in United States service members. (2) Describe the process of case identification and adjudication using the 2003 CDC nationally defined myocarditis/pericarditis epidemiologic case definitions to include consideration of case-specific diversity and evolving evidence.BACKGROUND:Between 2002 and 2016, 2.546 million service members received a smallpox Vaccinia vaccine. Acute MP is associated with vaccinia, but the long-term outcomes have not been studied.METHODS:Records of vaccinia-associated MP reported to the Vaccine Adverse Event Reporting System by vaccination date were adjudicated using the 2003 MP epidemiologic case definitions for inclusion in a retrospective observational cohort study. Descriptive statistics of clinical characteristics, presentation, cardiac complications, and time course of clinical and cardiac recovery were calculated with comparisons by gender, diagnosis and time to recovery.RESULTS:Out of over 5000 adverse event reports, 348 MP cases who survived the acute illness, including 276 myocarditis (99.6% probable/confirmed) and 72 pericarditis (29.2% probable/confirmed), were adjudicated for inclusion in the long-term follow-up. Demographics included a median age of 24 years (IQR 21,30) and male predominance (96%). Compared to background military population, the myocarditis and pericarditis cohort had a higher percentage of white males by 8.2% (95% CI: 5.6, 10.0) and age <40 years by 4.2% (95% CI: 1.7,5.8). Long-term follow-up documented full recovery in 267/306 (87.3%) with 74.9% recovered in less than a year (median ~3 months). Among patients with myocarditis, the percentage who had a delayed time to recovery at time of last follow-up was 12.8% (95% CI: 2.1,24.7) higher in those with an acute left ventricular ejection fraction (EF) of ≤50% and 13.5% (95% CI: 2.4,25.7) higher in those with hypokinesis. Patient complications included 6 ventricular arrhythmias (2 received implanted defibrillators) and 14 with atrial arrhythmias (2 received radiofrequency ablation). Three of 6 patients (50%) diagnosed with cardiomyopathy had clinical recovery at their last follow-up date.CONCLUSIONS:Hypersensitivity myocarditis/pericarditis following the smallpox vaccine is associated with full clinical and functional ventricular recovery in over 87% of cases (74.9% <1 year). A minority of MP cases experienced prolonged or incomplete recovery beyond 1 year.

Objective: In March 2018, the US Department of Defense (DOD) added the smallpox vaccination, using ACAM2000, to its routine immunizations, increasing the number of persons receiving the vaccine. The following month, Fort Hood reported a cluster of 5 myopericarditis cases. The Centers for Disease Control and Prevention and the DOD launched an investigation. Methods: The investigation consisted of a review of medical records, establishment of case definitions, causality assessment, patient interviews, and active surveillance. A 2-sided exact rate ratio test was used to compare myopericarditis incidence rates. Results: This investigation identified 4 cases of probable myopericarditis and 1 case of suspected myopericarditis. No alternative etiology was identified as a cause. No additional cases were identified. There was no statistically significant difference in incidence rates between the observed cluster (5.23 per 1000 vaccinated individuals, 95% CI: 1.7-12.2) and the ACAM2000 clinical trial outcomes for symptomatic persons, which was 2.29 per 1000 vaccinated individuals (95% CI: 0.3-8.3). Conclusions: Vaccination with ACAM2000 is the presumptive cause of this cluster. Caution should be exercised before considering vaccination campaigns for smallpox given the clinical morbidity and costs incurred by a case of myopericarditis. Risk of myopericarditis should be carefully weighed with risk of exposure to smallpox.

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. (C) 2013 Elsevier Ltd. All rights reserved.

Background: On February 20, 2010, a 23 year old male Army Reservist (index case) with symptom onset 4 h after receiving inactivated monovalent pandemic 2009 (H1N1) vaccine (MIV) was hospitalized with possible Guillain-Barre syndrome (GBS). Within 1-2 days, 13 reservists from the same unit presented to the emergency department and 14 filed Vaccine Adverse Event Reporting System (VAERS) reports of nonspecific symptoms following MIV.Objectives: To describe the spectrum of adverse events (AE) among reservists in the unit after MIV and to identify factors contributing to this cluster of reports.Methods: We reviewed the reservists' VAERS reports and hospital records for demographics, influenza vaccination status, diagnostic results and outcome. All VAERS reports after vaccination from the same MIV lot were also screened. We conducted a survey of unit reservists to identify contributing factors for this cluster.Results: The presumptive diagnosis of GBS in the index case was not confirmed. All other reservists demonstrated normal exam findings and laboratory investigations. VAERS reports following vaccination from the same MIV lot revealed no consistent pattern. Our survey of factors contributing to the cluster was returned by 55 reservists (response rate 28%). AEs following MIV were significantly more often reported by female and black reservists. There was a tendency for concern about the safety of the 2010-2011 seasonal influenza vaccine to be higher for reservists that reported an AE to MIV (p = 0.13) or that sought medical attention for their symptoms (p = 0.08).Conclusions: This cluster represents possible stimulated reporting following receipt of inactivated pandemic 2009 (H1N1) vaccine among service personnel. Published by Elsevier Ltd.