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
±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
DTP
Tdap
DTaP
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and
1922-1949, passive reports to the Public Health Service
23
DTaP Coverage among Children Aged
19 through 35 months — 2004-2011
CDC National Immunization Survey
24
Reported pertussis incidence by
age group: 1990-2011
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
Percentage (%)
Tdap Coverage among Adolescents
Aged 13–17 years — 2006–2010
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
Incidence of Reported Pertussis — 1990–2010
Tdap
CDC unpublished data
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*
DTP
Tdap
DTaP
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
* 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
* 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
* 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
58%
10%
* Through 9/1/2012
55
Pertussis Incidence by Age Group — Connecticut,
2006–2011
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