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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
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Outline
• Introduction to pneumococcal disease
• Secular trends
–Antimicrobial drug resistance (macrolides)
–Serotype replacement
• Geographic patterns
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Survival from pneumococcal bacteremia 1952-1962
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Penicillin Resistance in S. pneumoniae United States 1979-2000
1979-1994: CDC Sentinel Surveillance Network
1995-2002: CDC Active Bacterial Core Surveillance (ABCs) /Emerging Infections Program
Sentinel ABCs
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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
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Participating hospitals in the Delaware Valley
Emerging Infectious Diseases 2001
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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
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Time Trends
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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
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Temporal trends in risk of invasive pneumococcal disease: children
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Temporal trends in risk of invasive pneumococcal disease: adults
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What is Herd Immunity?
Picture courtesy of Dr. C. Whitney
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Early Successes with Vaccination R
ate
of
VT
IP
D p
er 1
00
,00
0 p
op
ula
tion
Indirect effect:
65% decrease
CDC. MMWR 2005; 54: 893-7.
Direct effect:
94% decrease
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Vaccination of children reduces risk of disease in adults
0
20
40
60
80
100
Any child vaccinated Youngest child
vaccinated
%
Cases
Controls
Vaccine. 2006
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Archives of IM 2010
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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
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Genotype Year
2001-2
(n=55)
2002-3
(n=41)
2003-4
(n =42)
2004-5
(n=57)
2005-6
(n=84)
2006-7
(n=93)
2007-8
(=89)
p-value
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
(A2059G)
3.6% 2.4% 7.1% 0.0% 1.2% 1.1% 1.1% .17
[1]
Macrolide Resistance Genotypes
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Emerging Macrolide Resistance
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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
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Pediatric Carriage of Pneumococcal Serotypes 2008-2010
0
2
4
6
8
10
12
14
16
18
20
2008 2009 2010
% o
f i
sola
tes
YEAR
6C
35B
19A
11A
15C
23B
23A
15A
21
15B like
16F
22F
15B
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Spatial Trends
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“Everything is related to everything else, but near things are more related than distant things’’
Tobler’s First Law of Geography
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Pneumococcal Case Distribution
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Disease risk varies by neighborhood
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Significant hot spots exist
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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
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PFGE Analysis of Pneumo Isolates
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Genetic clustering vs. geographic clustering
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Children as Vectors
Huang CID 2005
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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
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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.
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Thanks • Robert Austrian
• Lou Bell
• Catherine Berjohn
• Charlie Branas
• Linda Crossette
• Chris Czaja
• Paul Edelstein
• Kristen Feemster
• Neil Fishman
• James Flory
• Marshall Joffe
• Ebb Lautenbach
• Yimei Li
• Zhenying Liu
• Russell Localio
• Mat Macdonald
• Irv Nachamkin
• Samir Shah
• Justine Shults
• Tony Smith