1. 2015 CSTE Annual Conference
Serogroup B Meningococcal Disease Outbreak and Carriage Evaluation at a College — Rhode Island, 2015
Hello there.
Heidi M. Soeters, PhD MPH
2015 CSTE Annual Conference
June 16, 2015
National Center for Immunization & Respiratory Diseases
Division of Bacterial Diseases / Meningitis and Vaccine Preventable Diseases Branch

2. Rhode Island Department of Health notified
Cases of Serogroup B Meningococcal Disease at College A, Rhode Island, 2015
Case 1: 19-year-old undergraduate
Case 2: 20-year-old undergraduate
Rare sequence type: ST-9069
Rhode Island Department of Health notified
A case of meningococcal disease occurred in a 19-year-old student at College A on January 31st, 2015.
**The Rhode Island Department of Health was notified about this case on February 2nd.
**A second case occurred in a 20-year-old student on February 5th, and was reported the same day.
The 2 cases resided in different dormitories and had no known epidemiologic links.
Both were determined to be caused by serogroup B Neisseria meningitidis, and to have a **rare sequence type, 9069, never before seen in the U.S.
January
April
Case of serogroup B meningococcal disease 2

3. Meningococcal Disease
Neisseria meningitidis
10-15% case-fatality ratio
Serogroups A B C W Y and X
Conjugate vaccine protects against A C W and Y
Neisseria meningitidis
10-15% case-fatality ratio
Serogroups A B C W Y and X
Conjugate vaccine protects against A C W and Y
Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a serious illness with a 10-15% case-fatality ratio.
Serogroups B, C, and Y are the most common in the U.S.
The current meningococcal conjugate vaccine protects against A, C, W, and Y.
Photo by D. Scott Smith, MD, taken at Stanford University Hospital ( 3

4. Meningococcal Transmission
Nasopharyngeal carriage
Asymptomatic
Invasive disease rarely occurs
Spread through close contact
Respiratory or oral secretions
Patients or asymptomatic carriers
Risk factors for disease and carriage among adolescents:
Age1,2
Social mixing3
Smoking1
Meningococcal bacteria are carried in the nasopharynx, and most carriers remain completely asymptomatic.
Only rarely does invasive disease occur.
The bacteria are spread through close contact, specifically via respiratory or oral secretions from patients or asymptomatic carriers.
Important risk factors among adolescents include age, social mixing, and smoking.
Sources:
Harrison et al. JID (US)
Jeppesen et al. J Infect (UK)
Mandel et al. JID (US) 4

5. Serogroup B Meningococcal Disease
Meningococcal conjugate vaccine does not protect against serogroup B
Persons aged 16 to 21 years at increased risk for serogroup B meningococcal disease
Serogroup B outbreaks:
Serogroup B caused 4 university outbreaks during last 2 years
Outbreak definition*:
≥2 unrelated cases in organization with <5000 persons
≥3 unrelated cases in organization with ≥5000 persons
The meningococcal conjugate vaccine routinely administered to all adolescents does not protect against serogroup B,
…leaving persons aged 16 to 21 years at increased risk for serogroup B meningococcal disease.
In fact, serogroup B caused FOUR university outbreaks during the last 2 years. [PAUSE]
*Interim Guidance for Control of Serogroup B Meningococcal Disease in Organizational Settings. 5

6. Serogroup B Meningococcal (MenB) Vaccines
2 vaccines recently licensed in U.S. for persons aged years
Trumenba, 3 doses (Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.) – Oct 2014
Bexsero, 2 doses (Novartis Vaccines and Diagnostics) – Jan 2015
Understanding of impact on nasopharyngeal carriage is limited
…This outbreak at College A was the first to occur since two serogroup B, or MenB, vaccines were licensed for use in the U.S. : Trumenba and Bexsero.
Currently, our understanding of vaccine impact on nasopharyngeal carriage is limited.
Image: Pfizer 6

7. College A Outbreak Response
Ciprofloxin chemoprophylaxis for 71 close contacts
Mass MenB vaccination campaign
Trumenba
1st dose (Feb): 94% of 3,745 eligible students vaccinated
2nd dose (April): 80% of 3,741 eligible students vaccinated
Case of serogroup B meningococcal disease
Rhode Island Department of Health notified
January
1st dose
vaccination clinics
2nd dose
April
In response to the outbreak, College A and Rhode Island Department of Health provided chemoprophylaxis to 71 close contacts.
During a MenB vaccination campaign, 94% of eligible students received the first of three doses of Trumenba in February, and 80% received the second dose in April. 7

8. CDC Meningococcal Carriage Evaluation
Objectives:
Determine baseline prevalence of nasopharyngeal carriage of N. meningitidis
Assess impact of MenB vaccination on carriage
Methods:
Questionnaire & oropharyngeal swab
Specimen evaluation via bacterial culture, real-time PCR, and molecular testing
Case of serogroup B meningococcal disease
Rhode Island Department of Health notified
January
1st dose
vaccination clinics
Carriage evaluation
2nd dose
vaccination clinics &
April
Additionally, CDC conducted a meningococcal carriage evaluation, with 2 objectives:
To determine the baseline prevalence of nasopharyngeal carriage of Neisseria meningitidis, and
To assess the impact of MenB vaccination on carriage.
The evaluation consisted of a short questionnaire assessing risk factors for meningococcal carriage and disease and laboratory testing of an oropharyngeal swab. The first of 3 planned evaluations was conducted in February, and the second took place in April along with the 2nd dose vaccination clinics. All undergraduate students at College A and graduate students who lived on campus were eligible to participate. 8

9. Meningococcal Carriage Evaluation Results, College A, Rhode Island, 2015
Total N
N. meningitidis
carriage, N (%)
February
717
176 (25)
April*
878
211 (24)
In the February evaluation, 717 students participated and 176, or 25%, were carriers of Neisseria meningitidis.
[PAUSE]
In April, 2 months following the first dose of Trumenba, 878 students participated, of whom 211, or 24% had meningococcal carriage.
*2 months following the first dose of Trumenba 9

10. None with outbreak strain (ST-9069)
Meningococcal Carriage Evaluation Results, College A, Rhode Island, 2015
February:
None with outbreak strain (ST-9069)
April:
1 with
outbreak strain (ST-9069)
Serogrouping by PCR revealed that in both February and April, 4% of students specifically had serogroup B carriage,
and of those 4%…
**none were found to be carrying the outbreak strain in February,
**while 1 student was carrying the outbreak strain in April. 10

11. N. meningitidis carriage, N (%)
Meningococcal Carriage Evaluation Results, College A, Rhode Island, 2015
Characteristic
Total N
N. meningitidis carriage, N (%)
Prevalence Ratio
p-value
Male
600
184 (31)
1.5 ( )
<0.001
Female
995
203 (20)
1.0
Smoke1
406
138 (34)
1.6 ( )
Second-hand smoke1
701
194 (28)
1.3 ( )
0.005
Visit bars, clubs, parties ≥1x/wk
1,132
330 (29)
2.4 ( )
School Year
Freshman
432
79 (18)
Sophomore
529
161 (30)
1.7 ( )
Junior
314
86 (27)
1.5 ( )
0.003
Senior
315
60 (19)
1.0 ( )
0.792
Graduate student 5
1 (20)
1.1 ( )
0.921
Associations with meningococcal carriage did not substantially differ between the 2 evaluations, therefore I am presenting pooled results.
Overall,
**Males,
**Smokers,
**Those reporting second-hand smoke exposure,
**or visiting bars, clubs, or parties at least once per week,
**and sophomores and juniors had increased carriage prevalences. 11

12. N. meningitidis carriage, N (%)
Meningococcal Carriage Evaluation Results, College A, Rhode Island, 2015
Characteristic
Total N
N. meningitidis carriage, N (%)
Prevalence Ratio
p-value
Recent antibiotic use1
196
20 (10)
0.4 ( )
<0.001
Live on campus
1,389
333 (24)
0.9 ( )
0.480
Recent upper respiratory infection symptoms2
671
177 (26)
1.2 ( )
0.092
Received first dose MenB vaccine
1,530
372 (24)
1.1 ( )
0.821
Received ACWY vaccine
1,480
358 (24)
1.0 ( )
0.803
Whereas, recent antibiotic use was associated with decreased carriage,
**and living on campus, recent upper respiratory infection symptoms, and meningococcal vaccination were not associated with carriage.
1In the past 30 days
2In the past 2 weeks 12

13. Conclusions Next Steps
Mass MenB vaccination campaign quickly achieved high vaccine coverage
No further serogroup B meningococcal disease cases associated with College A have been identified
Despite high carriage prevalence, only 1 carrier of outbreak strain identified
MenB vaccination had no apparent immediate impact on carriage
In conclusion, the mass MenB vaccination campaign quickly achieved high vaccination coverage and no further serogroup B meningococcal disease cases associated with College A have been identified.
Despite a high meningococcal carriage prevalence of 24 to 25%, only 1 student was found to be carrying the outbreak strain.
In the 2 months after the first dose, MenB vaccination had no apparent immediate impact on decreasing overall or serogroup B carriage.
A third carriage evaluation is planned for September 2015 in conjunction with final dose of MenB, so stay tuned.
Next Steps
Third carriage evaluation planned for September 2015 13

14. Rhode Island Meningococcal Carriage Evaluation Team
CDC
Manisha Patel* Lucy McNamara* Melissa Whaley* Xin Wang* Jessica MacNeil* Stacey Martin* Jeni Vuong* Anna Acosta Amy Blain How-Yi Chang Jennifer Farrar Amanda Faulkner Temi Folaranmi Mollie Harrison Adria Lee James Lee Leonard Mayer Sarah Meyer Jennifer Milucky Christine Miner Max Nerlander Heather Paulin Conrad Quinn Nathan Raines Tushar Singh Tami Skoff Tej Tiwari
Rhode Island Department of Health
Nicole Alexander-Scott*
Diane Brady
Ewa King
Michelle Wilson
Cindy Vanner*
John Fulton
Akshar Patel
Utpala Bandy*
Chris Goulette
Daniela Quilliam
Dave Balbi
Cheryl Josephson
James Rajotte
I’d like to acknowledge the following individuals and agencies for their fantastic work.
Koren Kanadanian*
Kenneth Sicard*
Kris Monahan
Steve Sears*
Kathy Kelleher
Michael Kraten
College A
*Co-authors 14

15. Thank you.
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.
National Center for Immunization & Respiratory Diseases
Division of Bacterial Diseases / Meningitis and Vaccine Preventable Diseases Branch 15