1. Jennifer L. Liang DVM, MPVM
Update on recent changes to use of Tdap vaccines for adolescents and adults in the United States
Jennifer L. Liang DVM, MPVM
2011National Immunization Conference
March 23, 2011
National Center for Immunization & Respiratory Diseases
Meningitis and Vaccine Preventable Diseases Branch/Division of Bacterial Diseases

2. Objectives Present recent changes to ACIP Tdap recommendations
Discuss rationale for changes to recommendations
Good afternoon. Today I’d like to take the opportunity to present an update on recent changes to the Tdap recommendations for adolescents and adults and discuss the rationale for these changes.

3. In 2005, the Advisory Committee on Immunization Practices (ACIP) recommended both adolescents and adults should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis. Two separate statements were published, one for adolescent recommendations and the other for adults. There are two licensed Tdap vaccines available in the United States: Boostrix manufactured by GlaxoSmith Klein and Adacel manufactured by sanofi pasteur.

4. Tdap coverage among adolescents aged 13-17 years – 2006-2009
Percentage (%)
Since the 2005 recommendations, Tdap coverage among adolescents has been increased. In 2009, coverage was reported to be over 55%.
Compared to adolescents, coverage of Tdap among adults was reported to be less than 6% in 2008.
2006
2007
2008
2009
CDC. National, State, and Local Area Vaccination Coverage among Adolescents Aged Years - United States, MMWR 2010; 59(32)
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)

5. Reasons for changes to 2005 Tdap recommendations
New data on Tdap
Facilitate the uptake of Tdap across age groups by removing identified barriers and programmatic challenges
Reasons for changes to the 2005 Tdap recommendations include
The availability of new data on Tdap both safety and programmatic considerations since the 2005 recommendations
And to facilitate the uptake of Tdap across age groups by removing identified barriers and programmatic challenges.
I want to note that these recent Tdap recommendations are off-licensed

6. Timing of TDAP FOLLOWING TD

7. 2005 ACIP recommendation for interval between Td and Tdap
Adolescent
An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used.
Adult
Intervals <10 years since the last Td may be used to protect against pertussis. Particularly in settings with increased risk for pertussis or its complications, the benefit of using a single dose of Tdap at an interval <10 years to protect against pertussis generally outweighs the risk for local and systemic reactions after vaccination. The safety of an interval as short as approximately 2 years between Td and Tdap is supported by a Canadian* study; shorter intervals may be used.
The language around the 2005 ACIP Tdap recommendation addressing interval between Td and Tdap in the both the adolescent and adult statements was not specific.
Limited safety data?
* Halperin SA, et. al. How soon after a prior tetanus-diphtheria vaccination can one give adult formulation tetanus-diphtheria-acellular pertussis vaccine? Pediatr Infect Dis J (3):

8. 2005 language creates barrier
Survey of primary care physicians on use of Tdap in adolescents
48% - shortest acceptable interval before providing Tdap – 5 years
44% - would wait at least 2 years
27% of health care workers did not plan to receive Tdap because they had received Td within the last two years
74% Obstetricians/Gynecologists reported the major barrier postpartum and/or pregnant women vaccination was not knowing date of Td booster
Most parents with infants in the NICU could not recall their last tetanus booster
The 2005 language created a perceived barrier to use of Tdap. The following are examples of how the language addressing interval created a barrier to Tdap vaccination:
A survey among primary care physicians on the interpretation of the adolescent recommendations: 48% of physicians indicated 5 yrs would be the shortest acceptable interval before providing Tdap, 44% would wait at least 2 years.
27% of health care workers did not plan to receive Tdap because they had received a Td booster within last 2 years.
And the last two bullets note that the major barrier to vaccinating parents with infants was not knowing the date of recent Td booster.
Dempsey AF, et. al. Adolescent Tdap vaccine use among primary care physicians. J Adolesc Health Apr;44(4):
Goins WP, et. al. Healthcare workers' knowledge and attitudes about pertussis and pertussis vaccination. Infect Control Hosp Epidemiol Nov;28(11):
Clark SJ, et. al. Attitudes of US obstetricians toward a combined tetanus-diphtheria-acellular pertussis vaccine for adults. Infect Dis Obstet Gynecol. 2006;2006:87040
Dylag AM, Shah SI. Administration of tetanus, diphtheria, and acellular pertussis vaccine to parents of high-risk infants in the neonatal intensive care unit. Pediatrics Sep;122(3):e550-5.

9. Updated ACIP recommendation
Tdap should be administered regardless of interval since the last tetanus or diphtheria toxoid-containing vaccine
While longer intervals between Td and Tdap vaccination could decrease the occurrence of local reactions, the benefits of protection against pertussis from shorter intervals outweigh the potential risk for adverse events.
After consideration of recent safety data, ACIP approved the following change to the language addressing interval between Td and Tdap:
Tdap should be administered regardless of interval since the last tetanus or diphtheria toxoid-containing vaccine
While longer intervals between Td and Tdap vaccination could decrease the occurrence of local reactions, the benefits of protection against pertussis from shorter intervals outweigh the potential risk for adverse events.
Centers for Disease Control and Prevention. Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine from the Advisory Committee on Immunization Practices, MMWR 2011; 60:13-15.

10. Adults Aged 65 Years and Older

11. Source of pertussis transmission to infants
Household members responsible for 75%–83%
Parents and siblings were common sources
Parents (55%)
Siblings (16%-20%)
Aunts/uncles (10%)
Friends/cousins/others (10%-24%)
Grandparents (6%)
Caretakers (2%)
Several studies have provided evidence that household members were primarily responsible for transmission of pertussis to infants with grandparents having been identified as a source.
Wendelboe AM., et al. Transmission of Bordetella pertussis to Young Infants. Pediatr Infect Dis J 2007;26: 293–299
Bisgard KM, Pascual FB, Ehresmann KR, Miller CA, Cianfrini C, Jennings CE et al. Infant pertussis: who was the source? Pediatr Infect Dis J 2004; 23(11):

12. 2005 Tdap recommendations Adults aged ≥65 years
Tdap is not licensed for use among adults aged >65 years. The safety and immunogenicity of Tdap among adults aged ≥65 years were not studied during U.S. pre-licensure trials. Adults aged ≥65 years should receive a dose of Td every 10 years for protection against tetanus and diphtheria and as indicated for wound management .
Research on the immunogenicity and safety of Tdap among adults aged ≥65 years is needed. Recommendations for use of Tdap in adults aged ≥65 years will be updated as new data become available.
The 2005 Tdap recommendation for adults ages 65 years and older. Both Tdap vaccines are licensed through persons 64 years of age. The 2005 language did not allow for permissive use of Tdap in this age group, and left a gap in the pertussis vaccination program.
CDC. Prevention of Pertussis, Tetanus, and Diphtheria among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR 2006;55(No. RR-17).

13. Updated ACIP recommendation Adults aged 65 years and older
Those who have or anticipate having close contact with an infant aged less than 12 months should receive a single dose of Tdap.
Other adults ages 65 years and older may be given a single dose of Tdap.
Review of data showed that there was no demonstrated increased risk of severe local reactions or serious adverse events in adults ages 65 years and older.
ACIP approved on the expanded use of Tdap in adults ages 65 years and older. For adults ages 65 years and older who have or anticipate having close contact with an infant aged less than 12 months should receive a single dose of Tdap. And other adults ages 65 years and older may be given a single dose of Tdap.
Centers for Disease Control and Prevention. Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine from the Advisory Committee on Immunization Practices, MMWR 2011; 60:13-15.

14. Undervaccinated Children Aged 7 through 10 Years

15. Pertussis immunization in the U.S.
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
I want to remind everyone of the pertussis vaccine schedule for both the pediatric pertussis vaccine (DTaP) and the adolescent/adult pertussis vaccine (Tdap).
The last childhood booster with DTaP is for pre-school age at 4 to 6 years. Then the Tdap adolescent booster at 11 years.
The 2005 adolescent Tdap statement recommended that under-vaccinated 7 to 10 year olds wait until they reached 11 years of age to receive a Tdap booster. This left a gap for providing protection from pertussis to children ages 7 through 10 years with incomplete or unknown pertussis vaccine history.

16. Updated ACIP recommendation: Under-vaccinated children ages 7 through10 years
Those not fully vaccinated against pertussis* and for whom no contraindication to pertussis vaccine exists should receive a single dose of Tdap.
Those never vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccination status should receive a series of three vaccinations containing tetanus and diphtheria toxoids. The first of these three doses should be Tdap.
In October 2010, ACIP recommended that 7 to 10 year olds not fully vaccinated against pertussis should receive a single dose of Tdap.
* Fully vaccinated is defined as 5 doses of DTaP or 4 doses of DTaP if the fourth dose was
administered on or after the fourth birthday
Centers for Disease Control and Prevention. Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine from the Advisory Committee on Immunization Practices, MMWR 2011; 60:13-15.

17. Vaccinating Health Care Personnel

18. Pertussis in health-care personnel
12-14 million HCP in the United States
Protecting HCP from acquiring and transmitting infectious diseases is a public health goal
There are 12 to 14 million health care personnel in the United States. Protecting HCP from acquiring and transmitting infectious diseases is a public health.
Wright, SW, Decker MD, Edwards KM Incidence of pertussis infection in healthcare workers. Infect. Control Hosp. Epidemiol. 20:

19. 2005 ACIP language: HCP§§ (1)
HCP in hospitals or ambulatory care settings who have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap. Although Td booster doses are routinely recommended at an interval of 10 years, an interval as short as 2 years from the last dose of Td is recommended for the Tdap dose among these HCP. These HCP include but are not limited to physicians, other primary care providers, nurses, aides, respiratory therapists, radiology technicians, students (e.g., medical, nursing, and other), dentists, social workers, chaplains, volunteers, and dietary and clerical workers.
Other HCP (i.e., not in hospitals or ambulatory care settings or without direct patient contact) should receive a single dose of Tdap to replace the next scheduled Td according to the routine recommendation at an interval no greater than 10 years since the last Td. They are encouraged to receive the Tdap dose at an interval as short as 2 years following the last Td.
The 2005 recommendations for use of Tdap in health care personnel are here and on the next slide. ACIP recommends health care personnel with direct patient contact to receive Tdap as soon as feasible and other health care personnel receive Tdap when they are scheduled for next Td. The recommendations also address interval since last dose of Td.
§§ Recommendations for use of Tdap among HCP were reviewed and are supported by the members of HICPAC.
¶¶ Hospitals, as defined by the Joint Commission on Accreditation of Healthcare Organizations, do not include long-term care facilities such as nursing homes, skilled-nursing facilities, or rehabilitation and convalescent care facilities. Ambulatory-care settings include all outpatient and walk-in facilities.

20. HCP Tdap coverage rates
Hospital-based coverage rates
60% all employees 1
72% healthcare personnel 2
15.9% among health-care personnel 3
So where are we?
Two papers report that hospital-based coverage rates were 60% and 72%, but these were part of vaccination campaigns which occurred after a pertussis outbreak. But, from the 2008 National Health Interview Survey, self-reported Tdap vaccination coverage among health care personnel was less than 16%.
1 Leekha S, Thompson RL, Sampathkumar P. Epidemiology and Control of Pertussis Outbreaks in a Tertiary Care Center and the Resource Consumption Associated With These Outbreaks. Infect Control Hosp Epidemiol 2009; 30:
2 Fontanilla JM, Kirkland KB , Cotter JG, Talbot EA. Ability of Healthcare Workers to Recall Previous Receipt of Tetanus-Containing Vaccination. Infect Control Hosp Epidemiol 2010; 31(6):
3 CDC. Tetanus and Pertussis Vaccination Coverage Among Adults Aged ≥18 Years --- United States, 1999 and MMWR. 59(40);

21. Approved ACIP language: Use of Tdap in HCP
Health-care personnel (HCP), regardless of age, should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap and regardless of the time since last Td dose.
Tdap is not currently licensed for multiple administrations. After receipt of Tdap, HCP should receive routine booster immunization against tetanus and diphtheria according to previously published guidelines.
Hospitals¶¶ and ambulatory-care facilities should provide Tdap for HCP and use approaches that maximize vaccination rates (e.g., education about the benefits of vaccination, convenient access, and the provision of Tdap at no charge).
In continued support for direct language to remove barriers to facilitate the uptake of Tdap, ACIP now recommends
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In background: Vaccinating HCP with Tdap will protect them against pertussis and is expected to reduce transmission to patients, other HCP, household members, and persons in the community.
¶¶ Hospitals, as defined by the Joint Commission on Accreditation of Healthcare Organizations, do not include long-term–care facilities such as nursing homes, skilled-nursing facilities, or rehabilitation and convalescent care facilities. Ambulatory-care settings include all outpatient and walk-in facilities.

22. Health Care Personnel & PostExposure Prophylaxis
The 2005 Tdap statement provided guidance on the use of postexposure prophylaxis and vaccinated health care personnel.
Health Care Personnel & PostExposure Prophylaxis

23. Is PEP necessary? Vanderbilt pertussis exposure study
Objective:
Is symptom monitoring without PEP following pertussis exposure non-inferior to antibiotic PEP among Tdap-vaccinated HCP?
Results
116 exposures occurred among 94 different HCP
Pertussis infection did not occur in
40/44 (90.9%) exposed persons without PEP
41/42 (97.6%) exposed persons with PEP
Pre-defined non-inferiority criteria were not met
ACIP interpretation
There may be a benefit to PEP in vaccinated HCP
Low risk of pertussis suggests both strategies acceptable
Is postexposure prophylaxis necessary?
Based on the 2005 recommendations, there has been one study which tried to answer the question: Is symptom monitoring without post exposure prophylaxis following pertussis exposure non-inferior to antibiotic postexposure prophylaxis among Tdap-vaccinated health care personnel? During the study period, 116 exposures occurred among 94 different health care personnel. Pertussis infection did not occur in 90% of exposed health care personnel who did not receive postexposure prophylaxis , and in 98% of exposed health care personnel who did receive post exposure prophylaxis. Pre-defined non-inferiority criteria were not met which suggests there may be a benefit to postexposure prophylaxis in vaccinated health care personnel. This study did not assess whether vaccinated health care personnel will transmit pertussis.
ACIP interpretations were that post exposure prophylaxis may reduce infection; Ability of vaccinated health care personnel to transmit pertussis was not assessed; and the low risk of pertussis in both groups suggests both strategies may be acceptable. ACIP concluded this study does not rule out postexposure prophylaxis for vaccinated health care personnel.
Goins W, Edwards KM, Vnencak-Jones CL, Thayer, VS, Swift M, Schaffner W, Talbot T. A Comparison of Two Strategies to Prevent Pertussis in Vaccinated Healthcare Personnel Following Pertussis Exposure. Presented at SHEA 2010.

24. ACIP considerations for reducing risk of transmission of pertussis in healthcare facilities
Sub-optimal Tdap coverage
Adjunct to other pertussis prevention measures
Droplet precautions
Postexposure prophylaxis
Cautious interpretation of data
Language needs to allow flexibility in implementation
ACIP considered the following for reducing risk of transmission of pertussis in healthcare facilities. Tdap coverage in health care personnel is sub-optimal and the duration of protection afforded by Tdap is unknown. Also vaccinating HCP with Tdap is an adjunct to other pertussis prevention measures. The Vanderbilt study provides some data that both strategies are acceptable. Although data on the need for postexposure prophylaxis in Tdap-vaccinated health care personnel was not definitive, the ACIP felt that vaccine status does not change the approach to evaluating the need for postexposure prophylaxis. Different institutions have different approaches, and therefore language needs to allow flexibility in implementation of a postexposure recommendation.
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goal of the WG-to allow some flexibility in decision making re: PEP based on individual situation.

25. Approved ACIP language: Recommendation for PEP in HCP
Health-care facilities should maximize efforts to prevent transmission of Bordetella pertussis. Respiratory precautions should be taken to prevent unprotected exposure to pertussis.
Data on the need for postexposure antimicrobial prophylaxis in Tdap-vaccinated HCP are inconclusive. Some vaccinated HCP are still at risk for B. pertussis. Tdap may not preclude the need for postexposure antimicrobial prophylaxis.
Postexposure antimicrobial prophylaxis is recommend for all HCP who have unprotected exposure to pertussis and are likely to expose a patient at risk for severe pertussis (e.g., hospitalized neonates and pregnant women). Other HCP should either receive postexposure antimicrobial prophylaxis or be monitored daily for 21 days after pertussis exposure and treated at the onset of signs and symptoms of pertussis.
The following is the approved ACIP language:
Health-care facilities should maximize efforts to prevent transmission of Bordetella pertussis. Respiratory precautions should be taken to prevent unprotected exposure to pertussis.
Data on the need for postexposure prophylaxis in Tdap-vaccinated HCP are inconclusive. Some vaccinated HCP are still at risk for B. pertussis. Tdap may not preclude the need for postexposure prophylaxis.
Postexposure prophylaxis is recommend for all HCP who have unprotected exposure to pertussis and are likely to expose a patient at risk for severe pertussis (e.g., hospitalized neonates and pregnant women). Other HCP should either receive postexposure prophylaxis or be monitored for 21 days after pertussis exposure and treated at the onset of signs and symptoms of pertussis.
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In background: Treatment is most effective if initiated at the earliest signs of upper respiratory illness during this period of monitoring. Unvaccinated HCP who are being evaluated for an exposure to pertussis should also be offered Tdap.

26. Future considerations for Tdap
Maternal vaccination
Cocooning strategies
Revaccination with Tdap
Tdap licensure for ages 65 years and older
Future considerations for Tdap include:
Use of Tdap in pregnant women
Cocooning strategies
Revaccination with Tdap – currently Tdap is recommended only for a single dose across all age groups
Tdap licensure for ages 65 years and older – we know that one of the pharmaceutical companies has filed for expanded licensure of Tdap to be used in this older age group. If FDA grants licensure, the recommendation will be re-considered.

27. Acknowledgements ACIP Pertussis Vaccines Working Group Thomas Clark
Nancy Messonnier
Acknowledge the members of the Pertussis Vaccines Working Group for their work and dedication as well as my co-authors.

28. Thank You National Center for Immunization & Respiratory Diseases
Meningitis and Vaccine Preventable Diseases Branch/Division of Bacterial Diseases