Statistical and Ontological Analysis of Adverse Events Associated with Monovalent and Combination Vaccines against Hepatitis A and B Diseases.
Vaccinations often induce various adverse events (AEs), and sometimes serious AEs (SAEs). While many vaccines are used in combination, the effects of vaccine-vaccine interactions (VVIs) on vaccine AEs are rarely studied. In this study, AE profiles induced by hepatitis A vaccine (Havrix), hepatitis B vaccine (Engerix-B), and hepatitis A and B combination vaccine (Twinrix) were studied using the VAERS data. From May 2001 to January 2015, VAERS recorded 941, 3,885, and 1,624 AE case reports where patients aged at least 18 years old were vaccinated with only Havrix, Engerix-B, and Twinrix, respectively. Using these data, our statistical analysis identified 46, 69, and 82 AEs significantly associated with Havrix, Engerix-B, and Twinrix, respectively. Based on the Ontology of Adverse Events (OAE) hierarchical classification, these AEs were enriched in the AEs related to behavioral and neurological conditions, immune system, and investigation results. Twenty-nine AEs were classified as SAEs and mainly related to immune conditions. Using a logistic regression model accompanied with MCMC sampling, 13 AEs (e.g., hepatosplenomegaly) were identified to result from VVI synergistic effects. Classifications of these 13 AEs using OAE and MedDRA hierarchies confirmed the advantages of the OAE-based method over MedDRA in AE term hierarchical analysis.
Key Laboratory of Dependable Service Computing in Cyber Physical Society, Ministry of Education, Chongqing University, Chongqing, 400044, China.|University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
Jiangan
J
Xie
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
Lili
L
Zhao
Key Laboratory of Dependable Service Computing in Cyber Physical Society, Ministry of Education, Chongqing University, Chongqing, 400044, China.
Shangbo
S
Zhou
University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
Yongqun
Y
He
D000328:Adult; D005260:Female; D022362:Hepatitis A Vaccines / Q000009:adverse effects*; D006509:Hepatitis B / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000009:adverse effects*; D006526:Hepatitis C / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008390:Markov Chains; D009010:Monte Carlo Method; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects*
D022362:Hepatitis A Vaccines; D017325:Hepatitis B Vaccines; D017778:Vaccines, Combined
MMWR Morb Mortal Wkly Rep. 1999 Nov 5;48(43):1007
10577495
Rev Gastroenterol Disord. 2007 Winter;7(1):1-21
17392626
Drug Saf. 2003;26(3):145-58
12580645
Vaccine. 1992;10 Suppl 1:S142-5
1335647
J Am Med Inform Assoc. 2014 Oct;21(e2):e278-86
24644270
Am J Obstet Gynecol. 2012 Jul;207(1):59.e1-7
22727350
Ann Intern Med. 1997 Jul 15;127(2):156-8
9230008
MMWR Morb Mortal Wkly Rep. 2001 Sep 21;50(37):806-7
11785573
PLoS Comput Biol. 2011 Dec;7(12):e1002323
22219721
J Biomed Inform. 2016 Apr;60:294-308
26903152
Pediatr Infect Dis J. 2013 Feb;32(2):e77-81
23334341
Pharmacoepidemiol Drug Saf. 2005 Sep;14(9):601-9
15954077
MMWR Recomm Rep. 2011 Jan 28;60(2):1-64
21293327
Vaccine. 2011 Dec 30;29 Suppl 4:D7-9
22188929
Neurology. 2004 Sep 14;63(5):838-42
15365133
J Travel Med. 2015 Mar-Apr;22(2):105-14
25483566
Am J Obstet Gynecol. 2011 Nov;205(5):473.e1-9
21861964
N Engl J Med. 1991 Dec 19;325(25):1774-9
1719418
Vaccine. 2007 Jan 5;25(3):570-6
16945455
Am J Manag Care. 2003 Jan;9(1 Suppl):S6-12
12564784
Drug Saf. 2002;25(3):145-52
11945111
J Investig Allergol Clin Immunol. 2011;21(5):389-93
21905502
BMC Res Notes. 2010 Jun 22;3:175
20569493
Acta Trop. 2015 May;145:31-8
25697866
Am J Obstet Gynecol. 2014 Jun;210(6):561.e1-6
24378675
Vaccine. 2006 Mar 24;24(14):2685-91
16310295
World J Gastroenterol. 2005 Jul 14;11(26):4114-6
15996042
Pharmacoepidemiol Drug Saf. 2001 Oct-Nov;10(6):483-6
11828828
J Biomed Semantics. 2013 Nov 26;4(1):40
24279920
Autoimmunity. 2005 Jun;38(4):295-301
16206512
J Biomed Semantics. 2014 Jul 05;5:29
25093068
J Immunother Cancer. 2015 May 19;3:18
25992289
J Digit Imaging. 2007 Nov;20 Suppl 1:34-46
17687607
Drug Saf. 1999 Feb;20(2):109-17
10082069
Clin Exp Rheumatol. 2000 Nov-Dec;18(6):789-90
11138356
Biom J. 2015 Mar;57(2):286-303
25287055
J Med Virol. 1994 Dec;44(4):452-6
7897380
Drug Metab Rev. 2009;41(3):486-527
19601724
J Am Med Inform Assoc. 2012 Jan-Feb;19(1):79-85
21676938
Am J Obstet Gynecol. 2011 Feb;204(2):146.e1-7
20965490
Vaccine. 2000 Jan 6;18(11-12):1074-80
10590328
Clin Exp Rheumatol. 2004 Nov-Dec;22(6):749-55
15638050
Clin Exp Rheumatol. 2002 Jan-Feb;20(1):119
11892701
MMWR Surveill Summ. 2003 Jan 24;52(1):1-24
12825543
Vaccine. 2008 May 2;26(19):2428-32
18406499
Vaccine. 2001 Sep 14;19(32):4710-9
11535321
Drug Saf. 2016 Jul;39(7):697-707
27003817
Pediatr Infect Dis J. 2004 Apr;23(4):287-94
15071280
Clin Exp Rheumatol. 2002 Nov-Dec;20(6):767-71
12508767
Autoimmun Rev. 2012 Dec;12(2):144-9
22498789
PLoS One. 2012;7(11):e49941
23209624
Stat Med. 2012 May 20;31(11-12):1238-48
21905065
Vaccine. 1994 May;12(6):542-50
8036829