Diphtheria, Tetanus, and Pertussis (Whooping Cough) Vaccination: Information for Health Care Providers

Tetanus and diphtheria (Td) only vaccines

There are two Td vaccines used in the United States: TENIVAC® and TDVAX®.

Each 0.5-mL dose of Td (MassBiologics) contains the following active ingredients: 2 Lf of tetanus toxoid and 2 Lf of diphtheria toxoid. Each 0.5-mL dose also contains aluminum adjuvant (not more than 0.53 mg aluminum by assay), < 100 µg (0.02%) of residual formaldehyde, and a trace amount of thimerosal (< 0.3 µg mercury/dose) (not as a preservative) from the manufacturing process.

Each 0.5-mL dose of TENIVAC® (Sanofi Pasteur) contains the following active ingredients: 5 Lf of tetanus toxoid and 2 Lf of diphtheria toxoid. Other ingredients per 0.5-mL dose include 1.5 mg of aluminum phosphate (0.33 mg of aluminum) as the adjuvant and ≤5.0 µg of residual formaldehyde.

Diphtheria, tetanus, and pertussis (DTaP) vaccines

There are 7 pediatric DTaP vaccines licensed and currently used in the United States: Daptacel®, Infanrix®, Kinrix®, Pediarix®, Pentacel®, Quadracel®, and Vaxelis™.

Each 0.5-mL dose of DAPTACEL® (Sanofi Pasteur) contains 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, and acellular pertussis antigens [10 µg detoxified pertussis toxin (PT), 5 µg filamentous hemagglutinin (FHA), 3 µg pertactin, and 5 µg fimbriae types 2 and 3 (FIM)]. Other ingredients per 0.5-mL dose include 1.5 mg aluminum phosphate (0.33 mg of aluminum) as the adjuvant, ≤5 µg residual formaldehyde, <50 nanogram (ng) residual glutaraldehyde and 3.3 mg [0.6% volume per volume (v/v)] 2-phenoxyethanol (not as a preservative).

Each 0.5-mL dose of Infanrix® (GlaxoSmithKline) contains 25 Lf of diphtheria toxoid, 10 Lf of tetanus toxoid, 25 µg of inactivated PT, 25 µg of FHA, and 8 µg of pertactin (69 kiloDalton outer membrane protein). Each 0.5-mL dose contains aluminum hydroxide as adjuvant (not more than 0.625 mg aluminum by assay) and 4.5 mg of sodium chloride. Each dose also contains ≤100 µg of residual formaldehyde and ≤100 µg of polysorbate 80 (Tween 80).

Each 0.5-mL dose of Kinrix® (GlaxoSmithKline) includes the same diphtheria, tetanus, and pertussis components listed in Infanrix® above, and includes 40 D-antigen Units (DU) of Type 1 poliovirus (Mahoney), 8 DU of Type 2 poliovirus (MEF-1), and 32 DU of Type 3 poliovirus (Saukett). Each 0.5-mL dose contains aluminum hydroxide as adjuvant (not more than 0.6 mg aluminum by assay) and 4.5 mg of sodium chloride. Each dose also contains ≤100 µg of residual formaldehyde and ≤100 µg of polysorbate 80 (Tween 80). The manufacturing process of the poliovirus vaccine uses neomycin sulfate and polymyxin B. Those ingredients may be present in the final vaccine at ≤0.05 ng neomycin and ≤0.01 ng polymyxin B per dose.

Each 0.5-mL dose of Pediarix® (GlaxoSmithKline) includes the same diphtheria, tetanus, and pertussis components listed in Infanrix® above, the poliovirus components listed in Kinrix® above, and 10 µg of hepatitis B virus surface antigen (HBsAg). Each 0.5-mL dose contains aluminum salts as adjuvant (not more than 0.85 mg aluminum by assay) and 4.5 mg of sodium chloride. Each dose also contains ≤100 µg of residual formaldehyde and ≤100 µg of polysorbate 80 (Tween 80). The manufacturing process of the poliovirus vaccine uses neomycin sulfate and polymyxin B. Those ingredients may be present in the final vaccine at ≤0.05 ng neomycin and ≤0.01 ng polymyxin B per dose. The procedures used to manufacture the HBsAg antigen result in a product that contains ≤5% yeast protein.

Each 0.5-mL dose of Pentacel® (Sanofi Pasteur) contains 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens (20 µg detoxified PT, 20 µg FHA, 3 µg pertactin, 5 µg FIM), inactivated polioviruses [40 DU Type 1 (Mahoney), 8 DU Type 2 (MEF-1), 32 DU Type 3 (Saukett)], and 10 µg polyribosyl-ribitol-phosphate (PRP) of H. influenzae type b covalently bound to 24 µg of tetanus toxoid (PRP-T). Other ingredients per 0.5-mL dose include 1.5 mg aluminum phosphate (0.33 mg aluminum) as the adjuvant, polysorbate 80 (approximately 10 parts per million by calculation), 42.5 mg sucrose, ≤5 µg residual formaldehyde, <50 ng residual glutaraldehyde, ≤50 ng residual bovine serum albumin, 3.3 mg (0.6% v/v) 2-phenoxyethanol (not as a preservative), <4 picogram (pg) of neomycin, and <4 pg polymyxin B sulfate.

Each 0.5-mL dose of Quadracel® (Sanofi Pasteur) contains 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens (20 µg detoxified PT, 20 µg FHA, 3 µg pertactin, 5 µg FIM), and inactivated polioviruses [40 DU Type 1 (Mahoney), 8 DU Type 2 (MEF-1), 32 DU Type 3 (Saukett)]. Other ingredients per 0.5-mL dose include 1.5 mg aluminum phosphate (0.33 mg aluminum) as the adjuvant, polysorbate 80 (approximately 10 parts per million by calculation), ≤5 µg residual formaldehyde, <50 ng residual glutaraldehyde, ≤50 ng residual bovine serum albumin, 3.3 mg (0.6% v/v) 2-phenoxyethanol (not as a preservative), <4 pg of neomycin, and <4 pg polymyxin B sulfate. Quadracel® does not contain a preservative.

Each 0.5 mL dose of Vaxelis^™ (MCM Vaccine Company) contains 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens (20 µg detoxified PT, 20 µg FHA, 3 µg pertactin, 5 µg FIM), inactivated polioviruses [29 DU Type 1 (Mahoney), 7 DU Type 2 (MEF-1), 26 DU Type 3 (Saukett)], 3 µg PRP of H. influenzae type b covalently bound to 50 µg of the outer membrane protein complex (OMPC) of Neisseria meningitidis serogroup B, and 10 µg HBsAg. Each 0.5 mL dose also contains 319 µg aluminum from aluminum salts used as adjuvants. Other ingredients per 0.5 mL dose include <0.0056% polysorbate 80 and the following residuals from the manufacturing process: ≤14 mcg formaldehyde, ≤50 ng glutaraldehyde, ≤50 ng bovine serum albumin, <5 ng of neomycin, <200 ng streptomycin sulfate, <25 ng polymyxin B sulfate, ≤0.125 μg ammonium thiocyanate, and ≤0.1 mcg yeast protein (maximum 1% relative to HBsAg protein).

Tetanus, diphtheria, and pertussis (Tdap) vaccines

There are two Tdap vaccines used in the United States: Adacel® and Boostrix®. The Food and Drug Administration (FDA) approved both Boostrix® and Adacel® for use during pregnancy.

Each 0.5-mL dose of Adacel® (Sanofi Pasteur) contains 5 Lf tetanus toxoid, 2 Lf diphtheria toxoid, and acellular pertussis antigens (2.5 µg detoxified PT, 5 µg FHA, 3 µg pertactin, 5 µg FIM). Other ingredients per 0.5-mL dose include 1.5 mg aluminum phosphate (0.33 mg aluminum) as the adjuvant, ≤5 µg residual formaldehyde, <50 ng residual glutaraldehyde, and 3.3 mg (0.6% v/v) 2-phenoxyethanol (not as a preservative).

Each 0.5-mL dose of Boostrix® (GlaxoSmithKline) contains 5 Lf of tetanus toxoid, 2.5 Lf of diphtheria toxoid, 8 µg of inactivated PT, 8 µg of FHA, and 2.5 µg of pertactin (69 kiloDalton outer membrane protein). Each 0.5-mL dose contains aluminum hydroxide as adjuvant (not more than 0.39 mg aluminum by assay), 4.5 mg of sodium chloride, ≤100 µg of residual formaldehyde, and ≤100 µg of polysorbate 80 (Tween 80).

Diphtheria and tetanus

Today, diphtheria and tetanus are at historic low rates in the United States. No one has ever studied the efficacy of tetanus toxoid and diphtheria toxoid in a vaccine trial. However, experts infer efficacy from protective antitoxin levels. A complete vaccine series has a clinical efficacy of virtually 100% for tetanus and 97% for diphtheria. A complete series is 3 doses for people 7 years or older and 4 doses for children younger than 7.

Pertussis

In regard to pertussis, there has been an overall increasing trend in reported cases since the 1980s up until the COVID-19 pandemic in 2020. In spite of this, pertussis affects many fewer people today than before pertussis-containing vaccines became widely available in the 1940s. There are several reasons to help explain why we are seeing more cases recently:

• Increased awareness
• Improved diagnostic tests
• Better reporting
• More circulation of the bacteria
• Waning immunity

The acellular pertussis vaccines now used in the United States do not protect for as long as the prior whole cell pertussis vaccine. CDC is looking into whether molecular changes to may also be contributing to the resurgence.

In studies demonstrating the efficacy of the pertussis component for children who get all 5 doses on schedule, DTaP fully protects:

• 98% of children within the year following the last dose
• About 71% of children 5 years after getting the last dose of DTaP

In studies demonstrating the efficacy of the pertussis component, Tdap fully protects:

• About 73% of adolescents in the first year after vaccination
• About 34% of people 4 years after vaccination

In studies demonstrating the efficacy of the pertussis component when women get Tdap during pregnancy, the vaccine prevents:

• About 78% of pertussis cases in infants younger than 2 months old
• About 90% of hospitalizations for infants younger than 2 months old with pertussis

Consult the following package inserts for proper storage and handing details, shelf life, and reconstitution instructions:

• Adacel®
• Boostrix®
• DAPTACEL®
• Infanrix®
• Kinrix®
• Pediarix®
• Pentacel®
• Quadracel®
• TDVAX®
• TENIVAC®
• Vaxelis^™

Store diphtheria, tetanus, and pertussis vaccines refrigerated between 2°C and 8°C (36°F and 46°F).

Do not freeze vaccine or expose to freezing temperatures. If the vaccine has been exposed to inappropriate conditions/temperatures or handled improperly:

• Store the vaccine at the appropriate temperature
• Isolate from other vaccines
• Mark "Do NOT Use"
• Consult the vaccine manufacturer and/or your state or local immunization program for guidance

Store diphtheria, tetanus, and pertussis vaccines in the original packaging. For the diphtheria, tetanus, and pertussis vaccine that requires reconstitution, Pentacel^®, the manufacturer packages the diluent and vaccine together and they should be stored together in the refrigerator.

Diphtheria toxoid-, tetanus toxoid-, and acellular pertussis-containing vaccines (DTaP and Tdap) are easily confused, increasing the risk for error. Consider organizing vaccines in the storage unit by age group or color coding labels to distinguish vaccines from each other. Labeling the space where the vaccine is stored with name, age indications, and other information unique to the vaccine can help prevent vaccine administration errors.

For the diphtheria, tetanus, and pertussis vaccine that requires reconstitution, Pentacel^®, do NOT use if you cannot resuspend the reconstituted vaccine after thorough agitation.

• Only reconstitute Pentacel^® with the diluent provided by the vaccine manufacturer.
• Never use stock vials of normal saline to reconstitute Pentacel^®.

Discard vaccine vials and syringes in compliance with state and federal regulations.

Do not use any diphtheria, tetanus, and pertussis vaccine or diluent (if applicable) beyond the expiration date printed on the label.

Prior to administration, visually inspect the vaccine for particulate matter and/or discoloration. If these conditions exist, do NOT use.

Just before use, shake vial or manufacturer-filled syringe well. Do not use vaccine if you cannot resuspend it after thorough agitation.

• After shaking, Td should be a cloudy, whitish-gray colored liquid.
• After shaking, Tdap should be a cloudy, white-colored liquid.

Administer all diphtheria, tetanus, and pertussis vaccines (DTaP, Td, and Tdap) by the intramuscular route.

Infants and young children: The preferred injection site is the vastus lateralis muscle of the thigh.

Older children and adults: The preferred injection site is the deltoid muscle in the upper arm.

Use a needle length appropriate for the age and size of the person receiving the vaccine.

The number and timing of doses depends on the type of vaccine used and the person receiving the vaccine.

Infants and young children

CDC recommends DTaP for all infants and children younger than 7 years of age. If the pertussis component is contraindicated, use Td to complete the primary series in this age group.

• The recommended DTaP series is 5 doses, administered at 2, 4, and 6 months, 15 through 18 months, and 4 through 6 years.
• Administer the fourth dose of DTaP no earlier than 6 months after the third dose. However, you do not need to repeat the fourth dose if it was administered at least four months after the third dose.
• Do not administer the fourth dose of DTaP to children younger than 12 months of age. You can give it to children at 12 through 15 months of age if the child is unlikely to return at 15 through 18 months of age; this is an off-label recommendation from the Advisory Committee on Immunization Practices.
• The fifth dose of DTaP is not necessary if the patient received the fourth dose on or after their fourth birthday.

Older children and adults

CDC recommends 1 dose of Tdap for all adolescents.

• The preferred age for Tdap administration in adolescents is 11 to 12 years.
• If adolescents (13 through 18 years) missed getting Tdap at 11 to 12 years of age, administer at the next patient encounter or sooner if adolescent will have close contact with infants.
• You can administer Tdap regardless of interval since the last tetanus toxoid- and diphtheria toxoid-containing vaccine.

CDC recommends 1 dose of Tdap for women during each pregnancy.

• The preferred timing for Tdap administration in pregnancy is during the early part of gestational weeks 27 through 36.
• You can safely administer Tdap earlier in pregnancy if it is indicated for wound care or during a community pertussis outbreak. If you administer Tdap earlier in pregnancy, do not repeat vaccination between 27 and 36 weeks gestation; CDC recommends only one dose during each pregnancy.
• You can administer Tdap regardless of interval since the last tetanus toxoid- and diphtheria toxoid- containing vaccine.
• Do not offer Tdap as part of routine preconception care.
• CDC only recommends Tdap in the immediate postpartum period for new mothers who did not receive Tdap during their current pregnancy and did not receive a prior dose of Tdap (i.e., during adolescence, adulthood, or a previous pregnancy). If a woman did not receive Tdap during her current pregnancy but did receive a prior dose of Tdap, then she should not receive a dose of Tdap postpartum.

CDC recommends 1 dose of Tdap for healthcare personnel who have never received Tdap and who have direct patient contact.

• You can administer Tdap regardless of interval since the last tetanus toxoid- and diphtheria toxoid-containing vaccine.

Adults who have never received Tdap should receive a single dose of Tdap.

• Vaccinate adults as soon as feasible.
• You can administer Tdap regardless of interval since the last tetanus toxoid- and diphtheria toxoid-containing vaccine.

After receipt of Tdap, patients should continue to receive Td or Tdap for routine booster immunization every 10 years.

There are no data on the stability of vaccines stored in syringes filled by healthcare personnel. Therefore, CDC does not recommend predrawing vaccine doses.

Single-dose vials

Draw all of the vaccine into a sterile syringe using a sterile needle at the time of administration. Once you remove the protective cap from a single-dose vial, use the vaccine or discard it at the end of the workday. Single-dose vials do not contain a preservative and it is difficult to tell if a needle has penetrated the rubber stopper.

The manufacturer supplies Pentacel® in 2 vials that you must mix together before administration. Unused, reconstituted Pentacel® may be stored in the refrigerator between 2°C and 8°C (36°F and 46°F) for up to 30 minutes.

Manufacturer-filled syringes

Activate (i.e., remove syringe tip or attach needle) manufacturer-filled syringes when you administer it. Once activated, use a manufacturer-filled syringe that day or discard it at the end of the workday. The sterile seal has been broken.

There are no contraindications to the co-administration of diphtheria, tetanus, and pertussis vaccines. You may administer DTaP, Td, and Tdap with other indicated vaccines during the same visit. However, administer each vaccine using a separate syringe and, if possible, at a different anatomic site. COVID-19 vaccine should be administered in a separate limb, if feasible.

There is a small increased risk of febrile seizures in children 6 through 23 months of age when giving trivalent inactivated influenza vaccine (IIV3) with DTaP according to a Vaccine Safety Datalink study. However, CDC made no changes in the recommendations; you may give these vaccines at the same time.