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Title: A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

Abstract

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of riskmore » for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

Authors:
 [1];  [2];  [3];  [3];  [2];  [2];  [2];  [3];  [3];  [4];  [5];  [3];  [6];  [7];  [8];  [8];  [9];  [10];  [11];  [12] more »;  [13] « less
  1. Uniformed Services Univ. of the Health Sciences, Bethesda, MD (United States)
  2. Uniformed Services Univ. of the Health Sciences, Bethesda, MD (United States); Walter Reed National Military Medical Center, Bethesda, MD (United States)
  3. Walter Reed National Military Medical Center, Bethesda, MD (United States)
  4. Vassar Brothers Medical Center, Poughkeepsie, NY (United States)
  5. Fort Belvoir Community Hospital, Fort Belvoir, VA (United States)
  6. Allergy and Asthma Care Centers, Chantilly, VA (United States)
  7. Womack Army Medical Center, Fort Bragg, NC (United States)
  8. Mayo Clinic, Rochester, MN (United States)
  9. Cincinnati Children's Hospital Center for Global Health, Cincinnati, OH (United States)
  10. Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  11. Bill and Melinda Gates Foundation, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
  12. Univ. of Tennessee Health Sciences Center, Memphis, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  13. Univ. of British Columbia, Vancouver, BC (Canada)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1333076
Grant/Contract Number:
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 10; Journal Issue: 3; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; vaccines; myocarditis; electrocardiography; smallpox; troponin; adverse events; influenza; vaccination and immunization

Citation Formats

Engler, Renata J. M., Nelson, Michael R., Collins Jr., Limone C., Spooner, Christina, Hemann, Brian A., Gibbs, Barnett T., Atwood, J. Edwin, Howard, Robin S., Chang, Audrey S., Cruser, Daniel L., Gates, Daniel G., Vernalis, Marina N., Lengkeek, Marguerite S., McClenathan, Bruce M., Jaffe, Allan S., Cooper, Leslie T., Black, Steve, Carlson, Christopher, Wilson, Christopher, Davis, Robert L., and Horwitz, Marc S.. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. United States: N. p., 2015. Web. doi:10.1371/journal.pone.0118283.
Engler, Renata J. M., Nelson, Michael R., Collins Jr., Limone C., Spooner, Christina, Hemann, Brian A., Gibbs, Barnett T., Atwood, J. Edwin, Howard, Robin S., Chang, Audrey S., Cruser, Daniel L., Gates, Daniel G., Vernalis, Marina N., Lengkeek, Marguerite S., McClenathan, Bruce M., Jaffe, Allan S., Cooper, Leslie T., Black, Steve, Carlson, Christopher, Wilson, Christopher, Davis, Robert L., & Horwitz, Marc S.. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. United States. doi:10.1371/journal.pone.0118283.
Engler, Renata J. M., Nelson, Michael R., Collins Jr., Limone C., Spooner, Christina, Hemann, Brian A., Gibbs, Barnett T., Atwood, J. Edwin, Howard, Robin S., Chang, Audrey S., Cruser, Daniel L., Gates, Daniel G., Vernalis, Marina N., Lengkeek, Marguerite S., McClenathan, Bruce M., Jaffe, Allan S., Cooper, Leslie T., Black, Steve, Carlson, Christopher, Wilson, Christopher, Davis, Robert L., and Horwitz, Marc S.. Fri . "A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination". United States. doi:10.1371/journal.pone.0118283. https://www.osti.gov/servlets/purl/1333076.
@article{osti_1333076,
title = {A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination},
author = {Engler, Renata J. M. and Nelson, Michael R. and Collins Jr., Limone C. and Spooner, Christina and Hemann, Brian A. and Gibbs, Barnett T. and Atwood, J. Edwin and Howard, Robin S. and Chang, Audrey S. and Cruser, Daniel L. and Gates, Daniel G. and Vernalis, Marina N. and Lengkeek, Marguerite S. and McClenathan, Bruce M. and Jaffe, Allan S. and Cooper, Leslie T. and Black, Steve and Carlson, Christopher and Wilson, Christopher and Davis, Robert L. and Horwitz, Marc S.},
abstractNote = {Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.},
doi = {10.1371/journal.pone.0118283},
journal = {PLoS ONE},
number = 3,
volume = 10,
place = {United States},
year = {Fri Mar 20 00:00:00 EDT 2015},
month = {Fri Mar 20 00:00:00 EDT 2015}
}

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