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Amanda Cohn, MD CDR, US Public Health Service National Center for Immunization and Respiratory Diseases April 6, 2011 Epidemiology of Meningococcal Disease in Infants and Young Children and Vaccine Effectiveness of the Adolescent Program
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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
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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
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Meningococcal Disease Incidence, United States 1921-1996 NNDSS data, 1997-2008 ABCs data projected to U.S. population MCV4
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Meningococcal Disease Incidence by Year and Serogroup, 1999-2008 ABCs cases from 1999-2008 and projected to the U.S. population MCV4
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Meningococcal Disease Incidence by Age, 1999-2008 ABCs cases from 1999-2008 and projected to the U.S. population
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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
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Meningococcal Disease Incidence in Children <5 years, 1999-2008 ABCs cases from 1999-2008 and projected to the U.S. population *Other includes: serogroups W-135, nongroupables, other, and unknown
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Average Annual Cases of Meningococcal Disease in Children <5 years, 1999-2008 AgeSerogroup CSerogroup YC+Y (incidence) 0-2 months61824 (2.3) 3-5 months81927 (2.5) 6-8 months71421 (2.0) 9-11 months527 (0.7) 1 year11718 (0.4) 2 years16622 (0.5) 3 years718 (0.2) 4 years7512 (0.3) 0-59 months6772139 ABCs cases from 1999-2008 and estimated to the U.S. population
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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
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Average Annual Burden of Meningococcal Disease, 6-59 months vs. 11-19 years AgeNNDSS Average Annual Cases 2005- 2009 ABCs Proportion Serogroup C+Y ABCs Cases 2000-2009 Serogroup C+Y (Incidence) Estimated Cases of Serogroup C+Y (Incidence) 2005-2009 6-23 months11228.243 (0.5)32 (0.3) 24-59 months7226.837 (0.2)19 (0.2) 11-19 years17361.2173 (0.4)106 (0.3) 2005-2009 NNDSS reports, includes all case statuses; proportion of C+Y disease from ABCs reports
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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
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Meningococcal Cases in Children <2 years by Serogroup and Syndrome, ABCs, 2000-2009
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U.S. Multicenter Study of Pediatric Meningococcal Disease, 2001-2005 ≤5 years (n=105) 6-10 years (n=21) >10 years (n=33) Mechanical ventilation16.7%50.0%39.4% Hypotension12.4%0%9.1% Purpura34.3%52.4%39.4% Death3.8%9.5%21.2% ≤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.
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U.S. Multicenter Study: Sequelae at Hospitalization ≤5 years>5 years Serogroup BSerogroup C+Y Serogroup BSerogroup C+Y Necrosis5/60 (8.3)7/50 (14.0)1/22 (4.5)2/32 (6.3) Hearing loss6/56 (10.7)6/50 (12.0)3/17 (17.6)3/31 (9.7) Hemiplegia0/61 (0.0)1/50 (2.0)0/19 (0.0)1/34 (2.9) Death4/66 (6.1)0/20 (0.0)3/21 (14.3)4/34 (11.8) Personal communication, S. Kaplan
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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.
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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 a Merkelback et al., Acta Neurol Scand 2000, 102: 118-123. b Bedford et al., BMJ 2001, 323: 533-7.
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Average Annual Deaths and Case-Fatality Ratios by Serogroup and Age, 2000-2009 Serogroup BCYOverall <2 years16 (10.5)5 (22.5)1 (3.1)22 (9.9) 2-4 years7 (16.4)1 (8.0)1 (9.7)9 (12.2) 5-10 years7 (22.9)3 (12.6)1 (9.0)11 (16.7) 11-19 years9 (18.3)12 (17.8)3 (6.0)24 (13.3) 20+ years28 (17.0)36 (18.0)44 (16.6)118 (17.4) ABCs cases from 2000-2009 and projected to the U.S. population
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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
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Preliminary Results: Vaccine Effectiveness of Menactra®
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Matched Case-Control Study Design Enrollment ongoing (January 2006 – present) in 29 health departments Provider verified vaccination record (85%) N. meningitidis serogroup 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
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Cases by serogroup and vaccination status (n=120) Based on paperwork received by March 23, 2010 Vaccination statusSerogroup C (n=63) Serogroup Y (n=51) Serogroup W135 (n=6) Not vaccinated54405 Vaccinated <1 year220 Vaccinated 1<2 years221 Vaccinated 2<5 years570 Total controls enrolled100626
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Demographics Eligible Cases (n=207) Enrolled Cases (n=120) Controls (n=168) Mean Age:17.9 years (11- 24) 18.3 years (11-23)18.2 years (10-24) Male:59%62%52% Race: White71%78%89% Black18%15%4% Other3% 8% Unknown8%6%1% Case fatality ratio13%10% Analysis results based on paperwork received by March 23, 2010; excludes cases and controls vaccinated with MPSV4 only PRELIMINARY RESULTS, SUBJECT TO CHANGE.
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Proportion of Cases and Controls Vaccinated with MenACWY D by Year Based on paperwork received by March 11, 2011; unknown vaccination status excluded 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
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Preliminary VE, Menactra Effectiveness, (0-5 years) All Enrolled Cases Controlling for: VE (95% CI) Serogroups C, Y and W-135 combined74% (35-90%) Serogroup C 83% (38, 95%) Analysis results based on paperwork received by March 23, 2010. Controls for smoking status and underlying condition status PRELIMINARY RESULTS, SUBJECT TO CHANGE.
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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. Cases* VE (95% CI) All cases (n=120) VE (95% CI) Cases with no underlying illness (n=105) Vaccinated <1 year99% (0,100%) Vaccinated 1 to 2 years 80% (-3,96%) 89% (5, 99%) Vaccinated 2 to 5 years 46% (-66, 83%)56% (-48, 87%)
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Evolving Understanding of Protection Immunologic memory not enough* Boost response takes 5-7 days after exposure, incubation period of N. meningitidis is 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
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Menactra SBA-BR % of subjects with brSBA ≥1:128 post-vaccination, serogroup C n= 440n= 71 n=84n= 108 n=107 *Data courtesy of sanofi pasteur, 3 year follow-up of MTA02 (11-18 year-olds), 5 year follow-up of 603-02 (2-10 year-olds)
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Menveo and Menactra % of subjects with hSBA ≥ 1:8, Serogroup C Phase III, Persistence/Booster of Bactericidal Antibodies in Adolescents
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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
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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
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For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: cdcinfo@cdc.gov Web: 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!
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