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Dr Sarah Meyer @ Meningitis & Septicaemia in Children & Adults

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Responding to MenB outbreaks in universities in the UK and the US
https://www.meningitis.org/mrf-conference-2017

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Dr Sarah Meyer @ Meningitis & Septicaemia in Children & Adults

  1. 1. National Center for Immunization & Respiratory Diseases Serogroup B Meningococcal Disease Outbreaks at Universities and the Public Health Response – United States Sarah Meyer, MD MPH Centers for Disease Control and Prevention November 15, 2017
  2. 2. 2 Incidence of meningococcal disease – United States, 1996-2015 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Incidenceper100,000 Year Abbreviations: MenACWY = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccines = serogroup B meningococcal vaccines Source: 1996-2015 NNDSS Data 0.12 cases/100,000 population MenB vaccine MenACWY vaccine 1.3 cases/100,000 population
  3. 3. 3 Current meningococcal vaccine recommendations for adolescents and young adults in the United States  Quadrivalent conjugate meningococcal (MenACWY) vaccine: Routine vaccination of all adolescents aged 11-12 years with a booster dose at age 16 years.  Serogroup B (MenB) vaccine: Not routinely recommended; based on clinical discretion may be administered, with a preferred age of 16-18 years. – Recommended for outbreak response: • MenB-4C (Bexsero®): 2-dose series • MenB-FHbp (Trumenba®): 3-dose series
  4. 4. 4 Incidence of meningococcal disease among persons aged 18-24 years by student status – United States, 2015-2016 Unpublished data redacted
  5. 5. 5 Serogroup B meningococcal disease outbreaks among university populations – United States  Increased risk of meningococcal disease among university students is partly driven by outbreaks. – Although only ~5% of all U.S. cases are outbreak-associated, 40% of serogroup B cases among university students in 2015-2016 are outbreak-associated.  Since 2013, 8 serogroup B outbreaks with a total of 32 cases and 2 deaths (6.3%) have been reported at U.S. universities.  MenB vaccination implemented at all 8 universities: – MenB-4C: 5 universities (including 2 prior to U.S. licensure) – MenB-FHbp: 3 universities
  6. 6. 6 University Based Serogroup B Outbreaks† – United States, 2013–2017 †Where CDC consulted; *1 additional associated case identified after retrospective case review; **1 additional patient with inconclusive laboratory results State of University Location Outbreak Period Cases (deaths) # Undergraduates New Jersey Mar 2013 – Mar 2014 9 (1) 5,000 California Nov 2013 4* 18,000 Rhode Island Jan – Feb 2015 2 4,000 Oregon Jan – May 2015 7 (1) 20,000 California Jan – Feb 2016 2** 5,000 New Jersey Mar – Apr 2016 2 35,000 Wisconsin Oct 2016 3 30,000 Oregon Nov 2016 – Nov 2017 2 25,000
  7. 7. 7 Serogroup B meningococcal disease outbreaks and the public health response  What is the outbreak threshold for vaccination?  Which MenB vaccine should be used?  Who should be vaccinated (all students or a subset)?  What strategies should be used to achieve high coverage, especially for the 2nd and 3rd doses (when indicated)?  In 2017, based in part on the experiences in responding to serogroup B university outbreaks, CDC revised its meningococcal disease outbreak guidance1. 1 Publication pending, will be published at https://www.cdc.gov/meningococcal/outbreaks.
  8. 8. 8 What is the outbreak threshold for vaccination?  Previous threshold: ≥3 cases of the same serogroup with an incidence of >10 cases per 100,000 during a 3 month period.  Is this definition still appropriate in the current epidemiologic context?
  9. 9. 9 Timeline of serogroup B meningococcal disease cases and MenB vaccination at U.S. universities – 2013-2017 Unpublished data redacted
  10. 10. 10 Revised outbreak threshold for vaccination  Revised threshold (organization-based outbreaks): 2-3 outbreak-associated cases within a 3-month period. – Outbreak-associated case: all cases of the same serogroup unless molecular typing indicates that a strain is genetically different than the predominant outbreak strain.
  11. 11. 11 Which MenB vaccine (MenB-4C or MenB-FHbp) to use during an outbreak?  As MenB vaccines are strain-specific, outbreak response could be optimized by determining which vaccine affords the greatest protection against an outbreak strain.  Whole genome sequencing, performed on available isolates when an outbreak is suspected, can assess presence, but not expression or expected coverage of a particular vaccine. – Logistical challenges to conducting additional testing in real-time during an outbreak.
  12. 12. 12 Which MenB vaccine (MenB-4C or MenB-FHbp) to use during an outbreak?  During the 2016 New Jersey serogroup B university outbreak, whole genome sequencing results were used to make a preferential vaccine recommendation for MenB-FHbp1. – FHbp A22/2.19 – Por A P1.5-1,10-1 – NHba p0020 – NadA negative 1Soeters. 2017. EID. 2 Data courtesy of Dan Granoff, University of California at San Fransisco.
  13. 13. 13 Which MenB vaccine (MenB-4C or MenB-FHbp) to use during an outbreak?  During the 2016 New Jersey serogroup B university outbreak, whole genome sequencing results were used to make a preferential vaccine recommendation for MenB-FHbp1. – FHbp A22/2.19 – Por A P1.5-1,10-1 – NHba p0020 – NadA negative 1Soeters. 2017. EID. 2 Data courtesy of Dan Granoff, University of California at San Fransisco. Mismatch for MenB-4C
  14. 14. 14 Which MenB vaccine (MenB-4C or MenB-FHbp) to use during an outbreak?  During the 2016 New Jersey serogroup B university outbreak, whole genome sequencing results were used to make a preferential vaccine recommendation for MenB-FHbp1. – FHbp A22/2.19 – Por A P1.5-1,10-1 – NHba p0020 – NadA negative 1Soeters. 2017. EID. 2 Data courtesy of Dan Granoff, University of California at San Fransisco. MenB-FHbp expected to provide cross-protection
  15. 15. 15 Which MenB vaccine (MenB-4C or MenB-FHbp) to use during an outbreak?  During the 2016 New Jersey serogroup B university outbreak, whole genome sequencing results were used to make a preferential vaccine recommendation for MenB-FHbp1. – FHbp A22/2.19 – Por A P1.5-1,10-1 – NHba p0020 – NadA negative  However, later testing demonstrated low FHbp expression, with a similar immune response by human serum bactericidal activity for either vaccine2.  Revised CDC outbreak guidance states that whole genome sequencing results should not be used to drive MenB vaccine selection at this time. 1Soeters. 2017. EID. 2 Data courtesy of Dan Granoff, University of California at San Fransisco.
  16. 16. 16 Who is Affected in University Serogroup B Outbreaks?  Prior studies show increased risk of meningococcal disease cases in freshmen living in dormitories, Greek society (fraternity/sorority) members, high social mixing.1-5  In the recent U.S. university outbreaks, many cases had no identifiable risk factors, and no sub-groups of students at increased risk identified. 1Bruce et al. 2001, JAMA 286(6):688-93; 2Froeschle 1999, Clin Infect Dis 29(1):215-6; 3Harrison et al. 1999, JAMA 281(20):1906-10; 4Neal et al. 1999, Epidemiol Infect 122(3):351-7;5Mandal et al. 2013, Clin Infect Dis 57(3):344-8. Images from: http://www.scrippscollege.edu/life/residence, https://www.theodysseyonline.com/supoort-the-penn-state-greek-life-restrictions, http://www.barsandnightclubs.com.au/perth/leederville/hipe-club/photos/2/
  17. 17. 17 MenB vaccination campaigns at U.S. universities  Based on the epidemiology, unable to conduct targeted vaccination campaigns at any of the universities.  University-wide vaccination of all undergraduates and select other groups.  Vaccination coverage highly variable: 1st dose coverage 8-95% of targeted students
  18. 18. 18 MenB vaccine 1st dose coverage at U.S. universities that experienced serogroup B meningococcal disease outbreaks – 2013-2017 Unpublished data redacted
  19. 19. 19 Meningococcal disease outbreak preparedness plans at U.S. colleges and universities — 2017 (N=352) Unpublished data redacted
  20. 20. 20 Strategies to increase vaccination coverage  Evening hours  Schedule dorms/groups specific times to attend  Required attendance & opt-out forms  Keep wait times short  Clear cost information  Involve students in promoting vaccination campaigns  Get the word out: email, social media, posters, swag – 2 surveys1,2 demonstrated that email was how the overwhelming majority of students heard about vaccination campaigns and also the preferred method of communication. – Communicate with parents too 1Breakwell et al. 2016, J Adolesc Health 59(4):457-64; 2CDC/Oregon Health Authority unpublished data
  21. 21. 21 0 10 20 30 40 50 60 70 80 90 100 Meningitis is serious University says it's important Best way to protect myself My parents told me to I am unlikely to get meningitis I know signs/ symptoms and will seek treatment instead Concerned about side effects Percent(%) Reasons for vaccination (N=853) Reasons for non-vaccination (N=400) What motivates students to get vaccinated during serogoup B university outbreaks? Breakwell et al. 2016, J Adolesc Health 59(4):457-64
  22. 22. 22 Impact of MenB vaccination campaigns on serogroup B meningococcal disease  Difficult to assess the impact of vaccination on the course of MenB outbreaks and what would have happened in the absence of vaccination.  Of the 8 universities that implemented a campaign, 6 had no additional cases among students at the affected university following completion of the 1st dose campaign.
  23. 23. 23 Timeline of serogroup B meningococcal disease cases and MenB vaccination at U.S. colleges/universities – 2009-2017 Unpublished data redacted
  24. 24. 24 Impact of MenB-FHbp on serogroup B carriage during a university outbreak  Observational, cross-sectional carriage evaluations conducted at two U.S. universities that experienced a serogroup B outbreak and implemented mass vaccination campaigns primarily using MenB-FHbp1,2.  Carriage assessed at baseline and 3 subsequent timepoints in 2015-2016. – Round 1: Baseline/dose 1 – Round 2: Dose 2 – Round 3: Dose 3 – Round 4: 1 year post-outbreak/freshman dose 3 1 McNamara et al. JID. 2017; 2 Soeters et al. CID. 2017
  25. 25. 25 Impact of MenB-FHbp on serogroup B carriage during a university outbreak 1 McNamara et al. JID. 2017; 2 Soeters et al. CID. 2017 0 5 10 15 20 25 30 Round 1 Round 2 Round 3 Round 4 Prevalence(%) Overall Serogroup B 0 5 10 15 20 25 30 Round 1 Round 2 Round 3 Round 4 Prevalence(%) Overall Serogroup B Oregon 2015 (N=4,225)1 Rhode Island 2015 (N=2,843)2
  26. 26. 26 Impact of MenB-FHbp on serogroup B carriage during a university outbreak 1 McNamara et al. JID. 2017; 2 Soeters et al. CID. 2017 0 5 10 15 20 25 30 Round 1 Round 2 Round 3 Round 4 Prevalence(%) Overall Serogroup B 0 5 10 15 20 25 30 Round 1 Round 2 Round 3 Round 4 Prevalence(%) Overall Serogroup B Oregon 2015 (N=4,225)1 Rhode Island 2015 (N=2,843)2 • No association between MenB-FHbp vaccination and serogroup B carriage. • No large or rapid reduction in serogroup B carriage or prevention of carriage acquisition; herd protection unlikely. • Individual protection through vaccination is important
  27. 27. 27 When is an outbreak ‘over’?  Prolonged nature of some serogroup B university outbreaks make it difficult to know when public health interventions can be stopped.  CDC revised guidance: for the purposes of public health decision-making, risk of meningococcal disease likely returns to expected levels one year after the last reported case.  Thus, in many situations, universities may consider vaccinating incoming freshman the following academic year.
  28. 28. 28 Conclusions  Despite declines in the incidence of meningococcal disease in the United States, college/university students are at increased risk for serogroup B disease and outbreaks.  MenB vaccination is an important new tool for outbreak response. – Additional evaluations to optimize its use for outbreak response and understand its impact will be helpful to guide future interventions.  Outbreak preparedness planning and strong communication/social mobilization are essential for the success of a MenB vaccination campaign.
  29. 29. 29 Acknowledgements  CDC Meningitis and Vaccine Preventable Diseases Branch  State and local health departments
  30. 30. For more information, contact CDC 1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Thank you smeyer@cdc.gov

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