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Meningococcus () is the causative bacteria of invasive meningococcal disease (IMD), a major cause of meningitis and sepsis. In 2015–16, an outbreak caused by serogroup C meningococci (MenC), belonging to the hyperinvasive strain ST-11(cc-11), resulted in 62 IMD cases in the region of Tuscany, Italy.


We aimed to estimate the key outbreak parameters and assess the impact of interventions used in the outbreak response.


We developed a susceptible-carrier-susceptible individual-based model of MenC transmission, accounting for transmission in households, schools, discos/clubs and the general community, which was informed by detailed data on the 2015–16 outbreak (derived from epidemiological investigations) and on the implemented control measures.


The outbreak reproduction number (R) was 1.35 (95% prediction interval: 1.13–1.47) and the IMD probability was 4.6 for every 1,000 new MenC carriage episodes (95% confidence interval: 1.8–12.2). The interventions, i.e. chemoprophylaxis and vaccination of close contacts of IMD cases as well as age-targeted vaccination, were effective in reducing R and ending the outbreak. Case-based interventions (including ring vaccination) alone would have been insufficient to achieve outbreak control. The definition of age groups to prioritise vaccination had a critical impact on the effectiveness and efficiency of control measures.


Our findings suggest that there are no effective alternatives to widespread reactive vaccination during outbreaks of highly transmissible MenC strains. Age-targeted campaigns can increase the effectiveness of vaccination campaigns. These results can be instrumental to define effective guidelines for the control of future meningococcal outbreaks caused by hypervirulent strains.


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  1. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007;369(9580):2196-210.  https://doi.org/10.1016/S0140-6736(07)61016-2  PMID: 17604802 
  2. Urwin R, Maiden MCJ. Multi-locus sequence typing: a tool for global epidemiology. Trends Microbiol. 2003;11(10):479-87.  https://doi.org/10.1016/j.tim.2003.08.006  PMID: 14557031 
  3. Parikh SR, Campbell H, Bettinger JA, Harrison LH, Marshall HS, Martinon-Torres F, et al. The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination. J Infect. 2020;81(4):483-98.  https://doi.org/10.1016/j.jinf.2020.05.079  PMID: 32504737 
  4. Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. Vaccine. 2009;27(Suppl 2):B51-63.  https://doi.org/10.1016/j.vaccine.2009.04.063  PMID: 19477562 
  5. Trotter CL, Ramsay ME, Kaczmarski EB. Meningococcal serogroup C conjugate vaccination in England and Wales: coverage and initial impact of the campaign. Commun Dis Public Health. 2002;5(3):220-5. PMID: 12434692 
  6. Trotter CL, Gay NJ, Edmunds WJ. Dynamic models of meningococcal carriage, disease, and the impact of serogroup C conjugate vaccination. Am J Epidemiol. 2005;162(1):89-100.  https://doi.org/10.1093/aje/kwi160  PMID: 15961591 
  7. Trotter CL, Gay NJ, Edmunds WJ. The natural history of meningococcal carriage and disease. Epidemiol Infect. 2006;134(3):556-66.  https://doi.org/10.1017/S0950268805005339  PMID: 16238823 
  8. Gilmore A, Jones G, Barker M, Soltanpoor N, Stuart JM. Meningococcal disease at the University of Southampton: outbreak investigation. Epidemiol Infect. 1999;123(2):185-92.  https://doi.org/10.1017/S0950268899002794  PMID: 10579436 
  9. Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, Paul M, Leibovici L. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2013;2013(10):CD004785. PMID: 24163051 
  10. United States Centers for Disease Control and Prevention (CDC). Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997;46(RR-5):13-21. PMID: 9048847 
  11. Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62(RR-2) RR02;1-28. PMID: 23515099 
  12. Burmaz T, Selle V, Baldo V, Savoia E. Organization or community-based outbreak? responding to cases of meningitis under epidemiologic uncertainty. Disaster Med Public Health Prep. 2019;13(2):368-71.  https://doi.org/10.1017/dmp.2018.18  PMID: 29716663 
  13. Varaine F, Caugant DA, Riou JY, Kondé MK, Soga G, Nshimirimana D, et al. Meningitis outbreaks and vaccination strategy. Trans R Soc Trop Med Hyg. 1997;91(1):3-7.  https://doi.org/10.1016/S0035-9203(97)90371-0  PMID: 9093614 
  14. Miglietta A, Fazio C, Neri A, Pezzotti P, Innocenti F, Azzari C, et al. Interconnected clusters of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11), involving bisexuals and men who have sex with men, with discos and gay-venues hotspots of transmission, Tuscany, Italy, 2015 to 2016. Euro Surveill. 2018;23(34):1700636.  https://doi.org/10.2807/1560-7917.ES.2018.23.34.1700636  PMID: 30153883 
  15. Stefanelli P, Fazio C, Neri A, Ciammaruconi A, Balocchini E, Anselmo A, et al. Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11. J Infect. 2016;73(2):136-44.  https://doi.org/10.1016/j.jinf.2016.05.003  PMID: 27235364 
  16. Ciofi degli Atti ML, Merler S, Rizzo C, Ajelli M, Massari M, Manfredi P, et al. Mitigation measures for pandemic influenza in Italy: an individual based model considering different scenarios. PLoS One. 2008;3(3):e1790.  https://doi.org/10.1371/journal.pone.0001790  PMID: 18335060 
  17. Merler S, Ajelli M, Rizzo C. Age-prioritized use of antivirals during an influenza pandemic. BMC Infect Dis. 2009;9(1):117.  https://doi.org/10.1186/1471-2334-9-117  PMID: 19638194 
  18. Fumanelli L, Ajelli M, Manfredi P, Vespignani A, Merler S. Inferring the structure of social contacts from demographic data in the analysis of infectious diseases spread. PLOS Comput Biol. 2012;8(9):e1002673.  https://doi.org/10.1371/journal.pcbi.1002673  PMID: 23028275 
  19. Fumanelli L, Ajelli M, Merler S, Ferguson NM, Cauchemez S. Model-based comprehensive analysis of school closure policies for mitigating influenza epidemics and pandemics. PLOS Comput Biol. 2016;12(1):e1004681.  https://doi.org/10.1371/journal.pcbi.1004681  PMID: 26796333 
  20. Istituto Nazionale di Statistica (ISTAT). Indagine multiscopo sulle famiglie. Uso del tempo 2002-2003. [Multipurpose household survey "Time use". Years 2002-2003]. Rome: ISTAT; 2003. Italian. Available from: https://www.istat.it/it/archivio/277307
  21. Istituto Nazionale di Statistica (ISTAT). Cultura e tempo libero. In: Annuario statistico italiano. [Culture and free time. In: Italian Statistical Yearbook 2018] Rome: ISTAT; 2018. Italian. Available from: https://www.istat.it/it/files/2018/12/C10.pdf
  22. Ajelli M, Poletti P, Melegaro A, Merler S. The role of different social contexts in shaping influenza transmission during the 2009 pandemic. Sci Rep. 2014;4(1):7218.  https://doi.org/10.1038/srep07218  PMID: 25427621 
  23. Mossong J, Hens N, Jit M, Beutels P, Auranen K, Mikolajczyk R, et al. Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med. 2008;5(3):e74.  https://doi.org/10.1371/journal.pmed.0050074  PMID: 18366252 
  24. Kristiansen BE, Tveten Y, Jenkins A. Which contacts of patients with meningococcal disease carry the pathogenic strain of Neisseria meningitidis? A population based study. BMJ. 1998;317(7159):621-5.  https://doi.org/10.1136/bmj.317.7159.621  PMID: 9727987 
  25. Campbell H, Andrews N, Borrow R, Trotter C, Miller E. Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity. Clin Vaccine Immunol. 2010;17(5):840-7.  https://doi.org/10.1128/CVI.00529-09  PMID: 20219881 
  26. Pezzotti P, Miglietta A, Neri A, Fazio C, Vacca P, Voller F, et al. Meningococcal C conjugate vaccine effectiveness before and during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C/cc11, Tuscany, Italy. Vaccine. 2018;36(29):4222-7.  https://doi.org/10.1016/j.vaccine.2018.06.002  PMID: 29895504 
  27. McNamara LA, MacNeil JR, Cohn AC, Stephens DS. Mass chemoprophylaxis for control of outbreaks of meningococcal disease. Lancet Infect Dis. 2018;18(9):e272-81.  https://doi.org/10.1016/S1473-3099(18)30124-5  PMID: 29858150 
  28. Taha MK, Claus H, Lappann M, Veyrier FJ, Otto A, Becher D, et al. Evolutionary events associated with an outbreak of meningococcal disease in men who have sex with men. PLoS One. 2016;11(5):e0154047.  https://doi.org/10.1371/journal.pone.0154047  PMID: 27167067 
  29. Weiss D, Varma JK. Control of recent community-based outbreaks of invasive meningococcal disease in men who have sex with men in Europe and the United States. Euro Surveill. 2013;18(28):20522.  https://doi.org/10.2807/1560-7917.ES2013.18.28.20522  PMID: 23870094 
  30. United States Centers for Disease Control (CDC). Meningococcal disease outbreak among gay, bisexual men in Florida, 2021–23. Atlanta: CDC. [Accessed: 13 Apr 2023]. Available from: https://www.cdc.gov/meningococcal/outbreaks/FL2022.html
  31. Florida Department of Health. Reportable disease frequency. Tallahassee: Florida Department of Health [Accessed: 12 Apr 2023]. https://www.flhealthcharts.gov/ChartsReports/rdPage.aspx?rdReport=FrequencyMerlin.Frequency
  32. Trotter CL, Gay NJ, Edmunds WJ. Dynamic models of meningococcal carriage, disease, and the impact of serogroup C conjugate vaccination. Am J Epidemiol. 2005;162(1):89-100.  https://doi.org/10.1093/aje/kwi160  PMID: 15961591 
  33. Menichetti F, Fortunato S, Ricci A, Salani F, Ripoli A, Tascini C, et al. Invasive Meningococcal Disease due to group C N. meningitidis ST11 (cc11): The Tuscany cluster 2015-2016. Vaccine. 2018;36(40):5962-6.  https://doi.org/10.1016/j.vaccine.2018.08.050  PMID: 30172636 
  34. Miglietta A, Innocenti F, Pezzotti P, Riccobono E, Moriondo M, Pecile P, et al. Carriage rates and risk factors during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11) in Tuscany, Italy: a cross-sectional study. BMC Infect Dis. 2019;19(1):29.  https://doi.org/10.1186/s12879-018-3598-3  PMID: 30621624 
  35. Trotter CL, Gay NJ, Edmunds WJ. The natural history of meningococcal carriage and disease. Epidemiol Infect. 2006;134(3):556-66.  https://doi.org/10.1017/S0950268805005339  PMID: 16238823 
  36. Stefanelli P, Fazio C, Neri A, Isola P, Sani S, Marelli P, et al. Cluster of invasive Neisseria meningitidis infections on a cruise ship, Italy, October 2012. Euro Surveill. 2012;17(50):20336.  https://doi.org/10.2807/ese.17.50.20336-en  PMID: 23241233 
  37. Ferro A, Baldo V, Cinquetti S, Corziali P, Gallo G, Lustro G, et al. Outbreak of serogroup C meningococcal disease in Veneto region, Italy. Euro Surveill. 2008;13(2):3-4.  https://doi.org/10.2807/ese.13.02.08008-en  PMID: 18445389 
  38. Fazio C, Neri A, Tonino S, Carannante A, Caporali MG, Salmaso S, et al. Characterisation of Neisseria meningitidis C strains causing two clusters in the north of Italy in 2007 and 2008. Euro Surveill. 2009;14(16):19179.  https://doi.org/10.2807/ese.14.16.19179-en  PMID: 19389338 
  39. Lo Presti A, Neri A, Fazio C, Vacca P, Ambrosio L, Grazian C, et al. Reconstruction of dispersal patterns of hypervirulent meningococcal strains of serogroup C:cc11 by phylogenomic time trees. J Clin Microbiol. 2019;58(1):e01351-19.  https://doi.org/10.1128/JCM.01351-19  PMID: 31666361 
  40. Trotter CL, Fox AJ, Ramsay ME, Sadler F, Gray SJ, Mallard R, et al. Fatal outcome from meningococcal disease--an association with meningococcal phenotype but not with reduced susceptibility to benzylpenicillin. J Med Microbiol. 2002;51(10):855-60.  https://doi.org/10.1099/0022-1317-51-10-855  PMID: 12435065 

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