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Tdap Vaccine Effectiveness in

Adolescents During the 2012

Washington State Pertussis Epidemic
Anna M. Acosta, MDa,b, Chas DeBolt, RN, MPHc, Azadeh Tasslimi, MPHc, Melissa Lewis, MPHd, Laurie K. Stewart, MSc,
Lara K. Misegades, PhD, MSb, Nancy E. Messonnier, MDb, Thomas A. Clark, MD, MPHb, Stacey W. Martin, MSb,
Manisha Patel, MD, MSb

BACKGROUND:Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood abstract
vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid,
reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in
2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among
adolescents who have received all acellular vaccines are limited.
METHODS: To assess Tdap VE and duration of protection, we conducted a matched case-control
study during the 2012 pertussis epidemic in Washington among adolescents born during
19932000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were
included; 3 controls were matched by primary provider clinic and birth year to each case.
Vaccination histories were obtained through medical records, the state immunization registry, and
parent interviews. Participants were classied by type of pertussis vaccine received on the basis of
birth year: a mix of whole-cell and acellular vaccines (19931997) or all acellular vaccines
(19982000). We used conditional logistic regression to calculate odds ratios comparing Tdap
receipt between cases and controls.
RESULTS: Among adolescents who received all acellular vaccines (450 cases, 1246 controls),
overall Tdap VE was 63.9% (95% condence interval [CI]: 50% to 74%). VE within 1 year of
vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to
34% (95% CI: 20.03% to 58%).
Tdap protection wanes within 2 to 4 years. Lack of long-term protection after
vaccination is likely contributing to increases in pertussis among adolescents.

Epidemic Intelligence Service, Scientic Education and Professional Development Program Ofce, bMeningitis WHATS KNOWN ON THIS SUBJECT: Although
and Vaccine Preventable Disease Branch, Division of Bacterial Diseases, National Center for Immunization and
Respiratory Diseases, and dBiostatistics Ofce, Division of Bacterial Diseases, Centers for Disease Control and waning immunity with the childhood pertussis
Prevention, Atlanta, Georgia; and cCommunicable Disease Epidemiology, Washington State Department of Health, vaccination series has been reported, there are
Shoreline, Washington
limited data on duration of protection of the
Dr Acosta led the conceptualization and design of the study, oversaw the data collection, adolescent pertussis vaccine (Tdap), especially
performed data analyses, interpreted the data, drafted the initial manuscript, and nalized the
among those who have received only acellular
nal draft; Ms DeBolt assisted with data collection and interpretation and provided critical
revision of the manuscript for important intellectual content; Ms Tasslimi assisted with data vaccines.
collection, analyses, and interpretation and provided critical revision of the manuscript for
important intellectual content; Ms Lewis assisted with data collection and analyses and provided
WHAT THIS STUDY ADDS: This study reports
critical revision of the manuscript for important intellectual content; Ms Stewart assisted with that protection from Tdap wanes substantially
data collection and provided critical revision of the manuscript for important intellectual 2 to 4 years after vaccination among
content; Dr Misegades contributed to the study design and data interpretation and provided adolescents who received all acellular
critical revision of the manuscript for important intellectual content; Dr. Messonnier contributed
to the conceptualization of the study and data interpretation and provided critical revision of the vaccines during childhood. This waning
manuscript for important intellectual content; Dr Clark contributed to the conceptualization of protection is likely contributing to the increase
the study and data interpretation and provided critical revision of the manuscript for important in adolescent pertussis.
intellectual content;

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6, June 2015 from by guest on November 19, 2017 ARTICLE
Despite high childhood and protection among the rst cohort of a laboratory-conrmed case were
adolescent vaccination coverage, adolescents who received all acellular classied as probable cases. The
.48 000 pertussis cases were vaccines. Washington State Department of
reported in the United States in 2012, Health also included a suspected case
the greatest number reported since category dened as a positive
1955.1 In addition, there were new METHODS polymerase chain reaction test result
and concerning changes in the age with illness not meeting the clinical
Study Oversight
distribution of pertussis cases, with case denition.14
increasing incidence among fully This evaluation was conducted as
part of the public health response to We selected 3 controls for each case,
vaccinated children and adolescents matched by birth year and primary
within a few years of vaccination.13 the 2012 Washington pertussis
epidemic and was determined to be provider clinic. Controls were
Although infants ,1 year of age nonresearch program evaluation by randomly selected from a clinic-
continue to have the highest rates of the Centers for Disease Control and generated patient roster that included
pertussis, increased rates among 7- to Prevention Human Research all adolescents born in the same year
10-year-olds were recently Protection Ofce and the Washington as the case and who had at least 1
observed.3 Notably, this cohort of State Department of Social and Health clinic visit since 2005. Potential
children was among the rst to Services Institutional Review Board. controls were excluded and replaced
receive solely acellular pertussis with another randomly selected
vaccines for the childhood series. Study Design and Population control if the provider suspected or
Waning immunity after vaccination diagnosed pertussis during the study
To estimate Tdap VE and duration of
with diphtheria-tetanus-acellular period, the patient had been
protection, we conducted a matched
pertussis (DTaP) vaccines appears to discharged from the clinic, the patient
case-control study. The 7 Washington
be a major contributing factor for had an out-of-state home zip code, or
counties reporting .50 cases among
increased disease risk.46 patient medical records were
adolescents during the study period
Because tetanus toxoid, reduced unavailable. The symptom onset date
of January 1 to June 30, 2012, agreed
diphtheria toxoid, and acellular of the case was used as the
to participate (Clark, King, Pierce,
pertussis, adsorbed (Tdap) was enrollment date for each case and
Skagit, Snohomish, Yakima, and
recommended for adults and associated matched controls.
adolescents only in 2006, studies Demographic information (date of
The study included adolescents 11 to
estimating Tdap vaccine effectiveness birth, gender, home zip code,
19 years of age, born from January 1,
(VE) and duration of protection are ethnicity, race) and vaccination
1993, through December 31, 2000.
few. Several observational studies histories for cases and controls were
We included all suspected, probable,
noted an overall VE range of 64% to collected at provider clinics by using
and conrmed pertussis cases
78% within 2 years of a standardized protocol and medical
reported among residents of the 7
vaccination.710 To our knowledge, chart abstraction form. Vaccination
participating counties during the
only 1 study has measured Tdap date, product, manufacturer, and lot
study period. Cases were classied by
duration of protection for .2 years, number were recorded for all
using the Council of State and
and it concluded that VE waned over documented pertussis-, diphtheria-,
Territorial Epidemiologists case
time.11 or tetanus-containing vaccines,
denitions for probable and
In 2012, Washington State declared including the childhood series and
conrmed pertussis cases.13 A clinical
adolescent dose when available. To
a pertussis epidemic with nearly case was dened as cough for $14
5000 cases reported. An verify brand, we matched available
days with at least 1 of the following
unexpectedly high disease incidence lot numbers for the childhood series
symptoms: whoop, posttussive
was seen in adolescents 13 to and adolescent dose with known lot
vomiting, or paroxysmal cough.
14 years of age despite Tdap coverage numbers provided by the Washington
A conrmed case was dened as
of 86%.2,12 The emergence of disease State Department of Health and 2
cough illness of any duration plus
in this age group had not been pertussis vaccine manufacturers
isolation of Bordetella pertussis from
observed since the introduction of Tdap, (GlaxoSmithKline, Brentford, United
a clinical specimen or a clinical case
raising concerns for waning immunity Kingdom; Sano Pasteur, Swiftwater,
with either a positive polymerase
after the Tdap dose in adolescents chain reaction test result or contact PA).
who received all acellular pertussis with a laboratory-conrmed case We supplemented provider
vaccines as children. The epidemic in (epidemiologic link). Clinical cases vaccination histories with
Washington provided an opportunity to that were not laboratory-conrmed information from the Washington
estimate Tdap VE and duration of or epidemiologically linked to State Immunization Information

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System.15 If vaccination history was vaccines for the complete childhood Additional subgroup analyses
available in both sources but series occurred during 1997, after assessed the stability of the VE
discrepant, provider records were which we assumed that whole-cell estimates by restricting the analysis
used as the denitive source. If Tdap vaccines were no longer available. We to those with conrmed and probable
vaccination status remained veried this assumption by cross- case status, those with conrmed
unknown after reviewing these checking study-obtained lot numbers case status only, or those with
sources, parents or guardians were against manufacturer data. a complete and on-schedule
contacted to verify Tdap vaccine To evaluate the impact of the whole- childhood series. We also evaluated
receipt. cell or acellular pertussis childhood Tdap VE among participants who
vaccination series on Tdap VE, study received a mix of whole-cell and
The childhood series was considered
participants were stratied on the acellular vaccines (birth years
complete and on schedule if the
basis of birth year into 2 groups. The 19931997; ages 1519 years), as
participant had documentation in the
acellular group included adolescents well as differences in VE by Tdap
provider records or immunization
born from 1998 to 2000 and were product.
registry of 5 doses of diphtheria-
tetanus toxoids-pertussis (DTP) or assumed to have received all acellular Statistical comparison of
DTaP meeting the following criteria: pertussis vaccines for the childhood demographic characteristics between
doses 1 through 3 before the rst series, whereas the mixed group cases and controls was performed by
birthday, dose 4 on or after the rst included those born from 1993 to using conditional logistic regression.
birthday and before the second 1997 and were assumed to have We evaluated trends in Tdap vaccine
birthday, and dose 5 on or after the received a mix of whole-cell and status by birth year using the
fourth birthday and before the acellular pertussis vaccines. Cochran-Armitage test. All analyses
seventh birthday.16 were conducted in SAS software,
Statistical Analysis version 9.3 (SAS Institute, Cary, NC).
We classied participants as
vaccinated if a Tdap vaccination date To estimate the association between
was conrmed in the provider pertussis and Tdap receipt, we used RESULTS
records, the immunization registry, or conditional logistic regression to During the study period, 1153
by parent interview. We classied calculate odds ratios, accounting for pertussis cases among adolescents
participants as unvaccinated if no matching factors (provider and birth were reported in Washington. Of
record of Tdap vaccination date was year). VE was calculated as: 1 2 odds those, 959 were reported in the 7
found in the provider records or the ratio 3 100%. Tdap-unvaccinated participating counties, representing
immunization registry and Tdap participants were the reference group 83% of all Washington adolescent
nonreceipt was conrmed by in all models. We estimated duration cases and 73% of all Washington
a parent. In addition, participants of protection by measuring the providers reporting adolescent cases.
were classied as unvaccinated if association between pertussis and Pertussis incidence for this age group
Tdap receipt was conrmed but the time since Tdap vaccination was 182.3 per 100 000 persons
vaccination occurred after the (,12 months, 1223 months, 2447 during the study period.
enrollment date or if Tdap was months).
Data were collected for 887 cases and
received within 2 weeks before the We excluded cases and controls if 2599 matched controls. Data were
enrollment date. We considered Tdap vaccination status was not collected for 72 cases for the
a participants vaccination status to unknown, or if there was following reasons: a provider was not
be unknown if a Tdap vaccination documentation of inadvertent available for the patient (n = 45;
date was not documented in the administration of DTaP during 63.4%), the provider refused to
provider records or the immunization adolescence, Tdap before the age of participate (n = 14; 19.7%), or the
registry and the parent interview was 10 years, or $2 Tdap doses. In provider was located outside the
inconclusive. addition, controls were excluded if participating counties (n = 12;
The Washington State Childhood they had ever been reported to the 16.9%). An additional 51 cases
Vaccination Program has been the Washington State Department of (5.8%) and 277 controls (10.7%)
sole distributor of childhood and Health as having pertussis. were excluded from the analysis
adolescent vaccines to public and The primary analysis measured Tdap (Table 1). The nal analysis included
private health care providers since VE and duration of protection in 836 cases and 2322 controls. Of the
the early 1990s.17,18 We reviewed study participants who received all 836 cases, 656 (78.5%) were
available vaccine distribution data acellular pertussis vaccines for the classied as conrmed, 92 (11.0%)
and determined that the transition of childhood series (birth years as probable, and 88 (10.5%) as
whole-cell to acellular pertussis 19982000; ages 1114 years). suspect.

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TABLE 1 Exclusions From Analyses Estimating Tdap VE, Duration of Protection, and Brand dose number. Although
Effectiveness Against Pertussis documentation of childhood series lot
Reason excluded Cases (n = 887) Controls (n = 2599) numbers was limited, all childhood
Pertussis case in previous years Not applicable a
17 (0.7) vaccines administered in study
DTaP at adolescence 2 (0.2) 11 (0.4) participants during 1998 or later with
Tdap before age 10 5 (0.6) 7 (0.3) available lot numbers were conrmed
Two or more Tdap doses 15 (1.7) 77 (3.0)
to be acellular pertussis vaccines.
Tdap vaccination status unknown 29 (3.3) 165 (6.3)
Total excluded from the analyses 51 (5.8) 277 (10.7) Eighty-one percent of cases and 90%
Data are presented as n (%). of controls were vaccinated with
a Only controls were veried as to whether they had been reported as a pertussis case previously.
Tdap, and both had similar ages at
vaccination and time since
Table 2 lists demographic and vaccine documented in the medical records vaccination. Overall, .84% of study
characteristics of the cases and and therefore was unknown. participants were vaccinated with
controls included in the analysis. The Although 74% of cases and 75% of Tdap at the recommended ages of 11
median age among study participants controls had 5 documented doses for to 12 years.
was 14 years; 54% were born the childhood series, only 60% of For the primary analysis, which
between 1998 and 2000. Cases were cases and 58% of controls had a 5- included only those who received
more likely to be white (P = .003) and dose series that was on schedule. acellular vaccines for the primary
non-Hispanic (P = .03) than controls; Brand was identied by lot number series (450 cases, 1246 controls), the
however, a substantial amount of race for 25% to 29% of the childhood overall Tdap VE estimate against
and ethnicity data was not doses administered, depending on the pertussis was 63.9% (95%
condence interval [CI]: 49.7% to
TABLE 2 Demographic Characteristics of Participants Included in Analyses Estimating Tdap VE, 74.1%) (Table 3). When these
Duration of Protection, and Brand Effectiveness Against Pertussis participants were stratied by time
Characteristic Cases (n = 836) Controls (n = 2322) Pc since Tdap vaccination, the VE within
Birth year, n (%) 12 months was 73.1% (95% CI:
19931997 386 (46.2) 1076 (46.3) Not applicablea 60.3% to 81.8%). At 12 to 23 months
19982000 450 (53.8) 1246 (53.7) postvaccination, the VE estimate was
Gender, n (%) 54.9% (95% CI: 32.4% to 70.0%),
Male 428 (51.2) 1191 (51.3) .80
and by 24 to 47 months it was 34.2%
Female 406 (48.6) 1122 (48.3)
Unknown 2 (0.2) 9 (0.4) (95% CI: 20.03% to 58.0%).
Race, n (%) Subgroup analyses limited to
White 304 (36.3) 570 (24.5) .003 conrmed cases or those with on-
Other 79 (9.5) 232 (10.0) schedule childhood vaccinations were
Unknown 453 (54.2) 1520 (65.5)
not substantially different from the
Ethnicity, n (%)
Non-Hispanic 304 (36.4) 625 (26.9) .03 primary analysis, with overlapping
Hispanic 79 (9.4) 217 (9.4) CIs noted (Fig 1, Supplemental Tables
Unknown 453 (54.2) 1480 (63.7) 5 and 6). Similarly, a subgroup
Childhood series vaccination, n (%) analysis excluding those with suspect
Complete, on-schedule seriesb 506 (60.5) 1357 (58.4) .29
case status was not notably different
Tdap vaccination status, n (%)
No 162 (19.4) 229 (9.9) ,.0001 from the primary analysis (data not
Yes 674 (80.6) 2093 (90.1) shown).
Age at Tdap, median (range), y 11 (1017) 11 (1018) .43
Time since Tdap vaccination,
The overall Tdap VE for the mixed-
median (range), mo vaccine group (386 cases, 1076
Overall 33 (173) 31 (084) .02 controls) was 51.5% (95% CI: 26.1%
Birth years 19982000 22 (147) 19 (047) .10 to 68.1%). Because the mixed group
Birth years 19931997 44 (273) 45 (084) .16
was heavily weighted toward
Tdap brand, n (%)
Adacel 136 (20.2) 342 (16.3) .05 participants who received Tdap at
Boostrix 387 (57.4) 1245 (59.5) least 3 years before study enrollment
Unknown brand 151 (22.4) 506 (24.2) (Fig 2), Tdap duration of protection
a Cases and controls were matched on birth year, and therefore no P value was calculated. was stratied by less or more than
b A complete and on-schedule primary series is considered the following: doses 1 through 3 before the rst birthday, dose 4 years since vaccination. The VE
4 on or after the rst birthday and before the second birthday, and dose 5 on or after the fourth birthday and before the
seventh birthday. estimates for each of these time
c P values do not apply to unknown data. points were similar to the overall VE

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Boostrix (17% vs 59%, respectively).
Analyses of VE estimates by product
were stratied by vaccine group.
Regardless of group analyzed,
Boostrix had slightly higher
effectiveness than Adacel, although
CIs overlapped (Table 4). Product-
specic VE estimates in the mixed
group were slightly lower than in the
acellular group, but CIs again

Tdap was recommended in the early
FIGURE 1 2000s to address the burden of
Estimated Tdap duration of protection against pertussis among adolescents who received all pertussis among adolescents and
acellular vaccines (birth years 19982000), restricted to conrmed cases or participants with adults.19 The preferred
complete and on-schedule childhood series. Acellular vaccine group: adolescents born from 1998 to
2000, assumed to have received all acellular pertussis vaccines for the childhood series (cases =
administration age of 11 to 12 years
450, controls = 1256). Acellular vaccine group, conrmed case status: adolescents born from 1998 to targeted the peak of disease in
2000, assumed to have received all acellular pertussis vaccines for the childhood series and adolescence and supported the
restricted to conrmed cases and their associated controls (cases = 355, controls = 984). Acellular established adolescent vaccination
vaccine group, complete and on-schedule childhood series: adolescents born from 1998 to 2000,
assumed to have received all acellular pertussis vaccines for the childhood series and restricted to platform. Among adolescents,
cases and controls with 5 childhood doses on schedule (cases = 288, controls = 728). A complete national Tdap vaccine uptake has
and on-schedule primary series is considered the following: doses 1 through 3 before the rst increased steadily after its
birthday, dose 4 on or after the rst birthday and before the second birthday, and dose 5 on or after introduction, and early evaluations
the fourth birthday and before the seventh birthday. Refer to Table 3 and Supplemental Tables 5 and
6 for CIs for each of these time points. indicated it was effective in reducing
the adolescent disease burden.2022
However, it is notable that the group
estimate, with overlapping CIs (,48 respectively; P = .0007), and of adolescents who initially received
months: 51.5%; 95% CI: 24.3% to a signicant trend of increasing Tdap also received whole-cell
69%; 4884 months: 52.2%; 95% CI: unknown Tdap vaccination status vaccines during childhood. Despite
24.6% to 69.6%). Direct comparisons with increasing age (Cochran- promising indicators, the number of
between the mixed group and Armitage trend test, z = 26.04, P , pertussis cases among adolescents
acellular group could not be made for .0001). has climbed during 2012, mainly in
the following reasons: signicant The Tdap product (Boostrix; 13- to 14-year-olds who received
differences in the median age and GlaxoSmithKline; Adacel; Sano solely acellular vaccines.1 We have
time since vaccination between the Pasteur) was veried by lot number found that among adolescent
groups (P , .0001), a greater in 76% of recipients (Table 2). Cases recipients of all acellular vaccines,
proportion of participants with were more likely to have been overall Tdap VE is 64%, with
unknown Tdap vaccination status in vaccinated with Adacel compared substantial waning of protection after
the mixed group compared with the with controls (P = .05), despite Adacel 2 years. Although the study
acellular group (7.2% vs 4.5%, being used less frequently than methodology differed substantially,
our results were consistent with
a recent Tdap VE study in
TABLE 3 Estimated Tdap VE and Duration of Protection Against Pertussis Among Adolescents Who Wisconsin.11 The waning protection
Received All Acellular Vaccines (Birth Years 19982000) revealed in both studies indicates that
Cases Controls Odds Ratio Estimated VE it likely is a major contributor to the
(n = 450) (n = 1246) (95% CI) (95% CI), % increasing pertussis incidence in this
No Tdap 109 154 Reference Reference age group.
Tdap 341 1092 0.36 (0.26 to 0.50) 63.9 (49.7 to 74.1)
Although an initial study aim was to
Time since Tdap dose
No Tdap 109 154 Reference Reference compare Tdap VE between
,12 months 69 332 0.27 (0.18 to 0.40) 73.1 (60.3 to 81.8) adolescents who received a mix of
1223 months 124 389 0.45 (0.30 to 0.68) 54.9 (32.4 to 70.0) whole-cell and acellular vaccines with
2447 months 148 371 0.66 (0.42 to 1.03) 34.2 (20.03 to 58.0) those who received all acellular

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transmission. Both whole-cell and
acellular vaccines elicit pertussis-
specic antibodies, which decrease
after immunization.23,24 However,
other immunologic mechanisms, such
as cell-mediated immunity, have also
been associated with protection
against pertussis disease and may be
suboptimal after vaccination with
acellular vaccines.2528 In addition,
recent data from a novel nonhuman
primate model showed that although
acellular vaccines prevented
symptomatic disease, they failed to
prevent infection and transmission.29
FIGURE 2 Recently observed genetic variation
Time since Tdap vaccination, by vaccine group. Acellular vaccine group: adolescents born from 1998 in pertussis strains may also be
to 2000, assumed to have received all acellular pertussis vaccines for the childhood series (cases = playing a role in VE. In particular, the
450, controls = 1256). Mixed-vaccine group: adolescents born from 1993 to 1997, assumed to have
received a mix of whole-cell and acellular pertussis vaccines (cases = 386, controls = 1076). rapid emergence of pertactin-
decient pertussis strains is
vaccines, this was not possible due to suggests that durability of protection concerning, because pertactin is one
the difference in time since after Tdap is limited regardless of of the major antigenic components of
vaccination between the groups. type of vaccines received during acellular pertussis vaccines.30,31 A
Seventy-seven percent of adolescents childhood, but that the rate of waning recent evaluation of available isolates
in the mixed-vaccine group received may be higher in those vaccinated obtained during the Washington
Tdap at least 3 years before study solely with acellular vaccines. 2012 outbreak revealed that over half
carried a particular mutation
enrollment in comparison with only Reasons for more rapid waning of resulting in pertactin deciency.30
4% in the acellular vaccine group. Of Tdap-induced protection in persons Because our study was not designed
note, however, was the nding that vaccinated with acellular pertussis to measure VE against these emerging
VE estimates in the mixed-vaccine vaccines may be related to the strains, further evaluation is needed.
group at less or more than 4 years immunologic response to acellular
since Tdap vaccination were similar vaccines and a potential limitation of Analysis of Tdap product revealed
(51.5% vs 52.2%). This nding acellular vaccines to prevent a trend toward slightly higher VE
estimates with Boostrix as opposed to
Adacel, regardless of vaccine group
TABLE 4 Estimated Tdap VE Against Pertussis, by Brand and Vaccine Group analyzed. However, CIs overlapped
Cases Controls Odds Ratio (95% CI) Estimated VE (95% CI), % between Tdap product and between
All birth years
vaccine group. On the basis of this
n 836 2322 analysis, denitive conclusions
Tdap-unvaccinated 162 229 Reference Reference cannot be drawn regarding specic
Boostrix 387 1245 0.40 (0.30 to 0.52) 60.1 (47.7 to 69.6) Tdap product effectiveness;
Adacel 136 342 0.51 (0.37 to 0.71) 48.8 (28.8 to 63.2) nevertheless, these trends mirror
Unknown brand 151 506 0.37 (0.27 to 0.50) 63.2 (49.9 to 73.0)
Acellular vaccine group (birth
ndings of the Wisconsin study,
years 19982000) which showed higher VE with
n 450 1256 Boostrix.11
Tdap-unvaccinated 109 154 Reference Reference
Boostrix 231 725 0.37 (0.27 to 0.53) 62.6 (47.4 to 73.4) As with all case-control studies,
Adacel 50 129 0.44 (0.28 to 0.71) 55.7 (29.3 to 72.2) unaddressed biases could inuence
Unknown brand 60 238 0.27 (0.17 to 0.42) 73.3 (58.5 to 82.8) our ndings. The likelihood and
Mixed-vaccine group (birth timing of Tdap receipt are strongly
years 19931997)
correlated with age; to control for this
n 386 1076
Tdap-unvaccinated 53 75 Reference Reference potential bias, we matched on birth
Boostrix 156 520 0.44 (0.28 to 0.68) 56.5 (31.7 to 72.3) year. We also matched on primary
Adacel 86 213 0.61 (0.37 to 0.99) 39.2 (0.04 to 62.8) provider clinic in an attempt to
Unknown brand 91 268 0.49 (0.31 to 0.78) 50.6 (22.2 to 68.7) control for differences in provider

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reporting and diagnostic testing population.33,34 In the interim, efforts Participating county health
practices and patient access to to protect infants, who are at highest departments included the following:
medical care. Cases were more likely risk of critical disease and death, Clark County Public Health; Public
to be white and non-Hispanic, but the should be prioritized by reinforcing Health Seattle and King County,
large proportion of missing data the recent recommendation for Tdap Communicable Diseases and
limited our ability to evaluate the use during each pregnancy.35 Epidemiology; Tacoma Pierce County
relevance of these potential Health Department; Skagit County
demographic differences. To CONCLUSIONS Public Health; Snohomish Health
minimize misclassication of District; Yakima Health District; and
controls, all were checked against We showed that Tdap protection Whatcom County Health Department.
surveillance records and excluded if substantially wanes within 2 to 4
years; this waning is likely We thank the following individuals
they had ever been reported as for contributions to data collection:
a pertussis case. Secondary analyses contributing to the increase in
pertussis among adolescents. Bayo Arthur, Albert E. Barskey, Celia
were also performed to conrm that Bird, Amy Blain, Kate Rose Bobseine,
inclusion of suspect or probable cases Advances in our understanding of the
immunology and bacteriology of B Elizabeth Briere, Kimberly Brinker,
in the analysis, which use a less Claire Brostrom-Smith, Jean Cadet,
specic case denition, did not affect pertussis are essential to optimize
future prevention and control Tegan Callahan, Abbey Canon, Emma
the VE estimates. Carroll, Julia Chang, Tabitha Cheng,
measures. However, novel pertussis
Expanding the vaccination program vaccines that effectively limit Natasha Close, Kpandja Djawe,
to include additional Tdap booster infection and transmission are also Stephanie Dunkel, Sarah Ekerholm,
doses is unlikely to result in likely needed to reduce the burden David Fitter, Leah Gilbert, Dan
signicant disease reduction given its of pertussis disease in the Gingold, Wendy Hancock, Geoffrey
short duration of protection and the United States. Hart-Cooper, Joni Hensley, Kristen N.
assumed lower burden of disease in Hosey, Hajime Kamiya, Emmaculate
adults.1 A cost-effectiveness analysis Lebo, Adria Lee, Kara Levri, Jessica
of a second dose of Tdap, modeling ACKNOWLEDGMENTS MacNeil, Sarah Meyer, Rebekah Miner,
a best-case scenario of VE and We acknowledge the Washington Janee Moore, Angela M. Orozco,
duration of protection, revealed only State Department of Health and the Carolyn Othieno, Megan Popielarczyk,
a small reduction in the number of local health jurisdictions of Clark, Anna T. Rapp, Charleen Ross,
cases while incurring very high King, Pierce, Skagit, Snohomish, Stephanie J. Salyer, Kerry Schnell,
costs.32 For these reasons, in addition Yakima, and Whatcom counties for Miriam Shiferaw, Reed Sorensen,
to the challenges of improving adult their leadership and strong support Mandy Stahre, Jamille Taylor, Tracy
vaccination coverage, the Advisory of this study. We also thank the Thomas, Rebecca Tsai, Joshua Van
Committee on Immunization members of the Epi-Aid team for Otterloo, Tristan Victoroff, Joanna
Practices has not supported successfully completing the Watson, Emily Weston, Melissa
a recommendation for additional important task of data collection in Whaley, Misha Williams, and Jonathan
Tdap doses for the general a very short time period. M. Wortham.

Ms Martin supervised the conceptualization and design of the study, contributed to data interpretation, and provided critical revision of the manuscript for
important intellectual content; Dr Patel supervised the conceptualization and design of the study, assisted with data collection, contributed to data interpretation,
and provided critical revision of the manuscript for important intellectual content; and all authors approved the nal manuscript as submitted.
The ndings and conclusions in this report are those of the authors and do not necessarily represent the ofcial position of the Centers for Disease Control and
DOI: 10.1542/peds.2014-3358
Accepted for publication Mar 16, 2015
Address correspondence to Anna M. Acosta, MD, 1600 Clifton Rd, NE, Mailstop C-25, Atlanta, GA 30329. E-mail:
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2015 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: No external funding.

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POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found on page 1130, and online at

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TIMING IS KEY: During the college football season, some games begin at noon while
others begin late in the evening. I have always wondered if the start time for the
game could affect athletic performance. I have noticed that when I exercise I seem
slower rst thing in the morning. As it turns out, athletes have a natural circadian
rhythm and performance depends on whether the event is in sync with the athletes
circadian rhythm.
As reported in The New York Times (Well: January 29, 2015), researchers evaluated
the athletic performance of 20 competitive eld hockey players and 22 competitive
squash players six times a day. When the results were assessed in aggregate, the
researchers found that overall, athletic performance peaked in the evening. This was
consistent with previous ndings by other researchers. However, when they looked
at peak performance based on time of day and whether the athlete was an early
morning, mid-morning, or late morning riser, they found that athletic performance
peaked 4 to 6 hours after waking. Early morning risers did their best at noon, while
late risers did their best in the evening. Nobody did well early in the morning. In fact,
performance diminished by as much as 26% if not in sync with the natural circadian
rhythm. While the study involved a limited number of adults, and the exercise
measured was not related to the sporting event, the data suggest that to maximize
performance athletes should consider the time of the event. If necessary, they should
stagger their sleep time to help ensure their circadian rhythm is in sync with the
timing of the event.
As for me, I do not think it matters too much what time of day I exercise. After all, I am
not in a competition. Still, it is nice to know there is a reason why I seem so sluggish
while exercising early in the morning.
Noted by WVR, MD

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Tdap Vaccine Effectiveness in Adolescents During the 2012 Washington State
Pertussis Epidemic
Anna M. Acosta, Chas DeBolt, Azadeh Tasslimi, Melissa Lewis, Laurie K. Stewart,
Lara K. Misegades, Nancy E. Messonnier, Thomas A. Clark, Stacey W. Martin and
Manisha Patel
Pediatrics 2015;135;981
DOI: 10.1542/peds.2014-3358 originally published online May 4, 2015;

Updated Information & including high resolution figures, can be found at:
Supplementary Material Supplementary material can be found at:
References This article cites 28 articles, 6 of which you can access for free at:
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Infectious Disease
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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright 2015 by the American Academy of Pediatrics. All rights reserved. Print

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Tdap Vaccine Effectiveness in Adolescents During the 2012 Washington State
Pertussis Epidemic
Anna M. Acosta, Chas DeBolt, Azadeh Tasslimi, Melissa Lewis, Laurie K. Stewart,
Lara K. Misegades, Nancy E. Messonnier, Thomas A. Clark, Stacey W. Martin and
Manisha Patel
Pediatrics 2015;135;981
DOI: 10.1542/peds.2014-3358 originally published online May 4, 2015;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright 2015 by the American Academy of Pediatrics. All rights reserved. Print

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