Academic journal article Bulletin of the World Health Organization

Do Childhood Vaccines Have Non-Specific Effects on Mortality? (A)

Academic journal article Bulletin of the World Health Organization

Do Childhood Vaccines Have Non-Specific Effects on Mortality? (A)

Article excerpt


A recent article by Kristensen et al. (1) suggested that measles vaccine and bacille Calmette--Guerin (BCG) vaccine might reduce mortality beyond what is expected simply from protection against measles and tuberculosis. The authors argued that measles vaccine was associated with dramatic reductions in mortality in the absence of measles disease, and that the reductions in mortality were unlikely to be due to selection factors associated with vaccination because analysis of children vaccinated with diphtheria--tetanus--pertussis vaccine (DTP) showed the opposite effect--that is, mortality was higher in DTP-vaccinated children than in children who had not received DTP (1). The Kristensen study raised at least three important questions that have implications for public policy (2, 3). First, does the introduction of vaccines into populations result in disease-specific reductions in mortality other than those expected? Second, is the receipt of some vaccines associated with an increase in mortality? Third, which observational study designs can best answer the latter question by controlling for selection factors associated with receipt of vaccination? If some vaccines produce unexpected effects on mortality and some study designs are better able to address the above issues, there would be important implications for vaccine implementation and the planning of clinical trials and post-marketing surveillance.

We undertook a structured review that included considerations of study methodology to explore potential relationships between vaccines and childhood mortality (4-6).

Methods and Results Identification of articles

We performed a structured review of articles describing childhood vaccines and mortality. Search, review, and selection criteria were developed before the initiation of the study. MEDLINE (1966 to March 2001), EMBASE (1980 to March 2001), and Current Contents were searched in March 2001. Studies of death were identified using the subject headings: "mortality", "cause of death", "sudden infant death", "fatal outcome", "death certificates", and "death, sudden". Studies of vaccine components were identified using the subject headings "diphtheria toxoid", "diphtheria-tetanus-pertussis vaccine", "tetanus toxoid", "diphtheria-tetanus-pertussis vaccine', "bacterial vaccines", "bcg vaccine', "measles vaccine', "mumps vaccine", "polio vaccine", "polio vaccine, oral", and "rubella vaccine". Studies of deaths and studies of vaccines were then combined and limited to studies of infants or children, studies in humans, and studies written in English.

One of the authors (TGB) reviewed the abstract of each of the 782 articles identified using the above search strategy and excluded articles that did not include children, study the vaccines of interest, include a control group, or assess mortality. If information regarding exclusion criteria was not included in the abstract, or was unclear (n = 102), the full article was independently reviewed by two other authors (WOC, MRG). At this stage of our review, articles were excluded for the above reasons or if they described only condition-specific mortality (that is, from a single condition such as diarrhoea or cancer).

Assessment of methodological quality

All articles that met the screening criteria were then reviewed by two of the authors (WOC, MRG) using assessment of methodological issues developed a priori. Study design was incorporated into assessment of methodology to account for differences among cohort studies and case-control studies. Methodological criteria included: (1) completeness of mortality ascertainment (i.e. was there independent verification of death? Was cause of death determined by a health care practitioner?); (2) adequacy of follow-up (i.e. was there differential follow-up among study groups?); (3) consideration of sociodemographic differences between study populations (i.e. was any attempt made to control for living conditions, parental education, or family income? …

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