What are the potential adverse effects of the Diphtheria, Pertussis, and Tetanus (DPT) vaccine in pediatric patients?

Adverse Effects of DPT Vaccine

The DPT vaccine commonly causes local reactions (pain, redness, swelling in 28-51% of cases) and systemic reactions (fever in 32-66%, fretfulness in 53%, drowsiness in 32%), but serious neurological events like encephalopathy are extremely rare (0-10.5 per million doses), and most adverse effects resolve without permanent sequelae. 1, 2

Common Local Reactions

• Local reactions occur in the majority of vaccinated children, including pain at injection site (41-51%), redness (28-37%), and swelling (41%) within 48 hours of vaccination 3, 2
• Subcutaneous nodules may persist at the injection site for several weeks, occurring in approximately 20% of cases 1, 3
• Sterile abscesses at the injection site are rare (6-10 per million doses) 1
• Local reactions increase in frequency with subsequent doses and with increasing age 3, 4
• Large local reactions (≥5 cm of redness or swelling) occur in up to 71% of children receiving the fifth (preschool) dose, primarily attributable to the diphtheria toxoid component 4

Common Systemic Reactions

• Fever is the most frequent systemic reaction, occurring in 32-66% of children, with temperatures <39.5°C being most common 3, 5, 2
• Fretfulness/irritability occurs in 38-53% of vaccinated children 3, 2
• Drowsiness affects approximately 32% of children 2
• Loss of appetite occurs in 21-25% of cases 3, 2
• Vomiting occurs in 6-8% of children 3, 2
• Sleep disorders affect approximately 20% of vaccinated children 3

Serious Adverse Events (Precautions, Not Contraindications)

The following events, while previously considered absolute contraindications, are now classified as precautions because they are not associated with permanent sequelae: 1

High Fever

• Temperature ≥40.5°C (≥105°F) within 48 hours occurs uncommonly and is primarily attributed to the pertussis component 1
• Such fever is a precaution due to likelihood of recurrence with subsequent doses, but does not contraindicate continuation with DT vaccine 1

Hypotonic-Hyporesponsive Episodes

• Collapse or shock-like state within 48 hours has not been recognized to cause death or permanent neurological sequelae 1
• When this occurs, continue vaccination with DT, omitting the pertussis component 1

Persistent Crying

• Inconsolable crying lasting ≥3 hours within 48 hours occurs without long-term sequelae 1
• This reaction is most frequent after the first dose and likely represents a pain reaction rather than neurological event 1
• Crying >30 minutes predicts increased likelihood of recurrence with subsequent doses 1

Seizures

• Convulsions with or without fever occurring within 3 days have not been shown to cause permanent sequelae 1
• Short-lived convulsions do not substantially increase risk for subsequent seizures in otherwise normal children 1
• The risk for subsequent seizures is significantly increased (p=0.018) only in children who are neurologically abnormal before the seizure episode 1
• If seizure occurs after first or second dose, delay subsequent doses until neurologic status is clarified 1
• Administer acetaminophen 15 mg/kg at vaccination and every 4 hours for 24 hours to reduce fever-related seizure risk 1, 6

Rare but Serious Neurological Events

Encephalopathy (True Contraindication)

• Acute, severe CNS disorder occurring within 7 days following vaccination, consisting of major alterations in consciousness, unresponsiveness, or generalized/focal seizures persisting >few hours with failure to recover within 24 hours 1
• Estimated risk: 0 to 10.5 episodes per million DTP vaccinations 1
• No subsequent doses of pertussis vaccine should be given if this occurs 1
• The National Childhood Encephalopathy Study found evidence that DTP can cause acute encephalopathy, though the mechanism remains unclear 1
• The increased risk occurs primarily during the first 3 days after DTP administration, not throughout the full 7-day window 1

Chronic Nervous System Dysfunction

• Evidence suggests possible association between DTP-related acute neurologic illness and chronic nervous system dysfunction 10 years later, though causation remains uncertain 1
• Three possible explanations exist: DTP directly causes both acute and chronic dysfunction; DTP triggers events in children with underlying abnormalities; or DTP reveals inevitable dysfunction in predisposed children 1

Important Clinical Pitfalls to Avoid

Timing of Fever Assessment

• Fever beginning ≥24 hours after vaccination or persisting >24 hours should NOT be assumed to be vaccine-related 1
• Evaluate for other causes (otitis media, meningitis) to avoid delayed treatment of serious conditions 1

Misconceptions About Contraindications

The following are NOT contraindications to DTP vaccination: 1

• Soreness, redness, or swelling at injection site
• Temperature <40.5°C (<105°F)
• Mild acute illness with low-grade fever
• Current antimicrobial therapy
• Recent exposure to infectious disease
• Prematurity (use chronological age from birth and full 0.5 mL doses)
• History of allergies or family history of allergies
• Family history of convulsions
• Family history of SIDS
• Family history of adverse events following DTP

Special Populations Requiring Individual Assessment

Children with underlying neurologic disorders:

• Defer DTP (but not other vaccines) until neurologic status is clarified and condition stabilized 1
• Decision to use DTP vs. DT should be made no later than first birthday 1
• Children with stable neurologic conditions (including well-controlled seizures) may be vaccinated with prophylactic acetaminophen 1, 6

Children with history of seizures:

• Delay DTP until status assessed, treatment established, and condition stabilized 1
• When vaccinating, give acetaminophen 15 mg/kg at time of vaccination and every 4 hours for 24 hours 1, 6

Comparison: Whole-Cell vs. Acellular Vaccines

• Acellular DPT vaccines (DTPa) have significantly fewer adverse reactions than whole-cell vaccines (DTPw) 5
• Local and generalized reactions occur in 1.64% with DTPa vs. 5.4% with DTPw (p<0.01) 5
• Fever >38.5°C occurs in 3% with DTPw vs. 0.8% with DTPa 5
• Convulsions and collapse occurred only with DTPw (0.3%), not with DTPa 5

No Association with SIDS

• Multiple studies have found no causal relationship between DTP vaccination and Sudden Infant Death Syndrome 1