Out of order
Does the sequence of childhood vaccinations matter?

In 1992, the WHO stopped recommending the high-titre measles vaccine (HTMV) after studies showed raised death rates in girls. What caused this increase? Research by the Danish Epidemiology Science Centre showed that a change in the sequence of vaccinations, rather than HTMV itself, may lead to higher female mortality.

The diphtheria-tetanus-pertussis (DTP) vaccine has been linked to an increase in female mortality. So the researchers tried to find out whether vaccination with DTP or inactivated polio virus (IPV) after HTMV increases the female-male mortality ratio. They re-analysed data from several HTMV trials involving nearly 3000 children in Guinea-Bissau, Senegal and the Gambia.

They found that:

• there is no difference in mortality between high-titre recipients and controls in the period before receiving DTP or IPV vaccines. However, mortality rates are as high as 5-8% at this time
• the death rate is higher, particularly among girls, in the high-titre groups compared with controls after HTMV recipients get additional vaccination with DTP/IPV
• the female-male mortality ratio is not raised in high-titre recipients who do not get subsequent DTP or IPV vaccines.

The HTMV was designed to allow immunisation earlier in life. The three doses of DTP and oral polio vaccine are usually given before standard measles vaccination at nine months. But children who get HTMV earlier are much more likely to receive DTP or IPV after measles vaccination. This study suggests that this sequence of vaccinations leads to higher death rates among girls. The researchers conclude that:

• vaccines and the sequence in which they are given could have an effect on child survival
• health planners introducing new vaccines in developing countries should consider the possible impact of altering the sequence of routine immunisations
• policy-makers need more information about the non-specific effects of vaccines on mortality from other causes.

Peter Aaby
Danish Epidemiology Science Centre
Statens Serum Institut
Artillerivej 5
2300 Copenhagen S
Denmark

psb@mail.gtelecom.gw

See also:

‘Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies’, The Lancet 361: 2183-2188,
by P. Aaby et al, 2003

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