Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age

INTRODUCTION — Diphtheria, tetanus, and pertussis immunization in infants and children six weeks through six years of age will be discussed here. Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age and other childhood immunizations are discussed separately. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Standard immunizations for children and adolescents: Overview".)

ABBREVIATIONS USED IN THIS TOPIC REVIEW — Throughout this topic review, the following abbreviations will be used to refer to diphtheria toxoid, tetanus toxoid, and pertussis-containing vaccines:

●DTaP – Diphtheria and tetanus toxoids, and acellular pertussis

●DTwP – Diphtheria and tetanus toxoids, and whole-cell pertussis

●DT – Diphtheria and tetanus toxoids; also called pediatric DT

●Tdap – Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis

●Td – Tetanus toxoid, reduced diphtheria toxoid; also called adult Td, dT, and adult dT

VACCINE FORMULATIONS

●Diphtheria-tetanus-pertussis – Diphtheria, tetanus, and pertussis immunizations for children six weeks through six years of age include DTaP vaccine and DTwP vaccine [1-3]. DTwP vaccines are no longer available in the United States but are used elsewhere in the world, usually combined with hepatitis B and Haemophilus influenzae type b (Hib) in a pentavalent vaccine.

Two DTaP vaccines are available in the United States for the first five doses in children <7 years of age: Daptacel and Infanrix (table 1) [4].

DTaP vaccines are also available in combination with other childhood vaccines (table 1) [4-6]:

•DTaP and inactivated poliovirus vaccine (DTaP-IPV vaccine; Kinrix, Quadracel), which can be used for the dose at four through six years of age

•DTaP, hepatitis B virus, and IPV vaccine (DTaP-HepB-IPV vaccine; Pediarix) for all five doses

•DTaP, IPV, and Hib vaccine (DTaP-IPV/Hib vaccine; Pentacel) for a four-dose series for children six weeks through four years of age

•DTaP, IPV, Hib, and hepatitis B vaccine (DTaP-IPV-Hib-HepB vaccine; Vaxelis) for a three-dose series for children six weeks through four years of age

DTaP vaccines must be distinguished from Tdap vaccines, which generally are used for a single booster dose during adolescence or adulthood. DTaP vaccines typically contain more diphtheria toxoid and pertussis antigens, and may contain more tetanus toxoid than Tdap vaccines (table 1) [4]. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Vaccine formulations'.)

●Diphtheria and tetanus toxoids – DT vaccine has been used for children <7 years who have contraindications or precautions to pertussis-containing vaccines (table 2). However, as of early 2023, the sole manufacturer discontinued production and distribution of this vaccine. According to the Centers for Disease Control and Prevention, discussions are in progress regarding vaccine recommendations for this group of children [7]. (See 'Contraindications and precautions' below.)

DT vaccine must be distinguished from Td vaccine, which is typically used for booster doses in adolescents and adults. DT contains higher doses of diphtheria toxoid and may contain higher doses of tetanus toxoid than Td (table 1). (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Vaccine formulations'.)

●Diphtheria or tetanus toxoid in conjugate vaccines – Diphtheria toxoid, CRM₁₉₇ (a nontoxic variant of diphtheria toxin), and tetanus toxoid are used as protein conjugates in some childhood vaccines (eg, pneumococcal conjugate vaccine, Hib, meningococcal conjugate vaccine) to enhance the immune response. When used as protein conjugates, these toxoids do not substitute for diphtheria or tetanus toxoid immunization because they are not sufficiently immunogenic [8,9]. However, as vaccine components, they may contribute to adverse reactions. (See 'Adverse reactions' below and 'Contraindications and precautions' below.)

INDICATIONS — Routine immunization against diphtheria, tetanus, and pertussis during childhood provides protection against these diseases into adolescence. The World Health Organization recommends diphtheria, tetanus, and pertussis immunization during infancy for all children worldwide [10-12]. Infants <12 months of age, particularly those <4 months of age, have a higher incidence of pertussis than any other age group [13]. They also have the highest case fatality rate. Routine infant and childhood immunization prevents morbidity and mortality. (See "Clinical manifestations, diagnosis, and treatment of diphtheria" and "Tetanus" and "Pertussis infection in infants and children: Clinical features and diagnosis".)

Additional indications for diphtheria and tetanus toxoid containing vaccine include:

●Tetanus or diphtheria disease (even if fully immunized) (see 'Natural diphtheria or tetanus infection' below and "Tetanus", section on 'Active immunization' and "Clinical manifestations, diagnosis, and treatment of diphtheria", section on 'Treatment')

●Unimmunized or incompletely immunized close contact of an individual with diphtheria or pertussis disease (see 'Catch-up immunization' below and "Pertussis infection in infants and children: Treatment and prevention", section on 'Prevention' and "Clinical manifestations, diagnosis, and treatment of diphtheria", section on 'Immunization')

EFFICACY AND EFFECTIVENESS

Protection against disease

●Efficacy – Vaccine efficacy refers to either levels of antibody correlated with protection or protection from clinical disease. Estimates of efficacy vary depending upon which of these outcomes is used and the number of doses received.

•Diphtheria and tetanus toxoids – After a series of four appropriately spaced doses of diphtheria toxoid- and tetanus toxoid-containing vaccines, approximately 95 percent of infants and children achieve levels of diphtheria antitoxin correlated with protection (>0.1 international unit of antitoxin/mL), and virtually all infants and children achieve levels of tetanus antitoxin correlated with protection (>0.1 international unit of antitoxin/mL) [1,2].

The estimated clinical efficacy of diphtheria toxoid in the prevention of diphtheria disease is 97 percent [1]. The clinical efficacy of tetanus toxoid has not been studied in vaccine trials [2].

In a meta-analysis of studies of diphtheria outbreaks, receipt of three doses of diphtheria toxoid was 87 percent (95% credible interval [CrI] 68-97 percent) effective in preventing symptomatic disease, 81 percent (95% CrI 74-86 percent) effective in preventing severe disease, and 93 percent (95% CrI 90-96 percent) effective in preventing death [14].

•Pertussis – In systematic reviews of randomized trials, the clinical efficacy of acellular pertussis vaccines containing ≥3 pertussis antigens (table 1) was approximately 85 percent in preventing typical pertussis (≥21 days of cough with laboratory confirmation of pertussis in the vaccinee or household contact) [15,16]. Acellular pertussis vaccines also may provide cross-protection against Bordetella parapertussis [17,18].

Although whole-cell pertussis vaccines may be slightly more efficacious and provide more durable protection than acellular pertussis vaccines, whole-cell pertussis vaccines are associated with more adverse effects [11,15,16,19-25]. (See 'Adverse reactions' below.)

●Effectiveness – Vaccine effectiveness is a measure of how well a vaccine prevents infection when the vaccine is used in the community under routine circumstances.

The effectiveness of diphtheria, tetanus, and pertussis immunization is demonstrated by the decline of these diseases in the United States after the immunizations were added to the routine immunization schedule in the 1940s (figure 1A-C) [1-3,26].

The effectiveness of pertussis immunization in infants was illustrated in a case-control study that compared fatal and nonfatal cases of infant pertussis in the United States (1991 to 2008) [27]. Among infants ≥6 weeks of age (the minimum age for the first dose), the case fatality rate was 0.27 percent; having received ≥1 dose of pertussis vaccine was associated with decreased risk of death (adjusted odds ratio [aOR] 0.28, 95% CI 0.11-0.74), hospitalization (aOR 0.69, 95% CI 0.63-0.77), and pneumonia (aOR 0.80, 95% CI 0.68-0.95).

DTaP is also effective in preventing severe pertussis and laboratory-documented pertussis in older children. In a review of pertussis cases in the United States between 2011 and 2015, the risk of hospitalization was reduced in children age 1 through 11 years who had received age-appropriate pertussis vaccination (adjusted relative risk 0.34 percent, 95% CI 0.20-0.60) [28]. In another study, children who received any doses of acellular pertussis vaccine were less likely to have severe illness or require hospitalization than unvaccinated children, and children fully vaccinated with acellular pertussis vaccine had more rapid resolution of coughing [29]. Finally, in a prospective cohort of 469,982 children who received DTaP, the risk of pertussis was approximately 13 times greater in unvaccinated than in fully vaccinated children and approximately two times greater in undervaccinated than fully vaccinated children [30].

Despite the effectiveness of pertussis vaccines, many cases of pertussis occur in children fully vaccinated with DTaP [29,30]. Waning immunity contributes to development of pertussis among vaccinated children. Proliferation of strains of B. pertussis that have diverged from vaccine reference strains (eg, strains that are deficient in pertactin, one of the antigens contained in acellular pertussis vaccines (table 1)) may be another factor [31-33]. (See 'Duration of immunity' below and "Pertussis infection: Epidemiology, microbiology, and pathogenesis", section on 'Pathogenesis'.)

Duration of immunity — The protection provided by diphtheria and tetanus toxoids decreases over time, necessitating booster doses in childhood, adolescence, and adulthood [14,34,35].

The protection provided by acellular pertussis vaccine also decreases over time [36-38]. The effectiveness of acellular pertussis vaccines has been evaluated in several case-control studies during a statewide pertussis outbreak [20,21,39,40]. In the largest study (682 cases), receipt of five doses of DTaP vaccine was associated with decreased risk of pertussis (odds ratio 0.11, 95% CI 0.06-0.21); the estimated vaccine effectiveness was 89 percent (95% CI 79-94 percent) [40]. However, vaccine effectiveness decreased with increasing interval since the last dose of DTaP (from 98 percent in the first 12 months to 71 percent by ≥60 months). These findings are consistent with those of other observational studies and national surveillance [37,38,41-44].

Despite waning immunity, vaccination continues to be the most effective strategy to reduce pertussis morbidity and mortality [29,41,45-47]. (See 'Protection against disease' above.)

Waning pertussis immunity after Tdap immunization is discussed separately. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Efficacy and effectiveness'.)

SCHEDULES

United States

Routine immunization — In the United States, five doses DTaP vaccine are recommended between six weeks and seven years of age (figure 2) [4]. The childhood doses are routinely recommended at the following ages:

●Two months; the minimum age for this dose is six weeks

●Four months; the second dose should be given ≥4 weeks after the first

●Six months; the third dose should be given ≥4 weeks after the second

●Fifteen through 18 months; the minimum age for the fourth dose is 12 months; the fourth dose should be given ≥6 months after the third dose, but it may be counted as valid if it was given ≥4 months after the third dose and the child was ≥12 months old when it was given

●Four through six years; the minimum age for this dose is four years; the fifth dose should be given ≥6 months after the fourth dose; the fifth dose is not necessary if the fourth dose was given at ≥4 years of age and ≥4 months (preferably ≥6 months) after the third dose

An adolescent booster dose of Tdap is recommended at 11 through 12 years of age. Thereafter, booster doses with either Td or Tdap are recommended every 10 years [48]. (See 'Vaccine formulations' above and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Schedule'.)

Catch-up immunization — Children who are unimmunized or incompletely immunized should undergo catch-up immunization. In a cohort study, receiving fewer than the recommended number of doses of acellular pertussis vaccine was associated with increased risk of pertussis disease, whereas receiving doses within 30 days after the recommended age was not [49].

When catching up with diphtheria, tetanus, and pertussis immunizations, immunization should proceed with the next dose in the sequence, provided the minimum interval between doses has elapsed (table 3) [4]. The minimum intervals between doses are as follows:

●Dose 1 to dose 2 – Four weeks

●Dose 2 to dose 3 – Four weeks

●Dose 3 to dose 4 – Six months; the minimum age for this dose is 12 months

●Dose 4 to dose 5 – Six months; the fifth dose is not necessary if the fourth dose is given at ≥4 years and ≥4 months after the third dose

The Centers for Disease Control and Prevention has developed a "job aid" to provide guidance for catch-up of diphtheria, tetanus, and pertussis-containing vaccines.

Catch-up immunization is particularly important for:

●Close contacts of an individual with pertussis disease; catch-up should be completed with minimal intervals (see "Pertussis infection in infants and children: Treatment and prevention", section on 'Immunization')

●Children who have recovered from diphtheria or who are close contacts of an individual with diphtheria (see 'Natural diphtheria or tetanus infection' below and "Clinical manifestations, diagnosis, and treatment of diphtheria", section on 'Treatment')

●Children who have recovered from tetanus (see 'Natural diphtheria or tetanus infection' below and "Tetanus", section on 'Active immunization')

Maximum number of doses — Children <7 years of age should not receive more than six doses of diphtheria and tetanus toxoid-containing vaccines (eg, DTaP, DTwP, DT) because of concern about adverse reactions [4,50].

Other countries — Routine immunization schedules vary from country to country. Schedules for individual countries are available through the World Health Organization and the European Centre for Disease Prevention and Control.

ADMINISTRATION

Contraindications and precautions

●Contraindications – A contraindication is a condition that increases the risk of a serious adverse reaction [4]. Absolute contraindications to diphtheria-, tetanus-, and/or pertussis-containing immunizations include (table 2) [4]:

•Anaphylactic reaction to the diphtheria-, tetanus-, and/or pertussis-containing vaccine or vaccine constituent (contraindication to subsequent doses of all components) (see "Allergic reactions to vaccines")

-Defer vaccination with diphtheria toxoid, tetanus toxoid, and pertussis antigens because of uncertainty about which was responsible

-Refer to an allergist to evaluate allergy to tetanus toxoid and possibility of desensitization to tetanus toxoid

-Information about latex in DTaP vaccines is available in the prescribing information, available from the US Food and Drug Administration (FDA).

•Encephalopathy within seven days of the administration of a previous dose of the vaccine without another identifiable cause (contraindication to subsequent doses of pertussis vaccine)

-Children <7 years of age who have a contraindication to pertussis immunization should not receive subsequent doses of pertussis-containing vaccine [4]. They may receive DT, but that vaccine is no longer available. (See 'Vaccine formulations' above and 'Use of DT vaccine' below.)

●Precautions – Precautions are conditions that may increase the risk for a serious reaction to immunization, cause diagnostic confusion, or compromise the ability of the vaccine to produce immunity [51]. Although immunization is generally deferred in children with precautions, decisions regarding administering diphtheria toxoid, tetanus toxoid, and pertussis-containing vaccines to children with precautions should be individualized according the benefits and risks, and reassessed at subsequent immunization visits [4].

Precautions for administration of DTaP or DT include:

•Guillain-Barré syndrome (GBS) <6 weeks after previous dose of tetanus toxoid-containing vaccine

Although there have been case reports of GBS following tetanus toxoid-containing vaccines in adolescents and adults, an increased risk of GBS following diphtheria, tetanus, and pertussis immunization has not been observed in children [52]

•History of Arthus-type reaction after a previous dose of tetanus or diphtheria toxoid-containing vaccines; an Arthus-type reaction is a specific type of immune complex-mediated hypersensitivity reaction characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally necrosis at the injection site [4] (see "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Past cutaneous reactions involving skin necrosis (Arthus-type reaction)')

-Defer vaccination until ≥10 years after the most recent dose of the tetanus-toxoid-containing vaccine

•Moderate or severe illness with or without fever on the day of immunization. In this case, immunization should be administered upon recovery.

•An additional precaution for DTaP but not DT, is progressive or unstable neurologic disorder, including infantile spasms, uncontrolled seizures, or progressive encephalopathy; DTaP should be deferred until the neurologic status is clarified and stabilized [4] (see 'Progressive or unstable neurologic disease' below)

●Conditions incorrectly perceived as contraindications or precautions – Conditions that are neither contraindications nor precautions to DTaP and should not be used to defer immunization include [4,51]:

•Fever <40.5°C (105°F), fussiness, or mild drowsiness after a previous dose of DTaP or DTwP; fever ≥40.5°C (105°F) is uncommon following DTaP and is considered to be an adverse reaction [53] (see 'Adverse reactions' below)

•Family history of seizures

•Family history of sudden infant death syndrome

•Family history of adverse event after DTaP or DTwP administration

•Stable neurologic conditions (eg, cerebral palsy, well-controlled seizures, developmental delay)

•History of collapse or shock-like state (ie, hypotonic-hyporesponsive episode) within 48 hours after receiving a previous dose of DTaP or DTwP

•History of seizure with or without fever within three days after receiving a previous dose of DTaP or DTwP

•History of persistent, inconsolable crying lasting >3 hours within 48 hours after a previous dose of DTaP or DTwP

Choice of vaccine

●No contraindications to pertussis vaccine – In the United States and other countries that have replaced DTwP with DTaP, DTaP 0.5 mL intramuscularly (IM) is preferred to DT for children between six weeks and seven years, unless there are contraindications to pertussis vaccine (table 2) [4]. There is no preference among DTaP vaccines or DTaP combination vaccines within their approved age ranges (table 1). (See 'Contraindications and precautions' above.)

When it is feasible, the same brand of DTaP vaccine should be used for all doses of DTaP vaccine because data on efficacy were developed in populations using the same brand of vaccine for every dose [4,54]. However, an opportunity to administer a dose of DTaP vaccine to an eligible child should not be missed because the brand used for earlier doses is not available (or not known). Limited data suggest that using different brands to complete immunization does not adversely affect vaccine safety or immunogenicity [4].

Both DTaP and DTwP vaccines provide protection from tetanus, diphtheria, and severe pertussis [11]. The decision to use DTaP or DTwP vaccine is typically made at the national level. Most resource-rich countries have switched from DTwP to DTaP because DTaP has fewer adverse effects [25,55,56]. DTwP is not available in the United States. For countries that have not replaced DTwP with DTaP, the WHO suggests continued use of DTwP vaccines during childhood given relatively rapidly waning immunity with acellular DTaP [11,57]. (See 'Efficacy and effectiveness' above.)

●Contraindications to pertussis vaccine – For children age six weeks through six years with one or more contraindication to pertussis vaccine (table 2), DT 0.5 mL IM is recommended [4]. However, as of early 2023, the sole manufacturer discontinued production and distribution of the DT vaccine. (See 'Use of DT vaccine' below.)

Administration with other vaccines — Diphtheria-, tetanus-, and pertussis-containing vaccines can be administered at the same visit as other recommended vaccines (figure 2) [4,58,59]. DTaP vaccine should not be mixed in the same syringe with another vaccine unless the specific combination is licensed by the FDA (eg, Pentacel) (table 1) [50].

The risk of febrile seizures appears to be increased in children age 6 through 23 months when a DTaP-containing vaccine is administered on the same day as inactivated influenza vaccine (IIV) or both IIV and pneumococcal conjugate vaccine [60,61]. However, the absolute risk is small (maximum estimated absolute excess risk of febrile seizures was 30 per 100,000 vaccine recipients when all three vaccines were given on the same day compared with administration on separate days) [60]. Given the greater risk of prolonging susceptibility to vaccine-preventable infections if any of these vaccines is delayed, the Advisory Committee on Immunization Practices does not recommend administering them at separate visits or deviating from the recommended vaccine schedule [62]. In a randomized trial, the proportion of children who developed fever within two days of vaccination was similar (8 to 9 percent) whether IIV was administered on the same day as PCV and diphtheria, tetanus, and acellular pertussis vaccine or two weeks later [63]. (See 'Adverse reactions' below.)

Adverse reactions — Acellular pertussis-containing vaccines produce fewer local reactions, fever, and systemic symptoms than whole-cell pertussis-containing vaccines [4,15,64,65].

With the exception of anaphylaxis, the adverse reactions discussed below are not contraindications or precautions to subsequent doses of diphtheria-, tetanus-, and pertussis-containing vaccines (table 2).

Adverse reactions to diphtheria-, tetanus-, and pertussis-containing vaccines may include (from most to least frequent) [50,53]:

●Mild local and systemic reactions – Mild local and systemic reactions are the most common adverse reactions to DTaP vaccine [55]. They typically occur within several hours of vaccination and resolve spontaneously without sequelae. Mild local and systemic reactions are not contraindications or precautions to subsequent doses. Mild local and systemic reactions include [53,55]:

•Low-grade fever

•Redness and tenderness at the injection site

•Drowsiness or poor appetite

•Fussiness

•Vomiting

Children who receive the combination DTaP, hepatitis B virus, and inactivated poliovirus vaccine (IPV) may have higher rates of fever than those who receive the vaccines separately [66,67].

Local reactions rarely require medical attention [68,69]. In a retrospective cohort study, local reactions requiring medical attention occurred in <1 percent of children <3 years and approximately 1.5 percent of children three to six years [68]. The risk of local reaction appears to be lower with administration in the anterolateral thigh than in the deltoid [68,69]. (See 'Choice of vaccine' above.)

●Extensive local reactions and entire limb swelling – Extensive local reactions (>46 mm) of erythema or swelling are more common among children who receive four or five consecutive doses of DTaP than those who receive a mixture of DTaP and DTwP [70-73]. Extensive local reaction after the fourth DTaP is not predictive of a similar reaction after the fifth dose [73].

Swelling of the entire limb has been reported in 2 to 3 percent of children after receipt of the fourth or fifth dose of DTaP [50,74]. Limb swelling may be accompanied by erythema, pain, and fever. It may interfere with walking, but most children have no limitation of activity.

Administration of acetaminophen or ibuprofen before and 6 to 12 hours after the fifth dose does not appear to prevent extensive local reactions [75]. The potential benefits and risks of administration of prophylactic acetaminophen are discussed separately. (See "Standard immunizations for children and adolescents: Overview", section on 'Prophylactic medications'.)

●Fever ≥40.5°C (105°F) – Fever ≥40.5°C (105°F) is uncommon following DTaP [53]. It is not a contraindication or precaution to subsequent doses.

●Persistent inconsolable crying and hypotonic-hyporesponsive episodes – Prolonged (>3 hours), inconsolable crying and hypotonic-hyporesponsive episodes (collapse, shock-like state) are also uncommon following DTaP [53,76]. Both of these reactions have been associated with other vaccines [4,77]. Neither is known to be associated with long-term sequelae [4,77,78].

●Seizures – Seizures following pertussis-containing vaccines are usually simple febrile seizures [50]. (See "Clinical features and evaluation of febrile seizures" and "Patient education: Febrile seizures (Beyond the Basics)".)

The risk of seizures varies with the vaccine formulation. In large cohort studies, the risk of febrile seizures was not increased after DTaP [79]; was slightly increased (absolute risk <4 per 100,000 vaccinations) after the first and second doses of combination DTaP, IPV, H. influenzae type b vaccine [80]; and was slightly increased on the day of vaccination with DTwP (5.6 to 8.9 per 100,000 children) [81]. Vaccine-associated febrile seizures were not associated with an increased risk of afebrile seizures or neurodevelopmental disability.

The risk of febrile seizures also appears to be affected by simultaneous administration with other vaccines. (See 'Administration with other vaccines' above.)

Vaccine-associated seizures may be the initial presentation of severe myoclonic epilepsy of infancy (Dravet syndrome), which should be considered before attributing the seizures to DTaP [82,83]. (See "Dravet syndrome: Genetics, clinical features, and diagnosis", section on 'Clinical features and EEG findings'.)

●Anaphylaxis – Anaphylaxis following diphtheria, tetanus, and pertussis vaccinations is rare [53]. It is discussed separately. (See "Allergic reactions to vaccines".)

SPECIAL CIRCUMSTANCES

Natural diphtheria or tetanus infection — Natural infection with diphtheria or tetanus does not necessarily protect against reinfection. Children with diphtheria or tetanus infection should receive a diphtheria and tetanus toxoid-containing vaccine (eg, DTaP, DTwP, DT) during their convalescence (even if they were completely immunized before their illness) [1,2]. (See "Clinical manifestations, diagnosis, and treatment of diphtheria", section on 'Follow-up' and "Tetanus", section on 'Active immunization'.)

Natural pertussis infection — Well-documented pertussis disease (eg, positive culture, polymerase chain reaction, or epidemiologic linkage to a culture-proven case) confers short-term immunity [50]. However, the duration of protection is unknown. DTaP should be used to complete childhood immunization (if the child is younger than seven years). (See "Pertussis infection in infants and children: Clinical features and diagnosis", section on 'Laboratory confirmation' and "Pertussis infection in infants and children: Treatment and prevention", section on 'Immunization'.)

Progressive or unstable neurologic disease — Progressive or unstable neurologic disease (eg, infantile spasms, uncontrolled seizures, progressive encephalopathy) is a precaution to administration of pertussis-containing vaccines. (See 'Contraindications and precautions' above.)

We agree with the Advisory Committee on Immunization Practices that administration of pertussis-containing vaccines (eg DTaP) should be deferred in children with progressive or unstable neurologic disease until the condition is clarified or stabilized [4]. The decision to also defer diphtheria and tetanus toxoids while the neurologic condition is being clarified and stabilized should be individualized according to risk of exposure.

In countries where neither tetanus nor diphtheria are endemic, it is reasonable to defer administration of diphtheria and tetanus toxoids in children who are not walking because their risk of acquiring diphtheria and tetanus is very low [50]. However, when the child begins to walk (at or near 12 months of age), they are at increased risk for tetanus-prone wounds and administration of DT vaccine may be warranted.

Use of DT vaccine — The DT vaccine has been used for children with a contraindication to the acellular pertussis component. However, as of early 2023, the sole manufacturer discontinued production and distribution of the DT vaccine, and discussions are in progress regarding vaccine recommendations for this group of children.

When immunization with DT vaccine is given, the number of doses of DT vaccine needed to complete the series depends upon the child's age at the time of the first dose and previous exposure to diphtheria and tetanus toxoid-containing vaccines [4]:

●Previously unvaccinated children

•If the first dose of DT is administered at <12 months of age, four doses (total) are necessary to complete the series; if the fourth dose is administered at <4 years of age, a fifth dose of DT should be provided at four through six years of age and ≥6 months after the fourth dose.

•If the first dose of DT is administered at ≥12 months of age, three doses (total) are necessary to complete the series; if the third dose is administered at <4 years of age, a fourth dose of DT should be provided at four through six years of age and ≥6 months after the third dose.

●Previously vaccinated children – Children who received one or two doses of DT or DTaP after their first birthday and for whom pertussis-containing vaccine continues to be contraindicated should receive a total of three doses of diphtheria and tetanus toxoid-containing vaccines appropriate for age. The third dose should be given 6 to 12 months after the second.

Vaccine mix-up — Children <7 years of age may inadvertently receive Tdap instead of DTaP. The implications depend upon which dose was inadvertently administered [4]:

●If Tdap was administered for the first, second, or third dose, it should not be counted as a valid dose. DTaP should be administered on the same day or as soon as possible to keep the child on schedule. The interval between the replacement dose of DTaP and the subsequent dose should be ≥4 weeks for replacement of the first or second doses and ≥6 months for replacement of the third dose. (See 'Routine immunization' above.)

●If Tdap is administered as the fourth or fifth dose to a child <7 years, it should be counted as valid. A second dose of Tdap should be administered as scheduled at age 11 years. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Schedule'.)

Vaccine administration errors should be reported to the Vaccine Adverse Event Reporting System.

RESOURCES — Resources related to DTaP immunization and immunization in children younger than seven years include:

●Centers for Disease Control and Prevention

●American Academy of Pediatrics

●Vaccine information statement for DTaP

●Immunization Action Coalition

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pertussis" and "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Diphtheria, tetanus, and pertussis vaccination".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Whooping cough (The Basics)" and "Patient education: Tetanus (The Basics)" and "Patient education: Vaccines for babies and children age 0 to 6 years (The Basics)")

●Beyond the Basics topics (see "Patient education: Why does my child need vaccines? (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Indications – In agreement with the World Health Organization (WHO), we recommend diphtheria, tetanus, and pertussis immunization during infancy and early childhood (Grade 1A). Routine infant immunization prevents morbidity and mortality from diphtheria, tetanus, and pertussis infection. (See 'Indications' above and 'Efficacy and effectiveness' above.)

Additional target groups for diphtheria toxoid, tetanus toxoid, and pertussis-containing vaccines include (see 'Indications' above):

•Children who develop natural diphtheria or tetanus infection, even if they were completely immunized; diphtheria and tetanus toxoid-containing vaccine (eg, DTaP, DTwP, DT) should be provided during convalescence

•Unimmunized or incompletely immunized contacts of patients with diphtheria or pertussis disease

●Routine schedules

•In the United States, DTaP vaccine 0.5 mL intramuscularly (IM) is routinely recommended at 2 months, 4 months, 6 months, 15 through 18 months, and 4 through 6 years of age. (See 'Routine immunization' above.)

•Schedules for other countries are available through the WHO and the European Centre for Disease Prevention and Control. (See 'Schedules' above.)

●Catch-up schedule – Catch-up diphtheria, tetanus, and pertussis immunization is indicated for unimmunized or incompletely immunized children. Complete DTaP immunization for children <7 years of age is defined by four or five doses at appropriate minimum ages and intervals (table 3).

When catching up diphtheria, tetanus, and pertussis immunizations, immunization should proceed with the next dose in the sequence, provided the minimum interval between doses and minimum age criteria (if applicable) have been met (table 3). (See 'Catch-up immunization' above.)

●Administration – For children with no contraindications to pertussis vaccine (table 2), DTaP 0.5 mL IM is the preferred vaccine for children between six weeks and seven years in the United States and other countries that have replaced DTwP with DTaP. DTaP can be administered at the same visit as other recommended vaccines. (See 'Administration' above.)

●Adverse reactions – Mild local and systemic reactions are the most common adverse events after DTaP. Swelling of the entire limb occurs in 2 to 3 percent of recipients. More severe reactions are uncommon. (See 'Adverse reactions' above.)