Adverse Events After Immunisation With Aluminium-Containing DTP Vaccines: Systematic Review of the Evidence

Lancet Infect Dis. 2004 Feb;4(2):84-90. doi: 10.1016/S1473-3099(04)00927-2.

Abstract

We have reviewed evidence of adverse events after exposure to aluminium-containing vaccines against diphtheria, tetanus, and pertussis (DTP), alone or in combination, compared with identical vaccines, either without aluminium or containing aluminium in different concentrations. The study is a systematic review with meta-analysis. We searched the Cochrane Vaccines Field Register, the Cochrane Library, Medline, Embase, Biological Abstracts, Science Citation Index, and the Vaccine Adverse Event Reporting System website for relevant studies. Reference lists of retrieved articles were scanned for further studies. We included randomised and semi-randomised trials and comparative cohort studies if the report gave sufficient information for us to extract aluminium concentration, vaccine composition, and safety outcomes. Two reviewers extracted data in a standard way from all included studies and assessed the methodological quality of the studies. We identified 35 reports of studies and included three randomised trials, four semi-randomised trials, and one cohort study. We did a meta-analysis of data from five studies around two main comparisons (vaccines containing aluminium hydroxide vs no adjuvant in children aged up to 18 months and vaccines containing different types of aluminium vs no adjuvants in children aged 10-16 years). In young children, vaccines with aluminium hydroxide caused significantly more erythema and induration than plain vaccines (odds ratio 1.87 [95% CI 1.57-2.24]) and significantly fewer reactions of all types (0.21 [0.15-0.28]). The frequencies of local reactions of all types, collapse or convulsions, and persistent crying or screaming did not differ between the two cohorts of the trials. In older children, there was no association between exposure to aluminium-containing vaccines and onset of (local) induration, swelling, or a raised temperature, but there was an association with local pain lasting up to 14 days (2.05 [1.25-3.38]). We found no evidence that aluminium salts in vaccines cause any serious or long-lasting adverse events. Despite a lack of good-quality evidence we do not recommend that any further research on this topic is undertaken.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adolescent
  • Adult
  • Aluminum Hydroxide / adverse effects
  • Aluminum* / adverse effects
  • Aluminum* / chemistry
  • Child
  • Clinical Trials as Topic
  • Cohort Studies
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects*
  • Diphtheria-Tetanus-Pertussis Vaccine / chemistry
  • Erythema / chemically induced
  • Humans
  • Immunization / adverse effects*
  • Infant
  • Pain / chemically induced
  • Randomized Controlled Trials as Topic
  • Time Factors

Substances

  • Adjuvants, Immunologic
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Aluminum Hydroxide
  • Aluminum