A review of existing literature suggests that while some vaccines are associated with a reduction in all-cause mortality, others may have the opposite effect, depending on the sequence of administration.


Vaccination is generally recognized as being the most effective method for preventing the spread of infectious diseases. For example, vaccines played a key role in eradicating smallpox, and have also been instrumental in dramatically reducing the occurrence of diseases such as polio, measles, diphtheria and tetanus in many areas of the world.

However, the use of vaccines has provoked its share of controversy as well, particularly where they are administered to young children. Some research has suggested that while vaccines have a proven benefit in preventing the particular diseases they target, they may at the same time affect the risk of illness and death from other causes.

For example, research looking at the measles and Bacillus Calmette-Guérin (BCG – administered for tuberculosis) vaccines has suggested that, under certain circumstances, administration may reduce the risk of these “non-specific effects”; however, the diphtheria-tetanus-pertussis (DTP) vaccine may increase it.  Some studies have also suggested that factors such as gender and vitamin A intake may influence the risk impact of the vaccines.

The World Health Organization (WHO) provides recommendations about the age at which vaccines should be administered, and the order in which children should receive them. Currently, the recommendations are as follows:

  • BCG as soon as possible after birth;
  • DTP after 6 weeks, and two further doses at intervals of 4 to 8 weeks;
  • Measles vaccine at 9 to 12 months, and a further dose at least 4 weeks later.


A study recently published inThe BMJ has reviewed published studies investigating the use of these three vaccines in an attempt to clarify what we know about their effects in children under 5 years of age on mortality from causes other than the diseases they target, and on all-cause mortality. Researchers looked at clinical trials, cohort studies and case-control studies available in Medline, Embase, Global Index Medicus and the WHO International Clinical Trials Registry Platform. To avoid the possibility of duplication among children studied in different articles, researchers considered only data for non-overlapping birth cohorts.

Analysis of the literature suggests that both BCG and the measles vaccine may be associated with a reduction in all-cause mortality, beyond any reduction that could be expected from their effects on the disease that they target. DTP, however, appeared to be associated with a possible increase in all-cause mortality. This increase in risk appeared to affect girls more than boys.

Furthermore, seven of the studies that were reviewed provided data concerning the sequence of administering these three vaccines. A subset of them appear to suggest that administering DTP at the same time as, or later than, the measles virus may correlate with a higher mortality rate than administering it prior to the measles vaccine.

Based on this analysis of the literature, authors of the study suggest that randomized trials may be beneficial to try to better understand the impact of different sequencing of vaccines and their effect on mortality from all causes.


Written By: Linda Jensen

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