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Amanda Cohn, MD CDR, US Public Health Service

Epidemiology of Meningococcal Disease in Infants and Young Children and Vaccine Effectiveness of the Adolescent Program. Amanda Cohn, MD CDR, US Public Health Service National Center for Immunization and Respiratory Diseases April 6, 2011. Background.

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Amanda Cohn, MD CDR, US Public Health Service

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  1. Epidemiology of Meningococcal Disease in Infants and Young Children and Vaccine Effectiveness of the Adolescent Program Amanda Cohn, MD CDR, US Public Health Service National Center for Immunization and Respiratory Diseases April 6, 2011

  2. Background • Meningococcal disease affects all age groups • High case-fatality ratio substantial morbidity among survivors • Adolescent vaccination program may be informative to questions around infant vaccination • Initial ACIP recommendation in 2005, preferred age 11-12 years • Booster dose at age 16, January 2011

  3. Infant Burden of Disease: Data Sources • Active Bacterial Core surveillance (ABCs) • Active laboratory- and population-based surveillance • 10 sites (~13% of U.S. population) • Limited to culture confirmed cases • National Notifiable Diseases Surveillance System (NNDSS) • Passive surveillance • All states and territories • Limited serogroup information • Published reports of sequelae and estimates of severity

  4. Meningococcal Disease Incidence, United States MCV4 1921-1996 NNDSS data, 1997-2008 ABCs data projected to U.S. population

  5. Meningococcal Disease Incidence by Year and Serogroup, 1999-2008 MCV4 ABCs cases from 1999-2008 and projected to the U.S. population

  6. Meningococcal Disease Incidence by Age, 1999-2008 ABCs cases from 1999-2008 and projected to the U.S. population

  7. Estimated Annual Number of Cases of Meningococcal Disease, United States: Age 0 - 21 years ABCs cases from 1999-2008 and projected to the U.S. population

  8. Meningococcal Disease Incidence in Children <5 years, 1999-2008 *Other includes: serogroups W-135, nongroupables, other, and unknown ABCs cases from 1999-2008 and projected to the U.S. population

  9. Average Annual Cases of Meningococcal Disease in Children <5 years, 1999-2008 ABCs cases from 1999-2008 and estimated to the U.S. population

  10. Cases of Serogroup C + Y Meningococcal Disease in Children 6-59 months, 2000-2009 2000-2009 NNDSS reports, includes all case statuses; proportion of C+Y disease from ABCs reports

  11. Average Annual Burden of Meningococcal Disease, 6-59 months vs. 11-19 years 2005-2009 NNDSS reports, includes all case statuses; proportion of C+Y disease from ABCs reports

  12. Hospitalization of Meningococcal Cases, ABCs, 1999-2008 • 92% of all cases were hospitalized • Median length of hospitalization*: • <1 year: 7 days (0-373) • 1-10 years: 6 days (0-61) • 11-19 years: 6 days (0-79) • ≥20 years: 6 days (0-128) • Does not vary by month of age, serogroup or syndrome *Limited to hospitalized patients

  13. Meningococcal Cases in Children <2 years by Serogroup and Syndrome, ABCs, 2000-2009

  14. U.S. Multicenter Study of Pediatric Meningococcal Disease, 2001-2005 ≤5 years: 45% serogroup B, 44% serogroup A,C,Y,W135; 6-10 years: 43% serogroup B, 57% serogroup A,C,Y,W135; >10 years: 42% serogroup B, 58% serogroup A,C,Y,W135 Kaplan et al., Pediatrics 2006, 118(4):e979-84.

  15. U.S. Multicenter Study: Sequelae at Hospitalization Personal communication, S. Kaplan

  16. Quebec, Canada, 1990-1994: Sequelae from Serogroup C Disease Fig 1. Percentage of cases of meningococcal disease in Quebec with major complications (solid bars), minor complications (open bars), or fatal outcome (hatched bars), by age group Erickson and De Wals. CID 1998, 26:1159-64.

  17. Neurological Sequelae Associated With All Cause Bacterial Meningitis • Long-term neurological sequelae are difficult to measure • More than 2/3 of patients exhibit neurologic or neuropsychological deficits after acute bacterial meningitis (non-pathogen specific)a • Nearly 1/5 of children with meningitis have a permanent severe or moderate severe disability, and subtle deficits are also more prevalent (non-pathogen specific)b aMerkelback et al., Acta Neurol Scand 2000, 102: 118-123. bBedford et al., BMJ 2001, 323: 533-7.

  18. Average Annual Deaths and Case-Fatality Ratios by Serogroup and Age, 2000-2009 ABCs cases from 2000-2009 and projected to the U.S. population

  19. Summary • While infants age <1 year are at greatest risk, amount of potentially preventable disease in infants is low • Current nadir in disease incidence • Low proportion of serogroup C+Y disease • Declining incidence after first 6-8 months of life • Morbidity and mortality in infants is lower than in other age groups

  20. Preliminary Results: Vaccine Effectiveness of Menactra®

  21. Matched Case-Control Study Design • Enrollment ongoing (January 2006 – present) in 29 health departments • Provider verified vaccination record (85%) • N. meningitidisserogroup A, C, W-135, Y isolated from a normally sterile site, or detection by PCR • Challenges due to low disease incidence and difficulty enrolling adolescent age group • Matched by age and state (friend and school controls) • Conditional logistic regression • Controlling for underlying illness*, smoking • VE = 1- Odds Vaccinated vs Unvaccinated *Complement deficiency, asplenia, HIV, other immune disorder, cancer, diabetes, kidney disease

  22. Cases by serogroup and vaccination status (n=120) Based on paperwork received by March 23, 2010

  23. Demographics Analysis results based on paperwork received by March 23, 2010; excludes cases and controls vaccinated with MPSV4 only PRELIMINARY RESULTS, SUBJECT TO CHANGE.

  24. Proportion of Cases and Controls Vaccinated with MenACWYD by Year Cases n=23 Controls n=39 Cases n=25 Controls n=35 Cases n=11 Controls n=18 Cases n=26 Controls n=41 Cases n=36 Controls n=43 Based on paperwork received by March 11, 2011; unknown vaccination status excluded

  25. Preliminary VE, Menactra Effectiveness, (0-5 years) Analysis results based on paperwork received by March 23, 2010. Controls for smoking status and underlying condition status PRELIMINARY RESULTS, SUBJECT TO CHANGE.

  26. Preliminary Menactra VE Estimates: C, Y, and W-135, Duration of Protection* Analysis results based on paperwork received by March 23, 2010. Controls for smoking status and underlying condition status PRELIMINARY RESULTS, SUBJECT TO CHANGE.

  27. Evolving Understanding of Protection • Immunologic memory not enough* • Boost response takes 5-7 days after exposure, incubation period of N. meningitidisis 1-4 days. • Vaccine failures occur in person in whom immunologic memory can be demonstrated • Unlikely getting the additional benefits of herd immunity with the current U.S. program • Coverage increasing slowly, only now about 60% • Adolescent immunity at population level lower than 60% • Need circulating antibody at time of exposure *Snape et al, CID, 2006, Auckland et al, JID, 2006

  28. Menactra SBA-BR % of subjects with brSBA≥1:128 post-vaccination, serogroup C n= 440 n= 71 n=84 n= 108 n=107 *Data courtesy of sanofipasteur, 3 year follow-up of MTA02 (11-18 year-olds), 5 year follow-up of 603-02 (2-10 year-olds)

  29. Menveo and Menactra % of subjects with hSBA ≥ 1:8, Serogroup C Phase III, Persistence/Booster of Bactericidal Antibodies in Adolescents

  30. Does Observational Effectiveness Inform Interpretation of Serologic Data? • Vaccine effectiveness= 1- AR (vacc)x 100 AR (unvacc) • Serologic markers of protection do not incorporate natural protection in unvaccinated • VE is not directly inferred from serologic marker

  31. Conclusions • Trends in observational data and serologic data are consistent and indicate waning immunity • Serologic markers of protection should be correlated with post-licensure clinical efficacy

  32. Thank you!

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