Indirect Effects—
Multiplying the benefits of vaccinating
children
Cynthia Whitney, MD MPH
ISPPD-9
Hyderabad, India
March 2014
National Center for Immunization & Respiratory Diseases
Division of Bacterial Diseases
Conflicts of interest: None
Evolution of Thinking on Indirect Effects
• 2000
– First pneumococcal conjugate vaccine licensed
– Clinical trials showed protection in children who received
vaccine (direct effects)
– Unclear if vaccination would reduce disease in
unvaccinated persons in the community (indirect effects)
• 2013
– Second generation conjugates in use in many countries
– Indirect effects recognized as powerful driver of PCV
program benefits
Goals
• Explain how indirect effects work
• Review main lessons learned of last decade
– Children
– Adults
• Provide background for indirect effects
posters/presentations at ISPPD9
What are indirect effects*?
*sometimes called herd effects
Susceptible Population
Indirect Effects: Partially
Vaccinated Population
x
x
x
Rates of invasive pneumococcal disease
among U.S. children <5 years, 1998-2009
Overall
PCV7 type
19A
Cases per 100,000
120
100
Rapid decrease – was
some of this indirect
effects?
80
60
40
20
0
-76%
PCV7
introduction
+284%
-100%
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Year
Moore, IDSA, 2009
8
Evidence of herd effects reducing
disease among children
• Early (2003) observed reduction in VT disease in
children <5 yrs (94%) >> expected (64%)
– Expected reduction = vaccine coverage (68% 3+
doses) X vaccine efficacy (94%)
CDC MMWR September 16, 2005
• Drop in VT disease in children outside vaccinated age
group (~50% reduction in infants <2 mos and children
5-17 years by 2003)
Poehling K et al, JAMA 2006
• Multiple studies showed drop in carriage of vaccine
type strains following routine PCV use
What We’ve Learned
PCV7 Indirect Effects in Children
• VT invasive disease drops quickly in
young children following routine PCV
introduction
– Shown in multiple countries
– Both direct and indirect effects contribute
– Corresponds with shift in carried serotypes
• Indirect effects provide powerful
protection for children
– Children too young/too old for vaccination
– Vaccine-eligible children who miss doses
Transmission from Children to
Adults
+
VT
Rates of IPD caused by PCV7 serotypes
among adults >18 years-old, ABCs 1998-2009
40
Cases per 100,000
35
65+ yrs
30
Slightly slower
decrease compared to
vaccine-age children
25
20
15
50-64 yrs
10
18-49 yrs
5
PCV7
introduction
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Year
Moore, IDSA, 2009
Estimated IPD cases prevented among all ages,
United States 2001-2009
Age =>5
Age <5
40,000
Cases prevented
35,000
30,000
25,000
20,000
15,000
10,000
5,000
280,000 cases & 19,000 deaths prevented
0
2001
2002
2003
2004
Pilishvili JID 2010 & CDC unpublished
2005
Year
2006
2007
2008
2009
Cost Effectiveness of PCV7 Before
and After Incorporating Indirect Effects
$112,000
$120,000
$100,000
$80,000
$60,000
$40,000
$20,000
Before
After
$33,000
$7,800
$5,700
$0
Cost per IPD episode
prevented
G. Thomas Ray et al PIDJ
Cost per life-year
saved
Later estimate incorporating
indirect effects on pneumonia
showed program was cost saving
Indirect Effects on Pneumonia:
Powerful effect across age groups
• Modeled pneumococcal
pneumonia burden prevented by
PCV7 use from 2000 to 2006
• Health Care Utilization Project
State Inpatient Databases for
1996-2006 from 10 states
• ~ 789,000 fewer pneumococcal
pneumonia hospitalizations
– 90% age 18+
• ~84,000 fewer deaths
– 98% age 18+
Pneumonia hospitalizations among
adults ≥65 years, New Jersey
Simonsen L et al. MBio. 2011 Jan 25;2(1):e00309-10
Many populations have significant indirect
effects after PCV introduction
13 sites, observed/expected rate ratio: 0.42 (0.35–0.50)



Multi-country
evaluation of PCV
effects on rates of IPD
In adults, effects less
consistent than those
in children
Among adults age 65+
years, overall ~58%
reduction in vaccine
type rates at year 3
Feikin DR et al Plos Med 2013 10(9): e1001517.
What We’ve Learned
PCV7 Indirect Effects in Adults
• Vaccinating young children reduces
vaccine-type disease in adults
• Shown in multiple countries
• Lags a little behind effect in children (~1
year)
• In high-income settings, prevention of
disease in adults drives costeffectiveness of program (deaths mostly
in older adults)
Will Indirect Effects Occur in SE
Asia?

Yes!
 New data here at ISPPD9 will show
• Indirect effects with 2nd generation vaccines (PCV10 and PCV13)
• Reductions in disease in unvaccinated age groups
• Effects in a variety of populations – not just high income
 Therefore, effects should be seen in Asia

But….
 How quickly depends on vaccination coverage/catch-up
 Overall benefit from indirect effects will depend on
• Proportion/rate of disease caused by vaccine serotypes
• Can be smallish in some older children and adult populations
Unanswered Indirect Effects
Questions



Role of catch-up campaigns
 Do they speed up indirect effects?
 If so, what kind of campaign works best (<1 yo’s, <2
yo’s, <5 yo’s)?
How much coverage is needed to induce indirect
effects?
What schedule is best for indirect effects (does a
booster dose help)?
Thank you
For more information please contact Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30333
Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: [email protected] Web: http://www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases