VA Class:IM105

ATC Class:J07AF01

AHFS Class:

• Toxoids 80:08

Generic Name(s):

• Diphtheria and Tetanus Toxoids Adsorbed

• Tetanus and Diphtheria Toxoids Adsorbed

Diphtheria and tetanus toxoids adsorbed (DT) and tetanus and diphtheria toxoids adsorbed (Td) are fixed-combination preparations contain tetanus and diphtheria toxins (toxoids) adsorbed onto an aluminum adjuvant and are used to stimulate active immunity to diphtheria and tetanus.100,112,113,114 DT contains a higher dose of diphtheria toxoid than Td.112,113,114

Diphtheria and tetanus toxoids adsorbed (DT) is used to stimulate active immunity to diphtheria and tetanus in infants and children 6 weeks through 6 years of a 100,114,199 tetanus and diphtheria toxoids adsorbed (Td) is used to stimulate active immunity to diphtheria and tetanus in adults, adolescents, and children 7 years of age or older.112,113,199,200

The US Public Health Service Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), and other experts recommend that all individuals receive routine immunization against diphtheria, tetanus, and pertussis.100,105,195,196,199,200,201,205 Use of a combination vaccine generally is preferred over separate injections of the equivalent component vaccines;134,199 considerations should include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage requirements, cost), patient preference, and potential for adverse effects.134 Therefore, a fixed-combination preparation that contains antigens for all 3 diseases (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed; DTaP) is preferred for primary and booster immunization against these diseases in infants and children 6 weeks through 6 years of age unless pertussis antigens are contraindicated or should not be used.100,105,166,199 DT should be used for primary or booster immunization against diphtheria and tetanus only when DTaP cannot be used.100,105,114,134,166,199 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Td usually is the preparation of choice for primary and booster immunization against diphtheria and tetanus in adults, adolescents, and children 7 years of age or older.100,105,196,199,200,205 However, to reduce the morbidity associated with pertussis, ACIP, AAP, and other experts recommend that a single dose of a fixed-combination preparation that also contains pertussis antigens (tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed [Tdap]) be used in place of a required primary or booster dose of Td in individuals 7 years of age or older who have not previously received Tdap, unless pertussis antigens are contraindicated or should not be used.105,195,196,199,200,201,205,234,235,236,237,238 Individuals in this age group who previously received a dose of Tdap should then receive Td for subsequent primary or booster doses.195,196,200,201,205 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

DT or Td may be indicated for postexposure vaccination against diphtheria in addition to anti-infective postexposure prophylaxis in unvaccinated or inadequately vaccinated household and other close contacts of an individual with diphtheria.100,105,112 (See Uses: Postexposure Prophylaxis of Diphtheria.)

DT or Td may be indicated in conjunction with passive immunization with tetanus immune globulin (TIG) for postexposure prophylaxis against tetanus in individuals with tetanus-prone wounds who are inadequately immunized against tetanus or whose tetanus immunization history is unknown or uncertain.100,105,112,113,195,196,205 (See Uses: Postexposure Prophylaxis of Tetanus.)

DT and Td are not indicated for treatment of diphtheria or treatment of tetanus infection.113,114 However, because diphtheria and tetanus infections do not necessarily confer immunity, initiation or completion of active immunization against these diseases is indicated at the time of recovery in any previously unvaccinated or incompletely vaccinated individual.100,105,166

Risks of Diphtheria and Tetanus Exposure and Infection

Diphtheria

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, toxigenic strains of C. ulcerans .100,105,115,166,195,196,205,228 Diphtheria occurs worldwide, particularly in tropical countries.166 Although diphtheria occurs rarely in the US, C. diphtheriae continues to circulate in the US in areas where diphtheria previously was endemic.100,105,166,228

Before widespread immunization against diphtheria was initiated in the 1940s, diphtheria was a major cause of morbidity and mortality among children.166 During the 1920s, there were approximately 100,000-200,000 cases of diphtheria and 13,000-15,000 diphtheria-related deaths each year in the US.166 From 1980 through 2011, 55 cases of diphtheria were reported in the US with an average of 1-2 per year (range: 0-5 cases per year).166 In 1996, toxigenic C. diphtheriae was isolated from residents of a Native American community in South Dakota166,229 and toxigenic C. ulcerans was isolated from an individual in Indiana with respiratory diphtheria.229 In 2003, fatal respiratory diphtheria occurred in an unvaccinated Pennsylvania resident who had returned from a trip to rural Haiti (a country where diphtheria is endemic).228,229

Most cases of diphtheria occur in individuals who are unvaccinated or incompletely vaccinated against the disease.100,105,166

Diphtheria is endemic in many countries in Asia, the South Pacific, the Middle East, and Eastern Europe and also is endemic in Haiti and the Dominican Republic.115 Since 2011, large outbreaks of diphtheria have occurred in Indonesia, Thailand, and Laos.115 Individuals who are unvaccinated or inadequately vaccinated against diphtheria, especially travelers who will live or work with local populations in countries where diphtheria is endemic, are at risk.115

The US Centers for Disease Control and Prevention (CDC) Travelers' Health website ([Web]) should be consulted for information regarding where diphtheria is endemic.115

Tetanus

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani .105,113,114,115,166 Tetanus occurs worldwide,115,166 but is reported most frequently in densely populated regions in hot, damp climates with soil rich in organic matter.166

In the US, a marked decrease in mortality from tetanus occurred from the early 1900s to the late 1940s when immunization against tetanus became part of routine childhood immunization.166 From 2001 through 2008, 233 cases of tetanus were reported in the US (average of 29 per year) with a case fatality rate of 13%.166 From 2009 through 2012, an average of 29 cases of tetanus per year were reported in the US.166

Tetanus is not transmitted person-to-person.115,166 C. tetani usually enters the body through a wound.166 Any open wound can become contaminated with C. tetani , including tetanus-prone wounds (wounds contaminated with dirt, feces, soil, or saliva; deep wounds; burns; crush injuries; wounds containing devitalized or necrotic tissue) and apparently clean, superficial wounds (wounds from surgical procedures, insect bites, animal bites, dental infections, compound fractures, chronic sores and infections, IV drug use).105,115,166 Heroin users, particularly those who inject themselves subcutaneously, appear to be at high risk for tetanus.166 Most cases of tetanus in the US occur following an acute wound, usually a puncture or contaminated, infected, or devitalized wound considered tetanus-prone.166

Almost all reported cases of tetanus occur in individuals who are unvaccinated or inadequately vaccinated against the disease (i.e., received an incomplete primary immunization series or received a complete primary series but did not receive recommended booster doses).105,115,166

Because C. tetani spores are ubiquitous in the environment worldwide, travelers can acquire tetanus anywhere in the world if they are unvaccinated or incompletely vaccinated against the disease.115 Tetanus is more common in rural and agricultural regions, areas where contact with soil or animal excreta is more likely, and areas where immunization rates are inadequate.115

Primary and Booster Immunization with Diphtheria and Tetanus Toxoids Adsorbed (DT)

Infants and Children 6 Weeks Through 6 Years of Age

DT is used for primary and booster immunization against diphtheria and tetanus in infants and children 6 weeks through 6 years of age when initiation or continuation of immunization with DTaP is contraindicated because of the pertussis component.100,105,114,166 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

When DT is used in infants and children 6 weeks through 6 years of age (i.e., when DTaP cannot be used), primary immunization consists of a series of 4 or 5 doses.100,105,114 ACIP, AAP, and other experts recommend that the first 3 doses be given at 2, 4, and 6 months of age and a fourth dose be given at 15-18 months of age.100,105 In those who received 4 doses before their fourth birthday, a fifth dose is recommended at 4 through 6 years of age (usually just prior to entry into kindergarten or elementary school).100,105 This dose is not necessary if the last dose of the primary series was given on or after the fourth birthday.100,105

Primary immunization against diphtheria and tetanus may be integrated with primary immunization against pertussis, hepatitis A, hepatitis B, Haemophilus influenzae type b (Hib), influenza, poliomyelitis, measles, meningococcal disease, mumps, rubella, rotavirus, varicella, and pneumococcal disease.100,105,134,199 (See Drug Interactions: Vaccines.)

Primary and Booster Immunization with Tetanus and Diphtheria Toxoids Adsorbed (Td)

Primary Immunization in Children 7 through 10 Years of Age

Td is used for primary immunization against diphtheria and tetanus in children 7 through 10 years of age.100,105,112,113,199

Children 7 through 10 years of age who did not receive primary immunization against diphtheria and tetanus with DTaP, DT, or diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP; not commercially available in the US) in early childhood according to the recommended childhood immunization schedule and those who previously received fewer than the total recommended doses of DTaP, DT, Td, or DTP should receive catch-up immunization against these diseases.105,199,201

For catch-up vaccination in children 7 through 10 years of age, ACIP, AAP, and other experts recommend 3 doses of a preparation containing tetanus and diphtheria toxoids adsorbed.105,199 The preferred primary immunization schedule in previously unvaccinated or incompletely vaccinated children 7 through 10 years of age is a single dose of Tdap followed by a dose of Td given 1-2 months after the Tdap dose and a second dose of Td given 6-12 months after the first dose of Td;105,199 however, the Tdap dose may be substituted for any 1 of the 3 doses of Td.105 These children should not receive the booster dose of Tdap usually recommended at 11 through 12 years of age.105,199 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Booster Immunization in Adolescents 11 through 18 Years of Age

ACIP, AAP, and other experts recommend that all adolescents who received primary immunization with DTaP, DT, Td, or DTP (not commercially available in the US) receive a booster dose of a preparation containing diphtheria and tetanus toxoids adsorbed at 11 through 18 years of age (preferably at 11 through 12 years of age).100,105,196,199,201 Because adolescents also may be at risk for pertussis, these experts recommend that a single dose of Tdap be used (instead of Td) for the adolescent booster dose at 11 through 18 years of age (preferably at 11 through 12 years of age), unless pertussis antigens are contraindicated or should not be used.105,196,199,201,236 If Tdap is unavailable or was administered previously, Td should be used for this adolescent booster dose.195,199,201 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Primary and Booster Immunization in Adults 19 Years of Age or Older

Td is used for primary and booster immunization against diphtheria and tetanus in adults 19 years of age or older.100,112,113,195,200

Adults with an incomplete or uncertain history of primary immunization against diphtheria and tetanus should receive primary immunization with 3 doses of Td.100,113,195,200 However, because adults may also be susceptible to pertussis, ACIP recommends that primary immunization against diphtheria and tetanus in previously unvaccinated adults 19 years of age or older (including those 65 years of age or older) include a single dose of Tdap, unless pertussis antigens are contraindicated or should not be used.195,200,237 The preferred primary immunization schedule in previously unvaccinated adults 19 years of age or older is a single dose of Tdap followed by a dose of Td given at least 4 weeks after the Tdap dose and a second dose of Td given 6-12 months after the first dose of Td;195,200 however, the Tdap dose may be substituted for any 1 of the 3 doses of Td.195 This Tdap booster dose should only be used in those who have not previously received a dose of Tdap.200 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.) If Tdap is not available or was administered previously, Td should be used.195,200

Adults who have received primary immunization against diphtheria and tetanus should receive routine booster doses of Td every 10 years.100,112,113,134,195,200 In addition, an emergency booster dose of Td may be indicated in the event of injury and possible exposure to tetanus infection.100,112,166,195 (See Uses: Postexposure Prophylaxis of Tetanus.) Although Td usually is recommended for these booster doses, adults also may be at risk for pertussis and ACIP recommends that a single dose of Tdap be used (instead of Td) when a booster dose is needed in adults 19 years of age or older (including those 65 years of age or older).195,200,236,237 Although a 10-year interval between the last dose of a preparation containing tetanus and diphtheria toxoids and the booster dose of Tdap has been recommended to reduce the risk of local and systemic reactions,195 ACIP states that the Tdap dose should be given when indicated (regardless of the interval between doses) since this ensures protection against pertussis.200,237 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccines Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.) If Tdap is not available or was administered previously, Td should be given.195,200

Pregnant Women

Unless contraindicated, all women of childbearing potential should be adequately immunized against tetanus and diphtheria.100,105,195,205 Pregnant women who are immune to these diseases can confer protection to their infants through transplacental transfer of maternal antibody.105,195,205 Obstetric and neonatal tetanus and obstetric and neonatal diphtheria are prevented if protective levels of tetanus and diphtheria antitoxin (i.e., at least 0.1 international units when tested using enzyme-linked immunosorbent assay [ELISA]) are present in the mother.205 (See Pharmacology.)

Ideally, primary immunization against diphtheria and tetanus should be completed prior to pregnancy.100,105,195,205 However, because of the risks associated with diphtheria and tetanus, ACIP, AAP, and other experts state that pregnancy is not considered a contraindication for preparations containing diphtheria and tetanus toxoids.100,105,195,196,200,201,205,234

Pregnant women who have not received primary immunization with DTaP, DTP (not commercially available in the US), DT, Td, or single-antigen tetanus toxoid adsorbed (not commercially available in the US) and those whose tetanus immunization history is unknown or uncertain should receive a primary series of 3 doses of vaccine containing diphtheria and tetanus antigens beginning during pregnancy.205,234,238 Because of the risks of pertussis, ACIP and other experts recommend that a dose of Tdap be substituted for one of the required Td doses, preferably during the third trimester (optimally between 27 and 36 weeks of gestation).200,238 In addition, to ensure protection against pertussis, these experts recommend that a dose of Tdap be administered during each pregnancy, irrespective of the woman's prior vaccination history.200,238 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

If feasible, the primary vaccination series should be completed in those who previously received only 1 or 2 doses of a preparation containing tetanus and diphtheria antigens.100,105,205 Two doses of a preparation containing tetanus toxoid adsorbed given at least 4-6 weeks before delivery stimulate antitoxin levels that are sufficient to protect the mother and cross the placenta to protect the neonate against tetanus.205

When a pregnant woman's history of tetanus vaccination is uncertain, serologic testing can be done to determine whether she has protective levels of antitoxin.205 Those who have never been vaccinated against tetanus or have levels of tetanus antitoxin that are not protective should be vaccinated during pregnancy to ensure protection against maternal and neonatal tetanus.195,205 Because diphtheria is rare in the US, serologic testing for diphtheria antitoxin is not usually necessary in pregnant women.205

Pregnant women who were previously vaccinated but received the most recent dose of a preparation containing tetanus and diphtheria antigens 10 or more years previously should receive a booster dose of a preparation containing diphtheria and tetanus toxoids during the second or third trimester of pregnancy (and before 36 weeks of gestation).100,105,195,205 This dose is important if the woman does not have sufficient tetanus immunity to protect against maternal and neonatal tetanus or if protection against diphtheria is needed (e.g., for travel to an area where diphtheria is endemic).205 ACIP recommends that Tdap be used (instead of Td) when a booster dose is indicated in a pregnant woman.238

If postexposure prophylaxis of tetanus is indicated as part of wound management in a pregnant women, the usual recommendations regarding emergency booster doses should be followed.205 (See Uses: Postexposure Prophylaxis of Tetanus.) If 5 or more years have elapsed since she received a preparation containing tetanus antigen, a booster dose of a preparation containing tetanus toxoid be administered.234 ACIP recommends that Tdap be used (instead of Td) when a booster dose is indicated for postexposure prophylaxis of tetanus in a pregnant woman.238

HIV-infected Individuals

ACIP, AAP, and other experts state that recommendations regarding primary or booster immunization against tetanus and diphtheria in individuals with human immunodeficiency virus (HIV) infection are the same as those for individuals who are not HIV-infected.105,155,156 However, immunization may be less effective in HIV-infected individuals than in immunocompetent individuals.105,156

Health-care Personnel

Health-care personnel should have documentation of age-appropriate primary immunization with a preparation containing diphtheria and tetanus toxoids and a booster dose of Td every 10 years.235 In addition, ACIP recommends that all health-care personnel (regardless of age) receive a single dose of Tdap if they have not previously received a dose.235

Health-care personnel who do not have documentation of primary immunization against tetanus and diphtheria should receive a 3-dose vaccination series using Tdap for the first dose and Td for subsequent primary and booster doses.235 Previously vaccinated health-care personnel who have not received a dose of Tdap should receive a dose as soon as feasible, regardless of the interval since the last dose of vaccine containing diphtheria or tetanus toxoids (e.g., Td).235 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.) Td should be used for subsequent booster doses.235

Travelers

Tetanus, diphtheria, and pertussis occur worldwide, and travelers are at risk if they are unvaccinated or incompletely vaccinated against these diseases.115 (See Uses: Risks of Diphtheria and Tetanus Exposure and Infection.)

CDC recommends that all travelers, including children, be adequately immunized against diphtheria, tetanus, and pertussis before leaving the US.115

Because children 6 weeks through 6 years of age also should be immunized against pertussis, travelers in this age group who are unvaccinated or incompletely vaccinated should receive the remaining required doses of DTaP or, if the pertussis component is contraindicated, the remaining required doses of DT prior to travel.115 If necessary to complete the vaccination series before departure, an accelerated immunization schedule using the age-appropriate minimum intervals between doses can be used.105,115 (See Dosage and Administration: Dosage.)

Adults, adolescents, and children 7 years of age or older who are unvaccinated or incompletely vaccinated should receive a single dose of Tdap (unless pertussis antigens are contraindicated or should not be used) followed by the remaining recommended doses of Td prior to travel.115,236

Because immunity from childhood vaccination and natural disease wanes with time and to provide protection against pertussis in travelers, previously vaccinated adults and adolescents 11 years of age or older who have not received a dose of Tdap should receive a single booster dose of Tdap.115 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.) Individuals who have previously received Tdap should receive a booster dose of Td if indicated.115

Postexposure Prophylaxis of Diphtheria

Postexposure vaccination with a preparation containing diphtheria toxoid adsorbed may be indicated in addition to anti-infective postexposure prophylaxis in unvaccinated or inadequately vaccinated household and other close contacts of an individual with diphtheria.100,105,166

Regardless of vaccination status, ACIP, AAP, and CDC recommend that all household and other close contacts of an individual with culture-confirmed or suspected diphtheria promptly receive anti-infective postexposure prophylaxis (single IM dose of penicillin G benzathine or oral erythromycin given for 7-10 days).100,105,166,228 Samples for cultures should be taken prior to initiating anti-infective therapy and the individual should be observed for 7 days for evidence of diphtheria.105,166,228

Individuals exposed to diphtheria who previously received less than 3 doses of a preparation containing diphtheria toxoid adsorbed or whose vaccination status is unknown or uncertain should receive an immediate dose of an age-appropriate preparation containing diphtheria toxoid adsorbed, and the primary vaccination series should be completed.100,105,166 In addition, close contacts who previously completed the primary vaccination series against diphtheria should receive a booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed if it has been 5 years or longer since their last booster dose.100,105,166

Diphtheria carriers should receive an anti-infective regimen active against C. diphtheriae .166 Vaccination does not eliminate carriage of C. diphtheriae .100 However, diphtheria carriers who are unvaccinated or inadequately vaccinated should receive immunization using an age-appropriate preparation containing diphtheria toxoid adsorbed and those who are vaccinated but have not received a dose of a preparation containing diphtheria toxoid adsorbed within the last 5 years should receive a booster dose.105

Because diphtheria infection does not necessarily confer immunity, the primary vaccination series using an age-appropriate preparation of diphtheria toxoid adsorbed should be initiated or completed during convalescence.105

Diphtheria antitoxin (equine) (available in the US only from CDC under an investigational new drug [IND] protocol) is no longer routinely recommended for postexposure prophylaxis of diphtheria in contacts,100,105,166 but may be recommended in exceptional circumstances for postexposure prophylaxis in individuals with known or suspected exposure to toxigenic Corynebacterium .204,228 (See Diphtheria Antitoxin (Equine) 80:04.) To obtain diphtheria antitoxin (equine), clinicians should contact the CDC at 404-639-8257 from 8:00 a.m. to 4:30 p.m. EST Monday-Friday or the CDC Emergency Operations Center at 770-488-7100 after hours, on weekends, and holidays.166,204,228

Postexposure Prophylaxis of Tetanus

Td is used in individuals 7 years of age or older requiring primary or booster immunization against tetanus for routine wound management.100,105,112 When active immunization against tetanus is indicated for routine wound management in children younger than 7 years of age, use of DTaP is preferred; DT should be used only if pertussis antigens are contraindicated or should not be used.100,105

In the event of injury and possible exposure to tetanus infection, the need for active immunization against tetanus (with a preparation containing tetanus toxoid adsorbed) with or without passive immunization against tetanus (with tetanus immune globulin [TIG]) depends on the individual's history of tetanus immunizations and the likelihood of contamination with tetanus bacilli (e.g., condition of the wound, source of contamination).100,105,113,166,195,196,205 A thorough attempt must be made to determine whether the individual has previously received a full primary series of tetanus vaccination and any required booster doses.100,105,195,196,205 Because of the very small amount of tetanus toxin required to produce illness, there is no natural immunity to tetanus and individuals who recover will not be immune to future tetanus disease.100,166 Therefore, individuals recovering from tetanus should begin or complete active immunization against tetanus during convalescence.100,105,166

Wounds generally are characterized as being tetanus prone or as clean, minor wounds.100,105,166 Tetanus-prone wounds include, but are not limited to, wounds contaminated with dirt, feces, soil, or saliva, deep wounds, burns, crush injuries, and wounds containing devitalized or necrotic tissue.100,105,166 Tetanus also has been associated with apparently clean, superficial wounds, surgical procedures, insect bites, animal bites, dental infections, compounds fractures, chronic sores and infections, and IV drug abuse.166 Wound care is an essential part of postexposure prophylaxis of tetanus and is necessary regardless of vaccination status.100,105 Wounds should be properly cleaned and debrided, especially if dirt or necrotic tissue is present and all necrotic tissue and foreign material should be removed.105

Any individual whose tetanus immunization status is unknown or uncertain should be considered to have had no previous doses of tetanus toxoid adsorbed.100,195,196,205 An emergency booster dose of a preparation containing tetanus toxoid adsorbed is unnecessary if the wound is clean and minor (not tetanus prone) and the patient has previously received the complete primary vaccination series against tetanus and any indicated booster doses within the last 10 years.100,113,166,195,196 However, an emergency booster dose of a tetanus toxoid-containing preparation is necessary in individuals with a clean, minor wound if fewer than 3 doses were administered in the past (incompletely immunized) or if 10 or more years have elapsed since primary immunization or the last booster dose.100,113,166,195,196 If the wound is tetanus prone, an emergency booster dose of a tetanus toxoid-containing preparation should be given if fewer than 3 doses were administered in the past (incompletely immunized) or if 5 or more years have elapsed since primary immunization or the last booster dose.100,113,166,195,196 In addition, a dose of TIG should be administered concomitantly with the tetanus toxoid-containing preparation at a separate site if the wound is tetanus prone and if the patient received fewer than 3 doses of a tetanus toxoid-containing preparation in the past (incompletely immunized).100,195,196

ACIP, AAP, and other experts recommend that a single dose of Tdap be used in place of a dose of Td for postexposure prophylaxis of tetanus in adults and adolescents 11 years of age or older (including adults 65 years of age or older) who have not previously received a dose of Tdap, unless pertussis antigens are contraindicated or should not be used.195,196,201,205,237,238 If Tdap is unavailable or was administered previously, Td should be used for postexposure prophylaxis.195,196,201,205,237

Table 1 summarizes ACIP guidelines for active and passive immunization against tetanus in routine wound management.

Anti-infectives are not indicated for tetanus postexposure prophylaxis since anti-infectives do not neutralize exotoxin already formed and cannot eradicate C. tetani spores, which may revert to toxin-producing vegetative forms.100,166

Administration

Diphtheria and tetanus toxoids adsorbed (DT) and tetanus and diphtheria toxoids adsorbed (Td) are administered only by IM injection.112,113,114

To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, thickness of adipose tissue and muscle at the injection site, and the injection technique.134

Depending on patient age, IM injections of DT or Td should be made into the anterolateral muscles of the thigh or deltoid muscle of the arm.112,113,114,134 In adults, adolescents, and children 3 years of age or older, IM injections should preferably be made in the deltoid muscle.134 In infants and children 6 weeks to 2 years of age, IM injections should preferably be made into the anterolateral thigh;134 alternatively, the deltoid muscle can be used in those 1-2 years of age if muscle mass is adequate.134

The gluteal area or areas where there may be a major nerve trunk should be avoided.112,113,114 If the gluteal muscle is chosen for infants younger than 12 months of age because of special circumstances (e.g., physical obstruction of other sites), it is essential that the clinician identify anatomic landmarks prior to injection.134

DT and Td should be inspected visually for particulate matter and discoloration prior to administration.112,113,114 To ensure a uniform suspension of antigens, single-dose vials of DT or single-dose vials or single-dose prefilled syringes of Td should be shaken well prior to use.112,113,114 After shaking, a uniform, white, cloudy suspension should result; the vaccine should be discarded if it contains particulate matter, is discolored, or cannot be resuspended.112,113,114

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;114,134 such reactions may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements).134 Syncope occurs most frequently in adolescents and young adults.134 Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.134 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.134 If syncope occurs, the patient should be observed until symptoms resolve.134

DT and Td should not be diluted and should not be mixed with any other vaccine or solution.112,113,114

When passive immunization with tetanus immune globulin (TIG) is indicated in addition to active immunization with a preparation containing tetanus toxoid adsorbed for postexposure prophylaxis of tetanus, DT or Td may be given simultaneously with TIG using different syringes and different injection sites.112,100,134,195,196,205 (See Uses: Postexposure Prophylaxis of Tetanus.)

DT or Td may be given simultaneously with other age-appropriate vaccines.100,105,134,199 When multiple vaccines are administered during a single health-care visit, each parenteral vaccine should be given with a different syringe and at different injection sites.134 Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134

Dosage

DT and Td are administered in 0.5-mL doses.112,113,114

Each 0.5 mL of DT contains 25 flocculation units (Lf) units of diphtheria toxoid adsorbed and 5 Lf units of tetanus toxoid adsorbed.114

Each 0.5 mL of Td contains 2 Lf units of diphtheria toxoid adsorbed and, depending on the manufacturer, either 2 or 5 Lf units of tetanus toxoid adsorbed.112,113

The dosing schedule (i.e., number of doses) and specific preparation (i.e., DT, Td) for primary and/or booster immunization varies depending on age.100,112,113,114,199,200 The age-appropriate recommendations for the specific preparation used should be followed.112,113,114,199,200

DT is used only in infants and children 6 weeks through 6 years of age and only when diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) cannot be used (i.e., when pertussis antigens are contraindicated or should not be used).100,105,114

Td is used only in adults, adolescents, and children 7 years of age or older.100,112,113

The complete primary vaccination series and recommended booster doses must be administered to ensure optimal protection against diphtheria and tetanus.113,114 Interruption of the primary immunization series resulting in intervals between doses longer than recommended do not interfere with the final immunity achieved; therefore, it is not necessary to give additional doses or to start the series over.100,134,166

If an accelerated immunization schedule is necessary in infants and children 6 weeks through 6 years of age (e.g., for catch-up immunization, immunization prior to travel), the minimum intervals between the first, second, and third doses of DT are 4 weeks and the minimum intervals between the third, fourth, and fifth doses are 6 months.199 In adults, adolescents, and children 7 years of age or older, the minimum interval between the first and second dose of Td is 4 weeks and the minimum interval between second and third dose is 6 months.199,200

Primary and Booster Immunization

Infants and Children 6 Weeks Through 6 Years of Age (DT)

For primary immunization in infants and children 6 weeks through 6 years of age when DTaP cannot be used (i.e., when pertussis antigens are contraindicated or should not be used), the manufacturer, ACIP, American Academy of Pediatrics (AAP), and other experts recommend that DT be given in a series of 4 doses with or without a fifth (booster) dose.100,105,114,199 The first 3 doses are given 4-8 weeks apart (usually at 2, 4, and 6 months of age) and the fourth dose is given approximately 6-12 months after the third dose (usually at 15-18 months of age).100,105,114,199 The fourth dose may be administered as early as 12 months of age, provided at least 6 months have elapsed since the third dose.105,199

At 4 through 6 years of age (usually just prior to entry into kindergarten or elementary school), children who received primary immunization with DT before their fourth birthday should receive a fifth (booster) dose of the preparation.100,105,114,199 The fifth dose is not necessary if the last dose of the primary series was given on or after the fourth birthday.100,105,199

Previously Unvaccinated Children 7 through 10 Years of Age (Td)

For primary immunization in children 7 through 10 years of age who were not vaccinated at a younger age, Td is given in a series of 3 doses;112,113,199 the second dose is given 4-8 weeks after the first dose, and the third dose is given 6-12 months after the second dose.112,113,196,199

The preferred primary immunization schedule recommended by ACIP, AAP, and other experts for catch-up vaccination in previously unvaccinated children 7 through 10 years of age is a single dose of Tdap (unless pertussis antigens are contraindicated or should not be used) followed by a dose of Td given 1-2 months after the Tdap dose and a second Td dose given 6-12 months after the first Td dose.105,199 Alternatively, Tdap may be substituted for any 1 of the Td doses.105 Children who receive a dose of Tdap at 7 through 10 years of age should not receive a Tdap booster dose at 11 through 12 years of age.105,199 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Previously Unvaccinated Adolescents 11 through 18 years (Td)

For primary immunization in adolescents 11 through 18 years of age who were not vaccinated at a younger age, Td is given in a series of 3 doses;112,113,196,199 the second dose is given 4-8 weeks after the first dose, and the third dose is given 6-12 months after the second dose.113,196,199

The preferred primary immunization schedule recommended by ACIP, AAP, and other experts for previously unvaccinated adolescents 11 through 18 years of age is a single dose of Tdap (unless pertussis antigens are contraindicated or should not be used) followed by a Td dose given at least 4 weeks after the Tdap dose and a second dose of Td given 6-12 months after the Td dose.196,199 Alternatively, the Tdap dose may be substituted for any 1 of the 3 doses of Td.196,201 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.) Td should be used for all subsequent booster doses.195,201

Booster Doses in Adolescents 11 through 18 Years of Age (Td)

All individuals who received primary immunization with DTaP, diphtheria and tetanus toxoids adsorbed and whole-cell pertussis vaccine (DTP; not commercially available in the US), DT, or Td should receive a booster dose of a preparation containing diphtheria and tetanus toxoids adsorbed at 11 through 18 years of age (preferably at 11 through 12 years of age) and routine booster doses of Td every 10 years to maintain adequate immunity against diphtheria and tetanus.100,105,196,199

Because adolescents also may be at risk for pertussis, ACIP, AAP, and other experts recommend that a single dose of Tdap be used (instead of Td) for the adolescent booster dose given at 11 through 18 years of age (preferably at 11 through 12 years of age), unless Tdap has already been given or pertussis antigens are contraindicated or should not be used.195,199,201 If Tdap is unavailable or was administered previously, a dose of Td should be used for this adolescent booster dose.195,199 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Previously Unvaccinated Adults 19 Years of Age or Older (Td)

For primary immunization in previously unvaccinated adults and adults with an uncertain history of immunization against diphtheria and tetanus, ACIP and other experts recommend that Td be given in a series of 3 doses;100,113,195,200 the second dose is given 4-8 weeks after the first dose and the third dose is given 6-12 months after the second dose.100,113,195,200

The preferred primary immunization schedule recommended by ACIP and other experts for previously unvaccinated adults 19 years of age or older (including those 65 years of age or older) is a single dose of Tdap (unless pertussis antigens are contraindicated or should not be used) followed by a dose of Td given at least 4 weeks after the Tdap dose and a second dose of Td given 6-12 months after the first dose of Td.195,200 Alternatively, the Tdap dose may be substituted for any 1 of the 3 doses of Td.195,200 If Tdap is not available or was administered previously, Td may be given.195 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Booster Doses in Adults 19 Years of Age or Older (Td)

All adults who received primary immunization against diphtheria and tetanus should receive routine booster doses of Td every 10 years.100,112,113,195,200 In addition, an emergency booster dose of Td may be indicated in the event of injury and possible exposure to tetanus infection.100,166,195 (See Uses: Postexposure Prophylaxis of Tetanus.)

ACIP and other experts recommend that a single dose of Tdap should be used (instead of Td) when a booster dose is needed in adults 19 years of age or older (including those 65 years of age or older), unless pertussis antigens are contraindicated or should not be used.195,200,236,237 Thereafter, Td should be used whenever a booster dose is indicated.195,200,237

Postexposure Prophylaxis of Tetanus

For postexposure prophylaxis of tetanus, an emergency dose of a preparation containing tetanus toxoid adsorbed may be indicated with or without a dose of TIG.100,105,112,113,166,195,196,205 (See Table 1 in Uses: Postexposure Prophylaxis of Tetanus.)

Wound care is an essential part of postexposure prophylaxis of tetanus and wound care is necessary regardless of vaccination status.100,105 Wounds should be properly cleaned and debrided, especially if dirt or necrotic tissue is present and all necrotic tissue and foreign material should be removed.105

In the event of injury and possible exposure to tetanus infection in adults, adolescents, and children 7 years of age or older, an emergency booster dose of Td should be given as soon as possible if the individual has previously received less than 3 doses of any tetanus toxoid-containing preparation or if their immunization history is unknown or uncertain.100,105,113,166 If the injury is a clean, minor wound (not tetanus prone), the booster dose of a preparation containing tetanus toxoid adsorbed is given without passive immunization with TIG.100,105,113,166 However, for all other types of wounds (tetanus-prone wounds), a dose of TIG should be given in addition to the preparation of tetanus toxoid adsorbed. After the emergency booster dose, the primary vaccination series should be completed using a preparation containing tetanus toxoid adsorbed.100,105,113,166

In the event of injury and possible exposure to tetanus infection in adults, adolescents, and children 7 years of age or older who previously received 3 doses or more of a preparation containing tetanus toxoid adsorbed, an emergency booster dose of Td should be given if the injury is a clean, minor wound (not tetanus prone) and it has been 10 or more years since primary immunization against tetanus or the last booster dose of a preparation containing tetanus toxoid adsorbed.100,113,166 If the injury is a tetanus-prone wound, an emergency booster dose of Td should be given if it has been 5 or more years since primary immunization against tetanus or the last booster dose of a preparation containing tetanus toxoid adsorbed.100,113,166 In addition, those with tetanus-prone wounds should receive a dose of TIG.100,113,166

If the individual previously received only 3 doses of tetanus toxoid fluid (no longer commercially available in the US), a booster dose of a preparation containing tetanus toxoid adsorbed should be given.100

ACIP and other experts recommend that a single dose of Tdap should be used (instead of Td) in individuals 11 years of age or older (including those 65 years of age or older) who have not previously received a dose of Tdap, unless pertussis antigens are contraindicated or should not be used.195,196,200,201,237 If Tdap is not available or was administered previously, Td should be used.196,201,237 (See Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed 80:08.)

Postexposure Prophylaxis of Diphtheria

For postexposure prophylaxis of diphtheria, a dose of a preparation containing diphtheria toxoid adsorbed may be indicated in conjunction with anti-infective prophylaxis.100,105,166 (See Uses: Postexposure Prophylaxis of Diphtheria.)

All household and other close contacts of an individual with known or suspected diphtheria should receive an immediate dose of an age-appropriate preparation containing diphtheria toxoid adsorbed (DT or Td) if their vaccination status is unknown or they previously received less than 3 doses and the primary vaccination series should then be completed.100,105,166 Individuals who previously completed the primary vaccination series against diphtheria but have not received a dose of a preparation containing diphtheria toxoid adsorbed within the last 5 years should receive an immediate booster dose of an age-appropriate preparation (DT or Td).100,105,166

Adverse reactions to tetanus and diphtheria toxoids adsorbed (Td), especially Arthus-type hypersensitivity reactions, occur most frequently in individuals who have received a large number of booster doses of preparations containing diphtheria and/or tetanus toxoids.166

Local Effects

The most frequent adverse effects of preparations containing diphtheria and tetanus toxoids adsorbed are mild to moderate local reactions at the injection site that may persist for several days. These local effects include erythema,112,113 warmth,112,113 swelling,112,113 edema,112 induration,112,113 pain,112 tenderness,112,113 cellulitis,113 pruritus,112 urticaria, and rash. A nodule may be palpable at the injection site166 for several weeks.100,166 Sterile abscesses or subcutaneous atrophy have also been reported rarely.100

Rarely, extensive local reactions manifested by erythema and boggy edema (Arthus-type hypersensitivity reactions) occur after injection of preparations containing tetanus toxoid.100,195,196,201 These reactions generally begin 2-12 hours after administration and are a local inflammatory reaction (vasculitis) that can include severe pain, swelling, induration, edema, hemorrhage, and necrosis.166,195,196 In some cases, painful swelling may extend from the shoulder to the elbow.166 Arthus reactions usually resolve without sequelae.195,196 The reactions occur most frequently in individuals who have received multiple prior booster doses of preparations containing tetanus toxoid adsorbed or tetanus toxoid fluid (no longer commercially available in the US).166

Local reactions to preparations containing adsorbed diphtheria and tetanus toxoids (without other severe adverse effects) do not preclude future use of the toxoid.100 However, individuals who experienced an Arthus-type hypersensitivity reaction usually have high serum tetanus antitoxin levels and should not be given emergency doses of a tetanus toxoid-containing preparation any more frequently than every 10 years, even if they have a wound that is neither clean nor minor.100,113,166,195,196

Systemic Effects

Rarely, systemic reactions including fever, chills, malaise, fatigue, myalgia, arthralgia or generalized aches and pains, nausea and vomiting, erythema multiforme or other rash, flushing, generalized urticaria or pruritus, tachycardia, dizziness, and hypotension have been reported following administration of preparations containing diphtheria and tetanus toxoids adsorbed.100,112,113,117 Fever may be immediate (occurring within 1-3 hours) or delayed.117 Such reactions generally are self-limited and can be managed effectively with symptomatic treatment.100

Rarely, severe anaphylactic or anaphylactoid reactions, characterized by urticaria and angioedema, difficulty breathing, hypotension, and/or shock, have been reported following administration of preparations containing tetanus and/or diphtheria antigens.100,113,114,117,118 In one study, 94 of 95 individuals with a history of anaphylactoid manifestations following a previous dose of tetanus toxoid were nonreactive following intradermal testing and tolerated further full immunizing doses of adsorbed diphtheria and tetanus toxoids.100,117 Deaths have been reported in temporal association with the administration of tetanus toxoid adsorbed.113

Guillain-Barré syndrome (GBS) has been reported in temporal association with tetanus toxoid.113 A review by the Institute of Medicine (IOM) found evidence of a causal relationship between tetanus toxoid and brachial neuritis and GBS.112,113,114 Analysis of active surveillance data collected during 1991 failed to demonstrate an increased risk of GBS in children or adults within 6 weeks following vaccination with a preparation containing tetanus toxoid adsorbed.195,196,230 (See Guillain-Barré Syndrome and Other Neurologic Disorders under Cautions: Precautions and Contraindications.)

Precautions and Contraindications

DT and Td are contraindicated in individuals who have had a severe allergic reaction (e.g., anaphylaxis) after a previous dose of the vaccine, any vaccine component, or any other preparation containing diphtheria or tetanus toxoids.112,113,114 (See Sensitivity Reactions under Cautions: Precautions and Contraindications.)

To determine whether there are any contraindications to administration of DT or Td and to accurately assess the benefits and risks of the vaccines for each patient, the patient and/or the patient's parent or guardian should be questioned about the health status of the patient and the occurrence of sensitivity or any adverse events after previous doses.105,112,113,114

The patient and/or the patient's parent or guardian should be informed of the benefits and risks of immunization with DT or Td and should be provided with a copy of the appropriate Vaccine Information Statement (available at CDC website [Web]).112,113,114,226 Patient and/or the patient's parent or guardian also should be advised of the importance of completing the primary immunization series and receiving recommended booster doses to ensure the highest level of protection against tetanus and diphtheria.100,112,113,114

Patients and/or the patient's parent or guardian should be instructed to report any severe or unusual adverse reactions to their health-care provider.112,113,114 Clinicians or individuals can report any adverse reactions that occur following vaccination to VAERS at 800-822-7967 or [Web].112,113,114

If a contraindication to tetanus toxoid-containing preparations exists in an individual who has previously received less than 3 doses, only passive immunization with tetanus immune globulin (TIG) should be considered when postexposure prophylaxis of tetanus is indicated.100

Sensitivity Reactions

Prior to administration of DT or Td, the clinician should review the patient's health status and history regarding possible sensitivity or any other adverse reactions after previous doses and should take all precautions known for prevention of allergic or any other adverse effects.112,113 Epinephrine and other appropriate agents and equipment should be available for immediate use in case an anaphylactic reaction occurs.112,113,114

Some manufacturers suggest that individuals who have a history of severe allergic reaction to a previous dose may be referred to an allergist for evaluation if further doses are being considered (e.g., for tetanus postexposure prophylaxis).112,113 Although skin testing has been suggested to help determine whether additional doses of a tetanus toxoid-containing preparation can be used in an individuals who developed a systemic reaction to the toxoid, utility of skin testing has been questioned since mild, nonspecific skin-test reactivity to tetanus toxoid commonly occurs, particularly when the preparation is used undiluted.100

Arthus-type Hypersensitivity Reactions

Individuals who experience Arthus-type hypersensitivity reactions or fever greater than 39.4°C after administration of tetanus toxoid adsorbed (see Cautions: Local Effects) usually have very high serum tetanus antitoxin levels and usually should not receive additional routine or emergency booster doses of a preparation containing tetanus toxoid adsorbed more frequently than every 10 years, even if postexposure prophylaxis of tetanus is indicated.100,112,113,195,196

Latex Sensitivity

Some packaging components of Td (Tenivac^®) single-dose prefilled syringes (i.e., tip caps) contain dry natural latex.113 Because some individuals may be hypersensitive to natural latex proteins,137,138,139 appropriate precautions should be taken if this preparation is administered to individuals with a history of latex sensitivity.137,138,139

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex, unless the benefits of vaccination outweigh the risk of a potential allergic reaction.134 Contact-type allergy is the most common type of latex sensitivity.134

Precautions Related to Booster Doses

Booster doses of Td should only be administered when indicated.100,112,113 Booster doses given more frequently than recommended are associated with an increased incidence and severity of adverse effects.112,113

Routine booster doses of Td should be administered once every 10 years.112,113 Emergency booster doses are not usually indicated unless at least 5 years have elapsed since the last dose.112,113 If a booster dose is given earlier than 10 years after a previous dose, the next routine booster dose should not be given for 10 years.113

Guillain-Barré Syndrome and Other Neurologic Disorders

The risk of developing GBS may be increased in individuals with a history of GBS within 6 weeks after receiving a prior dose of any preparation containing tetanus toxoid.114 Some manufacturers state that a decision to administer a preparation containing tetanus toxoid adsorbed to an individual with a history of GBS within 6 weeks after receiving a prior dose of any preparation containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.112,113

ACIP states that a history of GBS occurring within 6 weeks after a previous dose of a preparation containing tetanus toxoid adsorbed should be considered a precaution for subsequent doses of such preparations.134,195,196

ACIP does not consider brachial neuritis a precaution or contraindication for further doses.134,195,196

Individuals with Altered Immunocompetence

If DT or Td is administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy, the possibility that the immune response to the vaccine and efficacy may be reduced should be considered.112,113,114,134

Recommendations regarding use of tetanus and diphtheria toxoids in individuals with human immunodeficiency virus (HIV) infection are the same as those for individuals who are not HIV-infected.105,155,156 However, immunization may be less effective in individuals with HIV infection than in immunocompetent individuals.105

Thimerosal Precautions

Although there is no convincing evidence that the low concentrations of thimerosal (a mercury-containing preservative) contained in some vaccines is harmful to vaccine recipients,131,134,147,148,151,153,154,157,158,216,217 efforts to eliminate or reduce the thimerosal content in vaccines is recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.127,128,129,131,134

It was suggested that thimerosal in vaccines theoretically could have adverse effects in vaccine recipients; however, there is no conclusive evidence that the low levels of thimerosal contained in vaccines cause harm in vaccine recipients.131,134,147,148,151,153,154,157,158,216,217

Td (manufactured by MassBiologics) contains trace amounts of thimerosal from the manufacturing process (no more than 0.3 mcg of mercury per 0.5-mL dose).112 The US Food and Drug Administration (FDA) states that trace amounts of thimerosal from the manufacturing process are not considered clinically important.104

DT and Td (Tenivac^®) do not contain thimerosal or any other preservatives.113,114

For additional information on thimerosal in vaccines, see Thimerosal Precautions under Cautions: Precautions and Contraindications, in Influenza Virus Vaccine Inactivated 80:12.

Concomitant Illnesses

A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.100,134 Minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever) generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever).100,134

Limitations of Vaccine Effectiveness

DT and Td may not protect all individuals from diphtheria and tetanus.112,113,114

Optimum protection against diphtheria and tetanus is achieved with a primary series of 3 doses of preparations containing diphtheria and tetanus toxoids adsorbed.100,166

Duration of Immunity

Following primary immunization, the duration of protection against diphtheria is approximately 10 years.166

Following primary immunization, the duration of protection against tetanus is approximately 10 years.105,166 Although some individuals may be protected for life, antitoxin levels decrease over time and only approach the minimal protective level in most individuals 10 years after the last dose.166 The antitoxin response induced by tetanus toxoid adsorbed has a longer duration than that induced by tetanus toxoid fluid (no longer commercially available in the US).166

Pre- and Postvaccination Serologic Testing

Routine prevaccination serologic testing is not recommended.195,196,235

When postexposure prophylaxis against tetanus or preexposure vaccination in high-risk groups (e.g., travelers) is indicated, individuals with an unknown or uncertain history of vaccination generally should be considered unvaccinated and should receive the complete primary vaccination series.100,115,195

To avoid unnecessary vaccination, ACIP states that prevaccination serologic testing for tetanus and diphtheria antitoxin antibodies can be considered in adults, adolescents, or children 7 years of age or older who probably were vaccinated but cannot produce vaccination records.195,196 If levels of tetanus and diphtheria antitoxin are both at least 0.1 international units/mL, previous vaccination with diphtheria and tetanus toxoids adsorbed can be assumed.195,196

Improper Storage or Handling

Improper storage or handling of vaccines may reduce vaccine potency and can result in reduced or inadequate immune responses in vaccinees.134

All vaccines should be inspected upon delivery and monitored during storage to ensure that the appropriate temperature is maintained.134 (See Chemistry and Stability: Stability.)

DT or Td that has been mishandled or has not been stored at the recommended temperature should not be administered.134

If there are concerns about mishandling, the manufacturer or state or local immunization or health departments should be contacted for guidance on whether the vaccine is usable.134

Pediatric Precautions

Safety and efficacy of DT have not been established in infants younger than 6 weeks of age or in children 7 years of age or older.114 DT contains a higher dose of diphtheria toxoid (25 Lf units) than Td (2 Lf units).112,113,114 Because individuals 7 years of age and older have an increased incidence of adverse reactions to preparations containing more than 2 Lf units of diphtheria toxoid, DT should not be used in individuals 7 years of age or older.113,114

Safety and efficacy of Td have not been established in children younger than 7 years of age.112,113

The most common adverse effects following administration of DT in infants and children 2 months through 6 years of age are crying, fever, loss of appetite, and local reactions (pain, tenderness, swelling, erythema).114

Apnea has been reported following IM administration of vaccines in some infants born prematurely.114 Decisions regarding when to administer an IM vaccine in infants born prematurely should be based on consideration of the individual infant's medical status and potential benefits and possible risks of vaccination.114

Geriatric Precautions

In a clinical study that included 449 adults 65 years of age or older (including 192 adults 75 years of age or older), the proportion of those 65 years of age or older who had seroprotective antibody levels following a dose of Td (Tenivac^®) was marginally lower for tetanus and lower for diphtheria compared with younger individuals.113 The rate of solicited adverse events in those 65 years of age and older generally was similar to the rate in younger adults.113

Mutagenicity and Carcinogenicity

Studies have not been performed to date to evaluate the mutagenic or carcinogenic potential of DT or Td.112,113,114

Pregnancy and Lactation

Pregnancy

Animal reproduction studies have not been performed with Td.112,113 It is not known whether the toxoids can cause fetal harm, and they should be used during pregnancy only when clearly needed.112,113 Tetanus toxoids have been administered to pregnant women to prevent tetanus in neonates considered to be at high risk for the disease.105,205

Because of the risks associated with tetanus and diphtheria infection, ACIP, American Academy of Pediatrics (AAP), and other experts state that preparations containing diphtheria and tetanus antigens are not contraindicated during pregnancy.100,105,134,195,196,200,201,205 Although there is no evidence that diphtheria and tetanus toxoids are teratogenic, waiting until the second or third trimester of pregnancy (and before 36 weeks of gestation) to administer Td is recommended.100,105,201,205

Ideally, primary immunization against tetanus and diphtheria should be completed prior to pregnancy.100,105,195,205 Pregnant women who have not received primary immunization with DTaP, DTP (not commercially available in the US), DT, Td, or single-antigen tetanus toxoid adsorbed (not commercially available in the US) and those whose tetanus immunization history is unknown or uncertain should receive a primary series of 3 doses of vaccine containing diphtheria and tetanus toxoids beginning during pregnancy.205,234,238

Although Td generally is the preferred preparation for primary immunization against diphtheria and tetanus during pregnancy,105,196,205 ACIP, AAP, and other experts state that a dose of Tdap should be substituted for one of the required primary Td doses, preferably in the third trimester (optimally between 27 and 36 weeks of gestation) in previously unvaccinated or incompletely vaccinated pregnant women.200,238 In addition, to ensure protection against pertussis, these experts recommend that a dose of Tdap be administered during each pregnancy, regardless of the woman's prior vaccination history.200,238 To maximize maternal antibody response and passive antibody transfer to the infant, optimal timing for the Tdap dose is between 27 and 36 weeks of gestation.238 (See Pregnant Women under Uses: Primary and Booster Immunization with Tetanus and Diphtheria Toxoids Adsorbed [Td].)

When a pregnant woman's history of tetanus vaccination is uncertain, serologic testing can be done to determine whether she has protective levels of tetanus antitoxin (i.e., at least 0.1 international units when tested using enzyme-linked immunosorbent assay [ELISA]).205 Those who have never been vaccinated against tetanus or have levels of tetanus antitoxin that are not protective should be vaccinated during pregnancy to ensure protection against maternal and neonatal tetanus.196,205 Because diphtheria is rare in the US, serologic testing for diphtheria antitoxin is not usually necessary in pregnant women.205 Two doses of a preparation containing tetanus toxoid adsorbed given at least 4-6 weeks before delivery stimulates tetanus antitoxin levels that protect the mother and readily cross the placenta to protect the neonate against tetanus.205 (See Pregnant Women under Uses: Primary and Booster Immunization with Tetanus and Diphtheria Toxoids Adsorbed [Td].)

Sufficient tetanus protection is likely if the pregnant woman is younger than 31 years of age and received the complete childhood tetanus and diphtheria vaccination series and a booster dose of Td during adolescence or received the complete adult vaccination series of 3 doses of Td or single-antigen tetanus toxoid adsorbed (not commercially available in the US).205 Sufficient tetanus protection may also be present if the pregnant woman is 31 years of age or older and received the complete childhood vaccination series and at least 2 booster doses of Td; if the pregnant woman received a primary vaccination series consisting of 3 doses of Td or single-antigen tetanus toxoid adsorbed during adolescence or as an adult; or if serologic testing indicates protective levels of serum tetanus antitoxin.205

If postexposure prophylaxis of tetanus is indicated as part of wound management in a pregnant woman, the usual recommendations regarding emergency booster doses should be followed.205 (See Uses: Postexposure Prophylaxis of Tetanus.) Tdap should be used for the booster dose (instead of Td).234,238

Lactation

It is not known whether diphtheria or tetanus toxoids are distributed into milk.112,113 The manufacturers state that Td for adult use should be used with caution in nursing women.112,113

ACIP states that breastfeeding is not considered a contraindication for diphtheria and tetanus toxoids adsorbed.205

Diphtheria Antitoxin (Equine)

If both diphtheria antitoxin (equine) (available in the US only from CDC under an investigational new drug [IND] protocol) and a dose of diphtheria and tetanus toxoids adsorbed (DT) or tetanus and diphtheria toxoids adsorbed (Td) are required, they should be given at separate sites using different syringes.100 Although specific studies are not available, diphtheria antitoxin (equine) is unlikely to impair the immune response to diphtheria toxoid adsorbed.100

Immune Globulins

DT or Td may be administered simultaneously with (using different syringes and injection sites) or at any time before or after immune globulin (e.g., immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific immune globulin (e.g., hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG]).134

When passive immunization with TIG is indicated in addition to active immunization with a preparation containing tetanus toxoid adsorbed for postexposure prophylaxis of tetanus (see Uses: Postexposure Prophylaxis of Tetanus), TIG and the preparation containing tetanus toxoid adsorbed may be given simultaneously at separate sites using different syringes.100,112,113,114,195,196

Immunosuppressive Agents

Individuals receiving immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation therapy) may have a diminished immunologic response to DT or Td.112,113,114 Short-term (less than 2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day, systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive in usual dosages.100,134 There is some evidence that children receiving immunosuppressive therapy, including those with malignancies receiving maintenance chemotherapy, may have adequate antibody responses to diphtheria and tetanus toxoids adsorbed.103 Therefore, it has been suggested that these children receive the usual recommended doses of these toxoids at the usual intervals.103

Vaccines

Although specific data are not available regarding concurrent administration of DT or Td with all other available vaccines,112,113,114 the US Public Health Service Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), and other experts state that primary immunization against diphtheria and tetanus can be integrated with primary immunization against pertussis, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, human papillomavirus (HPV), influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella.100,105,199 However, unless combination vaccines appropriate for the age and vaccination status of the recipient are used, each parenteral vaccine should be administered using a different syringe and different injection site.100,105,199

DT or Td may be administered simultaneously with or at any interval before or after live viral vaccines, including measles, mumps, and rubella virus vaccine live (MMR).105,134 In addition, DT or Td may be administered simultaneously with or at any interval before or after inactivated vaccines, including Hib vaccine, hepatitis B vaccine,134 meningococcal vaccine,142,201 and poliovirus vaccine inactivated (IPV).134

Meningococcal Vaccine

Td has been administered concomitantly with meningococcal (groups A, C, Y and W-135) polysaccharide diphtheria toxoid conjugate vaccine (MCV4; Menactra^®) at a different site in adolescents 11 through 17 years of age without a decrease in antibody responses to either vaccine or a clinically important increase in adverse effects.142,201 Although antibody responses to some meningococcal antigens (serogroups C, Y, W-135) were higher when MCV4 (Menactra^®) was administered concurrently with Td than when MCV4 (Menactra^®) was given 1 month after Td, the clinical importance of these findings has not been determined.142,201 Antibody responses to tetanus and diphtheria antigens were similar in both study groups.142

ACIP states that Td may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after MCV4 (Menactra^®, Menveo^®) or meningococcal polysaccharide vaccine, groups A, C, Y and W-135 combined (MPSV4; Menomune^®).134,196,201

Pharmacology

Diphtheria and tetanus toxoids adsorbed (DT) and tetanus and diphtheria toxoids adsorbed (Td) stimulate active immunity to diphtheria and tetanus by inducing production of specific antitoxin antibodies.105,112,113,114

The diphtheria toxoid adsorbed component provides protection against the exotoxin elucidated by Corynebacterium diphtheriae .113,114 Primary immunization against diphtheria reduces the risk of developing diphtheria and the severity of clinical illness,100 but does not prevent or eliminate colonization or carriage of C. diphtheriae in the pharynx, nose, or skin of vaccinees.100 A complete primary immunization series with the age-appropriate preparation is needed to induce optimum levels of antitoxin that provide protection.100,166 Protective levels of diphtheria antitoxin (defined as at least 0.1 international units/mL)113,114,166,195,196 are attained at least 95% of individuals after the primary vaccination series.113,114,166 Following primary immunization, protective levels of diphtheria antitoxin levels may persist for about 10 years.166

Tetanus toxoid adsorbed induces production of specific antitoxin antibodies that neutralize exotoxin produced by Clostridium tetani .105,113,114 A complete primary series of a preparation containing tetanus toxoid adsorbed results in protective levels of tetanus antitoxin that persist for approximately 10 years.100,105,166,195,196 Protective levels of tetanus antitoxin were previously defined as at least 0.01 international units/mL when measured by in vivo neutralization assay,114,205 but are currently defined as at least 0.1 international units/mL when measured by enzyme-linked immunosorbent assay (ELISA) or other methods.195,196,205 Although some individuals may be protected against tetanus for life following primary immunization with a preparation containing tetanus toxoid adsorbed, antitoxin levels decrease over time and only approach the minimal protective level in most individuals 10 years after the last dose of tetanus toxoid adsorbed.166 The antitoxin response induced by tetanus toxoid adsorbed has a longer duration than that induced by tetanus toxoid fluid (no longer commercially available in the US).166

Diphtheria Infection

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, toxigenic strains of C. ulcerans .100,105,115,166,195,196,205,228 Toxigenic strains of Corynebacterium produce an exotoxin that can affect the mucous membranes of the respiratory tract (respiratory diphtheria [nasal, pharyngeal, tonsillar, laryngeal]), the skin (cutaneous diphtheria), and occasionally mucous membranes at other sites (conjunctival, otic, or vulvovaginal diphtheria).100,105,166,205,228 The toxin interferes with enzymes necessary for protein synthesis, leading to cell damage and death.228 The toxin causes local tissue destruction and membrane formation and can be absorbed into the bloodstream from the site of infection and distributed throughout the body resulting in serious complications (e.g., myocarditis, neuritis, thrombocytopenia, renal dysfunction or failure).100,105,166,205,228

Humans are the only known reservoir of C. diphtheriae .105,166 Diphtheria is transmitted to close contacts by oral or respiratory droplets or by direct contact with discharge from skin lesions or, rarely, contact with items soiled with such discharge (fomites).105,115,166 Raw milk or unpasteurized dairy products also have been reported to transmit toxigenic C. ulcerans .105,196 Diphtheria can be acquired from carriers (i.e., asymptomatic individuals colonized with toxin-producing C. diphtheriae ).105,166,205

Following infection, the incubation period usually is 2-5 days (range 1-10 days).105,115,166,228 Although systemic complications of diphtheria can occur during the first week of illness, they usually occur later in the disease process (e.g., myocarditis usually occurs 1-2 weeks and neuritis usually occurs 2-8 weeks after disease onset).228 Most cases of diphtheria occur in individuals who are unvaccinated or incompletely vaccinated against the disease.100,105,166 The overall case-fatality rate for diphtheria is 5-10% with higher death rates (up to 20%) among individuals younger than 5 years of age and older than 40 years of age.166,229

Tetanus Infection

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by C. tetani .105,113,114,115,166 C. tetani spores are ubiquitous in the environment and are found in soil and in animal (e.g., horses, sheep, cattle, dogs, cats, rats, guinea pigs, chickens) and human intestinal tracts.100,105,115,166,195 The spores can contaminate open wounds, especially puncture wounds or those with devitalized tissue; anaerobic wound conditions allow the spores to germinate and produce exotoxins that disseminate through the blood and lymphatic system.105,166,195 Following infection of a wound, the incubation period for tetanus is 8-10 days (range 3-21 days).105,115,166

The most common form of tetanus is generalized tetanus characterized by rigidity and convulsive muscle spasms that usually involve the jaw (lockjaw) and neck and then become generalized.105,115,166,195 Neonatal tetanus (tetanus neonatorum) occurs in infants born under nonsterile conditions to women inadequately vaccinated against tetanus; infection usually involves a contaminated umbilical stump and occurs because the infant does not have passively acquired maternal antibodies against tetanus.100,105,166,195,205 Obstetric tetanus occurs within 6 weeks after delivery or termination of pregnancy because of contaminated wounds or abrasions or unclean deliveries or abortions.205

Chemistry and Stability

Chemistry

Diphtheria and tetanus toxoids adsorbed (DT) and tetanus and diphtheria toxoids adsorbed (Td) are sterile suspensions prepared by mixing suitable quantities of diphtheria and tetanus toxoids that have been formaldehyde-treated, purified, and adsorbed onto an aluminum adjuvant.112,113,114

DT and Td meet standards established by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. The antigen content of the toxoids is expressed in terms of flocculation units (Lf).112,113,114

DT appears as a uniform, white, cloudy suspension after shaking.114 Each 0.5 mL of DT contains 25 Lf units of diphtheria toxoid, 5 Lf units of tetanus toxoid, 1.5 mg of aluminum phosphate adjuvant, and less than 100 mcg of residual formaldehyde.114 Commercially available single-dose vials of DT do not contain thimerosal or any other preservative;114

Td appears as a uniform, white, cloudy suspension after shaking.112,113 Each 0.5 mL of Td (Tenivac^®) contains 2 Lf units of diphtheria toxoid, 5 Lf units of tetanus toxoid, 1.5 mg of aluminum phosphate (0.33 mg of aluminum) adjuvant, and no more than 5 mcg of residual formaldehyde.113 Td (Tenivac^®) commercially available in single-dose vials or single-dose prefilled syringes does not contain thimerosal or any other preservative.113 Each 0.5 mL of Td (manufactured by MassBiologics) contains 2 Lf units of diphtheria toxoid, 2 Lf units of tetanus toxoid, no more than 0.53 mg of aluminum adjuvant, and less than 100 mcg of residual formaldehyde.112 Td (manufactured by MassBiologics) commercially available in single-dose vials does not contain preservatives, but does contain trace amounts of thimerosal from the manufacturing process (no more than 0.3 mcg of mercury per 0.5-mL dose).112

Stability

DT and Td should be stored at 2-8°C and should not be frozen.112,113,114 DT or Td that has been frozen should be discarded.112,113,114

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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