|Background: Both observational studies and randomised trials (RCT) have documented that vaccines and micronutrients have non-specific effects (NSE) on child mortality. These effects may be even more important than the specific effects. NSEs are often sex-differential. Objective: To optimise vaccine and micronutrient delivery, childhood interventions will need to be evaluated for their overall effect on mortality and morbidity for both sexes, ie. for their NSE as well as their specific effects on the targeted disease/micronutrient deficiency. Activities: As part of PhD projects, monitoring of current health intervention practice will be initiated at 6 INDEPTH Health Demographic Surveillance System (HDSS) sites in 4 African countries and India. The PhD projects will then examine variation in implementation of interventions and assess the impact on overall child mortality. Outputs: 5-6 PhDs with a critical perspective on assessment, 4-5 papers per site; increasing understanding that it is necessary to assess NSEof health interventions. Project organization: In collaboration with INDEPTH Network, the Danish team will coordinate the project. Capacity building: Senior scientists at all sites will take part in supervision of the PhD/post-doc projects. Learning from other sites will be an important component of the research training program. Communication: Conferences, int. journals, WHO's Global Advisory Committee Vaccine Safety, donors|
Project Completion Report
We managed to conduct the local research training and to national researchers qualified at the PhD or post-doc levels.
Though with some delays (due to factors outside our control) we also managed to submit the theses and publish many papers. We have also managed to create much more interest in the non-specific effects of vaccines and the potential sex-differential effects of vaccines.
The key results include: The project has documented major reductions in under-five mortality in recent years; for example, Bandim and Navrongo have reached the Millennium Development Goal 4 (MDG4) of reducing mortality by 2/3 between 1990 and 2015. Since improvement in health services and general wealth cannot always explain these trends, these results for under-five mortality should generate a new research agenda of what have been the driving mechanism in the decline.
Though there was little difference in vaccination coverage for girls and boys, we found marked sex-differential association for mortality and different vaccines. DTP and Penta vaccine were associated with increased female-male mortality rate ratio (F/M MRR). On the other hand, MV was associated with lower F/M MRR.
The data from the different sites support an emerging pattern where live vaccines are associated with lower female mortality but inactivated vaccines like DTP, Penta, HBV, IPV and RTS,S are associated with increased female mortality. This pattern was very pronounced in the Bangladesh study, which had data from before the introduction of the routine vaccination programme (EPI). There has been a complete inversion of the femalemale MRR in the age groups where DTP and MV, respectively, were the predominant
We are also examined the implications of the many variations in actual vaccination
practice. For example, administering DTP and BCG simultaneously reduces the negative effect of DTP. Receiving DTP with or after MV, i.e. out-of-sequence vaccinations, increases mortality markedly compared with having MV as the most recent vaccination. It is therefore important that vaccination programmes function well. For example, 25 years ago 86% of MV and DTP vaccinations were out-of-sequence in Navrongo, Ghana. Today this is less than 1%. This change in implementing the vaccination programme has reduced mortality after one year of age with 30% and has therefore contributed importantly to reaching the MDG4.The general vaccination campaigns with OPV and MV have had major beneficial effects for child survival and may be an important part of why under-five mortality has declined so much.