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

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

Bordetella pertussis

• Fastidious gram-negative bacteria

• Antigenic and biologically active components:

– pertussis toxin (PT)

– filamentous hemagglutinin (FHA)

– agglutinogens

– adenylate cyclase

– pertactin

– tracheal cytotoxin

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)

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

Pertussis Clinical Features

• Catarrhal stage 1-2 weeks

• Paroxysmalcough stage 1-6 weeks

• Convalescence Weeks tomonths

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

Pertussis Complications*

ConditionPneumoniaSeizuresEncephalopathyHospitalizationDeath

Percent reported4.90.70.1160.2

*Cases reported to CDC 2001-2003 (N=28,998)

Pertussis Deaths in the United States, 2004-2006

2004

2005

2006

Total

CDC, unpublished data, 2007

<3 mos

24

32

13

69

(84%)

>3 mos

3

7

3

13

(16%)

Total

27

39

16

82

Age at onset

Pertussis Complications by Age

0

10

20

30

40

50

60

70

<6 m 6-11 m 1-4 y 5-9 y 10-19 y 20+ y

Age group

Per

cen

t

Pneumonia Hospitalization

*Cases reported to CDC 1997-2000 (N=28,187)

Pertussis Epidemiology

• Reservoir HumanAdolescents and adults

• Transmission Respiratory droplets

• Communicability Maximum in catarrhal stageSecondary attack rateup to 80%

0

50000

100000

150000

200000

250000

1940 1950 1960 1970 1980 1990 2000

Cas

esPertussis—United States, 1940-2006

Year

0

5000

10000

15000

20000

25000

30000

1980 1985 1990 1995 2000 2005

Ca

se

sPertussis—United States, 1980-2006

Year

Reported Pertussis by Age Group, 1990-2006

0

5000

10000

15000

20000

25000

30000

1990 1993 1996 1999 2002 2005

Year

Cas

es

<11 11-18 >18

Pertussis Incidence, 2004

0

10

20

30

40

50

60

70

80

90

<1 1-4 5-14 15-24 >25

Age group (years)

Rat

e p

er 1

00,0

00 p

op

ula

tio

n

N=25,172. MMWR 2004;53(53):30.

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

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

Composition* of Acellular Pertussis Vaccines

Product

Tripedia

Infanrix

Daptacel

Boostrix

Adacel

PT

23

25

10

8

2.5

PERT

--

8

3

2.5

3

FHA

23

25

5

8

5

*mcg per dose

FIM

--

--

5

--

5

DTaP Clinical Trials

Product

Daptacel

Tripedia

Infanrix

Location

Sweden

Germany

Italy

VE (95% CI)

85% (80-89)

80% (59-90)

84% (76-89)

Routine DTaP Primary Vaccination Schedule

DosePrimary 1Primary 2Primary 3Primary 4

Age2 months4 months6 months

15-18 months

MinimumInterval

---4 wks4 wks6 mos

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 15-18 months

*15-20 months for Daptacel

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

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

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

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

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

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

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*

*off-label ACIP recommendation www.cdc.gov/vaccines/programs/vfc/downloads/resolutions/1003hepb.pdf

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*

Delay and assess*

Delay and assess*

Vaccinate

*vaccinate after treatment initiated and condition stabilized

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.

DTaP Adverse Reactions

• Local reactions 20%-40% (pain, redness, swelling)

• Temp of 101oF 3%-5% or higher

• More severe adverse reactions not common

• Local reactions more common following 4th and 5th doses

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

Adverse Reactions Reported Following 1st and 4th Doses of Infanrix

42

6

35

26 26

0

5

10

15

20

25

30

35

40

Swelling Pain Temp >101.4F

Symptom or sign

Per

cen

t

Infanrix1 Infanrix4

Source: Infanrix package insert, 2003

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

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

Pertussis Among Adolescentsand 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

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

Tdap Vaccines

• Boostrix (GlaxoSmithKline)

–Approved for persons 10-18 years of age

• Adacel (sanofi pasteur)

–Approved for persons 11-64 years of age

General Principles for Useof 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

Recommendations for Tdap Vaccination of Adolescents

• Adolescents 11-12 years of age should receive a single dose of Tdap instead of Td*

• Adolescents 13-18 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.

Tdap Vaccination of Adults19 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.

Tdap For Persons Without AHistory 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.

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

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.

Tdap and MCV

• MCV is recommended for all children at the 11-12-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

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

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.

Tdap Adverse Reactions

• Local reactions 21%-75% (pain, redness, swelling)

• Temp of 100.4oF 3%-5% or higher

• Adverse reactions occur at approximately the same rate as Td alone (without acellular pertussis vaccine)

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

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

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

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 fromwww.dhs.ca.gov/ps/dcdc/izgroup/pdf/IMM-508.pdf

Pertussis-Containing VaccinesStorage 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

CDC Vaccines and ImmunizationContact Information

• Telephone 800.CDC.INFO

• Email nipinfo@cdc.gov

• Website www.cdc.gov/vaccines