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The Optimunise project analysed data from the last two decades on implementation of public health interventions in real life. Health intervention programmes are typically assessed simply in terms of their impact on a targeted disease. However, it seems that child mortality has been reduced to a large extent thanks to non-specific effects of live vaccines even in poorly organised healthcare systems. So how do immunisation programmes contribute to child survival in resource-constrained settings?
Exploring the bigger picture
Optimunise analysed vaccinations — and other health interventions, such as Vitamin A supplementation — in terms of their impact on child mortality in general, notes Paul Welaga, who coordinated the research contributed by the Navrongo Health Research Centre in Ghana.
Taking this wider view for a detailed analysis of data collected in Burkina Faso, Ghana and Guinea-Bissau, the team did indeed observe an extra dimension. In particular, this concerns the effects of the live vaccines studied. Optimunise notably reports that these appear to prevent more deaths than initially expected.
This added impact is known as a ‘non-specific effect’ (NSE). ‘NSEs are effects that go beyond the effect a given intervention was designed to achieve’, Welaga explains. ‘For instance, the BCG vaccine is introduced to protect against tuberculosis, but Optimunise data show that it may have effects that go beyond protecting children from tuberculosis.’ He underlines, however, that the phenomenon and its impact are not universally acknowledged. ‘The NSEs of vaccines are a controversial area,’ says Welaga, who gained his PhD through his research in the project.
An increasing number of immunological studies are showing that both innate and adaptive immune mechanism may enhance/diminish protection against unrelated infections. However, ‘Many people — including many researchers and policy-makers — are still grappling with this concept,’ Welaga notes. ‘I think we should not be quick to dismiss findings on this topic, which do sometimes challenge current beliefs. We should be open-minded and willing to look into the matter to see how we can best improve child health.’
NSEs: a chance to seize
The Optimunise team seems in no doubt, and it notes that NSEs can amplify the impact of a public health intervention very considerably indeed. In the case of the live vaccines it reviewed, the researchers surmise that the serendipitous gains may well exceed the anticipated benefits.
Examples include the measles vaccine, particularly if the children’s mothers had already received it. The illness itself may soon be eradicated, but discontinuing routine vaccination at this stage could adversely affect child health nonetheless, the researchers note.
This observation does, however, come with a very significant caveat. While Optimunise identified beneficial NSEs for many of the analysed interventions, it did report also negative outcomes for several non-live vaccines — and that these more specifically affect girls. NSEs, the researchers note, appear to differ for the sexes.
The Optimunise team points out that intervention programmes should take NSEs into consideration as a number of factors can boost or attenuate the NSEs. The team reports that interventions interact, timing matters, and the sequence in which they are delivered is relevant too. In addition, the consortium stressed the importance and value of monitoring the impact of interventions over the long term.
The project ended in August 2016, having delivered recommendations for ways to optimise child health interventions and proposed intriguing leads for further investigation. It submitted its findings to the World Health Organization, where the questions surrounding NSEs have already been picked up by the Strategic Advisory Group of Experts on Immunization (SAGE). SAGE is planning large randomised studies on the issue.
Along with its three West African partners, Optimunise involved institutions in five EU countries and was led by Statens Serum institute in Denmark. ‘We were able to build strong bonds between the researchers here and the researchers abroad, and we are looking for opportunities to pursue the cooperation,’ Welaga concludes.