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The Dynamic Epidemiology of        Streptococcus pneumoniae.                    Joshua P. Metlay, MD, PhD              Div...
Outline• Introduction to pneumococcal disease• Secular trends   –Antimicrobial drug resistance    (macrolides)   –Serotype...
Survival from pneumococcal bacteremia               1952-1962
Penicillin Resistance in S. pneumoniae          United States 1979-2000                                               Sent...
The Delaware Valley Hospital Network• Hospital based reporting of cases of  pneumococcal bacteremia• Established in 2001• ...
Participating hospitals in the Delaware                Valley                Emerging Infectious Diseases 2001
Risk Factors for Pneumococcal                BacteremiaCharacteristic      Cases per 100,000     95% CIAge 18-49          ...
Time Trends
Pneumococcal Conjugate Vaccine• Seven valent conjugate vaccine licensed in  February 2000• 4, 6B, 9V, 14, 18C, 19F, 23F• W...
Temporal trends in risk of invasive pneumococcal disease: children
Temporal trends in risk of invasive  pneumococcal disease: adults
What is Herd Immunity?   Picture courtesy of Dr. C. Whitney
Early Successes with Vaccination Rate of VT IPD per 100,000 population                                         Direct effe...
Vaccination of children reduces risk of          disease in adults    100                                            Cases...
Archives of IM 2010
CLSI Breakpoints 2011Drug                               MIC (ug/mL)                              Interpretive Standard    ...
[1]         Macrolide Resistance Genotypes      Genotype                                 Year                   2001-2   2...
Emerging Macrolide Resistance
PCV-13• Introduction of PCV-13 in 2000• Coverage of PCV-7 serotypes:   –4,6B,9V,14,18C,19F,23F• Additional serotypes:  –1,...
Pediatric Carriage of Pneumococcal       Serotypes 2008-2010                20                18                16        ...
Spatial Trends
Tobler’s First Law of Geography“Everything is related to everythingelse, but near things are more relatedthan distant thin...
Pneumococcal Case Distribution
Disease risk varies by neighborhood
Significant hot spots exist
Why are there clusters of disease?• Small area outbreaks from highly virulent  clones  – Pathogen Hypothesis• Neighborhood...
PFGE Analysis of Pneumo Isolates
Genetic clustering vs. geographic clustering
Children as Vectors               Huang CID 2005
Child Exposure is Associated with          Reduced Risk of DiseaseCharacteristic     Cases per 100,000          95% CI# of...
Key Points• Overall risk of pneumococcal disease has  declined but new serotypes are emerging• Emerging serotypes are prim...
Thanks•   Robert Austrian        •   Marshall Joffe•   Lou Bell               •   Ebb Lautenbach•   Catherine Berjohn     ...
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
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Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD

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Eastern PA Branch-ASM, 41st Annual Symposium, Nov 17, 2011

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Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD

  1. 1. The Dynamic Epidemiology of Streptococcus pneumoniae. Joshua P. Metlay, MD, PhD Division of General Internal Medicine University of Pennsylvania Presented at the 41st Annual Symposium“Global Movement of Infectious Pathogens and Improved Laboratory Detection” Eastern PA Branch-American Society for Microbiology November 17, 2011 Thomas Jefferson University, Philadelphia
  2. 2. Outline• Introduction to pneumococcal disease• Secular trends –Antimicrobial drug resistance (macrolides) –Serotype replacement• Geographic patterns
  3. 3. Survival from pneumococcal bacteremia 1952-1962
  4. 4. Penicillin Resistance in S. pneumoniae United States 1979-2000 Sentinel ABCs1979-1994: CDC Sentinel Surveillance Network1995-2002: CDC Active Bacterial Core Surveillance (ABCs) /Emerging Infections Program
  5. 5. The Delaware Valley Hospital Network• Hospital based reporting of cases of pneumococcal bacteremia• Established in 2001• Centralized susceptibility testing• 48 hospitals in the 5 county region of Southeastern Pennsylvania• 3.7 million population• 400 annual cases
  6. 6. Participating hospitals in the Delaware Valley Emerging Infectious Diseases 2001
  7. 7. Risk Factors for Pneumococcal BacteremiaCharacteristic Cases per 100,000 95% CIAge 18-49 8.3 7.5 – 9.2 50-64 15.9 14.4 – 17.6 65-79 26.4 26.4 – 29.5 80+ 59.4 52.7 – 67Race White 13.7 12.9 – 14.7 African American 26.4 24.2 – 28.9
  8. 8. Time Trends
  9. 9. Pneumococcal Conjugate Vaccine• Seven valent conjugate vaccine licensed in February 2000• 4, 6B, 9V, 14, 18C, 19F, 23F• Widespread use by June 2000.• 2,4, 6, 13-15 month immunization schedule• Efficacy for otitis media, invasive disease, pneumonia.• Reduction in carriage of vaccine serotypes
  10. 10. Temporal trends in risk of invasive pneumococcal disease: children
  11. 11. Temporal trends in risk of invasive pneumococcal disease: adults
  12. 12. What is Herd Immunity? Picture courtesy of Dr. C. Whitney
  13. 13. Early Successes with Vaccination Rate of VT IPD per 100,000 population Direct effect: 94% decrease Indirect effect: 65% decrease CDC. MMWR 2005; 54: 893-7.
  14. 14. Vaccination of children reduces risk of disease in adults 100 Cases Controls 80 60% 40 20 0 Any child vaccinated Youngest child vaccinated Vaccine. 2006
  15. 15. Archives of IM 2010
  16. 16. CLSI Breakpoints 2011Drug MIC (ug/mL) Interpretive Standard S I RPenicillin (Meningitis) ≤ 0.06 0.12-1 ≥2Penicillin (Non-meningitis) ≤2 4 ≥8Erythromycin ≤0.25 0.5 ≥1
  17. 17. [1] Macrolide Resistance Genotypes Genotype Year 2001-2 2002-3 2003-4 2004-5 2005-6 2006-7 2007-8 p-value (n=55) (n=41) (n =42) (n=57) (n=84) (n=93) (=89) mefA+ermB- 72.7% 70.7% 52.4% 50.9% 40.5% 44.1% 34.8% <.0001 mefA-ermB+ 20.0% 26.8% 26.2% 36.8% 40.5% 31.2% 46.1% .01 ermB+mefA 1.8% 0.0% 9.5% 10.5% 17.9% 23.7% 19.1% <.0001 + 23S rRNA 3.6% 2.4% 7.1% 0.0% 1.2% 1.1% 1.1% .17 (A2059G)
  18. 18. Emerging Macrolide Resistance
  19. 19. PCV-13• Introduction of PCV-13 in 2000• Coverage of PCV-7 serotypes: –4,6B,9V,14,18C,19F,23F• Additional serotypes: –1,3,5,6A,7F,19A
  20. 20. Pediatric Carriage of Pneumococcal Serotypes 2008-2010 20 18 16 6C 14 35B 19A% of isolates 12 11A 15C 10 23B 23A 8 15A 21 6 15B like 16F 4 22F 15B 2 0 2008 2009 2010 YEAR
  21. 21. Spatial Trends
  22. 22. Tobler’s First Law of Geography“Everything is related to everythingelse, but near things are more relatedthan distant things’’
  23. 23. Pneumococcal Case Distribution
  24. 24. Disease risk varies by neighborhood
  25. 25. Significant hot spots exist
  26. 26. Why are there clusters of disease?• Small area outbreaks from highly virulent clones – Pathogen Hypothesis• Neighborhood level exposures influence risk of transmission – Vector Hypothesis• Heterogenous population distribution – Host Hypothesis
  27. 27. PFGE Analysis of Pneumo Isolates
  28. 28. Genetic clustering vs. geographic clustering
  29. 29. Children as Vectors Huang CID 2005
  30. 30. Child Exposure is Associated with Reduced Risk of DiseaseCharacteristic Cases per 100,000 95% CI# of children inhome 0 21.5 20.3 – 22.8 1 8.3 6.8 – 9.9 2+ 3.3 2.6 – 4.2 Archives of Internal Med 2010
  31. 31. Key Points• Overall risk of pneumococcal disease has declined but new serotypes are emerging• Emerging serotypes are primarily multidrug resistance, reflecting selection of MDR clones and expansion of previously low prevalence serotypes• Variation in disease risk likely reflects host factors, but vector and pathogen factors are rapidly changing in pneumococcal disease.
  32. 32. Thanks• Robert Austrian • Marshall Joffe• Lou Bell • Ebb Lautenbach• Catherine Berjohn • Yimei Li• Charlie Branas • Zhenying Liu• Linda Crossette • Russell Localio• Chris Czaja • Mat Macdonald• Paul Edelstein • Irv Nachamkin• Kristen Feemster • Samir Shah• Neil Fishman • Justine Shults• James Flory • Tony Smith

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