Epidemiology of invasive

pneumococcal disease in adults

CDR Matthew R. Moore, MD, MPHCenters for Disease Control & Prevention

U.S. Department of Health & Human Services

2

Outline

• Review effects of PCV7 on invasive pneumococcal disease in children– Direct effects– Indirect effects– Replacement disease

• Indirect effects of PCV7 on adults– By age group– By syndrome– By underlying disease status

• Expected serotype coverage in adults for different conjugate (7, 9, 11, 13-valent) & 23-valent polysaccharide vaccine formulations

• Opportunities for evaluation of conjugate vaccines in adults

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AreasOR (3 counties)CA (1 county)MN (7 counties)GA (20 counties)MD (6 counties)CT (entire state)NY (7 counties)TN (10 counties)CO (8 counties)NM (entire state)

Active Bacterial Core Surveillance (ABCs)Emerging Infections Program Network

Established

New

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ABCs methods (1)

• Case Definition: Streptococcus pneumoniae isolated from a normally sterile site (e.g. blood, CSF)

• Chart review for each case

• Data aggregated at CDC

• Isolates sent to reference laboratories for serotyping, antimicrobial resistance testing, & genotyping via multilocus sequence typing (MLST)

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ABCs methods (2)

• Rates of disease expressed as cases per 100,000 population, by age group (<5, 5-17, 18-49, 50-64, 65-79, >80) based on sites with continuous participation in ABCs since 1998 (17.4 million persons) using 2003 U.S. Census data

• All changes expressed as percent increase / decrease (95% confidence intervals) in rate comparing 2004 to 1998/99 baseline

• VT IPD cases directly & indirectly prevented calculated based on 1998/99 average number of VT IPD cases, PCV7 coverage , & PCV7 effectiveness for VT IPD

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Change in incidence of common Non-PCV7 Serotypes among children <5 years, ABCs 1998/9 vs. 2004

0

1

2

3

4

5

6

7

8

9

19

A 3 15

22

F

33

F 35

Serotype

Cas

es/1

00,0

00 p

op

ula

tio

n

98/99

2004

KaplanByington

Hicks IDSA 2005Kaplan et al. Pediatrics 2004;113:443-9Byington Clin Infect Dis 2005;41(1):21-29

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Summary of PCV7 impact in children

• Dramatic (97%) reduction in vaccine type invasive disease among <5 year olds

• Substantial indirect effect among older children

• Concerning increases in non-PCV7-type disease, especially 19A, 3, 15, 22F, 33F, 35

• Evidence for capsular switching as a means of evading vaccine-induced immunity

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Change in incidence of common Non-PCV7 Serotypes among adults >65 years, ABCs 1998/9 vs. 2004

0

1

2

3

4

5

619

A 3 15

22F

33F 35

Serotype

Cas

es/1

00,0

00 p

op

ula

tio

n

98/992004

*19A, 15, 33F, 35 significant, p<0.05

**

*

Hicks IDSA 2005

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Change in mortality due to invasive disease 1998/1999 (Baseline) vs. 2004, by serotype

Disease

Deaths/100,000 population

Baseline 2004 Baseline

2004

<5 years >65 years

PCV7 0.53 0.16 4.69 2.88

NVT 0.08 0.15 5.45 6.60

Overall

0.61 0.31 10.14 9.48

Hicks IDSA 2005

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Trends in invasive disease among adults >50 years: syndromes & comorbid conditions

• Syndromes– Incidence of meningitis unchanged– Bacteremia decreased 57% (95% CI -62, -52)– Invasive pneumonia decreased 20% (95% CI -24, -

15)

• Comorbid conditions– Proportion of case-patients with HIV, diabetes,

COPD, immunosuppressive therapy all increased– Proportion of case-patients with >1 indication for

PPV23 increased from 62.3% to 72.0% (P<0.001)

Lexau, JAMA October 26, 2005; 294(16):2043-2051

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Summary of PCV7 impact in adults

• Dramatic (64-77%) reduction in invasive disease among adults over 18 years of age

• Concerning increases in invasive disease caused by serotypes 19A, 15, 33F, 35

• Remaining cases more likely to have comorbid conditions

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PCV7-type invasive pneumococcal disease prevented by direct & indirect effects of

pneumococcal conjugate vaccine—ABCs 2003

9,140

20,460

0

5,000

10,000

15,000

20,000

25,000

Direct effects Indirect effects

Esti

mat

ed

no

. ca

ses

pre

ven

ted

* Direct VT IPD cases prevented in 2003 = 1998/99 average number of VT IPD cases in children < 5 years of age x 2003 PCV7 coverage with three doses (68.1%) x PCV7 effectiveness for VT IPD (93.9%).† Indirect VT IPD cases prevented in 2003 = (1998/99 average number of VT IPD cases across all ages – 2003 number of VT IPD cases across all ages) – 2003 direct VT IPD cases prevented. Note: Calculation of indirect cases prevented does not account for replacement disease.

CDC MMWR Sep 16, 2005

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In the absence of a controlled clinical trial, how could we evaluate the impact of conjugate vaccines

in adults?

• Post-marketing surveillance for invasive disease– Will occur routinely through ABCs– Could also occur through administrative systems such as

Medicare• Less specific (e.g., not all cases will be pneumococcal) • No serotype information

– Ecologic / temporal relationships only, difficult to assign causality

• Case-control study to evaluate effectiveness of conjugate vaccine in adults– Reliable method, recent experience in children– Could adjust for routine use of PPV23– Expensive, labor intensive

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AcknowledgementsABCs Surveillance

CDCCynthia WhitneyChris Van BenedenBernard Beall Anne SchuchatElizabeth ZellTamara PilishviliMoe KyawKatherine RobinsonTami SkoffCarolyn WrightBrendan NoggleLaShondra ShealeyDee Jackson

ABCs sitesMonica FarleyWendy BaughmanDavid StephensNana BennettShelley ZanskyNancy BarrettJim HadlerLee HarrisonLauri Thompson SanzaKaren StefonekPaul CieslakArt ReingoldPam DailyRuth LynfieldCatherine LexauJohn Besser

Sue JohnsonPam GahrAllen CraigBill SchaffnerBrenda BarnesMatt FinkeKen GershmanB. KoziolB. JuniUTHSC San AntonioJim JorgensenLettie McElmeelSharon Crawford

Emory UniversityKeith Klugman