1. Adult Tdap Rationale and Recommended Use Katrina Kretsinger M.D., M.A. Lieutenant Commander, U.S. Public Health Service National Center for Immunization and Respiratory Diseases, CDC National Immunization Conference March 8, 2007

2. Pertussis and Adults Pertussis (whooping cough) – a poorly controlled vaccine-preventable disease Incidence increasing In 2005, 25,616 US cases reported (40 year high) Adults vulnerable to pertussis 27% reported cases among adults Pertussis immunity wanes 5 to 10 years after childhood DTaP* series First pertussis vaccines (Tdap) † for adolescents and adults licensed in 2005 *Diphtheria and tetanus toxoids and acellular pertussis vaccine † Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine

3. Presentation Outline: Tdap for Adults Epidemiology and clinical characteristics of adult pertussis Tdap product information Immunogenicity and Efficacy Safety Recommendations for adult Tdap use

4. Burden of Adult Pertussis Underreported among adults Often considered a childhood disease and not recognized by clinicians Difficult to diagnose Significant burden of illness Almost 8,000 cases of adult pertussis reported in 2005 in United States Estimate of true disease ~ 600,000 cases / year among adults aged 19-64 years Pertussis is costly Societal cost / adult pertussis case ~$773 Outbreaks burden public health system (controlled by contact tracing and prophylactic antimicrobials)

5. Reported Pertussis Cases – United States, 1922-2005* DTP 11-18 yrs > 18 yrs < 11 yrs *1950-2005, National Notifiable Diseases Surveillance System and 1922-1949, passive reports to the Public Health Service, courtesy of Kristin Brown Tdap DTaP

6. Clinical Pertussis Upper respiratory illness x 1-2 weeks, followed by cough illness Median duration of cough illness >2 months Antimicrobials do not modify the course of illness after cough established Will decrease infectivity of patients if given early Can result in repeated medical visits and time lost from work High risk groups for pertussis not well defined

7. Selected Clinical Characteristics and Complications Among Adults >19 years with Reported Pertussis *Sources: Lee GM et al. Clin Infect Dis 2004;39:1572-80; National Notifiable Diseases Surveillance System and Supplemental Reported Pertussis Surveillance System, 1996- 2004. Characteristic Frequency (% reported) * N=1,139 Paroxysmal cough 84-86 Cough duration >9 weeks 55 Difficulty breathing 86 Post-tussive vomiting 45-54 Whoop37-41 Weight Loss 33 Pneumonia (CXR confirmed) 2-5 Rib Fracture 4 Hospitalization3

8. Pertussis Transmission to Infants Infants <12 months of age greatest risk for death and complications from pertussis From 2000-2004 Accounted for 92 / 100 U.S. pertussis deaths Risk of death highest among youngest infants Over 60% infants with pertussis hospitalized Adults transmit to infants* Among 264 known source-cases 55% identified as mother, father or grandparent 51% were adults >19 years of age * 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):985-989.

9. Pertussis in Health-Care Settings Health-care personnel (HCP) at increased risk of pertussis exposure and infection HCP can transmit to vulnerable patients, including infants Pertussis outbreaks reported in pediatric and adult inpatient wards, maternity units and obstetric units Infection control activities are resource- intensive, disruptive and costly

10. Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines (Tdap) First U.S. pertussis vaccines for adolescents and adults licensed in 2005 Vaccines combined with tetanus, diphtheria No pertussis-only vaccines licensed Licensed for single use only (not for sequential use as booster) Two Tdap vaccines Only one (ADACEL ® ) licensed for adults None licensed for adults >65 years

11. Tdap Products Licensed in the United States BOOSTRIX ® (GlaxoSmithKline Biologicals) * ADACEL ® (sanofi pasteur) † Date of FDA licensure May 3, 2005 June 10, 2005 Age Indication (years) 10–18 11–64 Usage Active booster immunization for prevention of tetanus, diphtheria, and pertussis as a single dose † Product label available at http://www.vaccineplace.com/products/http://www.vaccineplace.com/products/ * Product label available at http://us.gsk.com/products/assets/us_boostrix.pdf http://us.gsk.com/products/assets/us_boostrix.pdf

12. Composition of Tdap Vaccine Pertussis Antigen and Diphtheria & Tetanus Toxoid Content sanofi pasteur DAPTACEL ® (DTaP) Tripedia ® (DTaP) DECAVAC ® (Td) ADACEL ® (Tdap) ug/dose Pertussis toxin (PT) 1023.4---2.5 Filamentous haemagglutinin (FHA) 523.4 --- ---5 Pertactin (PRN) 3--- --- ---3 Fimbriae 2&3 (FIM) 5------5 Lf/dose Tetanus toxoid 5555 Diphtheria toxoid 156.722

13. Tdap Immunogenicity for Pertussis No accepted serologic correlate of protection Efficacy for licensure inferred from immunogenicity data Serologic bridge Immune responses in adults after 1 dose ADACEL ® not inferior to immune responses in infants after 3 doses DAPTACEL ® during pertussis efficacy trials* Adult booster responses after Tdap acceptable *Vaccine efficacy 3 doses DAPTACEL® against pertussis, defined as ≥3 weeks paroxysmal cough with lab evidence (culture and/or serologic testing results) of pertussis or epidemiologic link to culture-confirmed household contact 85% (95% CI: 80%, 89%) (Gustafsson LH et al. NEJM 1996;334:349-355)

14. Tdap Immunogenicity for Tetanus and Diphtheria* Efficacy inferred from immungenicity data for licensure Accepted serologic correlate of protection (≥0.1 IU/ml) Adult immune responses after Tdap not inferior to Td (standard of care) Seroprotective rate Tetanus: 100% Diphtheria: 94% Booster responses acceptable * Product label available at http://www.vaccineplace.com/products/ http://www.vaccineplace.com/products/

15. Clinical Efficacy of Adult Acellular Pertussis Vaccine: US Adult Pertussis Trial (APERT)* Vaccine efficacy: 92% (95% CI 32-99%) *Ward et al. NEJM 2005; 353(15):1555-63. ‡ Pertussis defined as a cough illness lasting ≥ 5 days with laboratory evidence of pertussis by culture, PCR, and/or serologic testing results † Three component acellular pertussis vaccine (PT, FHA, PRN) without tetanus and diphtheria toxoids (manufactured by GlaxoSmithKline biologicals; same pertussis components used in BOOSTRIX ® )

16. ADACEL ® Safety Rates of Selected Solicited Adverse Events In Adults Aged 18─64 Within 15 Days After a Single Dose of Tdap or Td Source: Product label available at http://www.vaccineplace.com/products/ http://www.vaccineplace.com/products/

17. Objectives of Adult Pertussis Vaccination Policy Primary objective - Protect vaccinated adult against pertussis Secondary objective - Reduce the reservoir of pertussis in population Decrease exposure of persons at increased risk for complicated infection Reduce the cost and disruption of pertussis in health-care settings

18. Recommendations For Tdap Use Advisory Committee on Immunization Practices (ACIP) reviewed evidence for use of Tdap in 2005 and 2006 June 2005 – voted to recommend Tdap for routine adolescent use October 2005 – voted to recommend Tdap use for routine adult vaccination and for adults in close contact with infants February 2006 – voted to recommend Tdap for health-care personnel June 2006 – voted on recommendations to guide use of Td and Tdap among pregnant women

19. Routine Adult Tdap Use Routine recommendations apply to adults who Are aged 19-64 years Have not previously received a dose of Tdap Licensed for single use only After receipt of Tdap, subsequent doses of boosters should be with Td according to previously published guidance ADACEL ® only Tdap licensed for adults

20. Routine Adult Tdap Use General Use Adults should receive a single dose of Tdap to replace a single dose of Td if they received their last dose of Td >10 years earlier. If Tdap and another vaccine is indicated, they should be administered during the same visit (i.e., simultaneous vaccination).

21. Interval Between Td and Tdap Intervals <10 years since the last Td may be used to protect against pertussis. Particularly in settings wih increased risk for pertussis, 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 intervals as short as ~2 years is supported by data from a Canadian study*; shorter intervals may be used. * Canadian study of ~7,000 children/adolescents. Halperin et al. Pediatr Infect Dis J. 2006;25(3):195-200.

22. Routine Adult Tdap Use Adults in Contact With Infants Adults who have or who anticipate having close contact with an infant aged <12 months should receive a single dose of Tdap An interval as short as 2 years from last Td suggested Ideally at least 2 weeks before contact with the infant. Infants should receive DTaP on schedule When possible, women should receive Tdap before conception. Pregnant women should receive Tdap in the immediate post-partum period. Pregnant women should receive Tdap in the immediate post-partum period.

23. Routine Adult Tdap Use Health-care Personnel Recommendations supported by HICPAC Health-care personnel (HCP) in hospitals* or ambulatory care settings who have direct patient contact should receive Tdap as soon as feasible at an interval as short as 2 years from the last Td. Priority to HCP in contact with infants Hospitals and ambulatory care facilities should provide Tdap for HCP and use approaches that maximize vaccination rates. *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, rehabilitation and convalescent facilities. Ambulatory care settings include all outpatient and walk-in facilities.

24. Routine Adolescent Tdap Use Adolescents aged 11–18 years should receive Tdap instead of Td if they have not received Td or Tdap. The preferred age for Tdap vaccination is 11–12 years. Adolescents aged 11–18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap. A 5 year interval between Td and Tdap is encouraged to reduce risk for local and systemic reactions

25. Selected Contraindications and Precautions for Tdap and DTaP Event DTaP (infant/child) Tdap (adolescent/adult) Serious allergic reaction to vaccine component ContraindicationContraindication Encephalopathy within 7 days of DTP/DTaP ContraindicationContraindication Neurologic conditions Progressive Progressive Unstable UnstableContraindication Precaution (adolescent) Precaution (adult) Guillain-Barr é syndrome ≤6 weeks after tetanus toxoid- containing vaccine PrecautionPrecaution Certain adverse events after DTP/DTaP* PrecautionNone * Temperature ≥105 ◦ F (≥40.5 ◦ C) within 48 hours after DTP/DTaP; collapse or shock-like state (hypotonic hyporesponsive episode) within 48 hours; persistent crying lasting ≥3 hours, within 48 hours; convulsions with or without fever, within 3 days

26. Selected Special Situations Situation Recommendations for adolescents who have not received Tdap Pertussis outbreak Tdap can be used at shorter intervals since most recent Td History of Pertussis Use Tdap Wound management Tdap preferred to Td if tetanus prophylaxis indicated; use standard algorithm Incomplete schedule Use Tdap as one of the doses for catch-up; use Td for other doses

27. Inadvertent Administration of Tdap (BOOSTRIX ® ) or Pediatric DTaP If BOOSTRIX ® or pediatric DTaP is administered to an adult aged >19 years, this dose should count as the Tdap dose and the patient should not receive an additional dose of Tdap (ADACEL®). Source: www.vaccineshoppe.com www.vaccineshoppe.com

28. Vaccination During Pregnancy Provisional recommendations Routine post-partum Tdap: Pregnant women who have not received a dose of Tdap (including breastfeeding) should receive Tdap after delivery, before discharge from the hospital. Tetanus, diphtheria and neonatal tetanus protection: Pregnant women for whom 10 years or more have elapsed since last Td booster may defer Td and use Tdap post-partum if tetanus protection is likely. Td recommended if tetanus and diphtheria protection required during pregnancy Pregnancy not contraindication for Tdap

29. Adults Aged >65 Years Tdap is not licensed for use among 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 >65 years of age should receive a dose of Td every 10 years for protection against tetanus and diphtheria, and as indicated for wound management

30. Where to Find Tdap Recommendations CDC. Preventing Tetanus, Diphtheria, and Pertussis Among Adolescents: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine: Recommendations of ACIP. MMWR. 2006 (RR-3):55:1-43. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5503a1.htm CDC. Preventing Tetanus, Diphtheria, and Pertussis Among Adults: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine: Recommendations of ACIP and Recommendation of ADIP, supported bythe Heatlhcare Infection Control Practices Advisory Committee (HICPAC), for Use of Tdap among Health-Care Personnel. MMWR. 2006 (RR-17): 55:1-37. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm CDC. Prevention of Tetanus, Diphtheria and Pertussis Among Pregnant Women: Provisional ACIP Recommendations for the Use of Tdap Vaccine. http://www.cdc.gov/nip/recs/provisional_recs/tdap-preg.pdf

31. Acknowledgements Karen Broder Kristin Brown Amanda Cohn Margarete Cortese John Iskander Kashif Iqbal Pat Joyce Grace Lee Nancy Rosenstein Messonnier Christina Mijalski Stacey Martin John Moran Trudy Murphy Ismael Ortega-Sanchez Manisha Patel Larry Pickering Pam Srivastava Ben Schwartz Barbara Slade Tej Tiwari

32. Thank you

33. Backup Slides

34. Tetanus prophylaxis in routine wound management Clean, minor wound All other wounds* Tetanus dosesTdap or Td † TIGTdap or Td † TIG Unknown or <3YesNoYes ≥3No § NoNo ¶ No *Such as, but not limited to, wounds contaminated with dirt, feces, soil, and saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns and frostbite. † Tdap is preferred to Td for adults who have never received Tdap. Td is preferred to TT for adults who received Tdap previously or when Tdap is not available. (If TT and TIG are both used, Tetanus Toxoid Adsorbed rather than Tetanus Toxoid for Booster Use Only [fluid vaccine] should be used). §Yes, if >10 years since the last tetanus toxoid-containing vaccine dose. ¶ Yes, if >5 years since the last tetanus toxoid-containing vaccine dose (see text for discussion of Arthus reactions).