Investigating novel approaches to the detection of virus neutralising antibodies to rabies and Rift Valley fever virus

Serosurveillance is a powerful tool fundamental to understanding infectious disease dynamics. The presence of virus neutralising antibody (VNAb) in sera is considered the best evidence of infection, or indeed vaccination, and the gold standard serological assay for their detection is the virus neutralisation test (VNT). However, VNTs are labour intensive, costly and time consuming. In addition, VNTs for the detection of antibodies to highly pathogenic viruses require the use of high containment facilities, restricting the application of these assays to the few laboratories with adequate facilities. As a result, robust serological data on such viruses are limited. In this thesis I develop novel VNTs for the detection of VNAb to two important, highly pathogenic, zoonotic viruses; rabies and Rift Valley fever virus (RVFV). The pseudotype-based neutralisation test developed in this study allows for the detection of rabies VNAb without the requirement for high containment facilities. This assay was utilised to investigate the presence of rabies VNAb in animals from a variety of ecological settings. In this thesis I present evidence of natural rabies infection in both domestic dogs and lions from rabies endemic settings. The assay was further used to investigate the kinetics of VNAb response to rabies vaccination in a cohort of free-roaming dogs. The RVFV neutralisation assay developed herein utilises a recombinant luciferase expressing RVFV, which allows for rapid, high-throughput serosurveillance of this important neglected pathogen. In this thesis I present evidence of RVFV infection in a variety of domestic and wildlife species from Northern Tanzania, in addition to the detection of low-level transmission of RVFV during interepidemic periods. Additionally, the investigation of a longitudinal cohort of domestic livestock also provided evidence of rapid waning of RVF VNAb following natural infection. Collectively, the serological data presented in this thesis are consistent with existing data in the literature generated using the gold standard VNTs. Increasing the availability of serological assays will allow the generation of robust serological data, which are imperative to enhancing our understanding of the complex, multi-host ecology of these two viruses.

Conceptualisation, design and development of a primary school based child healthy weight intervention

INTRODUCTION: In common with much of the developed world, Scotland has a severe and well established problem with overweight and obesity in childhood with recent figures demonstrating that 31% of Scottish children aged 2-15 years old were overweight including obese in 2014. This problem is more pronounced in socioeconomically disadvantaged groups and in older children across all economic groups (Scottish Health Survey, 2014). Children who are overweight or obese are at increased risk of a number of adverse health outcomes in the short term and throughout their life course (Lobstein and Jackson-Leach, 2006). The Scottish Government tasked all Scottish Health Boards with developing and delivering child healthy weight interventions to clinically overweight or obese children in an attempt to address this health problem. It is therefore imperative to deliver high quality, affordable, appropriately targeted interventions which can make a sustained impact on children’s lifestyles, setting them up for life as healthy weight adults. This research aimed to inform the design, readiness for application and Health Board suitability of an effective primary school-based curricular child healthy weight intervention. METHODS: the process involved in conceptualising a child healthy weight intervention, developing the intervention, planning for implementation and subsequent evaluation was guided by the PRECEDE-PROCEED Model (Green and Kreuter, 2005) and the Intervention Mapping protocol (Lloyd et al. 2011). RESULTS: The outputs from each stage of the development process were used to formulate a child healthy weight intervention conceptual model then develop plans for delivery and evaluation. DISCUSSION: The Fit for School conceptual model developed through this process has the potential to theoretically modify energy balance related behaviours associated with unhealthy weight gain in childhood. It also has the potential to be delivered at a Health Board scale within current organisational restrictions.