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

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. Outline
• Introduction to pneumococcal disease
• Secular trends
–Antimicrobial drug resistance
(macrolides)
–Serotype replacement
• Geographic patterns

4. Survival from pneumococcal bacteremia
1952-1962

5. Penicillin Resistance in S. pneumoniae
United States 1979-2000
Sentinel ABCs
1979-1994: CDC Sentinel Surveillance Network
1995-2002: CDC Active Bacterial Core Surveillance (ABCs) /Emerging Infections Program

7. 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

8. Participating hospitals in the Delaware
Valley
Emerging Infectious Diseases 2001

9. Risk Factors for Pneumococcal
Bacteremia
Characteristic Cases per 100,000 95% CI
Age
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 – 67
Race
White 13.7 12.9 – 14.7
African American 26.4 24.2 – 28.9

10. Time Trends

11. 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

12. Temporal trends in risk of invasive
pneumococcal disease: children

13. Temporal trends in risk of invasive
pneumococcal disease: adults

14. What is Herd Immunity?
Picture courtesy of Dr. C. Whitney

15. 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.

16. 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

17. Archives of IM 2010

18. CLSI Breakpoints 2011
Drug MIC (ug/mL)
Interpretive Standard
S I R
Penicillin (Meningitis) ≤ 0.06 0.12-1 ≥2
Penicillin (Non-meningitis) ≤2 4 ≥8
Erythromycin ≤0.25 0.5 ≥1

21. [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)

22. Emerging Macrolide Resistance

24. 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

25. 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

26. Spatial Trends

27. Tobler’s First Law of Geography
“Everything is related to everything
else, but near things are more related
than distant things’’

28. Pneumococcal Case Distribution

29. Disease risk varies by neighborhood

30. Significant hot spots exist

31. 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

34. PFGE Analysis of Pneumo Isolates

35. Genetic clustering vs. geographic clustering

37. Children as Vectors
Huang CID 2005

40. Child Exposure is Associated with
Reduced Risk of Disease
Characteristic Cases per 100,000 95% CI
# of children in
home
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

41. 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.

42. 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