1. Hospitalizations of Pneumococcal Meningitis in the Era of Pneumococcal Conjugate Vaccine
C. Jillian Tsai, Ph.D.
Department of Preventive Medicine
Vanderbilt University

2. Streptococcus pneumoniae
Gram-positive (diplo)cocci
Main pathogenic factor:
polysaccharide capsule
>90 serotypes
Type-specific antibody is protective
High risk
Extremes of age
Chronic diseases
Immune compromised

3. Pneumococcal Disease in Children < 5 Years of Age
Invasive
pneumococcal
disease
Meningitis
Bacteremia
Pneumonia
Otitis media

4. Pneumococcal Meningitis
#1 Cause of community-acquired bacterial meningitis
Mortality 16-37%
Among survivors, 30-52% risk of neurological complications
Deafness
Impaired mental status
Seizures
Intellectual impairment
Hearing loss and cranial neuropathies
Subdural effussion and empyema
Weisfelt M et al, Lancet Neurology, 2006
Kastenbauer S et al, Brain, 2003

5. Pneumococcal Vaccines
23-valent polysaccharide vaccine
2000-present
7-valent conjugate vaccine (PCV7)
7 serotypes >80% of invasive disease in children
T cell dependent immune response – immunogenicity in children <2 yrs
RCT: 89% efficacy against invasive disease
Pediatr Infect Dis J. 2002;21:810–815
Pediatr Infect Dis J. 2003;22:10–16
Lancet. 2005;365: 1139–1146
N Engl J Med. 2001;344:403–409
N Engl J Med. 2003;349:1341–1348

6. Pneumococcal Conjugate Vaccine (PCV7)
Universal vaccination
Children < 2 years old
2, 4, 6 months, booster at months
2-4 years with specific chronic diseases
Vaccine coverage (2005)
~83% children between months of age had at ≥ 3 doses of PCV7

7. Incidence of Invasive Pneumococcal Disease
among Children under 2 Years of Age
Kyaw et al. N Engl J Med 2006; 354(14)

8. Objectives
To estimate pneumococcal meningitis hospitalization rates from 1994 to 2004, by age groups
To estimate the number of hospitalizations prevented after routine immunization was recommended

9. Source of Data Nationwide Inpatient Sample (NIS) Study period
Largest inpatient database publicly available
~1,000 community hospitals (~20%)
Stratified probability sampling in 5 strata
ownership/control, bed size, teaching status, urban/rural, and US region
Hospital and discharge weights to obtain national estimates
Study period

10. Methods Exposure of interest Outcome – hospitalizations due to:
PCV7 (surrogate marker: calendar year)
Outcome – hospitalizations due to:
Pneumococcal meningitis
Streptococcal meningitis
Non-bacterial meningitis + non-specified meningitis
Definition of cases
Principal discharge diagnosis (ICD9-CM)

11. Methods (cont.) Analysis Data collected during 1994-2004
Stratified by calendar years and age
Data collected during
79,498,751 hospitalizations
 weighted national estimate of 365,259,792 hospitalizations
21,372 pneumococcal meningitis
Rate =
Weighted No. of Cases
Census Population

12. Number of Pneumococcal Meningitis Hospitalizations, by Year

13. Rates of Pneumococcal Meningitis Hospitalizations, by Age and Year

14. Rates of Pneumococcal Meningitis Hospitalizations, by Sex and Year

15. Estimating PCV7 Vaccination Program Effect
Study period divided into 3 segments
Pre-PCV7 ( ): reference
Transition (2000)
Post-PCV7 ( )
Rate difference
= (average post-PCV7 rate
– average pre-PCV7 rate)

16. Pneumococcal Meningitis Hospitalization Rates (per 100,000)
-5.1
(-66%)*
-0.4
(-33%)*
-0.4
(-52%)*
-0.1
(-11%)
-0.1
(-26%)*
-0.1
(-16%)

17. Streptococcal Meningitis Hospitalization Rates (per 100,000)
-4.6
(-41%)*
*p<0.05
-0.3
(-48%)*

18. Non-Bacterial and Unspecified Meningitis Hospitalization Rates (per 100,000)
-11.2
(-11%)
*p<0.05
+11.2
(90%)*
+5.7
(37%)* +7
(54%)*
+2.7
(36%)
+0.7
(9%)*

19. Summary: pneumococcal meningitis
66% decline in children < 2 years
11-52% declines in other ages
Coincident with PCV7 program
Similar to declines in all invasive diseases previously reported
No similar decline in non-related meningitis

20. Limitations of the Study
Ecological design
Potential misclassification of cases
Could not rule out the impact of secular trends, outbreaks, and changes in diagnosis/management of the disease
Incomplete race/ethnicity data

21. Conclusion
Both children and the elderly have benefited from the routine PCV7 immunization program
Estimated pneumococcal meningitis hospitalizations prevented in :
Children <2 years old: 554
People of all ages: 1,659

22. Acknowledgment Vanderbilt University CDC Source of Funding
Marie R. Griffin, MD, MPH
Carlos G. Grijalva, MD, MPH
CDC
J. Pekka Nuorti, MD, DSc
Source of Funding
Association for Prevention Teaching and Research and Centers for Disease Control and Prevention Cooperative Agreements (TS-1392).

24. Age Distribution (%) of Pneumococcal Meningitis Hospitalizations, by Year

25. Sex Distribution (%) of Pneumococcal Meningitis Hospitalizations, by Year

26. Trends of pneumococcal meningitis hospitalization rates

27. Trends of streptococcal meningitis hospitalization rates

28. Trends of other specified meningitis hospitalization rates

29. Trends of all other meningitis hospitalization rates