Abstract
Introduction. Post-licensure vaccine safety studies are essential to identify uncommon events that may be difficult to assess during prelicensure studies. The aim of our study was to evaluate the safety of serogroup C meningococcal conjugate (MCC) vaccine in Tuscany from 2005 to 2012. Methods. All adverse events (AEs) to MCC vaccine notified from 2005 to 2012 were obtained from the regional health authority.
Results. Following 451,570 doses administered, 110 suspected AEs were notified (mean annual reporting rate: 2.8/10,000 doses). The most frequently AE reported was fever (60%), fol- lowed by swelling at the injection site (11%) and febrile seizures (10%). Overall, 77.3% of cases were not severe, while 21.8% required hospitalization. Almost four months after the receipt of the vaccine, a one-year-old infant was diagnosed with a pervasive developmental disorder with disturbance of speech, but any link with the vaccinations received was refuted. Most AEs (80.9%) occurred after co-administration with other vaccines, especially with MMR or MMRV vaccines (42.7%) or the DTPa-HBV-IPV/ Hib vaccine (33.7%).
Discussion. Our study confirmed the high level of safety of MCC vaccine in Tuscany: AEs proved rare and all cases had only tem- porary and self-resolving consequences. As usually only the most severe suspected AEs are reported, the true proportion of AEs requiring hospitalization was most probably overestimated, and it is plausible that most of these cases were in fact only temporally related.
References
Wilder-Smith A. Meningococcal vaccine in travelers. Curr Opin Infect Dis 2007;20(5):454-460. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=17762777 PubMed PMID: 17762777. doi: 10.1097/QCO.0b013e3282a64700. [Google Scholar]
for Disease Prevention and Control , author. Surveillance of invasive bacterial diseases in Europe. Stockholm: European Centre; 2011. [Google Scholar]
Jafri RZ, Ali A, Messonnier NE, Tevi-Benissan C, Durrheim D, Eskola J, et al. Global epidemiology of invasive meningococcal disease. Popul Health Metr 2013;11(1):17. Available from: http://pophealthmetrics.biomedcentral.com/articles/10.1186/1478-7954-11-17 PubMed PMID: 24016339. doi: 10.1186/1478-7954-11-17. [Google Scholar]
World Health Organization , author . Meningococcal vaccines: WHO position paper, November 2011. Wkly Epidemiol Rec 2011;47(47):521-539. Available from: http://www.who.int/wer/2011/wer8647.pdf?ua=1 PubMed PMID: 22128384. [Google Scholar]
Bonanni P, Bechini A, Boccalini S, et al. Igiene e Sanità Pubblica. 2012. Epidemiologia e prevenzione delle malattie infettive; pp. 355–447.
Stephens DS. Biology and pathogenesis of the evolutionarily successful, obligate human bacterium Neisseria meningitidis.. Vaccine 2009 May;27 Suppl 2(Suppl 2). Available from: http://europepmc.org/abstract/MED/19477055 PubMed PMID: 19477055. doi: 10.1016/j.vaccine.2009.04.070. [Google Scholar]
Trotter CL, Ramsay ME. Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines. FEMS Microbiol Rev 2006 Dec;31(1):101-107. Available from: http://femsre.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17168998 PubMed PMID: 17168998. doi: 10.1111/j.1574-6976.2006.00053.x. [Google Scholar]
Giunta Regionale Regione Toscana. DGR n. 379 del 7/03/2005. Direttive in materia di vaccinazioni e indirizzi per la stesura del nuovo calendario regionale delle vaccinazioni. Modifiche alla delibera G.R. 24.11.2003 n°1249. 2005.
Giunta Regionale Regione Toscana. DGR n. 1020 del 27-12- 2007. Aggiornamento direttive regionali in materia di vaccinazioni. Revoca delibere n. 1249 del 24/11/2003, n.379 del 7/3/2005 e n.1060 del 10/10/2000. Modifica delibera n. 1386 del 17/12/2001. 2008.
Regione Toscana DGR n. 1020 del 27/12/2007. Aggiornamento direttive regionali in materia di vaccinazioni. Revoca delibere n. 1249 del 24/11/2003. n.379 del 7/3/2005 e n.1060 del 10/10/2000. Modifica delibera n. 1386 del 17/12/2001. BURT n;2:9-1. [Google Scholar]
Ministero della Salute. Decreto 12 Dicembre 2003, Nuovo modello di segnalazione di reazione avversa a farmaci e vaccini. 2003
Miller E, Salisbury D, Ramsay M. Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story.. Vaccine 2001 Oct;20 Suppl 1(Suppl 1). Available from: https://www.nlm.nih.gov/medlineplus/meningococcalinfections.html PubMed PMID: 11587814. [Google Scholar]
Richmond P, Borrow R, Goldblatt D, Findlow J, Martin S, Morris R, et al. Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers.. J Infect Dis 2001;183(1):160-163. Available from: http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11078484 PubMed PMID: 11078484. doi: 10.1086/317646. [Google Scholar]
MacLennan JM, Shackley F, Heath PT, Deeks JJ, Flamank C, Herbert M, et al. Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial.. JAMA 2000 Jun;283(21):2795-2801. Available from: https://www.lens.org/lens/search?q=citation_id:10838647 PubMed PMID: 10838647. doi: 10.1001/jama.283.21.2795. [Google Scholar]
Medicines Control Agency , author. Report of the Committee on Safety of Medicines Expert Working Group on Meningococcal Group C Conjugate Vaccines. 2002
Australian Government. Deaprtment of Health , author. Therapeutic Goods Administration. Reporting medicine and vaccine adverse events
Lakshman R, Jones I, Walker D, McMurtrie K, Shaw L, Race G, et al. Safety of a new conjugate meningococcal C vaccine in infants. Arch Dis Child 2001;85(5):391-397. Available from: http://adc.bmj.com/cgi/pmidlookup?view=long&pmid=11668101 PubMed PMID: 11668101. doi: 10.1136/adc.85.5.391. [Google Scholar]
Andre FE, Booy R, Bock HL, Clemens J, Datta SK, John TJ, et al. Vaccination greatly reduces disease, disability, death and inequity worldwide. Bull World Health Organ 2008;86(2):140-146. Available from: http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862008000200016&lng=en&nrm=iso&tlng=en PubMed PMID: 18297169. doi: 10.2471/BLT.07.040089. [Google Scholar]
Plotkin S, Plotkin S. A short history of vaccination. In: Plotkin S, Orenstein W, Offit P, editors. Vaccines. Philadelphia: Elsevier- Saunders; 2013. [Google Scholar]
Barlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, Mullooly JP, et al. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine.. N Engl J Med 2001 Aug;345(9):656-661. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa003077?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov PubMed PMID: 11547719. doi: 10.1056/NEJMoa003077. [Google Scholar]
Farrington P, Pugh S, Colville A, Flower A, Nash J, Morgan-Capner P, et al. A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines. Lancet 1995;345(8949):567-569. Available from: http://www.diseaseinfosearch.org/result/2292 PubMed PMID: 7619183. doi: 10.1016/S0140-6736(95)90471-9. [Google Scholar]
MacDonald SE, Dover DC, Simmonds KA, Svenson LW. Risk of febrile seizures after first dose of measles-mumps-rubella-varicella vaccine: a population-based cohort study.. CMAJ 2014 Jun;186(11):824-829. Available from: http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=24914115 PubMed PMID: 24914115. doi: 10.1503/cmaj.140078. [Google Scholar]
Andrews N, Stowe J, Miller E, et al. Post-licensure safety of the meningococcal group C conjugate vaccine. Hum Vaccin 2007;3(2):59-63. Available from: http://www.tandfonline.com/doi/abs/10.4161/hv.3.2.3878 doi: 10.4161/hv.3.2.3878. [Google Scholar]
Maglione MA, Das L, Raaen L, Smith A, Chari R, Newberry S, et al. Safety of vaccines used for routine immunization of U.S. children: a systematic review.. Pediatrics 2014 Jul;134(2):325-337. Available from: http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=25086160 PubMed PMID: 25086160. doi: 10.1542/peds.2014-1079. [Google Scholar]
France EK, Glanz J, Xu S, Hambidge S, Yamasaki K, Black SB, Marcy M, Mullooly JP, Jackson LA, Nordin J, Belongia EA, Hohman K, Chen RT, Davis R , Vaccine Safety Datalink Team. . Risk of immune thrombocytopenic purpura after measles-mumps-rubella immunization in children.. . Available from: http://www.ncbi.nlm.nih.gov/pubmed/18310189 PubMed PMID: 18310189. doi: 10.1542/peds.2007-1578. [Google Scholar]
Andrews N, Stowe J, Miller E, Svanström H, Johansen K, Bonhoeffer J, et al. A collaborative approach to investigating the risk of thrombocytopenic purpura after measles-mumps-rubella vaccination in England and Denmark.. Vaccine 2012;30(19):3042-3046. Available from: http://www.diseaseinfosearch.org/result/4535 PubMed PMID: 21699947. doi: 10.1016/j.vaccine.2011.06.009. [Google Scholar]
Rajantie J, Zeller B, Treutiger I, Rosthöj S. Vaccination associated thrombocytopenic purpura in children. Vaccine 2007;25(10):1838-1840. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0264410X06011935 PubMed PMID: 17126957. doi: 10.1016/j.vaccine.2006.10.054. [Google Scholar]
Black C, Kaye JA, Jick H. MMR vaccine and idiopathic thrombocytopaenic purpura. Br J Clin Pharmacol 2003;55(1):107-111. Available from: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0306-5251&date=2003&volume=55&issue=1&spage=107 PubMed PMID: 12534647. doi: 10.1046/j.1365-2125.2003.01790.x. [Google Scholar]
Miller E, Waight P, Farrington CP, Andrews N, Stowe J, Taylor B. Idiopathic thrombocytopenic purpura and MMR vaccine.. Arch Dis Child 2001;84(3):227-229. Available from: http://adc.bmj.com/cgi/pmidlookup?view=long&pmid=11207170 PubMed PMID: 11207170. doi: 10.1136/adc.84.3.227. [Google Scholar]
Jonville-Béra AP, Autret E, Galy-Eyraud C, Hessel L. Thrombocytopenic purpura after measles, mumps and rubella vaccination: a retrospective survey by the French regional pharmacovigilance centres and pasteur-mérieux sérums et vaccins.. Pediatr Infect Dis J 1996;15(1):44-48. Available from: http://www.diseaseinfosearch.org/result/4535 PubMed PMID: 8684875. doi: 10.1097/00006454-199601000-00010. [Google Scholar]
GlaxoSmithKline . PRIORIX-TETRA® Combined measles, mumps, rubella and varicella vaccine, live, attenuated. Product monograph. Mississauga, Ontario: 2014. [Google Scholar]
Knuf M, Zepp F, Meyer CU, Habermehl P, Maurer L, Burow H, et al. Safety, immunogenicity and immediate pain of intramuscular versus subcutaneous administration of a measles-mumps-rubella-varicella vaccine to children aged 11-21 months.. Eur J Pediatr 2010 Feb;169(8):925-933. Available from: http://www.diseaseinfosearch.org/result/4535 PubMed PMID: 20148263. doi: 10.1007/s00431-010-1142-6. [Google Scholar]
Klein NP, Lewis E, Baxter R, Weintraub E, Glanz J, Naleway A, et al. Measles-containing vaccines and febrile seizures in children age 4 to 6 years.. Pediatrics 2012 Apr;129(5):809-814. Available from: http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=22473362 PubMed PMID: 22473362. doi: 10.1542/peds.2011-3198. [Google Scholar]