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

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

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 (http://emedicine.Medscape.com/article/221473-clinical) 3

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 2014. (US) Jeppesen et al. J Infect 2015. (UK) Mandel et al. JID 2013. (US) 4

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

Serogroup B Meningococcal (MenB) Vaccines 2 vaccines recently licensed in U.S. for persons aged 10-25 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

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

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

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

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

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 (1.3-1.8) <0.001 Female 995 203 (20) 1.0 Smoke1 406 138 (34) 1.6 (1.4-1.9) Second-hand smoke1 701 194 (28) 1.3 (1.1-1.5) 0.005 Visit bars, clubs, parties ≥1x/wk 1,132 330 (29) 2.4 (1.9-3.1) School Year Freshman 432 79 (18) Sophomore 529 161 (30) 1.7 (1.3-2.1) Junior 314 86 (27) 1.5 (1.1-2.0) 0.003 Senior 315 60 (19) 1.0 (0.8-1.4) 0.792 Graduate student 5 1 (20) 1.1 (0.2-6.4) 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

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 (0.3-0.6) <0.001 Live on campus 1,389 333 (24) 0.9 (0.7-1.2) 0.480 Recent upper respiratory infection symptoms2 671 177 (26) 1.2 (1.0-1.4) 0.092 Received first dose MenB vaccine 1,530 372 (24) 1.1 (0.7-1.7) 0.821 Received ACWY vaccine 1,480 358 (24) 1.0 (0.7-1.3) 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

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

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

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