Our evidence against the current paradigm has not been refuted. We are now taking the next steps towards a paradigm shift. The findings1,3 with the greatest potential to reduce mortality and morbidity and prove the existence of NSEs will be tested in RCTs in Guinea-Bissau and in Denmark (Work packages (WP) 1-3). We will document the gains in cost-effectiveness of new health intervention programs taking into account both specific vaccines effects and NSEs (WP4). We will continue observational studies in several sites to monitor the real-life effects of new interventions and programmatic changes (WP5-7). RCTs offer unique possibilities to study the immunological effects of vaccines and micronutrients in both sexes (WP8). The most promising explanations for NSEs will be pursued in animal studies (WP9).
In the next 10 years, CVIVA aims for
- Several changes in health intervention programs in low-income countries (see Figure 1);
- A more general acceptance of the idea that males and females may react differently and may have to receive different interventions;
- More researchers studying NSEs of vaccines and micronutrients;
- A new understanding of how the immune system is modulated by vaccines and micronutrients to reduce or enhance susceptibility to unrelated infections.
The consequences are major: Future health interventions would need to be tested for their potential NSE in both males and females, and for interactions with existing interventions. We may have to treat males and females differently to treat them equally. A challenging implication is that stopping live vaccines after eradication of the targeted infections may increase mortality3,18-21. Since measles infection is likely to be eradicated in the next decades we have devoted efforts to document the beneficial NSEs of MV before it is too late (WP1-2).
Figure 1: The research process, testing policy and exploring the immunological effects