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

Renata J.M. Engler, Michael R. Nelson, Limone C. Collins, Christina Spooner, Brian A. Hemann, Barnett T. Gibbs, J. Edwin Atwood, Robin S. Howard, Audrey S. Chang, Daniel L. Cruser, Daniel G. Gates, Marina N. Vernalis, Marguerite S. Lengkeek, Bruce M. McClenathan, Allan S. Jaffe, Leslie T. Cooper, Steve Black, Christopher Carlson, Christopher Wilson, Robert Davis

Research output: Contribution to journalArticle

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Abstract

Background 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. Purpose 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. Methods 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 TIVvaccinated group. Conclusions 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.

Original languageEnglish (US)
Article numbere0118283
JournalPLoS ONE
Volume10
Issue number3
DOIs
StatePublished - Mar 20 2015

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Smallpox Vaccine
pericarditis
myocarditis
Smallpox
Pericarditis
Myocarditis
prospective studies
influenza
Human Influenza
signs and symptoms (animals and humans)
Vaccination
vaccination
Prospective Studies
vaccines
incidence
Immunization
Incidence
immunization
monitoring
Influenza Vaccines

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. / Engler, Renata J.M.; Nelson, Michael R.; Collins, 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.

In: PLoS ONE, Vol. 10, No. 3, e0118283, 20.03.2015.

Research output: Contribution to journalArticle

Engler, RJM, Nelson, MR, Collins, LC, Spooner, C, Hemann, BA, Gibbs, BT, Atwood, JE, Howard, RS, Chang, AS, Cruser, DL, Gates, DG, Vernalis, MN, Lengkeek, MS, McClenathan, BM, Jaffe, AS, Cooper, LT, Black, S, Carlson, C, Wilson, C & Davis, R 2015, 'A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination', PLoS ONE, vol. 10, no. 3, e0118283. https://doi.org/10.1371/journal.pone.0118283
Engler, Renata J.M. ; Nelson, Michael R. ; Collins, 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. / A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. In: PLoS ONE. 2015 ; Vol. 10, No. 3.
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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 = "Background 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. Purpose 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. Methods 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 TIVvaccinated group. Conclusions 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.",
author = "Engler, {Renata J.M.} and Nelson, {Michael R.} and Collins, {Limone C.} and Christina Spooner 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 Steve Black and Christopher Carlson and Christopher Wilson and Robert Davis",
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T1 - A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

AU - Engler, Renata J.M.

AU - Nelson, Michael R.

AU - Collins, Limone C.

AU - Spooner, Christina

AU - Hemann, Brian A.

AU - Gibbs, Barnett T.

AU - Atwood, J. Edwin

AU - Howard, Robin S.

AU - Chang, Audrey S.

AU - Cruser, Daniel L.

AU - Gates, Daniel G.

AU - Vernalis, Marina N.

AU - Lengkeek, Marguerite S.

AU - McClenathan, Bruce M.

AU - Jaffe, Allan S.

AU - Cooper, Leslie T.

AU - Black, Steve

AU - Carlson, Christopher

AU - Wilson, Christopher

AU - Davis, Robert

PY - 2015/3/20

Y1 - 2015/3/20

N2 - Background 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. Purpose 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. Methods 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 TIVvaccinated group. Conclusions 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.

AB - Background 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. Purpose 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. Methods 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 TIVvaccinated group. Conclusions 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.

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