Adult Tdap Rationale and Recommended Use

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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 Current Issues in Immunization
NetConference January 18, 2007
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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

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Presentation OutlineTdap for Adults

• Epidemiology and clinical characteristics of
  adult pertussis
• Tdap product information
• Immunogenicity and Efficacy
• Safety
• Recommendations for adult Tdap use

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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)

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• Reported Pertussis Cases
• United States, 1922-2005

gt 18 yrs
11-18 yrs
lt 11 yrs
1950-2005, National Notifiable Diseases
Surveillance System and 1922-1949, passive
reports to the Public Health Service, courtesy of
Kristin Brown
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Clinical Pertussis

• Upper respiratory illness x 1-2 weeks, followed
  by cough illness
• Median duration of cough illness gt2 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

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Selected Clinical Characteristics and
Complications Among Adults gt19 years with
Reported Pertussis
Sources Lee GM et al. Clin Infect Dis
2004391572-80 National Notifiable Diseases
Surveillance System and Supplemental Reported
Pertussis Surveillance System, 1996-2004.
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Pertussis Transmission to Infants

• Infants lt12 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 gt19 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.
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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

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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 gt65 years

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Tdap Products Licensed in the United States

• Product label available at http//us.gsk.com/prod
  ucts/assets/us_boostrix.pdf

Product label available at http//www.vaccinepla
ce.com/products/
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Composition of Tdap Vaccine Pertussis Antigen
and Diphtheria Tetanus Toxoid Content
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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
1996334349-355)
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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.vaccineplac
e.com/products/
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Clinical Efficacy of Adult Acellular Pertussis
Vaccine US Adult Pertussis Trial (APERT)

• Vaccine efficacy 92 (95 CI 32-99)

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• ADACEL SafetyRates 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/
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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

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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

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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

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Routine Adult Tdap UseGeneral Use

• Adults should receive a single dose of Tdap to
  replace a single dose of Td if they received
  their last dose of Td gt10 years earlier.
• If Tdap and another vaccine is indicated, they
  should be administered during the same visit
  (i.e., simultaneous vaccination).

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Interval Between Td and Tdap

• Intervals lt10 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 lt10 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.
200625(3)195-200.
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Routine Adult Tdap Use Adults in Contact With
Infants

• Adults who have or who anticipate having close
  contact with an infant aged lt12 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.

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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.
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Routine Adolescent Tdap Use

• Adolescents aged 1118 years should receive Tdap
  instead of Td if they have not received Td or
  Tdap. The preferred age for Tdap vaccination is
  1112 years.
• Adolescents aged 1118 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

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Selected Contraindications and Precautions for
Tdap and DTaP

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
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Selected Special Situations

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Inadvertent Administration of Tdap (BOOSTRIX)
or Pediatric DTaP
Source www.vaccineshoppe.com

• If BOOSTRIX or pediatric DTaP is administered to
  an adult aged gt19 years, this dose should count
  as the Tdap dose and the patient should not
  receive an additional dose of Tdap (ADACEL).

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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

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Adults Aged gt65 Years

• Tdap is not licensed for use among adults aged
  gt65 years.  
• The safety and immunogenicity of Tdap among
  adults aged gt65 years were not studied during
  U.S. pre-licensure trials.
• Adults gt65 years of age should receive a dose of
  Td every 10 years for protection against tetanus
  and diphtheria, and as indicated for wound
  management

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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)551-43.
  
• 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)
  551-37.
• http//www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a
  1.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

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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
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Thank you
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Backup Slides
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Tetanus prophylaxis in routine wound management
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 gt10 years since the last tetanus
toxoid-containing vaccine dose. Yes, if gt5
years since the last tetanus toxoid-containing
vaccine dose (see text for discussion of Arthus
reactions).