# Presentation: 927663

## Epidemiology of invasive pneumococcal disease in adults

- CDR Matthew R. Moore, MD, MPH
- Centers for Disease Control & Prevention
- U.S. Department of Health & Human Services

## 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

## Areas
OR (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)

**Areas**
- OR (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

## 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)

## 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

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

**Kaplan**

**Byington**

**Hicks IDSA 2005**

**Kaplan et al. Pediatrics 2004;113:443-9**

**Byington Clin Infect Dis 2005;41(1):21-29**

## 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

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

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

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**Hicks IDSA 2005**

## 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**

## 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**

## 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

## PCV7-type invasive pneumococcal disease prevented by direct & indirect effects of pneumococcal conjugate vaccine—ABCs 2003

- * 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**

## 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

## AcknowledgementsABCs Surveillance

_**CDC**_
**Cynthia Whitney**
**Chris Van Beneden**
**Bernard Beall **
**Anne Schuchat**
**Elizabeth Zell**
**Tamara Pilishvili**
**Moe Kyaw**
**Katherine Robinson**
**Tami Skoff**
**Carolyn Wright**
**Brendan Noggle**
**LaShondra Shealey**
**Dee Jackson**

_**ABCs sites**_
**Monica Farley**
**Wendy Baughman**
**David Stephens**
**Nana Bennett**
**Shelley Zansky**
**Nancy Barrett**
**Jim Hadler**
**Lee Harrison**
**Lauri Thompson Sanza**
**Karen Stefonek**
**Paul Cieslak**
**Art Reingold**
**Pam Daily**
**Ruth Lynfield**
**Catherine Lexau**
**John Besser**

**Sue Johnson**
**Pam Gahr**
**Allen Craig**
**Bill Schaffner**
**Brenda Barnes**
**Matt Finke**
**Ken Gershman**
**B. Koziol**
**B. Juni**
_**UTHSC San Antonio**_
**Jim Jorgensen**
**Lettie McElmeel**
**Sharon Crawford**
_**Emory University**_
**Keith Klugman**