1. Meningococcal Conjugate Vaccine Failures in the United States
National Immunization Conference
April 2, 2009
Jessica MacNeil, Amanda Cohn, and Elaine Miller for the Active Bacterial Core Surveillance (ABCs) Team and MeningNet Surveillance Partners

2. Meningococcal Disease
Caused by the bacterium Neisseria meningitidis
Typically presents as meningitis or bacteremia
Case-fatality rate is 10-15%, and as many as 20% of survivors have permanent sequelae

3. Underlying Immune Defects as Risk Factors
Deficiencies in terminal complement pathway
Asplenia
Diseases associated with immunosuppression (e.g. HIV)
Diseases associated with transient complement deficiencies (e.g. Lupus, nephrotic syndrome)

4. Cross-Sectional View of the Cell Membrane
Capsular polysaccharide (serogroup)
Outer-membrane proteins
(serotype/
subserotype)

5. Quadrivalent Meningococcal Conjugate Vaccine: MCV4
Protects against serogroups A, C, Y, W135
Licensed for use in 2-55 year olds
ACIP recommendations:
Routine use in year olds
Persons at increased risk of disease

6. Estimated Annual Number of Cases of Meningococcal Disease, United States: Age 0-21 years
ABCs cases from projected to the US population

7. NIS-Teen Coverage: MCV4 2006-2007
MMWR August 31,2007; 56 (34): MMWR October 10, 2008; 57 (40):

8. MCV4 Post-licensure Evaluation
Case-Control Study
Enrollment started in January 2006
Enrollment has been slow
Difficult to enroll adolescents
Incidence of disease continues to be very low
Screening Method
Surveillance for breakthrough cases

9. Objectives
To determine the number of cases of meningococcal disease in vaccinated persons since licensure of MCV4
To describe the epidemiology of breakthrough cases

10. Case Definition
Isolation of Neisseria meningitidis (serogroup A, C, Y, or W-135), or detection of N. meningitidis DNA using a standardized polymerase chain reaction (PCR)
In a clinical specimen taken from a normally sterile site
≥10 days after vaccination with MCV4

11. Identification of Cases
January 2005-December 2008
Active Bacterial Core Surveillance (ABCs) and MeningNet sites participating in the MCV4 effectiveness case-control study
VAERS reports

12. Surveillance for Breakthrough Cases
ABCs: Active surveillance
Laboratory based surveillance for cases of culture confirmed N. meningitidis
MeningNet: Enhanced surveillance
Surveillance for culture confirmed or PCR positive N. meningitidis
VAERS: Passive surveillance
Reports of any adverse event following vaccination

13. ABCs and MeningNet Sites

14. Meningococcal Disease in Vaccinated Persons
13 confirmed cases*
8 identified by ABCs or MeningNet sites only
1 identified by VAERS only
4 identified through both sources
No common lot of vaccine
Cases identified in 6 of 20 participating sites
*Cases identified through December 31, 2008

15. Descriptive Epidemiology
6 (46%) cases were male
7 (54%) cases were attending college
2 (15%) cases were military recruits
Median age at vaccination was 18.3 years (range )
Median age at time of disease 19.6 years (range years)

16. Laboratory Confirmation
12 (92%) cases culture confirmed, 1 PCR+ with clinically compatible illness
8 (62%) serogroup C and 5 (38%) serogroup Y
MLST patterns consistent with circulating strains

17. Clinical Description 12 (92%) cases were hospitalized
Median hospitalization time was 3 days (range 0-46 days)
3 fatal cases; 23% case fatality
Meningitis was reported in 6 (46%) cases and bacteremia in 7 (54%) cases

18. Underlying Medical Conditions
Case
Description 1
Pulmonary embolism and deep vein thrombosis 2
Diabetes and mitrovalve prolapse 3
Irritable bowel syndrome, eczema 4
Current smoker 5
History of pyelonephritis 6
None reported 7
Seasonal allergies 8 9
Prior history of bacterial meningitis, recurrent infections 10 11 12 13
Aplastic anemia and receiving cyclosporines

19. Time from Vaccination to Disease Onset, n=13*
days
6 (46%)
days
3 (23%)
730-1,095 days
4 (31%)
*Cases identified through December 31, 2008

20. Cases by Month of Disease and Year of Vaccination, n=13*
*Cases identified through December 31, 2008

21. Summary of Breakthrough Cases
Breakthrough cases occurring as vaccination coverage increases
Most cases among college students and military
Several may have contributory underlying conditions

22. What Does This Mean? Breakthrough cases expected
Response to MCV4 in pre-licensure studies
81% serogroup Y
91% serogroup C
Immunogenicity at 28 days

23. Why Would a Breakthrough Case Occur?
Host
Non-response to vaccine
Duration of protection
Immune deficiencies
Environment
Organism

24. Next Steps MCV4 effectiveness case-control study is ongoing
Increasing sites under surveillance for cases of breakthrough disease
Vaccine effectiveness using observed data
Identification of risk factors and immune profiles

25. Acknowledgements CDC (MVPDB) Amanda Cohn Nancy Messonnier Tom Clark
Brian Plikaytis
Elizabeth Zell
CDC (ISO)
Elaine Miller
ABCs Sites:
California
Colorado
Connecticut
Georgia
Maryland
Minnesota
New Mexico
New York
Oregon
Tennessee
MeningNet Sites:
Maine
Massachusetts
Michigan
New Hampshire
New York City
Pennsylvania
South Carolina
Texas
West Virginia
Wisconsin

26. Thank you!