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

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

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

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

Pneumococcal Vaccines 1983-1999 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

Pneumococcal Conjugate Vaccine (PCV7) Universal vaccination Children < 2 years old 2, 4, 6 months, booster at 12-15 months 2-4 years with specific chronic diseases Vaccine coverage (2005) ~83% children between 19-35 months of age had at ≥ 3 doses of PCV7

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

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

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 1994-2004

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)

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

Number of Pneumococcal Meningitis Hospitalizations, by Year

Rates of Pneumococcal Meningitis Hospitalizations, by Age and Year

Rates of Pneumococcal Meningitis Hospitalizations, by Sex and Year

Estimating PCV7 Vaccination Program Effect Study period divided into 3 segments Pre-PCV7 (1994-1999): reference Transition (2000) Post-PCV7 (2001-2004) Rate difference = (average post-PCV7 rate – average pre-PCV7 rate)

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%)

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

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%)*

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

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

Conclusion Both children and the elderly have benefited from the routine PCV7 immunization program Estimated pneumococcal meningitis hospitalizations prevented in 2001-2004: Children <2 years old: 554 People of all ages: 1,659

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).

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

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

Trends of pneumococcal meningitis hospitalization rates

Trends of streptococcal meningitis hospitalization rates

Trends of other specified meningitis hospitalization rates

Trends of all other meningitis hospitalization rates