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Effectiveness of the US pneumococcal conjugate vaccination program on preventing pneumonia hospitalizations. Carlos G. Grijalva, MD MPH Department of Preventive Medicine Vanderbilt University School of Medicine Nashville, Tennessee. Overview. Pneumococcal diseases Importance of pneumonia
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Effectiveness of the US pneumococcal conjugate vaccination program on preventing pneumonia hospitalizations Carlos G. Grijalva, MD MPH Department of Preventive Medicine Vanderbilt University School of Medicine Nashville, Tennessee
Overview • Pneumococcal diseases • Importance of pneumonia • PCV7 efficacy against pneumonia • Study design considerations • PCV7 uptake & secular trends • Population-based changes after PCV7 introduction
Invasive pneumococcal diseases Active Bacterial Core Surveillance System, 1999 http://www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu99.pdf
Meningitis Bacteremia Pneumonia Otitis media/Sinusitis Pneumococcal-related Diseases More severe Study focus Invasive Pneumococcal Disease (IPD) More common
Polysaccharide vs. Conjugate vaccines Property Polysaccharide Conjugate Immunogenicity children <2 years NO YES B cell dependent immune response YES YES T cell dependent immune response NO YES Immune memory NO YES Booster effect NO YES Long term protection NO YES Reduction of carriage NO YES Herd immunity NO YES Adapted from Granoff DM. Vaccines. 2004
Impact of PCV7 on IPD, US PCV7 Active Bacterial Core Surveillance (ABCs) Report, Emerging Infections Program Network, Streptococcus pneumoniae, 1997-2009, Centers for Disease Control and Prevention. http://www.cdc.gov/ncidod/dbmd/abcs/survreports.htm. Accessed Sep 16th, 2010.
WHO: Major Causes of Death in Children <5 Years Causes of neonatal deaths Malaria 8% Pneumonia 19% Measles 4% Other 7% Pneumonia is the leading killer of children Tetanus 7% Diarrhea 17% Diarrhea 3% Injuries 3% Sepsis or pneumonia 26% Other 10% Asphyxia 23% HIV/AIDS 3% Congenital 8% Preterm 28% Neonatal 37% Bryce J, et al. Lancet. 2005;365:1147-1152
Pneumonia • Leading infectious cause of death • 3% to 18% of all childhood hospitalizations • Streptococcus pneumoniae is the leading bacterial cause of pneumonia • 17–44% pneumonia admissions in children • 13–34% pneumonia admissions in adults Marston BJ, et al. Arch Intern Med. 1997;157:1709-1718 Farha T, Thomson AH. Paediatr Respir Rev. 2005;6:76-82 Michelow I, et al. Pediatrics. 2004;113:701-707 Drummond P, et al. Arch Dis Child. 2000; 83:408-412 The British Thoracic Society and the Public Health Laboratory Service. Q J Med. 1987; 62:195-220
PCV7 Efficacy (Pneumonia) : NCKP • Black et al. PIDJ. 2002;21:810–15 • Hansen et al. PIDJ. 2006;25:779–81
Objectives • To estimate the impact of PCV7 • Pneumonia hospitalization rates in children aged <2 years (target population) • To evaluate indirect effects
Annual No. of PCV7 Doses (millions)Coverage with 3 or more doses CDC. Biosurveillance 2000–2005 and National Immunization Survey Grijalva CG, et al. Expert Rev Vaccines. 2008;7:83–95
Source of Information: NIS • HCUP: Nationwide Inpatient Sample • Sponsored by AHRQ • Largest inpatient database publicly available • ~20% of US hospital discharges • Discharge level information • De-identified data, diagnoses, procedures, no lab, no chest x-rays • Complex sampling design
Methods • Monthly hospitalization rates (annualized): • All-cause pneumonia • Pneumococcal pneumonia • Dehydration (control condition) • Segmented regression analysis: ITS • Log-transformed rates as outcomes • Quantified vaccine effect by end of 2004 Grijalva CG, et al. Lancet. 2007;369:1179–1186
Interrupted Time-series Analysis • Quasi-experimental design Wagner AK, et al. J Clin Pharm Therap. 2002;27:299–309
Evaluate longitudinal effects of time-delimited interventions Account for seasonal and secular trends With a control group can assess non-specific changes Impact of an Intervention:Before and After Comparison
Impact of an Intervention:Before and After Comparison Intervention (2000)
Intervention (2000) Impact of an Intervention:Before and After Comparison Overestimation of Effect
Intervention (2000) Impact of an Intervention:Before and After Comparison
Impact of an Intervention:Before and After Comparison Intervention (2000) Underestimation of Effect
Pneumococcal Pneumonia Rates/100,000 US Children <2 Years 100 Pre-PCV7 Post-PCV7 75 Hospitalizations per 100,000 50 25 0 1997 1998 1999 2000 2001 2002 2003 2004 Years Grijalva CG, et al. Lancet. 2007;369:1179–1186
Pneumococcal Pneumonia Rates/100,000 US Children <2 Years 100 Pre-PCV7 Post-PCV7 75 Hospitalizations per 100,000 50 25 0 1997 1998 1999 2000 2001 2002 2003 2004 Years Grijalva CG, et al. Lancet. 2007;369:1179–1186
Pneumococcal Pneumonia Rates/100,000 US Children <2 Years 100 Pre-PCV7 Post-PCV7 75 Hospitalizations per 100,000 50 25 0 1997 1998 1999 2000 2001 2002 2003 2004 Years Grijalva CG, et al. Lancet. 2007;369:1179–1186
∆ Pneumococcal Pneumonia Rates/100,000 US Children <2 Years 100 Pre-PCV7 Post-PCV7 –65% (–47, –77) 75 Hospitalizations per 100,000 50 25 0 1997 1998 1999 2000 2001 2002 2003 2004 Years Grijalva CG, et al. Lancet. 2007;369:1179–1186
–39% (–22, –52) 3000 ∆ 2500 2000 1500 Hospitalizations per 100,000 1000 500 0 Years 1997 1998 1999 2000 2001 2002 2003 2004 All-cause pneumonia Rates/100,000 US Children <2 Years Pre-PCV7 Post-PCV7 Grijalva CG, et al. Lancet. 2007;369:1179–1186
–0% 3000 ∆ 2500 2000 1500 Hospitalizations per 100,000 1000 500 0 Years 1997 1998 1999 2000 2001 2002 2003 2004 Dehydration Rates/100,000 US Children <2 Years Pre-PCV7 Post-PCV7 Grijalva CG, et al. Lancet. 2007;369:1179–1186
<2 2-4 5-17 18-39 40-64 >64 0 -20 -40 Percent (%) change -60 -80 -100 Pneumococcal Pneumonia Hospitalizations Grijalva CG, et al. Expert Rev Vaccines. 2008 Feb;7(1):83-95
All-cause Pneumonia Hospitalizations 20 <2 2-4 5-17 18-39 40-64 >64 0 -20 -40 Percent (%) change -60 -80 -100 Grijalva CG, et al. Expert Rev Vaccines. 2008 Feb;7(1):83-95
Estimated Absolute Declines in Pneumonia Hospitalizations Grijalva CG, et al. Lancet. 2007;369:1179–1186
Healthcare Use for Pneumonia; US Children <2 Years, 1997–1999 vs 2004 Zhou F, et al. Arch Pediatr Adolesc Med. 2007;161:1162–1168
Changes in Non-pneumonia ARI hospitalizations, US 1997-2006 ↓22% NC Grijalva et al, 2009 MMWR 58(1): 1-4
All-cause pneumonia Rates/100,000 US Children <2 Years Grijalva et al. Clin Infect Dis. 2010; 50(6):805-13
Conclusions • Major declines in all-cause and pneumococcal pneumonia after PCV7 program introduction • Sustained declines consistently observed in different studies/settings • Large national database (HCUP NIS) allowed detection and monitoring of direct and indirect effects
Acknowledgement • Marie R. Griffin, MD MPH • Professor of Medicine and Preventive Medicine. VUMC • J. PekkaNuorti, MD DSc • Epidemiologist, CDC