Amanda Cohn, MD CDR, US Public Health Service
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Transcript of Amanda Cohn, MD CDR, US Public Health Service
Amanda Cohn, MDCDR, 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
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
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
Meningococcal Disease Incidence, United States
1970
1972
1974
1976
1978
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
0
0.5
1
1.5
2
Year
Rat
e pe
r 100
,000
1921-1996 NNDSS data, 1997-2008 ABCs data projected to U.S. population
MCV4
0
5
10
15
1921
1925
1929
1933
1937
1941
1945
1949
1953
1957
1961
1965
1969
1973
1977
1981
1985
1989
1993
1997
2001
2005
Year
Rate
per
100
,000
Meningococcal Disease Incidence by Year and Serogroup, 1999-2008
1999 2000 2001 2002 2003 2004 2005 2006 2007 20080
0.1
0.2
0.3
0.4
0.5
B C Y
Year
Rat
e pe
r 100
,000
ABCs cases from 1999-2008 and projected to the U.S. population
MCV4
Meningococcal Disease Incidence by Age, 1999-2008
0-4 5-910
-1415
-1920
-2425
-2930
-3435
-3940
-4445
-4950
-5455
-5960
-6465
-6970
-7475
-7980
-84 85+
0
0.5
1
1.5
2
2.5
Age (years)
Rat
e pe
r 100
,000
ABCs cases from 1999-2008 and projected to the U.S. population
Estimated Annual Number of Cases of Meningococcal Disease, United States: Age 0 -
21 years
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 210
50
100
150
200
250 Serogroups A,C,Y,W-135 Serogroup B
Age
Num
ber
of c
ases
ABCs cases from 1999-2008 and projected to the U.S. population
Meningococcal Disease Incidence in Children <5 years,
1999-2008
<1 1 2 3 40123456
Serogroup B Serogroup C Serogroup Y Other*
Age (years)
Rat
e pe
r 100
,000
ABCs cases from 1999-2008 and projected to the U.S. population
*Other includes: serogroups W-135, nongroupables, other, and unknown
Average Annual Cases of Meningococcal Disease in Children <5
years, 1999-2008
Age Serogroup C
Serogroup Y
C+Y (incidence)
0-2 months 6 18 24 (2.3)3-5 months 8 19 27 (2.5)6-8 months 7 14 21 (2.0)9-11 months 5 2 7 (0.7)1 year 11 7 18 (0.4)2 years 16 6 22 (0.5)3 years 7 1 8 (0.2)4 years 7 5 12 (0.3)0-59 months 67 72 139
ABCs cases from 1999-2008 and estimated to the U.S. population
Cases of Serogroup C + Y Meningococcal Disease in Children
6-59 months, 2000-2009
2000 2001 2002 2003 2004 2005 2006 2007 2008 20090
20406080
100120140160 6-23 months 24-59 months
2000-2009 NNDSS reports, includes all case statuses; proportion of C+Y disease from ABCs reports
Average Annual Burden of Meningococcal Disease, 6-59 months
vs. 11-19 yearsAge NNDSS
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 months 112 28.2 43 (0.5) 32 (0.3)24-59 months
72 26.8 37 (0.2) 19 (0.2)
11-19 years 173 61.2 173 (0.4) 106 (0.3)
2005-2009 NNDSS reports, includes all case statuses; proportion of C+Y disease from ABCs reports
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
Meningococcal Cases in Children <2 years by Serogroup and Syndrome,
ABCs, 2000-2009
62%38%
Serogroup CMeningitis BacteremiaOther
44%40%
17%
Serogroup YMeningitis BacteremiaOther
U.S. Multicenter Study of Pediatric Meningococcal Disease, 2001-2005
≤5 years(n=105)
6-10 years(n=21)
>10 years(n=33)
Mechanical ventilation 16.7% 50.0% 39.4%
Hypotension 12.4% 0% 9.1%
Purpura 34.3% 52.4% 39.4%
Death 3.8% 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.
U.S. Multicenter Study: Sequelae at Hospitalization
≤5 years >5 years
Serogroup B Serogroup C+Y
Serogroup B Serogroup C+Y
Necrosis 5/60 (8.3) 7/50 (14.0) 1/22 (4.5) 2/32 (6.3)
Hearing loss 6/56 (10.7) 6/50 (12.0) 3/17 (17.6) 3/31 (9.7)
Hemiplegia 0/61 (0.0) 1/50 (2.0) 0/19 (0.0) 1/34 (2.9)
Death 4/66 (6.1) 0/20 (0.0) 3/21 (14.3) 4/34 (11.8)
Personal communication, S. Kaplan
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.
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.
Average Annual Deaths and Case-Fatality Ratios by Serogroup and Age,
2000-2009Serogroup
B C Y Overall
<2 years 16 (10.5) 5 (22.5) 1 (3.1) 22 (9.9)
2-4 years 7 (16.4) 1 (8.0) 1 (9.7) 9 (12.2)
5-10 years 7 (22.9) 3 (12.6) 1 (9.0) 11 (16.7)
11-19 years 9 (18.3) 12 (17.8) 3 (6.0) 24 (13.3)
20+ years 28 (17.0) 36 (18.0) 44 (16.6) 118 (17.4)
ABCs cases from 2000-2009 and projected to the U.S. population
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
Preliminary Results: Vaccine Effectiveness of Menactra®
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
Cases by serogroup and vaccination status (n=120)
Based on paperwork received by March 23, 2010
Vaccination status Serogroup C(n=63)
Serogroup Y(n=51)
Serogroup W135 (n=6)
Not vaccinated 54 40 5
Vaccinated <1 year 2 2 0
Vaccinated 1<2 years
2 2 1
Vaccinated 2<5 years
5 7 0
Total controls enrolled
100 62 6
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: White 71% 78% 89% Black 18% 15% 4% Other 3% 3% 8% Unknown 8% 6% 1%Case fatality ratio
13% 10% Analysis results based on paperwork received by March 23, 2010; excludes cases and controls vaccinated with MPSV4 only
PRELIMINARY RESULTS, SUBJECT TO CHANGE.
Proportion of Cases and Controls Vaccinated with MenACWYD by Year
Based on paperwork received by March 11, 2011; unknown vaccination status excluded
2006 2007 2008 2009 20100
102030405060
Cases Controls
Year
Perc
ent V
acci
nate
d
Cases n=23Controls n=39
Cases n=25Controls n=35
Cases n=11Controls n=18
Cases n=26Controls n=41
Cases n=36Controls n=43
Preliminary VE, Menactra Effectiveness, (0-5 years)
All Enrolled Cases Controlling for: VE (95% CI)
Serogroups C, Y and W-135 combined 74% (35-90%)
Serogroup C 83% (38, 95%)
Analysis results based on paperwork received by March 23, 2010.Controls for smoking status and underlying condition statusPRELIMINARY RESULTS, SUBJECT TO CHANGE.
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 statusPRELIMINARY RESULTS, SUBJECT TO CHANGE.
Cases* VE (95% CI)All cases (n=120)
VE (95% CI)Cases with no underlying illness (n=105)
Vaccinated <1 year 99% (0,100%) 99% (0, 100%)
Vaccinated 1 to 2 years
80% (-3,96%) 89% (5, 99%)
Vaccinated 2 to 5 years
46% (-66, 83%) 56% (-48, 87%)
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
Menactra SBA-BR % of subjects with brSBA ≥1:128 post-vaccination,
serogroup C
1 mo 3 years 5 years0
102030405060708090
100 98.9
74.6
54.644 42.1
MCV4 Age-matched naive
% >
= 1:
128
n= 440 n= 71 n=84 n= 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)
Menveo and Menactra % of subjects with hSBA ≥ 1:8,
Serogroup C Phase III, Persistence/Booster of Bactericidal Antibodies in
Adolescents
1 month 22 months 36 months persistence
0102030405060708090
100
Menveo Menactra
% h
SBA
≥ 1
:8
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
1 mo0
102030405060708090
100
54.6
42.1
MCV4
Age-matched naive
% >
= 1:
128
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
For more information please contact Centers for Disease Control and Prevention1600 Clifton Road NE, Atlanta, GA 30333Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348E-mail: [email protected] 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!