Dr Kudish Ms Faulkner Presentation
Download
Report
Transcript Dr Kudish Ms Faulkner Presentation
Responding to the Rise in Pertussis
CT AAP CME Program
Kathy Kudish, DVM, MSPH
Immunization Program
Connecticut Department of Public Health
Amanda Faulkner, MPH
Meningitis and Vaccine Preventable Diseases Branch
Centers for Disease Control and Prevention
September 25, 2012
National Center for Immunization and Respiratory Diseases
Division of Bacterial Diseases
Pertussis (Whooping Cough)
Highly contagious respiratory disease
Severe, debilitating cough illness (“100 day cough”) in
persons of all ages
Highest morbidity and mortality among infants
Estimated worldwide deaths > 300,000/yr
Vaccine-preventable
Poorly controlled, despite high vaccine coverage
First U.S. pertussis vaccines for adolescents and adults
(Tdap)† licensed in 2005
†Tetanus
toxoid, reduced diphtheria toxoid and acellular pertussis vaccine
2
Clinical Course (in weeks)
Communicable period
(onset to 3 weeks after
start of paroxysmal cough)
Incubation period
(typically 5-10 days;
max 21 days)
-3
Catarrhal stage
(1-2 weeks)
0
Onset
2
Convalescent stage
(weeks to months)
8
12
Paroxysmal stage
(1-6 weeks)
3
Clinical Stages
Catarrhal
Watery eyes, low-grade fever, malaise, mild eye inflammation, runny
nose, late-phase nonproductive cough
Paroxysmal
Paroxysms (bursts of coughing during a single exhalation) followed by
an inspiratory "whooping" sound, post-tussive cyanosis, and vomiting
In infants younger than six months (especially those younger than four
weeks): apnea, bradycardia, prolonged cough, poor feeding, no
paroxysms
Convalescent
Paroxysms gradually improve but recur with respiratory infections
www.aafp.prg
4
Infant Pertussis
Young infants at highest risk of
disease and complications
Atypical symptoms:
Source: Shot of Prevention, Brady passed away at
just 2 months from pertussis
Catarrhal stage and cough may be
minimal or absent
Apnea (sometimes with seizures)
Sneezing
Gagging, choking, vomiting
Whoop infrequent
Cough illness among close
contacts
Presumptive treatment should
begin immediately
5
Pertussis among Adolescents
and Adults
Wide spectrum of presentation
Disease often milder than in infants and children
May be asymptomatic
Can be quite severe and with classic presentation
Clinically difficult to distinguish from other causes of cough
illness
Persons with mild disease can transmit infection
6
Pertussis Treatment
When to treat
Adults, adolescents, children
• Antimicrobials may modify course if given early (reduce duration and
severity of symptoms and lessen communicability)
• Treatment >3 weeks after cough onset limited benefit
Infants and pregnant women near term
• Treatment up to 6 weeks after cough onset should be considered
Recommended treatment
Macrolide / azolide antimicrobial
• 5 day course azithromycin
• 7 day course clarithromycin
• 14 day course erythromycin
Alternative agent:
• 14 day course trimethoprim-sulfamethoxazole (Bactrim)
7
LABORATORY TESTING
8
Diagnostic Challenges
Stage of disease
Quality/timely collection of clinical specimen (s)
Antimicrobial administration
Vaccination status
Transport conditions
Contamination of clinical specimen
Lack of clinically validated/ standardized tests
9
Diagnostic Needs
Clinical vs. Public Health
Clinical setting
Optimizes sensitivity
Rapid turnover
Public health setting
Optimizes specificity
Confirmation of etiology
Prevention and control measures
10
Pertussis Diagnostics at CDC
Culture
100% specific
Low sensitivity
Incubation time 4-10 days
Multi-target real-time PCR
4 targets
Speciate 3 Bordetella spp.
Co-infections
IgG anti-PT ELISA
Quantitative/qualitative
Adolescents and adults
Late phase of disease
11
Commercial Pertussis Serologic Assays
Commercial assays are not standardized and clinical accuracy
is unknown
CDC is conducting a study to better understand the
usefulness of commercially available assays for clinical
diagnosis
Not included in CDC/CSTE pertussis case definition
CDC ELISA is not commercially available
Tech transfer is ongoing in collaboration with APHL and state public
health laboratories
12
R-PCR Assay IS481
Present in three Bordetella spp.
50 to >200 copies in B. pertussis
8 to 10 copies in B. holmesii
0 to 7 copies in B. bronchiseptica
High Ct value could indicate
Positive test for B. pertussis
False positive
Positive for
• B. holmesii
• B. bronchiseptica
Real-Time PCR Amplification Plot
13
Falsely-positive PCR Results during Outbreak
Investigations
Hospital: NH, 2006
Community: CO, 2009
Community: NY, 2010
14
Falsely-positive PCR Results
Use of IS481 as a single target assay
•
High Ct values interpreted as positive results
Contamination of clinical specimens during collection
•
•
•
B. pertussis DNA present in some vaccines
Confirmed by environmental sampling of clinics
Key factors likely ungloved hands and use of liquid transport media
+
+
+
+
False Positives
15
CDC Best Practices Guidance for Healthcare Professionals
on the Use of PCR for Diagnosing Pertussis
Target clinicians to optimize the use of PCR
Testing patients with signs and symptoms of pertussis
Optimal timing and specimen collection for PCR testing
Avoiding contamination of clinical specimens with B. pertussis DNA
Understanding and interpreting PCR results
Available at:
http://www.cdc.gov/pertussis/clinical/diagnostic-testing/diagnosis-pcr-bestpractices.html
16
Specimen Collection for Pertussis PCR
Acceptable samples:
Nasopharyngeal swabs
Nasopharyngeal aspirates
Nasal swabs are not acceptable
Visit www.cdc.gov/pertussis for
instructions on specimen collection
17
Optimal Timing in Weeks for
Diagnostic Testing
Cough Onset
0
2
4
6
8
10
12
Culture
PCR
Serology
18
EPIDEMIOLOGY AND VACCINATION
19
Pertussis Surveillance and Reporting
Nationally notifiable
Clinical (Probable) case
Cough ≥2 weeks AND
One among paroxysms, whoop, post-tussive vomiting
Confirmed case
Culture OR
Clinical case and PCR positive OR
Clinical case and epi-linked to confirmed case
20
Reported Pertussis Cases by Diagnosis±, 1990-2010
30000
Number of Cases
25000
Unknown
20000
Sero+(MA)
15000
Epi-linked
DFA
10000
PCR
Culture
5000
0
1990
1995
2000
Year
2005
2010
±Data collection for PCR and Epi-Link began in 1995
Source: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System, 2010
21
Pertussis Immunization in the US
Infants/children
Widely used since 1940s
Transitioned from DTP to DTaP throughout the 1990s
DTaP at 2, 4, 6 months; 15-18 months; 4-6 years
Children 7 through 10 years not fully immunized against pertussis
should receive a single dose of Tdap
Adolescents/adults
Licensed in 2005, recommended in 2006
Single Tdap, preferred at 11-12 years
All adolescents/adults who did not receive at 11-12 years should
receive a single dose as soon as feasible (includes those 65 yr and
older)
• Tdap can be administered regardless of interval since the previous Td dose
22
Reported NNDSS pertussis cases: 1922-2011
30,000
300,000
25,000
20,000
DTP
Number of cases
250,000
15,000
10,000
200,000
5,000
0
1990
150,000
1995
2000
2005
2011
Tdap
100,000
DTaP
50,000
0
1922
1930
1940
1950
1960
1970
1980
1990
2000
2011
Year
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and
1922-1949, passive reports to the Public Health Service
23
Coverage %
DTaP Coverage among Children Aged
19 through 35 months — 2004-2011
98
96
94
92
90
88
86
84
82
80
78
3+
4+
2004 2005 2006 2007 2008 2009 2010 2011
Year
CDC National Immunization Survey
24
Reported pertussis incidence by
age group: 1990-2011
Incidence rate
(per 100,000)
100
80
<1 yr
1-6 yrs
60
7-10 yrs
11-19
40
20+ yrs
20
0
1990
1995
2000
2005
2011
Year
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System
25
Annual Incidence by State, 2010
2010 incidence 9.0
(n=27,550)
Incidence
1.1-3.6
3.7-6.5
6.6-10.2
10.3-23.2
Incidence is per 100,000 population
Source : CDC National Notifiable Disease Surveillance System, *2010 data accessed July 22, 2011
CDC Wonder Population Estimates (Vintage 2009)
26
Annual incidence by State, 2011
2011 incidence 6.1
(n=18,719)
Incidence
0.7-2.8
2.9-5.1
5.2-9.3
9.4-23.3
Incidence is per 100,000 population
Source : CDC National Notifiable Disease Surveillance System, 2011
2010 Census data used for population estimates
27
Tdap IMPLEMENTATION AND IMPACT
28
Tdap Vaccine Effectiveness
Bridging studies of ADACEL and BOOSTRIX1
85-89%
APERT study2
92% (95% CI: 32.0-99.0)
Australia3 – screening method
78.0% (95% CI: 60.7-87.6)
St. Croix outbreak4
65.6% (95% CI: -35.8-91.3)
MN case-control study
72.3% (95% CI: 38.8-87.4)
1 Schmitt
HJ et al. JAMA 1996;275:37-41; Gustafsson LH et al. NEJM 1996;334:349-355
JI et al. N Engl J Med. 2005 Oct 13;353(15):1555-63.
3 Rank C, et al. Pediatr Infect Dis J. 2009 Feb;28(2):152-3.
4 Wei SC, et al. CID 2010; 51(3):315-321.
2 Ward
29
Tdap Coverage among Adolescents
Aged 13–17 years — 2006–2010
100
90
80
68.7
Percentage (%)
70
55.6
60
50
40.8
40
30.4
30
20
10
10.8
0
2006
2007
2008
2009
2010
CDC. National, State, and Local Area Vaccination Coverage Among Adolescents Aged 33-17 Years - United States, 2008. MMWR 2008;58(36);997-1001.
CDC. Vaccination Coverage Among Adolescents Aged 13-17 Years – United States, 2007. MMWR 2008;57(40)1100-1103.
CDC. Vaccination Coverage Among Adolescents Aged 13-17 Years– United States, 2006. MMWR 2007;56(34) 885-888.
CDC. National, State, and Local Area Vaccination Coverage among Adolescents Aged 13-17 Years - United States, 2009 MMWR 2010 ;59(32);1018-1023.
30
Cases/100,000 Population
Incidence of Reported Pertussis — 1990–2010
Tdap
10
9
8
7
6
5
4
3
2
1
0
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010
Year
CDC unpublished data
Overall
31
Accelerated Decline of Pertussis
Rate ratios of pertussis incidence among
adolescents 11-18 years, 1990-2009
Slope = -0.4752, p<.0001
Slope = +0.2225, p<.0001
Skoff et al. Arch Pediatr Adolesc Med. 2012 Jan 11. [ePub ahead of print]
32
Absence of Indirect Effects of Tdap
Mean incidence of reported pertussis among infants
1990-2003
(pre-peak)
Mean
incidence
(per 100,000)
52.1
2006-2009 p-value
(post-peak)
55.4
0.64
Skoff et al. Arch Pediatr Adolesc Med. 2012 Jan 11. [ePub ahead of print]
33
EMERGENCE OF DISEASE AMONG
CHILDREN AGED 7 – 10 YEARS
34
Proportion of all Pertussis Cases contributed
by Children Aged 7–10 years
25
15
10
5
2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
1991
0
1990
Percent
20
Year
35
Pertussis Cases by Age – 2002-2005
450
400
350
300
250
200
150
100
50
0
2003
800
700
600
Cases
Cases
2002
500
400
300
200
100
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18
1
Age (years)
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18
Age (years)
2004
2005
1800
1600
1600
1400
1400
1200
1200
1000
1000
Cases
Cases
2
800
800
600
600
400
400
200
200
0
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Age (years)
Age (years)
36
Pertussis Cases by Age – 2006-2009
2006
2007
800
700
500
Cases
Cases
600
400
300
200
100
0
1
2
3
4
5
6
7
8
450
400
350
300
250
200
150
100
50
0
9 10 11 12 13 14 15 16 17 18
1
Age (years)
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18
Age (years)
2008
2009
1200
1600
1400
1000
1200
1000
Cases
Cases
800
600
800
600
400
400
200
200
0
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Age (years)
Age (years)
37
EVALUATION OF DTaP VACCINE
EFFECTIVENESS (VE) AND DURATION OF
PROTECTION
38
California VE Study
Cases & controls 4-10 yrs at illness onset or enrollment
Reported pertussis cases in 15 CA counties
Unmatched controls from case-patient providers (3:1)
Vaccine histories collected by in-person visits to providers
Logistic regression, accounting for clustering
250 provider offices, 4,000 charts abstracted
39
Pertussis Disease among Unvaccinated compared to
Vaccinated Children
Pertussis
Vaccination Status
Case
Control
OR (95% CI) *
Unvaccinated
53
19
8.9 (4.9 – 16.1)
5 DTaP doses
629
1,997
* Accounting for clustering by county and provider
40
Overall VE & Duration of Protection Estimates
Model *
Case (n) Control (n)
VE, %
95% CI
Overall VE, All
Ages
0 dose
53
19
Ref
--
5 doses
629
1,997
88.7
79.4 – 93.8
0 doses
53
19
Ref
--
< 12 months
19
354
98.1
96.1 – 99.1
12 – 23 months
51
391
95.3
91.2 – 97.5
24 – 35 months
79
366
92.3
86.6 – 95.5
36 – 47 months
108
304
87.3
76.2 – 93.2
48 – 59 months
141
294
82.8
68.7 – 90.6
60+ months
231
288
71.2
45.8 – 84.8
Time since 5th dose
* Accounting for clustering by county and provider
41
Overall VE & Duration of Protection Estimates
Model *
Case (n) Control (n)
VE, %
95% CI
Overall VE, All
Ages
0 dose
53
19
Ref
--
5 doses
629
1,997
88.7
79.4 – 93.8
0 doses
53
19
Ref
--
< 12 months
19
354
98.1
96.1 – 99.1
12 – 23 months
51
391
95.3
91.2 – 97.5
24 – 35 months
79
366
92.3
86.6 – 95.5
36 – 47 months
108
304
87.3
76.2 – 93.2
48 – 59 months
141
294
82.8
68.7 – 90.6
60+ months
231
288
71.2
45.8 – 84.8
Time since 5th dose
* Accounting for clustering by county and provider
42
Tdap and DTaP Studies
Summary and Conclusions
Tdap program has reduced the burden of pertussis in
adolescents
No evidence for “herd immunity”
Excellent initial DTaP vaccine effectiveness
Modest but immediate waning of immunity from DTaP
Pertussis burden in children aged under 10 years appears to
be a “cohort effect” from change to all aP vaccines
i.e. a problem of susceptibility despite vaccination
43
2012 U.S. PERTUSSIS ACTIVITY
44
Reported NNDSS pertussis cases: 1922-2012*
35,000
300,000
30,000
25,000
Number of cases
250,000
DTP
20,000
15,000
10,000
200,000
5,000
0
1990
150,000
1995
2000
2005
2012*
Tdap
100,000
DTaP
50,000
0
1922
1930
1940
1950
1960
1970
1980
1990
2000
Year
2012
*
* 2012 NNDSS data are provisional and reflect cases reported to NNDSS as of Week 37
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and 1922-1949,
passive reports to the Public Health Service
45
Changes in Pertussis Reporting by State
from 2011 to 2012* †
Decrease/No change
< 2-fold increase
2 to 3-fold increase
> 3-fold increase
*Data for 2012 are provisional and subject to change.
†Cases reported through Week 37 in 2011 were compared with cases reported through Week 37 in
2012; fold-changes were calculated for each state.
46
Pertussis cases by age — United States, 2012
3 DTaPs
35
National Incidence
without Washington
30
National Incidence
Cases/100,000
25
4th DTaP
5th DTaP
Tdap
20
15
10
5
0
<1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Age (years)
Vaccine
Type
Received*
Acellular Only
Transition
Period
Whole Cell and
Acellular
47
PREVENTION AND CONTROL
GUIDELINES
48
Revised CDC Guidelines for the Prevention and
Control of Pertussis: Objectives
Primary: Preventing death and serious complications in
individuals at increased risk of severe and/or complicated
disease, including infants <12 months
Secondary:
Limit transmission in outbreak setting
Limit further spread and duration of transmission within closed
communities
Decrease morbidity in affected populations
Lower risk of dissemination to unaffected groups within an outbreak
49
Revised CDC Pertussis Outbreak and
Control Guidelines: Overview
Emphasis on those at highest risk
Lack of evidence of broad-scale prophylaxis
Tiered approach offers flexibility but encourages judicious
use of antibiotics
Alternatives to prophylaxis
Cough exclusion and “watchful waiting”
Opportunity to increase pertussis vaccine coverage
50
PERTUSSIS SURVEILLANCE—
CONNECTICUT, 2006–2012
51
Cumulative Number of Cases by Month Reported—
Connecticut, 2006–2012
140
Number of Cases
120
100
2006
80
2007
2008
60
2009
2010
40
2011
20
2012*
0
Month
* Through 9/19/2012; current state-wide incidence is 5.3 cases/100,000 population
52
Cumulative Number of Cases by Month Reported—
Fairfield County Connecticut, 2006–2012
80
Number of Cases
70
60
2006
50
2007
40
2008
30
2009
20
2010
2011
10
2012*
0
Month
* Through 9/19/2012; current incidence in Fairfield County is 8.7 cases/100,000 population
53
Cumulative Number of Cases by Month Reported—
Litchfield County Connecticut, 2006–2012
60
Number of Cases
50
40
2006
2007
30
2008
2009
20
2010
2011
10
2012*
0
Month
* Through 9/19/2012; current incidence in Litchfield County is 26.9 cases/100,000 population
54
Percent of Cases by Confirmation Type—
Connecticut, 2006–2012
100%
90%
Percent of Cases
80%
70%
60%
58%
50%
Culture
PCR
40%
Epi link
30%
Probable (no test)
20%
10%
10%
0%
2006
2007
2008
2009
2010
2011
2012
Year
* Through 9/1/2012
55
Incidence per 100,000 Population
Pertussis Incidence by Age Group — Connecticut,
2006–2011
35
30
29.7
25
20
15
10
7.7
5
2.8
5.2
1.0
0
<1
1–6
7–10
Age Group
11–19
>19
56
Culture Submissions to the Department of Public
Health (DPH) Laboratory
• Culture is still considered to be the gold standard (100% specific)
• The DPH encourages providers to submit cultures alongside PCR,
particularly in situations where a clinical practice is seeing an
increase in the number of pertussis diagnoses among patients
that share a common setting, such as a school or daycare
• Availability of culture has contracted over the past decade
• Culture continues to be available at the DPH Laboratory
• Successful culture isolation of the organism declines if the
patient has received prior antibiotic therapy effective against B.
pertussis, if specimen collection has been delayed beyond the
first 2 weeks of illness or if the patient has been vaccinated
57
Pertussis Culture
• Samples can be sent to the state either directly by
healthcare providers or by a hospital laboratory
• If specimen collection is to take place in the office:
Specimen collection kits which include the transport media for B.
pertussis may be obtained by calling the DPH Laboratory at (860) 9206674 or 6675
Kits should be requested ahead of time so they are accessible at the
time of specimen collection
Instructions for specimen collection are provided with the kits
Transport media has a finite shelf life (3-6 months)
• Once a nasopharyngeal swab has been collected it should be
plated directly or placed into transport medium immediately
58
VACCINATION STRATEGIES TO
PROTECT INFANTS
59
Pregnancy and Cocooning
ACIP Recommendations
Pregnant women vaccinated preferably during the third or
late second trimester. Alternatively, administer Tdap
immediately postpartum
Cocooning is the strategy of vaccinating all close contacts of
infants with Tdap to reduce the risk of transmission
Ideally at least 2 weeks before contact with the infant
Parents, siblings, grandparents, child-care providers and health-care
personnel
60
Shifting the timing of mother’s Tdap dose:
postpartum to pregnancy
Provides earlier benefit to mother, thereby protecting infant
at birth
High levels of transplacental maternal antibodies in infants
of mothers vaccinated during pregnancy
Likely provides direct immunity to infant
Pregnancy
Postpartum
61
CONNECTICUT ACTIVITIES TO COMBAT
PERTUSSIS
62
Tdap Cocoon Program
• Hospital-based program to vaccinate new mothers and family
members of newborns with Tdap upon the birth of their child
• Of the 28 birth hospitals in Connecticut, 23 are participating in
the DPH Tdap Cocoon Program
– Began fall of 2008
– Close to 55,000 doses administered through this program,
with the number increasing every year
• List of “referral sites” where family members of infants <12
months can receive Tdap on the DPH Immunization Tdap
Cocoon Program web page:
http://www.ct.gov/dph/immunizations
63
Tdap Cocoon Program Evaluation
• Surveyed birth hospitals in fall 2011 about use of Tdap
– 24 (86%) hospitals reported routinely offering Tdap to
postpartum patients
– Mean Tdap immunization rate for postpartum patients
where Tdap was offered was 61% (confidence interval
54%–67%; median 63%, range 16%–87%)
– Manuscript submitted for publication
64
Tdap Vaccination Effectiveness for Preventing Infant
Pertussis
• Case control study in 6 states participating in the Emerging
Infections Program (EIP) to evaluate the effectiveness of the
Tdap “cocooning” strategy
• Just getting underway, results probably at least a couple of
years away
65
Enhanced Pertussis Surveillance
(EPS)
•
•
•
•
Part of EIP
Connecticut funded as an EPS site since 2011
One of 6 sites in the U.S.
Similar to previous surveillance activities with some
additional data collection
• Collect Bordetella culture isolates where feasible and
forward to CDC for molecular characterization
66
Emerging Infection Program Network Sites
Working on Pertussis
Areas
CO (5 counties)
CA (state)
CT (state)
MN (state)
NM (state)
NY (15 counties)
OR (3 counties)
67
Enhanced Pertussis Surveillance (EPS)
Overview
Builds upon existing pertussis surveillance infrastructure at
state
Improved completeness and quality of data
Augmented data collection
Objectives
10 - Collect epidemiologic information and isolates, when available, on
cases of B. pertussis
20 - Collect epidemiologic information and isolates, when available, on
other Bordetella species (B. parapertussis, B. bronchiseptica, and B.
holmesii)
68
Tdap Vaccination Strategies Evaluation:
Objectives
Measure effectiveness of vaccination during pregnancy at
preventing pertussis among infants <12 months
Age-specific effectiveness for infants <2months, and infants 2 - <6 months
Determine if infants 6 - <12 months born to women vaccinated during
pregnancy have a higher odds of pertussis compared to infants born to
women not vaccinated during pregnancy
Measure effectiveness cocooning at preventing pertussis among
infants <2 months
Effectiveness of maternal vaccination (at any time) at preventing pertussis
among infants <2 months
Effectiveness of vaccination of the infant cocoon (all household contacts and
infant caregivers) at preventing pertussis among infants <2 months
69
Final Thoughts…
Pertussis continues to be a significant public health problem
Vaccination is our best prevention tool
Goal is no infant deaths
Improve Tdap coverage in adults
Remove barriers to vaccination of pregnant women
Implement cocooning
Focus chemoprophylaxis efforts on high risk
Maintain high levels of coverage with DTaP
Continue to evaluate and refine vaccination policy and
prevention and control recommendations
70
Web Resources
CDC Pertussis Website
www.cdc.gov/pertussis
Disease overview, podcasts, vaccine recommendations,
specimen collection videos, etc.
Provider Resources for
Vaccine Conversations
with Parents
www.cdc.gov/vaccines/conv
ersations
Materials created by CDC,
AAP, and AAFP
71