1. Update on Pertussis – Epidemiology and Vaccination in the U.S.
Stacey W. Martin, MSc
Meningitis and Vaccine Preventable Diseases Branch
Centers for Disease Control and Prevention
NIC Online
March 2012
National Center for Immunization and Respiratory Diseases
Meningitis and Vaccine Preventable Diseases Branch

2. Background and overview

3. 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

4. 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

5. Reported Pertussis Cases by Diagnosis±, 1990-2010
SPSS coding recodes lab variables so missing are included in unknown.
The use of PCR as a diagnostic test has become more common, particularly since PCR was approved in 1997 by the Council of State and Territorial Epidemiologists (CSTE) for use in confirming pertussis cases. Laboratories have increasingly used it instead of culture during the last few years, and there are fewer culture positive cases in recent years. Interpretation of these data is limited by the amount of missing data.
±Data collection for PCR and Epi-Link began in 1995
Source: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System, 2010

6. Pertussis Immunization in the US
Infants (1997)
DTaP at 2, 4, 6 months
Toddler (1992)
DTaP at months
Pre-school (1992)
DTaP at 4-6 years
Adolescent/adult (2005)
Single Tdap preferred at years

7. Reported pertussis cases – 1922–2010
DTP
Tdap
This graph shows the number of pertussis cases in the United States from 1922 through During the pre-vaccine era, the number of pertussis cases culminated to about 2 hundred 70 thousand in the mid 1930s, with more than 10 thousand deaths. Since the introduction of whole cell vaccine, DTP, in the late 1940s, the number of reported pertussis cases has fallen dramatically. Despite this decrease, pertussis continues to be endemic.
Since 1980, there has been an increase in the number of reported cases from approximately 2 thousand cases per year to over 10 thousand cases per year, which is shown in the insert graph.
DTaP
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and , passive reports to the Public Health Service

8. DTaP coverage among children aged 19 through 35 months — 2004-2010
CDC National Immunization Survey

9. Reported pertussis incidence by age group — 1990–2010
This graph illustrates reported pertussis incidence by age group between 1990 and The pink line indicates incidence among those less than 1 year of age. Again, infants are most impacted by pertussis and as this graph shows, they experience the highest rates of disease nationwide. If you’ll look at the graph, all other age groups tended to group closely together during the 1990s. During the mid-2000s, however, incidence among adolescents and adults began to increase, shown bye the yellow and blue lines, respectively. Interestingly, 2009 and 2010 have yielded another emerging trend. The orange line shows children aged 7-10 years, and as you can see, rates have been increasing since We’ll discuss some of these trends in more detail in a moment.
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System

10. Annual incidence by State, 2010
Incidence
2010 Cases (as of 7/22/2011): 27, 550
Top Quartile:
Iowa – 23.17
Minnesota – 21.65
California – 19.47
Michigan – 15.69
Ohio – 15.65
Utah – 12.64
Idaho – 12.10
Nebraska – 11.91
Indiana – 11.63
Texas – 11.49
Colorado – 10.75
Wisconsin – 10.31
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)

11. Annual incidence by State, 2011*
Incidence
2010 Cases (as of 7/22/2011): 27, 550
Top Quartile:
Iowa – 23.17
Minnesota – 21.65
California – 19.47
Michigan – 15.69
Ohio – 15.65
Utah – 12.64
Idaho – 12.10
Nebraska – 11.91
Indiana – 11.63
Texas – 11.49
Colorado – 10.75
Wisconsin – 10.31
*2011 data are provisional. Incidence is per 100,000 population
Source : CDC National Notifiable Disease Surveillance System, 2011
CDC Wonder Population Estimates (Vintage 2009)

12. Tdap implementation and impact

13. Tdap Vaccine Effectiveness
Bridging studies of ADACEL and BOOSTRIX1
85-89%
APERT study2
92% (95% CI: )
Australia3 – screening method
78.0% (95% CI: )
St. Croix outbreak4
65.6% (95% CI: )
MN case-control study
72.3% (95% CI: )
At the time of licensure, Tdap efficacy was based on sero-bridging studies from infant efficacy studies. Immune response to Tdap was noninferior to the immune response of infants receiving DTaP.
From the adult pertussis trial, overall vaccine efficacy of an acellular pertussis vaccine was 92%.
Recent post-licensure studies of Tdap show vaccine effectiveness at 78% and 66%.
Although not statistically significant due to limited sample size, the effectiveness from the St. Croix outbreak is comparable to the Australian study.
====================================
St. Croix – received Tdap prior to outbreak
VE against lab confirmed pertussis 70% vs 65% confirmed and probable
Modified CSTE case definition
Australia – lab confirmed cases VE 84% (PCR); serology (88%)
1 Schmitt HJ et al. JAMA 1996;275:37-41; Gustafsson LH et al. NEJM 1996;334:
2 Ward JI et al. N Engl J Med Oct 13;353(15):
3 Rank C, et al. Pediatr Infect Dis J Feb;28(2):152-3.
4 Wei SC, et al. CID 2010; 51(3):

14. Tdap coverage among adolescents aged 13–17 years — 2006–2009
Percentage (%)
Compared to adolescents, coverage of Tdap among adults was reported to be less than 6% in 2008.
2006
2007
2008
2009
2010
CDC. National, State, and Local Area Vaccination Coverage Among Adolescents Aged Years - United States, MMWR 2008;58(36);
CDC. Vaccination Coverage Among Adolescents Aged Years – United States, MMWR 2008;57(40)
CDC. Vaccination Coverage Among Adolescents Aged Years– United States, MMWR 2007;56(34)
CDC. National, State, and Local Area Vaccination Coverage among Adolescents Aged Years - United States, 2009 MMWR 2010 ;59(32);

15. Incidence of reported pertussis — 1990–2010
Tdap
Now before we look into the potential impact of Tdap, remember, rates of pertussis increased gradually in the US between 1990 and 2003, before reaching a peak of 8.8 cases per 100 thousand population in 2004.
The introduction of Tdap in 2005 occurred at the height of this peak when rates of disease in the US were significantly elevated.
Since 2005, there has been almost a 50% decline in incidence. By 2008, rates of disease were 4.3 per 100 thousand.
CDC unpublished data

16. Accelerated decline of pertussis Rate ratios of pertussis incidence among adolescents years,
Slope = , p<.0001
Slope = , p<.0001
To look at the impact of Tdap in adolescents, we calculated rate ratios by dividing the incidence of pertussis among adolescents, by the incidence of disease in all other age groups. We used rate ratios because this allowed us to evaluate how trends change in one age group, in our case adolescents, relative to all other ages.
We observed a significant, steady increase in rate ratios prior to Tdap and then a reversal in the direction of the slope to a significant decrease post-Tdap. This tell us that the rate of disease among year olds in the pre-Tdap period was increasing at a faster rate than disease in all other ages combined. In the post-Tdap period, rates of disease among adolescents declined at a faster rate than other age groups.
We believe that this reversal in the direction of the slope is being driven, at least in part, by the introduction of Tdap.
=====================================================
Indirect effects of Tdap: significant changes were not observed among infants, but Tdap uptake has been slow among adolescents and adults. Therefore it is likely too early to see the indirect benefits of vaccination.
Skoff et al. Arch Pediatr Adolesc Med Jan 11. [ePub ahead of print]

17. Absence of Indirect Effects of Tdap Mean incidence of reported pertussis among infants
(pre-peak)
(post-peak)
p-value
Mean incidence (per 100,000)
52.1
55.4
0.64
Skoff et al. Arch Pediatr Adolesc Med Jan 11. [ePub ahead of print]

18. Emergence of disease among children aged 7 – 10 years

19. Reported pertussis incidence by age group — 1990–2010
This graph illustrates reported pertussis incidence by age group between 1990 and The pink line indicates incidence among those less than 1 year of age. Again, infants are most impacted by pertussis and as this graph shows, they experience the highest rates of disease nationwide. If you’ll look at the graph, all other age groups tended to group closely together during the 1990s. During the mid-2000s, however, incidence among adolescents and adults began to increase, shown bye the yellow and blue lines, respectively. Interestingly, 2009 and 2010 have yielded another emerging trend. The orange line shows children aged 7-10 years, and as you can see, rates have been increasing since We’ll discuss some of these trends in more detail in a moment.
SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System

21. Pertussis cases by age – 2002-2005

22. Pertussis cases by age – 2006-2009

23. Evaluation of dtap vaccine effectiveness and duration of protection

24. 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

25. Vaccination Characteristics
Case (%)
N=682
Control (%)
N=2,016
P-Value
Unvaccinated
Yes
7.8
0.9
<
Vaccinated age at 5th Dose
N=629
N=1,997 4
68.7
71.9
0.11* 5
31.1
27.3 6
0.5
0.8

26. California VE Study Findings
Overall VE was 88.7%
VE waned over time
98% VE in the first year following the 5th dose
Each year out resulted in a modest decrease in VE
By 5 or more years from last dose, VE had fallen to 71%

27. 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
Pertussis continues to be a public health problem, despite well-implemented vaccination program

28. Current and Future CDC Activities
Improving diagnostic testing to improve surveillance
Enhanced Pertussis Surveillance sites
Enhanced case ascertainment and improved data quality
Platform for analyses and studies
Evaluating cocooning/maternal vaccination effectiveness
Evaluating Tdap duration of protection
Assessing temporal trends in susceptibility/infection
Serosurvey
Modeling
Increasing the evidence base for new vaccines or strategies

29. Thank you

30. Reported Pertussis-Related Deaths, by Ethnicity, 1990-2010
Source: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System, 2010

31. Incidence rate ratios of pertussis among children 7-10 years and adolescents 11-18 years — 1990–2010