Application of multiplex bead serological assays to integrated monitoring of neglected tropical diseases

BACKGROUND: Neglected tropical diseases remain a significant burden to global health, despite substantial efforts among global governments and partnerships to control these diseases. In recent years, there has been considerable attention directed towards integrating control platforms across these geographically co-endemic diseases due to demonstrated resource efficacy and sustainability moving forward. As surveillance is a key component of disease control, effective surveillance tools are needed to support these integrated disease platforms. Serological multiplex bead assays are capable of monitoring numerous pathogens simultaneously by using antigens of specific pathogens. However, gaps in knowledge pertaining to the interpretation of serological data from these assays and their utility in public health surveillance necessitates further research to determine their capabilities in supporting concurrent surveillance of multiple diseases. This thesis aims to determine appropriate methods of interpreting serological data from multiplex bead assays and assess their utility in the context of public health surveillance of neglected tropical diseases. METHODS: Three datasets from Haiti (2015 Tracking Results Continuously Survey, n=4438 ; 2017 Artibonite Easy Access Group Survey, n= 6004 ; and 2017 Artibonite Community Household Survey; n=21222 ) and one dataset from Malaysia (2015 Sabah Household Cluster Survey, n=10100 ) were used in this thesis. Collectively, these datasets included antigens of twelve different pathogens that were analysed using serological multiplex bead assays . The first objective of this thesis was to identify existing methods of characterising serological data from neglected tropical diseases using multiplex bead assays. This was done through a systematic review of literature which examined existing and potential methods of characterizing antibody responses from these assays. Several of these methods were then applied to two case studies to evaluate potential implications pertaining to method choice on public health interpretation. The second objective was to assess the utility of multiplex bead assays for multi-disease surveillance. To do this, panels of diverse tropical disease antigens (encompassing twelve different pathogens collectively) from three datasets in Haiti and one dataset from Malaysia were used to analyse concurrent monitoring of multiple diseases and to assess demographic and spatial disease risk factors for co-endemic pathogens. The third 3 objective of this thesis was to determine the capacity of serological multiplex bead assays to support different sampling strategies. This was done by formally comparing outputs from serological multiplex bead assays from a community household active sampling strategy and an easy-access group convenient sampling strategy in Haiti. RESULTS: The review of literature revealed that serological data from multiplex bead assays are typically converted to seroprevalence for programme interpretation, however there is currently an absence of a standard approach to determine serological prevalence estimates. Instead, seven different approaches were identified in the literature. Comparing three different approaches resulted in varying disease prevalence estimates in both Haiti and Malaysia, suggesting potential impacts of classification approaches on postliminary programmatic interpretation in both case studies. Multiplex bead assays provided concurrent estimates of exposure to various pathogens simultaneously at the national and subnational levels of surveillance within Haitian and Malaysian study populations. Demographic and spatial data collected alongside serologic surveys determined several consistent risk factors across antigens assessed, including age, wealth, gender, and also allowed for visualization of any spatial trends in disease exposure in both settings. Using multiplex bead assays in two different sampling approaches demonstrated its capacity to support multi-disease surveillance in different sampling approaches. In comparing prevalence estimates between surveys, observed differences may be attributable to inherent biases in sampling populations and design. CONCLUSIONS:The research in this thesis contributes to the understanding of the utility of serological multiplex bead assays to support multi-disease surveillance and provides a foundation in the broader study of applying these platforms to neglected tropical disease control. This thesis also highlights the need to develop standardized approaches in sampling, laboratory protocols, and analysis for these platforms to ensure consistent and confident disease estimates and data reporting.