VACCINE RESOURCE COMMITTEE
of the Edmonton Zone Medical Staff Association
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Diphtheria, Tetanus and Pertussis Vaccine Question #1:
What are the adverse event risks of the vaccine?
Soreness or swelling where the vaccine was given, fever, fussiness, feeling tired, loss of appetite, and vomiting sometimes happen after diphtheria, tetanus and pertussis vaccination.
Diphtheria-toxoid containing vaccines
Redness, swelling and pain at the injection site are the most common adverse reactions to childhood diphtheria toxoid-containing combination vaccines. A nodule may be palpable at the injection site and persist for several weeks. Abscess at the injection site has been reported.
In clinical trials, injection site adverse reactions, including tenderness, erythema, swelling or any combination of these findings, were reported in 10% to 40% of children after each of the first 3 doses of diphtheria-toxoid containing vaccine. Mild systemic reactions such as fever, irritability fussiness or any combination of these findings were commonly reported (8% to 29%), as well as drowsiness (40% to 52%).
In two clinical studies, swelling (greater than 5 cm) and erythema were reported in 15% to 20% of vaccinees after the fourth or fifth doses of DTaP vaccines. Extensive limb swelling (greater than 10 cm in diameter) possibly involving the entire proximal limb may occur in 2% to 6% of children. While these injection site reactions produce significant swelling, pain is generally limited. There is some evidence that children with extensive limb swelling following the fourth dose of a DTaP vaccine are at increased risk of such an event following the fifth dose. The presence of a large injection site reaction to a previous dose, however, is not a contraindication to continuing the recommended schedule.
Among adults given a booster dose of Tdap vaccine, common reactions include pain, redness and swelling at the injection site, headache, and fatigue. Fever and chills also are common reactions. Adverse reactions following Td vaccine are similar. Overall, adverse reactions are less common in adults than adolescents. The interval between the childhood DTaP vaccine series or a dose of Td vaccine, and a dose of Tdap vaccine does not affect the rate of injection site or systemic adverse events.
DAtx
Diphtheria antitoxin may trigger allergic reactions of varying severity including: skin pruritus, pain, swelling or redness; urticaria; dry cough; hoarseness; nausea; vomiting; and asthma-like crisis. The frequency varies and the reactions occur within the first 24 hours after administration of DAtx. Persons previously treated with serum of equine origin may have a higher risk of reaction.
Less common and serious or severe adverse events
Diphtheria-toxoid containing vaccines
Serious adverse events are rare following immunization with diphtheria toxoid-containing vaccines and, in most cases, data are insufficient to determine that the vaccine has caused the reactions. Severe systemic reactions such as generalized urticaria, anaphylaxis, or neurologic complications have been reported rarely.
Severe (Arthus-type) injection site reactions are occasionally reported following receipt of diphtheria toxoid or tetanus toxoid-containing vaccines. There may be extensive, painful swelling around the injection site, often involving the arm from shoulder to elbow and generally beginning 2 to 8 hours after injection. Such reactions are most often reported in adults, particularly those who have received frequent doses of diphtheria or tetanus toxoid or both. Persons experiencing severe injection site reactions usually have very high serum antitoxin concentrations and should not receive further routine booster doses of Td vaccine for at least 10 years. A pregnant person with a history of Arthus-type injection site reaction within the past 10 years should be referred to a specialist prior to re-vaccination with Tdap.
DAtx
Severe reactions are uncommon. Fatal anaphylactic shock has been reported in 1:50,000 persons receiving DAtx. Serum sickness (fever, urticaria, arthralgia, adenomegaly and, more rarely, neurological or renal compromise) may occur between 5 and 24 days after the administration DAtx in approximately 8% of recipients.
Other reported adverse events and conditions
Cases of Guillain-Barre Syndrome (GBS) or polyneuritis have been reported following receipt of diphtheria toxoid-containing vaccine. While the evidence favours a causal relationship between tetanus toxoid and GBS, there is little evidence to support an independent association between receipt of diphtheria toxoid and GBS.
Tetanus-toxoid containing vaccines
Redness, swelling and pain at the injection site are the most common adverse reactions to childhood tetanus toxoid-containing combination vaccines. A nodule may be palpable at the injection site and persist for several weeks. Abscess at the injection site has been reported. These events are most often related to administering the vaccine subcutaneously in error.
In clinical trials, injection site adverse reactions, including tenderness, erythema, swelling, or any combination, were reported in 10% to 40% of children after each of the first 3 doses of tetanus toxoid-containing vaccine. Mild systemic reactions such as fever, irritability fussiness or any combination were commonly reported (8% to 29%), as well as drowsiness (40% to 52%).
In two clinical studies, swelling (greater than 5 cm) and erythema were reported in 15 % to 20% of vaccinees after the fourth or fifth doses of DTaP vaccines. Extensive limb swelling (greater than 10 cm in diameter) possibly involving the entire proximal limb may occur in 2% to 6% of children. While these injection site reactions produce significant swelling, pain is generally limited. There is some evidence that children with extensive limb swelling following the fourth dose of a DTaP vaccine are at increased risk of such an event following the fifth dose. The presence of a large injection site reaction to a previous dose is not a contraindication to continuing the recommended schedule.
Among adults given a booster dose of Tdap vaccine, very common reactions include pain, redness and swelling at the injection site, headache, and fatigue. Fever and chills are common reactions. Adverse reactions following Td vaccine are similar. Overall, adverse reactions are less common in adults than adolescents. The interval between the childhood DTaP vaccine series or a dose of Td vaccine, and a dose of Tdap vaccine does not affect the rate of injection site or systemic adverse events.
TIg
Mild soreness at the injection site and slight temperature elevation may occur following TIg injection.
Less common and serious or severe adverse events
Tetanus-toxoid containing vaccines
Serious adverse events are rare following immunization with tetanus toxoid-containing vaccines and, in most cases, data are insufficient to determine a causal association. Severe systemic reactions such as generalized urticaria, anaphylaxis, or neurologic complications have been reported rarely.
Serum sickness, brachial plexus neuropathy, encephalomyelitis and transverse myelitis have rarely been reported in association with tetanus vaccination.
Severe arthus-type injection site reactions are occasionally reported following receipt of diphtheria toxoid or tetanus toxoid-containing vaccines. There may be extensive painful swelling around the injection site, often involving the arm from shoulder to elbow and generally beginning 2 to 8 hours after injection. Such reactions are most often reported in adults, particularly those who have received frequent doses of diphtheria or tetanus toxoid-containing vaccines or both. Persons experiencing severe injection site reactions usually have very high serum antitoxin concentrations and should not receive further routine doses of Td vaccine for at least 10 years.
TIg
Angioneurotic edema, nephrotic syndrome, and anaphylaxis after injection have been reported rarely.
Other reported adverse events and conditions
Trismus (inability to normally open the mouth) associated with tetanus toxoid immunization has rarely been reported. The pathogenesis is unexplained and it may be attributable to a reporting bias. Outcomes have been favourable.
Cases of Guillain-Barré Syndrome (GBS) or polyneuritis have been reported following administration of tetanus toxoid-containing vaccine and there has been one case report of relapsing GBS following each of three doses of vaccine. However, population studies have not supported a causal association.
Pertussis-containing vaccines
Common adverse events (affect 1% or more of vaccinees)
Local reactions at and near the site of injection: 10-40% (refer to Tetanus Toxoid)
Extensive limb swelling: 2-6% of children; more commonly associated with the 4th or 5th dose but resolve spontaneously (refer to Tetanus Toxoid)
Fever, irritability and/or fussiness: 8 – 29% (refer to Tetanus Toxoid)
Drowsiness: 40-52% (refer to Tetanus Toxoid)
Uncommon (0.1-<1% of vaccinees) and rare (<0.1% of vaccinees) adverse events
Anaphylaxis following vaccination with pertussis-containing vaccine may occur, but is very rare
Severe arthus-type injection site reactions (refer to Tetanus Toxoid)
Hypotonic hyporesponsive episodes (HHE): The case definition of HHE includes sudden onset of hypotonia (muscle limpness), hyporesponsiveness (reduced responsiveness or unresponsiveness), and pallor or cyanosis. However, there is evidence that there are no adverse consequences to these events and the adverse consequences of being incompletely immunized have been well documented.
High fever with or without seizure: High fever and convulsions, both febrile and afebrile, are rarely reported and are not contraindications to further immunization with acellular pertussis-containing vaccine.
Other safety issues
Epidemiological studies do not support allegations of a causal relationship between pertussis-containing vaccines and either permanent neurological injury or Type 1 diabetes.
Cases of Guillain Barré Syndrome (GBS) have been reported very rarely following administration of a tetanus toxoid-containing vaccine. Refer to Tetanus Toxoid in Part 4 for additional information.
Sources:
Government of Canada: Pertussis (whooping cough) vaccines: Canadian Immunization Guide
Government of Canada: Tetanus toxoid: Canadian Immunization Guide
Government of Canada: Diphtheria toxoid: Canadian Immunization Guide