1. Pertussis and Pertussis Vaccines
Epidemiology and Prevention of Vaccine-Preventable Diseases
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
Revised March 2008

2. Pertussis
Highly contagious respiratory infection caused by Bordetella pertussis
Outbreaks first described in 16th century
Bordetella pertussis isolated in 1906
Estimated 294,000 deaths worldwide in 2002

3. Bordetella pertussis Fastidious gram-negative bacteria
Antigenic and biologically active components:
pertussis toxin (PT)
filamentous hemagglutinin (FHA)
agglutinogens
adenylate cyclase
pertactin
tracheal cytotoxin

4. Pertussis Pathogenesis
Primarily a toxin-mediated disease
Bacteria attach to cilia of respiratory epithelial cells
Inflammation occurs which interferes with clearance of pulmonary secretions
Pertussis antigens allow evasion of host defenses (lymphocytosis promoted but impaired chemotaxis)

5. Pertussis Clinical Features
Incubation period 5-10 days (range 4-21 days)
Insidious onset, similar to minor upper respiratory infection with nonspecific cough
Fever usually minimal throughout course of illness

6. Pertussis Clinical Features
Catarrhal stage 1-2 weeks
Paroxysmal cough stage 1-6 weeks
Convalescence Weeks to months

7. Pertussis Among Adolescents and Adults
Disease often milder than in infants and children
Infection may be asymptomatic, or may present as classic pertussis
Persons with mild disease may transmit the infection
Older persons often source of infection for children

8. Pertussis Complications*
Condition
Pneumonia
Seizures Encephalopathy
Hospitalization
Death
Percent reported
4.9
0.7
0.1 16
0.2
*Cases reported to CDC (N=28,998)

9. Pertussis Deaths in the United States, 2004-2006
Age at onset
<3 mos 24 32 13 69
(84%)
>3 mos 3 7 13
(16%)
Total 27 39 16 82
2004
2005
2006
Total
CDC, unpublished data, 2007

10. Pertussis Complications by Age
Most complications occur in children <12 months of age, especially those <6 months.
*Cases reported to CDC (N=28,187)

11. Pertussis Epidemiology
Reservoir Human Adolescents and adults
Transmission Respiratory droplets
Communicability Maximum in catarrhal stage Secondary attack rate up to 80%

12. Pertussis—United States, 1940-2006
Year

13. Pertussis—United States, 1980-2006
Year

14. Reported Pertussis by Age Group, 1990-2006

15. Pertussis Incidence, 2004 N=25,172. MMWR 2004;53(53):30.
Most complications occur in children <12 months of age, especially those <6 months.
N=25,172. MMWR 2004;53(53):30.

16. Whole-Cell Pertussis Vaccine
Developed in mid-1930s and combined as DTP in mid-1940s
70%-90% efficacy after 3 doses
Protection for 5-10 years
Local adverse reactions common

17. Pertussis-containing Vaccines
DTaP (pediatric)
approved for children 6 weeks through 6 years (to age 7 years)
contains same amount of diphtheria and tetanus toxoid as pediatric DT
Tdap (adolescent and adult)
approved for persons 10 through 18 years (Boostrix) and 11 through 64 years (Adacel)
contains lesser amount of diphtheria toxoid and acellular pertussis antigen than DTaP

18. Composition* of Acellular Pertussis Vaccines
Product Tripedia
Infanrix
Daptacel
Boostrix
Adacel PT 23 25 10 8
2.5
FHA 23 25 5 8
PERT -- 8 3
2.5
FIM -- 5
*mcg per dose

19. DTaP Clinical Trials Product Daptacel Tripedia Infanrix Location
Sweden
Germany
Italy
VE (95% CI)
85% (80-89)
80% (59-90)
84% (76-89)

20. Routine DTaP Primary Vaccination Schedule
Minimum
Interval
---
4 wks
6 mos
Dose
Primary 1
Primary 2
Primary 3
Primary 4
Age
2 months
4 months
6 months
15-18 months

21. DTaP Fourth Dose Recommended at 15-18 months*
May be given at 12 months of age if:
child is 12 months of age, and
6 months since DTaP3, and
unlikely to return at months
*15-20 months for Daptacel

22. School Entry (Fifth) Dose
Fifth dose recommended when 4th dose given before age 4 years
Infanrix and Tripedia licensed for 5th dose after DTaP series
The age and timing of the dose at school entry can also be confusing.
A fifth dose at 4 to 6 years of age is recommended when the fourth dose is given before age four years. Both Tripedia and Infanrix are now licensed for the fifth dose after a DTAP series.
In November 2000, ACIP published supplementary recommendations on the use of DTAP that provided guidance in this situation. In ACIP’s opinion, it’s preferable to use DTAP for an off label use rather than miss the opportunity to administer the fifth dose of the series.

23. Interchangeability of Different Brands of DTaP Vaccine
Whenever feasible, the same DTaP vaccine should be used for all doses of the series
Limited data suggest that “mix and match” DTaP schedules do not adversely affect safety and immunogenicity
If vaccine used for earlier doses is not known or not available, any brand may be used to complete the series

24. Pediatric DT Schedule
First dose of DT or DTaP at younger than one year of age
Total of 4 doses
First dose of DT or DTaP at one year of age or older
Total of 3 doses
Fourth or fifth dose at school entry not needed if pertussis vaccine is not being administered

25. The “6 before 7” Rule
ACIP recommends no more than 6 doses of DT-containing vaccine before the 7th birthday
General guidance, not an absolute requirement
Intended to reduce the frequency of local reactions
If the decision is made to administer more than 6 doses of DT-containing vaccine parents should be aware of an increased risk of local reactions and agree that the benefit outweighs the risk (local reaction)
MMWR 1991;40(No. RR-10);1-28

26. TriHIBit DTaP-Hib combination
Licensed only for 4th dose of DTaP and Hib series
Do not use for primary immunization at 2, 4, or 6 months of age
May be used as the final (booster) dose of the Hib series at 12 months of age or older following any Hib vaccine*
*booster dose should follow prior dose by at least 2 months

27. Pediarix DTaP – Hep B – IPV combination Minimum age 6 weeks
Approved for 3 doses at 2, 4 and 6 months
Not approved for booster doses
Licensed for children 6 weeks to 7 years of age
In December 2002, the US Food and Drug Administration approved a new combination vaccine- Pediarix- which is manufactured by Glaxo Smith Kline. This vaccine contains DTaP, inactivated polio and hepatitis B vaccines. The DTaP component is Infanrix, and the hepatitis B component is Engerix-B, which were previously licensed in the U.S.
Pediarix is approved for the first three doses of the DTAP and IPV series, which are usually given at about 2, 4, and 6 months of age. However, Pediarix is approved for use through 6 years of age.
The minimum age for the first dose of Pediarix is 6 weeks. So it can’t be used for the birth dose of the hepatitis B series.

28. Pediarix
May be used interchangeably with other pertussis-containing vaccines if necessary
Can be given at 2, 4, and 6 months in infants who received a birth dose of hepatitis B vaccine (total of 4 doses)
May be used in infants whose mothers are HBsAg positive or status unknown*
Interchangeable
Can be used after a birth dose of heaptitis B – total of 4 doses O.K.
Pediarix may be used in infants born to women who are hepatitis B surface antigen positive or whose hepatitis B status is unknown.
Like COMVAX, Pediarix is not approved for this use. But at it’s February 2003 meeting, ACIP voted to allow the use of Pediarix to complete the hepatitis B series in these infants. But remember that the minimum age for Pediarix is 6 weeks, so it must NOT be used for the birth or one month dose of the hepatitis B series.
Another important fact to remember about Pediarix is that the minimum intervals between doses are dictated by the single antigen with the longest minimum intervals. Therefore, Pediarix minimum intervals are determined by the hepatitis B component.
As for hepatitis B vaccine, the minimum interval between the first two doses of Pediarix is 4 weeks. The third dose must be administered at least 8 weeks after the second dose, and should follow the first dose by at least 16 weeks. The third dose should not be given before 6 months of age to be counted as a valid third dose of hepatitis B vaccine.
*off-label ACIP recommendation

29. Pertussis Vaccine Use in Children with Underlying Neurologic Disorders
Underlying Condition
Prior seizure
Suspected neurologic disorder
Neurologic event between doses
Stable/resolved neurologic condition
Recommendation
Delay and assess*
Vaccinate
*vaccinate after treatment initiated and condition stabilized

30. Pertussis Vaccination of Children Who Have Recovered From Pertussis
If documented disease, do not need additional doses of pediatric pertussis vaccine*
Satisfactory documentation of disease:
recovery of B. pertussis on culture, or
typical symptoms and clinical course when epidemiologically linked to a culture-proven case
*Tdap is recommended when the child is age eligible.

31. DTaP Adverse Reactions
Local reactions %-40%
(pain, redness, swelling)
Temp of 101oF %-5%
or higher
More severe adverse reactions not common
Local reactions more common following 4th and 5th doses

32. Adverse Reactions Following the 4th and 5th DTaP Dose
Local adverse reactions and fever increased with 4th and 5th doses of DTaP
Reports of swelling of entire limb
Extensive swelling after 4th dose NOT a contraindication to 5th dose

33. Adverse Reactions Reported Following 1st and 4th Doses of Infanrix
This graph shows the percentage of children reported with swelling, pain or fever of 101o Fahrenheit or higher following administration of Infanrix and Tripedia.
The red bar represents reactions following the first dose of Infanrix and the yellow bar is reactions after the 4th dose of Infanrix.
The green bar is reactions after the first dose of Tripedia and the pink bar is reactions after the 4th dose of Tripedia.
So red and green bars are 1st doses.
Yellow and pink bars are 4th doses. You can see the substantial increase in local reactions and fever after the 4th doses.
Source: Infanrix package insert, 2003

34. DTaP Contraindications
Severe allergic reaction to vaccine component or following a prior dose
Encephalopathy not due to another identifiable cause occurring within 7 days after vaccination

35. DTaP Precautions* Moderate or severe acute illness
Temperature >105°F (40.5°C) or higher within 48 hours with no other identifiable cause
Collapse or shock-like state (hypotonic hyporesponsive episode) within 48 hours
Persistent, inconsolable crying lasting >3 hours, occurring within 48 hours
Convulsions with or without fever occurring within 3 days
*may consider use in outbreaks

36. Pertussis Among Adolescents and Adults
Prolonged cough (3 months or longer)
Post-tussive vomiting
Multiple medical visits and extensive medical evaluations
Complications
Hospitalization
Medical costs
Missed school and work
Impact on public health system

37. Adolescent and Adult Pertussis Vaccination
Primary objective
protect the vaccinated adolescent or adult
Secondary objective
reduce reservoir of B. pertussis
potentially reduce incidence of pertussis in other age groups and settings

38. Tdap Vaccines Boostrix (GlaxoSmithKline)
Approved for persons years of age
Adacel (sanofi pasteur)
Approved for persons years of age

39. General Principles for Use of Tdap and Td
No brand preference
Tdap preferred to Td to provide protection against pertussis
Approved only for a single booster dose in persons who have received a full series of pediatric DTaP or DTP

40. Recommendations for Tdap Vaccination of Adolescents
Adolescents years of age should receive a single dose of Tdap instead of Td*
Adolescents years who have not received Tdap should receive a single dose of Tdap as their catch-up booster instead of Td*
*if the person has completed the recommended childhood DTaP/DTP vaccination series, and has not yet received a Td booster
MMWR 2006;55(RR-3):1-43.

41. Tdap Vaccination of Adults 19 Through 64 Years of Age
Single dose of Adacel to replace a single dose of Td
May be given at an interval less than 10 years since receipt of last tetanus toxoid-containing vaccine
Special emphasis on adults with close contact with infants (e.g., childcare and healthcare personnel, and parents)
MMWR 2006;55(RR-17):1-37.

42. Tdap For Persons Without A History of DTP or DTaP
All adolescents and adults should have documentation of having received a series of DTaP, DTP, DT, or Td
Persons without documentation should receive a series of 3 vaccinations
Preferred schedule:
Single dose of Tdap*
Td at least 4 weeks after the Tdap dose
Second dose of Td at least 6 months after the Td dose
*off-label recommendation. MMWR 2006;55(RR-3):1-43.

43. Tdap Use in Older Children
Tdap minimum ages
10 years for Boostrix
11 years for Adacel
Tdap not approved for children 7-9 years of age
Off-label use of Tdap in this age group NOT recommended

44. Minimum Interval Between Td and Tdap
ACIP did not define an absolute minimum interval between Td and Tdap
Interval between Td and Tdap may be shorter if protection from pertussis needed
Decision to administer Tdap based on whether the benefit of pertussis immunity outweighs the risk of a local adverse reaction
MMWR 2006;55(RR-3):1-43.

45. Tdap and MCV
MCV is recommended for all children at the year visit
Administer Tdap and MCV during the same visit, if both vaccines are indicated and available
If simultaneous administration of Tdap and MCV is not possible, these vaccines can be administered at any time before or after each other

46. Use of Tdap Among Pregnant Women*
Td is generally preferred during pregnancy
Women who have not received Tdap should receive a dose in the immediate post-partum period
Any woman who might become pregnant is encouraged to receive a single dose of Tdap
Clinician may choose to administer Tdap to a pregnant woman in certain circumstances (such as during a community pertussis outbreak)
Pregnancy is not a contraindication for Tdap
*Provisional recommendations approved by ACIP June 28, 2006

47. Tdap Vaccine and Healthcare Personnel
Healthcare personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap (Adacel only) as soon as feasible*
Priority should be given to vaccination of healthcare personnel who have direct contact with infants 12 months of age and younger
An interval as short as 2 years (or less) from the last dose of Td is recommended for the Tdap dose
*if they have not previously received Tdap.
MMWR 2006;55(RR-17):1-37.

48. Tdap Adverse Reactions
Local reactions %-75%
(pain, redness, swelling)
Temp of 100.4oF %-5%
or higher
Adverse reactions occur at approximately the same rate as Td alone (without acellular pertussis vaccine)

49. Tdap Contraindications
Severe allergic reaction to vaccine component or following a prior dose
Encephalopathy not due to another identifiable cause occurring within 7 days after vaccination with a pertussis-containing vaccine

50. Tdap Precautions
History of a severe local reaction (Arthus reaction) following a prior dose of a tetanus and/or diphtheria toxoid-containing vaccine
Progressive neurologic disorder until the condition has stabilized
History of Guillain-Barré syndrome within 6 weeks after a prior dose of tetanus toxoid-containing vaccine
Moderate or severe acute illness

51. Conditions NOT Precautions for Tdap
Following a dose of DTaP/DTP:
temperature 105oF (40.5oC) or higher
collapse or shock-like state
persistent crying lasting 3 hours or longer
convulsions with or without fever
history of an extensive limb swelling reaction
Stable neurologic disorder
Pregnancy
Breastfeeding
Immunosuppression including
HIV infection
Concurrent minor illness
Antimicrobial use

52. Resource to Help Reduce DTaP/Tdap Administration Errors
“Check Your Vials” poster showing images of DTaP/Tdap/Td vials and packaging
Developed by the California Immunization Branch
Free download from

53. Pertussis-Containing Vaccines Storage and Handling
Stored at 35°–46°F (2°–8°C) at all times
Must never be frozen
Vaccine exposed to freezing temperature must not be administered and should be discarded
Do not be used after the expiration date printed on the box or label

54. CDC Vaccines and Immunization Contact Information
Telephone CDC.INFO
Website