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

Background and overview

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

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

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

Pertussis Immunization in the US Infants (1997) DTaP at 2, 4, 6 months Toddler (1992) DTaP at 15-18 months Pre-school (1992) DTaP at 4-6 years Adolescent/adult (2005) Single Tdap preferred at 11-12 years

Reported pertussis cases – 1922–2010 DTP Tdap This graph shows the number of pertussis cases in the United States from 1922 through 2009. 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 1922-1949, passive reports to the Public Health Service

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

Reported pertussis incidence by age group — 1990–2010 This graph illustrates reported pertussis incidence by age group between 1990 and 2010. 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 2007. 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

Annual incidence by State, 2010 1.1-3.6 3.7-6.5 6.6-10.2 10.3-23.2 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)

Annual incidence by State, 2011* 0.4-2.0 2.1-4.5 4.6-7.7 7.8-15.2 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)

Tdap implementation and impact

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) 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;334:349-355 2 Ward 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.

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 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.

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

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 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 11-18 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. 2012 Jan 11. [ePub ahead of print]

Absence of Indirect Effects of Tdap Mean incidence of reported pertussis among infants 1990-2003 (pre-peak) 2006-2009 (post-peak) p-value Mean incidence (per 100,000) 52.1 55.4 0.64 Skoff et al. Arch Pediatr Adolesc Med. 2012 Jan 11. [ePub ahead of print]

Emergence of disease among children aged 7 – 10 years

Reported pertussis incidence by age group — 1990–2010 This graph illustrates reported pertussis incidence by age group between 1990 and 2010. 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 2007. 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

Pertussis cases by age – 2002-2005

Pertussis cases by age – 2006-2009

Evaluation of dtap vaccine effectiveness and duration of protection

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

Vaccination Characteristics Case (%) N=682 Control (%) N=2,016 P-Value Unvaccinated Yes 7.8 0.9 < 0.0001 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

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%

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

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

Thank you

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

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