# Presentation: 136469

## Pertussis and Pertussis Vaccines

**Epidemiology and Prevention of Vaccine-Preventable Diseases**
**National Immunization Program**
**Centers for Disease Control and Prevention**

**Revised January 2007**

## 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**** **
**Paroxysmal****cough stage****	****	****1-6 weeks**** **
**Convalescence****	****Weeks to****	****	****	****	****	****months**

## 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*

_**Condition**_
**Pneumonia**
**Seizures****Encephalopathy**
**Hospitalization**
**Death**

_**Percent reported**_
**4.9**
**0.7**
**0.1**
**16**
**0.2**

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

## Pertussis Deaths in the United States, 2004-2005

**2004**
**2005**
**Total**

**CDC, unpublished data, 2006**

_**<3 mos**_
**24**
**32**
**56**
**(85%)**

_**>3 mos**_
**3**
**7**
**10**
**(15%)**

_**Total**_
**27**
**39**
**66**

**Age at onset**

## Pertussis Complications by Age

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

**Notes:**
Most complications occur in children <12 months of age, especially those <6 months.

## Pertussis Epidemiology

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

## Pertussis—United States, 1940-2005

**Year**

## Pertussis—United States, 1980-2005

**Year**

## Reported Pertussis by Age Group, 1990-2005

## Pertussis Incidence, 2004

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

**Notes:**
Most complications occur in children <12 months of age, especially those <6 months.

## 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 10-18 years (Boostrix)  and 11-64 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

_**Dose**_
**Primary 1**
**Primary 2**
**Primary 3**
**Primary 4**

_**Age**_
**2 months**
**4 months**
**6 months**
**15-18 months**

**Minimum**
_**Interval**_** **** **
**---**
**4 wks**
**4 wks**
**6 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**

**Notes:**
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. 

## 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

**General guidance, not an absolute requirement**
**Intended to reduce the frequency of local reactions**
**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 following any Hib vaccine***

***booster dose should follow prior dose by **_**>**_**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**

**Notes:**
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. 

## 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*

**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***

- Pediarix

***off-label recommendation**

**Notes:**
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. 

## 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 101****o****F ****	****	****   ****	****  3%-5%**
**   ****or higher**
**More severe adverse reactions ****not common**
**Local reactions more common following 4****th**** and 5****th**** 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

**Source: Infanrix package insert, 2003**

**Notes:**
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. 

## 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 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**

## 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)**
**Licensed May 2005**
**Single dose**
**Approved for persons 10-18 years of age**
**Adacel (sanofi pasteur)**
**Licensed June 2005**
**Single dose**
**Approved for persons 11-64 years of age**

## 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**

## 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.**

## 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)

**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)**

- Recommendations for Tdap Vaccination of Adults

***MMWR***** 2006;55(RR-17):1-37.**

## 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. **

## 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**

## 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

**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 Vaccine and Healthcare Personnel

## Tdap Adverse Reactions

**Local reactions****	****	****     21%-75%**
**   ****(pain, redness, swelling)**
**Temp of 100.4****o****F ****	****	****   ****	****  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-Barr****é**** 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 105****o****F (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 from
**www.dhs.ca.gov/ps/dcdc/izgroup/pdf/IMM-508.pdf**

## 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 **

## National Immunization ProgramContact Information

**Telephone****	****800.CDC.INFO**** **
**Email****	****	****	****nipinfo@cdc.gov**** **
**Website****	****	****www.cdc.gov/nip**