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 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, 2004-2006 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3 mos 3 7 13 (16%) Total 27 39 16 82 2004 2005 2006 Total CDC, unpublished data, 2007

Pertussis Complications by Age Most complications occur in children <12 months of age, especially those <6 months. *Cases reported to CDC 1997-2000 (N=28,187)

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

Pertussis—United States, 1940-2006 Year

Pertussis—United States, 1980-2006 Year

Reported Pertussis by Age Group, 1990-2006

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.

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 FHA 23 25 5 8 PERT -- 8 3 2.5 FIM -- 5 *mcg per dose

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 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

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 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 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 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.

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 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* 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 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

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) Approved for persons 10-18 years of age Adacel (sanofi pasteur) 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.

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.

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

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 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

CDC Vaccines and Immunization Contact Information Telephone 800.CDC.INFO Email nipinfo@cdc.gov Website www.cdc.gov/vaccines