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

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
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
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
Incidence of meningococcal disease among persons aged
18-24 years by student status – United States, 2015-2016
Unpublished data redacted

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
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
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
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
Timeline of serogroup B meningococcal disease cases and
MenB vaccination at U.S. universities – 2013-2017
Unpublished data redacted

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
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
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
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
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
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
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
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
MenB vaccine 1st dose coverage at U.S. universities that
experienced serogroup B meningococcal disease outbreaks –
2013-2017
Unpublished data redacted

19. 19
Meningococcal disease outbreak preparedness plans
at U.S. colleges and universities — 2017 (N=352)
Unpublished data redacted

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
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
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
Timeline of serogroup B meningococcal disease cases and
MenB vaccination at U.S. colleges/universities – 2009-2017
Unpublished data redacted

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
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
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
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
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
Acknowledgements
 CDC Meningitis and Vaccine Preventable Diseases Branch
 State and local health departments

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