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Non-specific effects of vaccines: in context
  1. Paul Fine1,
  2. David Elliman2
  1. 1London School of Hygiene and Tropical Medicine, London, UK
  2. 2Great Ormond Hospital for Children, London, UK
  1. Correspondence to Professor Paul Fine, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; paul.fine{at}

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Frank Shann argues that the basic expanded programme on immunisation (EPI) schedule (Bacillus Calmette–Guérin (BCG) at birth, diphtheria, pertusis, tetanus (DPT)–oral polio vaccine at 6, 10 and 14 weeks, measles at 9 months) may not be optimal under certain circumstances. He suggests that some of these vaccines may be associated with timing-related ‘non-specific effects’ on the immune system which influence mortality attributable to conditions other than the specific targets of the vaccines.1 He reviews evidence that BCG and measles vaccines may have non-specific beneficial effects, and on the other hand, DPT might, under certain unusual circumstances (high background infectious disease risks but low pertussis risk) appear to have detrimental effects on all cause mortality. This complex subject needs to be considered in its proper context.

This article is part of a long and complex story. The viewpoint emphasising the timing sequence of particular vaccines, in particular in girls, reflects the current stage of a hypothesis which has evolved over more than 15 years (note references 23–36 in Shann's paper). Much of the evidence for these so-called ‘non-specific effects’ has been accrued in Guinea Bissau (see page 662), a country whose child health characteristics are far from typical (note references 23–36 in Shann's paper).

The claims of non-specific beneficial effects of BCG and measles vaccines are based on several observations and support efforts by WHO and The Global Alliance for Vaccines and Immunisation to increase the use of these vaccines. In contrast, the evidence for an adverse effect of DTP vaccines is the least well established and has only been suggested in populations in which the target diseases have been brought to very low levels, but which still have a high prevalence of other infections. Shann notes the overall benefits of DTP vaccines, stating that ‘it is likely that over 3 million deaths from measles, tetanus and pertussis are prevented by immunisation each year.’ Thus, any adverse effect, if real, might be seen as another example of one of the difficult paradoxes of public health, that is, the need to maintain high vaccination coverage in populations which have forgotten the once-devastating diseases which have been prevented.

As Shann acknowledges, it is likely that non-specific immunological effects, in so far as they exist at all, are a function of particular vaccine and infection exposure histories, which differ greatly between populations. This poses considerable difficulties for research as well as for policy, in its implication that observations in one population may not hold in another.

Finally, the non-specific effects story is only one of several arguments favouring a revision of the traditional EPI schedule. WHO's oversight committee for matters relating to vaccines (the Strategic Advisory Group of Experts has recognised this) noted in 2005 that ‘it is unlikely that a single uniform immunisation schedule would suit all countries’ and that WHO should provide advice on the parameters to be considered when a country is selecting a schedule.2 This resolution has led to projects for strengthening of national and regional vaccine advisory bodies, which must wrestle with the practical problems of optimising schedules in individual countries and, more recently, to a programme of research on optimising vaccine schedules (see for example and

Proper consideration of schedules raises many issues: availability of vaccine products, local epidemiological conditions, local health infrastructure and the need to link other interventions (such as micronutrients and malaria prophylaxis) to vaccination schedules, all of which should, ideally, be considered in the context of cost–benefit optimisation. All these factors need to be considered in designing immunisation programmes, not just as yet unproven non-specific effects.

The hypothesis that non-specific effects may be greater in females and are dependent upon prior infections or vaccines deserves further exploration, by independent groups of scientists, in different settings. Importantly, discussion of these effects should not blind us to the enormous gains in health which have been achieved through our immunisation programmes. Basic immunisation programmes must keep evolving with the times, in terms of the vaccines and services they provide and their precise schedules.



  • Provenance and peer review Commissioned; internally peer reviewed.

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