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Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age
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Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Oct 03, 2017.

INTRODUCTION — Childhood and adolescent immunizations are one of the most effective means of preventing serious illness. Diphtheria, tetanus, and pertussis immunization in infants and children zero 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".)

BACKGROUND — Diphtheria is an acute respiratory or cutaneous illness caused by Corynebacterium diphtheriae. Respiratory diphtheria has a case fatality rate of 5 to 10 percent; mortality is increased (up to 20 percent) among children younger than five years [1]. (See "Epidemiology and pathophysiology of diphtheria" and "Clinical manifestations, diagnosis, and treatment of diphtheria".)

Tetanus is a nervous system disorder characterized by muscle spasms. It is caused by Clostridium tetani, a toxin-producing anaerobe. Mortality is increased among unvaccinated persons [2]. (See "Tetanus".)

Pertussis, or "whooping cough", is an acute respiratory illness caused by Bordetella pertussis. The case fatality rate for pertussis is approximately 0.2 percent; mortality is increased among infants younger than three months of age. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis" and "Pertussis infection in infants and children: Clinical features and diagnosis".)

VACCINES — Vaccines for diphtheria, tetanus, and pertussis were introduced into the routine childhood immunization schedule in the United States during the 1940s, with dramatic effects on disease incidence (figure 1A-C) [1-3].

Vaccine components — Diphtheria, tetanus, and pertussis immunizations for infants and children (zero through six years) include diphtheria toxoid, tetanus toxoid, and acellular or whole-cell pertussis vaccine [1-3]. Whole-cell pertussis-containing vaccines are no longer available in the United States, but are used elsewhere in the world.

The pertussis antigens that are included in acellular pertussis vaccines and the amount of diphtheria and tetanus toxoids vary depending upon the vaccine product (table 1). Vaccines for children younger than seven years contain more diphtheria toxoid and pertussis antigens and may contain more tetanus toxoid than vaccines for children older than seven years and adults.

Conjugate vaccines that contain diphtheria toxoid or CRM197, a nontoxic variant of diphtheria toxin (eg, pneumococcal conjugate vaccine, meningococcal conjugate vaccine), are not substitutes for diphtheria toxoid immunization [4]. The conjugate Haemophilus influenzae vaccines that contain tetanus toxoid (PRP-T [ActHIB, Hiberix]) are not a substitute for tetanus toxoid immunization [5].

Vaccine preparations

Diphtheria-tetanus-pertussis – Two federally licensed combined diphtheria-tetanus-acellular pertussis (DTaP) vaccines are available in the United States for the first five doses: Daptacel and Infanrix [6]. DTaP also is available in combination with other vaccines (eg, inactivated polio vaccine, H. influenzae type b, hepatitis B) (table 1) [7-10]. Some preparations of DTaP may contain latex.

Diphtheria-tetanus-whole cell pertussis (DTwP) vaccines are no longer available in the United States, but are used elsewhere in the world.

Care must be taken to distinguish DTaP from the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine (Tdap), which is used for a single booster dose during adolescence or adulthood (table 1). (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Vaccine preparations'.)

Diphtheria and tetanus toxoids – A vaccine that includes diphtheria and tetanus toxoids, but not pertussis (DT, pediatric DT) is available for children younger than seven years in whom it is desirable to avoid pertussis vaccine. (See 'Contraindications' below and 'Precautions' below.)

Care must be taken to distinguish DT from the reduced diphtheria toxoid and tetanus toxoid vaccine (dT, Td, adult dT, adult Td) which is the vaccine typically used for booster doses in adolescents and adults (table 1). (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Vaccine preparations'.)

Choice of vaccine — DTaP is the vaccine of choice for children six weeks through six years of age [11]. The risk of adverse reactions is lower with acellular than whole-cell pertussis vaccines. (See 'Adverse reactions' below.)

When it is feasible, the same brand of DTaP vaccine should be used for all DTaP doses [3,11,12]. However, an opportunity to administer a dose of DTaP 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 the primary series does not adversely affect vaccine safety or immunogenicity [3,11].

Dose and route — The dose of diphtheria toxoid, tetanus toxoid, and pertussis vaccines is 0.5 mL. The vaccines are administered intramuscularly [11]. The anterolateral thigh is the preferred site for children younger than three years and the deltoid the preferred site for children older than three years [13].

In observational studies, local reactions requiring medical attention are uncommon following DTaP, occurring in <1 percent of children <3 years and approximately 1.5 percent of children three to six years [14]. Administration in the anterolateral thigh is associated with fewer such reactions than administration in the deltoid [14,15]. (See 'Adverse reactions' below.)

Storage and handling — Diphtheria toxoid-, tetanus toxoid-, and acellular pertussis-containing vaccines should be stored continuously at 36 to 46°F (2 to 8°C) [16]. During transport, the vaccine may be out of refrigeration for as long as four days, but it should be refrigerated immediately upon arrival. Freezing reduces the potency of the tetanus component; vaccine exposed to freezing temperature should not be administered.

EFFICACY AND EFFECTIVENESS — The efficacy and effectiveness of diphtheria, tetanus, and pertussis immunization vary depending upon the definition used for efficacy (ie, levels of antibody correlated with protection or protection from disease) and the number of doses received. Vaccine effectiveness is a measure of how well a vaccine works to protect against an infection when the vaccine is used in routine circumstances in the community.

After a series of four appropriately spaced doses of diphtheria-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 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 systematic reviews, the 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) [17,18]. Acellular pertussis vaccines also may provide cross-protection against Bordetella parapertussis [19,20]. Although diphtheria-tetanus-whole cell pertussis (DTwP) vaccine may be slightly more efficacious and provide more durable protection than diphtheria-tetanus-acellular pertussis (DTaP) [17,18,21-27], it is associated with more adverse effects [17,28-31].

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) [1-3,32]. 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 (1991-2008) [33]. Among infants ≥6 weeks of age (the minimum age for the first dose), receiving ≥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). However, 64 percent of the infant deaths occurred in infants too young to be vaccinated, highlighting the importance of maternal pertussis immunization during pregnancy and pertussis immunization the infant's close contacts, as recommended by the Global Pertussis Initiative [34]. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination' and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'General use'.)

The protection provided by acellular pertussis vaccine decreases with time since last vaccination [35-37]. A large pertussis outbreak in California in 2010 provided the opportunity to evaluate the effectiveness of acellular pertussis vaccines in several case-control studies [22,23,38,39]. 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) [39]. However, vaccine effectiveness decreased with increasing duration of time 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 (figure 2) [22,23,37,40-45].

Despite waning immunity, vaccination continues to be the most effective strategy to reduce pertussis morbidity and mortality [42,46-48]. In a 2010-2012 county-wide outbreak, 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 [47].

Further study of the safety and effectiveness of earlier and/or additional booster doses of acellular pertussis vaccine is necessary before changes to the routine immunization schedule are recommended [22,49].

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

INDICATIONS — The Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AFP) recommend routine immunization with diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine for infants and children aged six weeks through six years (figure 3)  

Children who are unimmunized or underimmunized should undergo catch-up immunization, as discussed below. (See 'Catch-up schedule' below.)

Catch-up immunization is particularly important for the following children [1-3]:

Close contact of individual with pertussis disease (should complete the primary series with minimal intervals (table 2)) (see "Pertussis infection in infants and children: Treatment and prevention", section on 'Immunization')

Diphtheria disease or close contact of individual with diphtheria disease (see "Clinical manifestations, diagnosis, and treatment of diphtheria")

Tetanus disease (see "Tetanus")

VACCINE SCHEDULE

Routine schedule — In the United States, five doses of diphtheria, tetanus, and pertussis vaccines are recommended between six weeks and seven years of age; a booster dose is recommended beginning at age 11 years (figure 3). For children who have an absolute contraindication to pertussis vaccine, diphtheria-tetanus toxoid (DT) is an acceptable alternative. (See 'Contraindications' below and 'Vaccine preparations' above.)

Administration of DTaP vaccine is typically recommended at 2 months, 4 months, 6 months, 15 through 18 months, and 4 to 6 years of age (figure 3).

The minimum age for administration of the first dose is six weeks (table 2).

The second and third doses should be given at minimum intervals of four weeks.

The minimum interval between the third and fourth doses is six months. Although a six-month interval is preferred, if the fourth dose is accidentally given at least four months after the third dose, it should be counted as valid [50]. The fourth dose may be given as early as 12 months of age if this interval is met and the child is considered unlikely to return for a visit at the recommended age of 15 to 18 months.

The minimum age for the fifth dose is four years (figure 3 and table 2). The minimum interval between the fourth and fifth doses is six months. If the fourth dose is delayed until after the patient is four years old, the fifth dose is not necessary, but may be given to increase pertussis antibody levels and decrease the risk of transmission to younger siblings who are not fully vaccinated [3].

Diphtheria-, tetanus-, and pertussis-containing vaccines can be administered at the same visit as other recommended vaccines (figure 3) [11,27,51-53]. Although there is a slight increased risk of febrile seizures in children 6 through 23 months of age if DTaP is administered on the same day as inactivated influenza vaccine, the Advisory Committee on Immunization Practices does not recommend administering them on separate days. (See 'Adverse reactions' below.)

DTaP vaccine should not be mixed in the same syringe with another vaccine unless the specific combination is licensed by the FDA (eg, Pentacel) [6].

Catch-up schedule — The catch-up schedule for children with lapsed or incomplete diphtheria, tetanus, and/or pertussis immunization is provided in the table (table 2).

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 been met (table 2) [6].

DTaP should be used to complete the immunization series for children younger than seven years with incomplete immunizations who received DTwP as part of the primary immunization series [6].

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.

Maximum number of doses — No more than six doses of diphtheria-tetanus toxoid should be given before the seventh birthday (eg, in children who received one or more DT vaccines as part of the primary series) [6].

Special circumstances

History of pertussis disease — Natural infection with diphtheria and tetanus disease does not induce immunity. Individuals with diphtheria or tetanus disease should receive diphtheria-tetanus toxoid 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'.)

Well-documented pertussis disease (eg, positive culture or epidemiologic linkage to a culture-proven case) confers short-term immunity [6]. However, the duration of protection is unknown. DTaP should be used to complete the primary series (if the child is younger than seven years). (See "Pertussis infection in infants and children: Treatment and prevention", section on 'Immunization'.)

Neurologic disease — In the United States, the administration of diphtheria and tetanus toxoids may be deferred until age 12 months for children in whom the decision is made to temporarily defer pertussis immunization (ie, during evaluation and/or observation of neurologic conditions) [6]. The risk of developing diphtheria or tetanus in such children is remote. However, at or near the first birthday, when the child becomes ambulatory, the risk of a tetanus-prone wound increases, and the decision to administer DT or DTaP must be made. (See 'Neurologic condition' below.)

Use of DT vaccine — The number of doses of DT vaccine needed to complete the primary series depends upon the child's age at the time of the first dose [1]:

If the first dose is administered at <12 months of age, four doses (total) are necessary to complete the primary series.

If the first dose is administered at ≥12 months of age, three doses (total) are necessary to complete the primary series.

Vaccine mix-up — Whether or not inadvertent administration of Tdap (rather than DTaP) to a child younger than seven years should be counted as a valid dose depends upon which dose was inadvertently administered [54].

If Tdap is 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 at least four weeks.

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 'Routine schedule'.)

Vaccine administration errors should be reported to the Vaccine Adverse Event Reporting System (telephone number: 1-800-822-7967).

CONTRAINDICATIONS AND PRECAUTIONS — Contraindications, precautions, and conditions that are neither contraindications nor precautions (and therefore should not be used to defer immunization) for diphtheria toxoid-, tetanus toxoid-, and/or acellular pertussis-containing vaccines are summarized in the table (table 3).

Contraindications — Absolute contraindications to diphtheria-, tetanus-, and/or pertussis-containing immunizations include [6,7,11,13]:

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")

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)

Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, progressive encephalopathy (administration of pertussis-containing vaccines should be deferred until the neurologic status is clarified and stabilized) (see 'Neurologic disease' above)

Some DTaP vaccines contain latex and are contraindicated in patients with anaphylactic reaction to latex

Children younger than seven years who have a contraindication to pertussis immunization should not receive subsequent doses of pertussis-containing vaccine, but they may receive DT [6]. (See 'Vaccine preparations' above.)

Precautions — Precautions are conditions that might increase the risk for a serious reaction to immunization, might cause diagnostic confusion, or might compromise the ability of the vaccine to produce immunity [13]. Precautions to immunization with pertussis-containing vaccines include [6,13]:

Moderate or severe illness with or without fever (immunization should be administered upon recovery)

Certain adverse reactions to previous doses (see 'Previous reaction' below)

Certain neurologic conditions, or awaiting further characterization of neurologic conditions (see 'Neurologic condition' below)

Previous reaction — The occurrence of any of the following conditions (without another identifiable cause) after administration of a pertussis-containing vaccine is considered a precaution to administration of subsequent doses of DTaP [6,13,55-57].

Temperature ≥105°F (40.5°C) within 48 hours of vaccine

Hypotonic-hyporesponsive episode (collapse or shock-like state) within 48 hours of vaccine

Seizure (with or without fever) within three days of vaccine

Persistent, inconsolable crying for ≥3 hours within 48 hours of vaccine

The risk of a subsequent similar reaction is unknown. The possibility of such a reaction may justify discontinuing administration of pertussis vaccine. However, in certain circumstances (eg, an outbreak of pertussis) the benefits of pertussis immunization may outweigh the risks [3]. Several reports describe uneventful vaccination with acellular pertussis vaccine in children who had a hypotonic-hyporesponsive episode after immunization with whole-cell pertussis vaccine (DTwP) [57-61]. Although the number of patients is small, vaccination of such patients with acellular pertussis vaccine appears to be safe [57].

Previous adverse reactions to diphtheria and/or tetanus toxoids that constitute precautions to subsequent doses of diphtheria- and/or tetanus-containing vaccines include [13]:

Guillain-Barré syndrome (GBS) within six weeks of tetanus or diphtheria toxoid-containing vaccine. Although there have been case reports of GBS following tetanus or diphtheria toxoid-containing vaccines in adolescents and adults, an increased risk of GBS following diphtheria, tetanus, pertussis immunization has not been observed in children [62,63].

History of Arthus-type reaction (a specific type III, immune complex mediated hypersensitivity reaction) following diphtheria or tetanus toxoid-containing vaccine, characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally necrosis at the injection site [54].

Neurologic condition — Temporary or indefinite deferral of pertussis immunization may be warranted for infants and children with certain neurologic conditions or children who are undergoing evaluation for these conditions [6,11,13].

Decisions regarding pertussis immunization in such children should be made on a case-by-case basis, after weighing the risks and benefits of immunization. The decision should be reassessed at subsequent immunization visits.

Neurologic conditions that are considered precautions to administration of pertussis-containing vaccines include [13]:

Conditions that predispose to seizures or neurologic deterioration – To avoid confusion about causation, children with unstable or evolving neurologic conditions that predispose to seizures or neurologic deterioration (eg, tuberous sclerosis complex, inherited metabolic or degenerative conditions) should not receive pertussis vaccine until the diagnosis and prognosis of the neurologic disorder are ascertained. Administration of pertussis-containing vaccine should be reconsidered at each visit. Pertussis immunization may be administered to children whose condition is resolved, corrected, or controlled.

History of seizures – Children with a history of seizures have an increased risk of seizures after pertussis vaccine. However, there is no evidence that vaccine-associated seizures induce permanent brain damage, cause epilepsy, or aggravate or affect the prognosis of the underlying neurologic disorder [64,65].

We suggest that pertussis immunization be deferred in children with a history of seizures until a progressive neurologic condition is excluded [65]. We suggest that pertussis vaccination be administered to infants and children with well-controlled seizures or those in whom seizures are unlikely to recur. Acetaminophen or other antipyretic may be administered before the immunization and at appropriate intervals during the ensuing 24 hours. 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'.)

Not contraindications or precautions — Conditions that are NOT considered contraindications or precautions to diphtheria-, tetanus-, and/or pertussis-containing immunization and should NOT be used to defer immunization include [11,13]:

Mild acute illness with or without fever

Family history of seizure, sudden infant death syndrome, or adverse event after DTwP or DTaP

Stable or resolved neurologic condition (eg, controlled idiopathic epilepsy, cerebral palsy, developmental delay)

Immunosuppression

Extensive local reaction after the fourth dose of DTaP

ADVERSE REACTIONS — Acellular pertussis-containing vaccines produce fewer local reactions, fever, and systemic symptoms than whole-cell pertussis-containing vaccines (table 4) [11,17,66,67].

Adverse reactions to diphtheria-tetanus-pertussis vaccines may include, (from most to least frequent) [1-3,6,68]:

Mild local and systemic reactions

Entire limb swelling

Persistent, inconsolable crying (≥3 hours)

Hypotonic-hyporesponsive episode (collapse or shock-like state)

Seizures

Fever ≥105°F (40.5°C)

Anaphylaxis (see "Allergic reactions to vaccines")

Mild local and systemic reactions are the most common adverse reactions to DTaP. These reactions include fever (1 in 4 children); redness and tenderness at the injection site (1 in 4 children); drowsiness or poor appetite (1 in 10 children); fussiness (1 in 3 children); and vomiting (1 in 50 children) [6,68]. These reactions occur within several hours of vaccination and resolve spontaneously without sequelae. Higher rates of low-grade fever have been reported among infants who receive the DTaP-HepB-IPV combination vaccine than among children who receive the vaccines separately [69,70].

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 whole-cell pertussis vaccine (DTwP) [71-74]. Extensive local reaction after the fourth DTaP is not predictive of a similar reaction after the fifth dose [74]. In a retrospective review, local reactions to the fifth dose of DTaP serious enough to require medical attention were uncommon (43.5 per 10,000 injections) [15]. However, they occurred more frequently after administration in the arm than in the thigh (47.4 versus 32.1 per 10,000 injections). 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'.)

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 [6,76]. Limb swelling may be accompanied by erythema, pain, and fever. It may interfere with walking, but most children have no limitation of activity.

Prolonged crying and hypotonic-hyporesponsive episodes have also been associated with other vaccines [6,58]. Neither of these reactions is known to be associated with long-term sequelae [6,57,58].

Seizures following pertussis-containing vaccines are usually febrile seizures [6] (see "Clinical features and evaluation of febrile seizures" and "Patient education: Febrile seizures (Beyond the Basics)"). The risk of seizures depends upon the vaccine preparation:

DTaP – In a cohort of more than 430,000 children who received DTaP at ages 6 through 23 months, the risk of seizures was not increased within zero to three days after vaccination (incidence rate ratio 0.87, 95% CI 0.72-1.05) [77].

DTaP combination – In a cohort of 378,834 Danish children who received combination DTaP-inactivated polio-H. influenzae type b (DTaP-IPV-Hib) vaccine at 3, 5, and 12 months, the risk of febrile seizure was increased on the day of the first (hazard ratio [HR] 6.02, 95% CI 2.86-12.65) and second (HR 3.94, 95% CI 2.18-7.10) dose compared with a reference cohort [78]. However, the absolute risk was small (<4 per 100,000 vaccinations). Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

DTwP – In a cohort of almost 680,000 children who received DTwP, the risk of febrile seizures was increased on the day of vaccination (adjusted RR 5.7) [79]. Vaccine-associated febrile seizures were not associated with an increased risk of afebrile seizures or neurodevelopmental disability.

Administration with other vaccines – 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 [80,81]. 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) [80]. 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 [82].

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 [83,84]. (See "Dravet syndrome: Genetics, clinical features, and diagnosis", section on 'Clinical features'.)

RESOURCES — Resources related to immunization in children zero through six years of age 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 5th to 6th 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 10th to 12th 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 e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (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

In accordance with the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians, we recommend immunization with diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine (DTaP) (table 1) for infants and children aged six weeks through six years (Grade 1A). (See 'Indications' above.)

Immunization is also indicated for unimmunized or underimmunized children with diphtheria or tetanus disease and unimmunized or underimmunized contacts of patients with diphtheria, tetanus, or pertussis disease. (See 'Indications' above.)

In the United States, DTaP vaccine is typically administered at 2 months, 4 months, 6 months, 15 through 18 months, and 4 to 6 years of age (figure 3). (See 'Routine schedule' above.)

The catch-up schedule for children with lapsed or incomplete diphtheria, tetanus, and/or pertussis immunization is provided in the table (table 2). (See 'Catch-up schedule' above.)

An alternate schedule may be necessary for infants and children who develop natural tetanus, diphtheria, or pertussis disease and children with certain neurologic conditions. (See 'Special circumstances' above.)

Absolute contraindications, precautions, and conditions that are neither contraindications nor precautions to administration of DTaP are listed in the table (table 3). (See 'Contraindications and precautions' above.)

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 rare (table 4). (See 'Adverse reactions' above.)

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REFERENCES

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