Introduction
Since 2005, a single dose of tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis (Tdap) vaccine has been recommended by the Advisory Committee on Immunization
Practices (ACIP) for adolescents and adults (
1
,
2
). After receipt of Tdap, booster doses of tetanus and diphtheria toxoids (Td) vaccine
are recommended every 10 years or when indicated for wound management. During the
October 2019 meeting of ACIP, the organization updated its recommendations to allow
use of either Td or Tdap where previously only Td was recommended. These situations
include decennial Td booster doses, tetanus prophylaxis when indicated for wound management
in persons who had previously received Tdap, and for multiple doses in the catch-up
immunization schedule for persons aged ≥7 years with incomplete or unknown vaccination
history. Allowing either Tdap or Td to be used in situations where Td only was previously
recommended increases provider point-of-care flexibility. This report updates ACIP
recommendations and guidance regarding the use of Tdap vaccines (
3
).
Background
Two Tdap vaccines are licensed for use in the United States. Boostrix (GlaxoSmithKline)
is approved for a single dose in persons aged ≥10 years; Adacel (Sanofi Pasteur) is
approved for persons aged 10–64 years. Since 2005, a single booster dose of Tdap has
been recommended for children and adolescents aged 11–18 years and adults aged 19–64
years (
1
,
2
) to increase protection against tetanus, diphtheria, and pertussis. Booster doses
of Td have been recommended every 10 years (decennial vaccination) to ensure continued
protection against tetanus and diphtheria. These recommendations were expanded to
include a single dose of Tdap for adults aged ≥65 years in 2012 (although only one
Tdap product is approved for use in persons aged ≥65 years, either vaccine administered
to a person aged ≥65 years is considered valid) (
4
). Pregnant women are recommended to receive a dose of Tdap during each pregnancy
to prevent pertussis in infants too young for routine vaccination (off-label use*)
(
3
). If a tetanus toxoid–containing vaccine is indicated for wound management, Td has
been recommended for nonpregnant persons aged ≥7 years who had previously received
Tdap. For pregnant women, Tdap is recommended in this setting. For previously unvaccinated
persons aged ≥7 years, a 3-dose catch-up immunization schedule included only 1 dose
of Tdap, preferably as the first dose in the series (off-label use in children aged
7–9 years), and 2 subsequent Td doses at specified intervals (
5
). No further doses of Tdap were routinely recommended, with two exceptions: pregnant
women should receive Tdap during each pregnancy (off-label use), and children aged
7–10 years who received Tdap as part of the catch-up schedule were recommended to
receive the routine adolescent Tdap booster dose at age 11–12 years (
1
,
2
). In 2010, ACIP evaluated the safety of administering Tdap at intervals <5 years
after Td administration (
6
,
7
) and recommended that the dose of Tdap, when indicated, should not be delayed and
should be administered regardless of the interval since the last tetanus or diphtheria
toxoid–containing vaccine.
In 2013, ACIP reviewed the most recent safety and immunogenicity data available at
that time to inform their recommendations regarding a second routine dose of Tdap.
ACIP concluded that a second dose of Tdap would be safe and immunogenic at 5- or 10-year
intervals (
8
–
12
). However, antipertussis antibodies decline rapidly after the first year (
10
,
13
–
20
), and vaccine effectiveness studies indicated that pertussis protection begins to
wane within 2–4 years after receipt of a single Tdap dose (
21
–
23
). This likely limits the impact of a second dose of Tdap on the overall burden of
pertussis in the United States (
24
). In addition, Tdap vaccines have an uncertain role in prevention of transmission
and in herd protection (
25
,
26
). ACIP concluded that the data did not support a general recommendation for a routine
second dose of Tdap, given the likely limited public health impact (
27
).
In January 2019, FDA approved Adacel for a second Tdap dose if administered ≥8 years
after the first Tdap dose and for use for tetanus prophylaxis when indicated for wound
management if ≥5 years have elapsed since the previous receipt of any tetanus toxoid–containing
vaccine (
28
). In light of the new indication for a second dose of Adacel and evidence of Tdap
being used frequently in place of Td (
29
), ACIP reassessed current Tdap recommendations. In October 2019, ACIP recommended
that either Tdap or Td vaccines could be used in situations where only Td vaccine
had been recommended previously. This report provides recommendations for the use
of Td or Tdap for the decennial Td booster, tetanus prophylaxis when indicated for
wound management, and catch-up immunization schedule for persons aged ≥7 years with
incomplete or unknown vaccination history.
Methods
Beginning in September 2018, the ACIP Pertussis Vaccines Work Group participated in
monthly telephone conferences to review Tdap vaccination recommendations. A search
of clinical trials published during January 2013–June 2019 that examined Tdap vaccination
in adolescents and adults who had previously received Tdap was performed, so the work
group could review data that had not previously been reviewed by ACIP. Because of
limited data on the use of >1 Tdap dose in the catch-up immunization schedule, the
work group also considered published and unpublished safety data on receipt of >1
Tdap dose within a 12-month period in both pregnant women and nonpregnant adolescents
and adults. Data from public sector orders (CDC, unpublished data, 2019), commercial
insurance claims (Truven Health Analytics, unpublished data, 2019), and a published
study from the Vaccine Safety Datalink (VSD) (
29
) were analyzed to assess stakeholders’ values attributed to perceived benefits and
harms, acceptability, and implementation considerations regarding use of Tdap in place
of Td.
Summaries of evidence, including the evidence to recommendations framework (https://www.cdc.gov/vaccines/acip/recs/grade/tdap-etr.html)
and assessment of programmatic considerations, were presented to ACIP at the October
2018, June 2019, and October 2019 meetings. Proposed recommendations were presented
to the committee at the October 2019 meeting, and, after a public comment period,
were approved by the voting members as follows: either Td or Tdap should be allowed
for use in situations where only Td is currently recommended for the decennial Td
booster, tetanus prophylaxis for wound management, and catch-up vaccination, including
in pregnant women (14 voted in favor, and none opposed).
Summary of Key Findings
Safety and immunogenicity. Two clinical trials found no increased risk for adverse
events among adults who received Tdap, compared with those who received Td 10 years
after receipt of the initial Tdap dose (
30
,
31
). In addition, the proportion of persons with seroprotective levels of antibodies
to tetanus and diphtheria was similar in the Tdap and Td groups. Another clinical
trial compared adults receiving a second dose of Tdap 9 years after their initial
Tdap dose with adults receiving Tdap for the first time as a control group (
32
). Solicited adverse events, the most frequent of which were injection site pain,
fatigue, and headache, were higher in the groups receiving a second dose of Tdap.
Grade 3 adverse events, defined in this study as redness and swelling with diameter
>50 mm, pain, headaches, fatigue, gastrointestinal symptoms preventing normal activity,
and fever with temperature >104°F(40°C), were similar in both groups. A retrospective
VSD study identified 68,915 adolescents and adults who had received an initial dose
of Tdap and then received another Td-containing vaccine, either a second Tdap (61,394,
89%) or Td (7,521, 11%). There was no statistically significant increase in medical
visits for cellulitis, limb swelling, pain in limb, seizure, cranial nerve disorders,
paralytic syndromes, encephalopathy, encephalitis, or meningitis among those who received
a subsequent dose of Tdap compared with those who received Td (
29
).
Data on the use of >1 Tdap dose in the catch-up immunization schedule are limited.
One double-blind, randomized controlled clinical trial enrolled 460 adults aged ≥40
years who had not received a diphtheria or tetanus vaccination for ≥20 years or who
had an unknown vaccination history. Subjects were randomized to receive either 3 doses
of a Tdap formulation; 1 Tdap-inactivated polio vaccine combination dose, which is
not licensed in the United States, followed by 2 Td doses; or 3 Td doses at 0, 1,
and 6 months. There was no significant difference in adverse events for subjects receiving
3 Tdap doses, compared with those receiving 3 Td doses, and no significant differences
in diphtheria and tetanus seroprotection rates among the three groups (
33
). An analysis of data collected as part of a published VSD retrospective study (
29
) identified 13,599 persons who had received an initial dose of Tdap and then received
another Td-containing vaccine within 12 months of the previous Tdap dose, either a
second Tdap (11,687, 86%) or Td (1,912, 16%). There was no elevated risk for medical
visits for adverse events among those who received a subsequent dose of Tdap compared
with those who received Td (CDC/VSD, unpublished data, 2019). Among 34,804 reports
to the Vaccine Adverse Event Reporting System (VAERS) (
34
) following receipt of Tdap in nonpregnant and pregnant persons of all ages during
January 1, 1990–June 30, 2019, 88 (0.3%) persons had received multiple Tdap doses
spaced ≤12 months apart. Among this small group of reports, 21 (24%) were associated
with adverse events, the most frequent of which was injection site reactions (8, 38%)
(CDC, unpublished data, 2019).
There are no published data comparing rates of adverse events among pregnant women
who received multiple doses of Tdap during a single pregnancy with those who received
a single Tdap dose and additional Td doses for catch-up vaccination. A cohort study
examining reactogenicity of Tdap in pregnant women included only eight study participants
who received >1 Tdap dose within a 12-month period; none experienced severe reactions
or fever (
35
). A VSD study examining safety of Tdap during pregnancy identified 187 women who
had received >1 Tdap dose during a single pregnancy among 633,542 singleton pregnancies
screened for potential study inclusion (
36
). Although these 187 women were excluded from the published study, the authors found
similar rates of adverse birth outcomes (i.e., small for gestational age, preterm
delivery, and low birthweight) in these women compared with women who had received
a single Tdap dose in pregnancy (29,155). Among these 187 women who received >1 Tdap
dose during pregnancy, one had a medically attended acute adverse event, which was
diagnosed as limb pain and swelling 7 days after vaccination. One woman received 3
Tdap doses during a single pregnancy; she did not experience any adverse events, and
her baby was born at term (CDC, unpublished data, 2019).
Acceptability to patients and providers. Analysis of commercial insurance claims indicated
that Tdap claims were 12 times as high as Td claims in adults aged 19–64 years during
2017 (Truven Health Analytics, unpublished data, 2019). In the same year, there were
approximately 10 times the number of Tdap doses (441,075) as Td doses (41,881) ordered
by providers for adults as public sector purchases (CDC, unpublished data, 2019).
These data, in addition to the one published VSD study (
29
) documented that Tdap was widely used in place of Td by clinicians in the United
States and suggested acceptability to both patients and health care providers.
Health impact and economic considerations. Tdap costs more than Td (
37
). The population-level effectiveness and economic impact of replacing Td with Tdap
has been modeled and previously reviewed by ACIP (
24
). However, this analysis and an updated model of the economic impact of substituting
Tdap for the decennial Td booster demonstrated that estimates of cost effectiveness
are dependent on values for parameters with a high degree of uncertainty, including
pertussis incidence, illness severity, initial vaccine effectiveness, duration of
protection, and the impact of Tdap on herd protection (
38
). Coupling such uncertainty with the evidence for notable widespread use of Tdap
in place of Td, programmatic issues were the main consideration in the decision-making
process.
Rationale for Recommendations
In 2013, ACIP did not support a general recommendation for a routine second dose of
Tdap; the rationale was described in previously published guidance (
3
). In 2019, ACIP again concluded that in light of the higher cost of Tdap relative
to Td and uncertainty about the impact that receipt of multiple Tdap doses would have
on pertussis control and transmission, there continues to be insufficient evidence
to preferentially recommend that Tdap replace Td. However, given the reassuring safety
profile and evidence of widespread use of Tdap in place of Td, to allow providers
more flexibility, either Tdap or Td was recommended for use in situations when previously
only Td was recommended. ACIP recommends that either Td or Tdap be used for the decennial
Td booster, tetanus prophylaxis for wound management, and for additional required
doses in the catch-up immunization schedule if a person has received at least 1 Tdap
dose.
General Recommendations
Persons aged 11–18 years. These persons should receive a single dose of Tdap, preferably
at a preventive care visit at age 11–12 years. To ensure continued protection against
tetanus and diphtheria, 1 booster dose of either Td or Tdap should be administered
every 10 years throughout life.
Persons aged ≥19 years. Regardless of the interval since their last tetanus or diphtheria
toxoid–containing vaccine, persons aged ≥19 years who have never received a dose of
Tdap should receive 1 dose of Tdap. To ensure continued protection against tetanus
and diphtheria, booster doses of either Td or Tdap should be administered every 10
years throughout life.
Pregnant women. No change has been made to the recommendations for routine Tdap immunization
during pregnancy. Pregnant women should receive 1 dose of Tdap during each pregnancy,
irrespective of their history of receiving the vaccine. Tdap should be administered
at 27–36 weeks’ gestation, preferably during the earlier part of this period, although
it may be administered at any time during pregnancy (
3
,
5
).
Tetanus Prophylaxis for Wound Management Recommendations
A tetanus toxoid–containing vaccine is indicated for wound management when >5 years
have passed since the last tetanus toxoid–containing vaccine dose. If a tetanus toxoid–containing
vaccine is indicated for persons aged ≥11 years, Tdap is preferred for persons who
have not previously received Tdap or whose Tdap history is unknown. If a tetanus toxoid–containing
vaccine is indicated for a pregnant woman, Tdap should be used. For nonpregnant persons
with documentation of previous Tdap vaccination, either Td or Tdap may be used if
a tetanus toxoid–containing vaccine is indicated. Complete information on tetanus
prophylaxis and the use of tetanus immunoglobulin when indicated for wound management
is available at https://www.cdc.gov/mmwr/volumes/67/rr/rr6702a1.htm.
Catch-Up Immunization Recommendations
Persons aged 7–18 years. If persons aged 7–18 years have never been vaccinated against
pertussis, tetanus, or diphtheria, these persons should receive a series of three
tetanus and diphtheria toxoid–containing vaccines, which includes at least 1 Tdap
dose. The preferred schedule is 1 dose of Tdap, followed by 1 dose of either Td or
Tdap ≥4 weeks afterward, and 1 dose of either Td or Tdap 6–12 months later. Persons
aged 7–18 years who are not fully immunized against tetanus and diphtheria should
receive 1 dose of Tdap, preferably as the first dose in the catch-up series; if additional
tetanus toxoid–containing doses are required, either Td or Tdap may be used. The vaccination
series does not need to be restarted for those with incomplete DTaP history, regardless
of the time that has elapsed between doses. The catch-up schedule and minimum intervals
between doses are available at https://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html.
Persons aged ≥19 years. If persons aged ≥19 years have never been vaccinated against
pertussis, tetanus, or diphtheria, these persons should receive a series of three
tetanus and diphtheria toxoid–containing vaccines, which includes at least 1 Tdap
dose. The preferred schedule is 1 dose of Tdap, followed by 1 dose of either Td or
Tdap at least 4 weeks afterward, and 1 dose of either Td or Tdap 6–12 months later.
Persons aged ≥19 years who are not fully immunized against tetanus and diphtheria
should receive 1 dose of Tdap, preferably as the first dose in the catch-up series;
if additional tetanus toxoid–containing doses are required, either Td or Tdap may
be used.
Prevention of Neonatal and Obstetric Tetanus
Pregnant women who have completed the childhood immunization schedule and were last
vaccinated >10 years previously should receive a booster dose of tetanus toxoid–containing
vaccine to prevent neonatal tetanus. The risk for neonatal tetanus is minimal if a
previously unvaccinated woman has received at least 2 properly spaced doses of a tetanus
toxoid–containing vaccine during pregnancy; at least 1 of the doses administered during
pregnancy should be Tdap, administered according to published guidance (
3
). If >1 dose is needed, either Td or Tdap may be used. The 3-dose primary series
should be completed at the recommended intervals.
CDC Guidance
Catch-up immunization. For persons aged 7–9 years who receive a dose of Tdap as part
of the catch-up series, an adolescent Tdap dose should be administered at age 11–12
years. If a Tdap dose is administered at age ≥10 years, the Tdap dose may count as
the adolescent Tdap dose.
Inadvertent Administration
Persons aged ≥7 years. DTaP is not indicated for persons aged ≥7 years. If DTaP is
administered inadvertently to a fully vaccinated
†
child aged 7–9 years, an adolescent Tdap dose should be administered at age 11–12
years. If DTaP is administered inadvertently to an undervaccinated child aged 7–9
years, this dose should count as the Tdap dose of the catch-up series, and the child
should receive an adolescent Tdap dose at age 11–12 years. If DTaP is administered
inadvertently to a person aged ≥10 years, this dose should count as the adolescent
Tdap dose routinely administered at age 11–12 years.
Fully vaccinated
children aged 7–10 years. If a fully vaccinated child aged 7–9 years receives Tdap,
the Tdap dose should not be counted as valid. The adolescent Tdap dose should be administered
as recommended when this child is aged 11–12 years. The preferred age at administration
for the adolescent Tdap dose is 11–12 years. However, if Tdap is administered at age
10 years, the Tdap dose may count as the adolescent Tdap dose.
Off-Label Use of Vaccine
Off-label indications based on age and pregnancy status have not changed (Table).
New off-label indications for Adacel would include any additional routine or catch-up
Td dose beyond a second dose administered ≥8 years after an initial Tdap dose, if
not given for wound prophylaxis within the specified guidance. Any additional doses
of Boostrix administered beyond the single licensed dose are considered off-label.
The work group did not find any reason to distinguish between these two products in
making its recommendations.
TABLE
Food and Drug Administration (FDA)–approved and off-label recommendations for licensed
tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) products
— United States, 2019
Licensed Tdap product
FDA-approved indications for use and administration
Off-label uses
Decennial Td booster
Tetanus prophylaxis for wound management
Catch-up immunization,* including during pregnancy†
Adacel
§
Age: 10–64 years
Age: ≥65 years
Age: <10 or ≥65 years
Age: 7–9 years
Routine booster ≥5 years after a dose of DTaP or Td vaccine, with a second dose
≥8 years after first (any) Tdap dose
Any dose beyond second Adacel dose administered ≥8 years after first Tdap dose
>1 Tdap dose
Tetanus prophylaxis if ≥5 years have elapsed since the last tetanus-containing
vaccine
Boostrix
§
Age: ≥10 years
Any dose if previously received Tdap
Age: <10 years
Age: 7–9 years
Single dose ≥5 years after a dose of DTaP or Td vaccine
Any dose if previously received Tdap
>1 Tdap dose
Tetanus prophylaxis if no previous Tdap
Abbreviations: DTaP = diphtheria and tetanus toxoids and acellular pertussis vaccine;
Td = tetanus and reduced diphtheria toxoid.
* Persons with incomplete or unknown vaccination history should receive a single dose
of Tdap, preferably as the first dose of the 3-dose catch-up series; if additional
tetanus toxoid–containing doses are needed, either Td or Tdap vaccine may be used.
†
Both Tdap vaccines may be administered during pregnancy with the same intervals and
restrictions (vaccine specific) as would apply to a nonpregnant person.
§ Package inserts for indications and intervals for wound management are available
at https://www.fda.gov/media/119862/download (Adacel) and https://www.fda.gov/media/124002/download
(Boostrix).
Contraindications and precautions. Contraindications and precautions are unchanged
from previous recommendations (
3
).
Reporting of vaccine adverse reactions. Adverse events occurring after administration
of any vaccine should be reported to VAERS. Reports can be submitted to VAERS online,
by fax, or by mail. Additional information about VAERS is available by telephone (1-800-822-7967)
or online (https://vaers.hhs.gov).
Future Research and Monitoring Priorities
ACIP will continue to review data on Td and Tdap as they become available, examine
the necessity and frequency of booster doses for protection against tetanus and diphtheria,
and consider any needed policy changes. As with all vaccines, CDC will use VAERS and
VSD to monitor adverse events following immunization.
Summary
What is already known about this topic?
Repeat doses of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis
(Tdap) vaccine at 5- and 10-year intervals are safe and immunogenic.
What is added by this report?
ACIP recommendations have been updated to allow either tetanus and diphtheria toxoids
(Td) vaccine or Tdap to be used for the decennial Td booster, tetanus prophylaxis
for wound management, and for additional required doses in the catch-up immunization
schedule if a person has received at least 1 Tdap dose.
What are the implications for public health practice?
Allowing either Tdap or Td to be used in situations where Td only was previously recommended
increases provider point-of-care flexibility.