Understanding dengue transmission in remote settings through innovative and integrated diagnostic and surveillance systems

Abstract

Introduction: Dengue is a major cause of acute febrile illness (AFI), health-seeking, morbidity and mortality across tropical nations. Current surveillance systems are incomplete and slow because they rely on sub-optimal, laboratory-based diagnostic tests and a lack of effective information transfer and analysis. Rural and remote settings are particularly affected. Hypothesis: Innovation in molecular and serological diagnostic techniques and their use within surveillance systems can enhance understanding of dengue transmission in remote settings. Methods: A pilot observational study described the presentation of dengue and use of available molecular diagnostics in a remote setting. A qualitative, focus group study described challenges and requirements for dengue diagnostics. The role of an emerging diagnostic solution, loop-mediated isothermal amplification (LAMP), was investigated in a systematic literature review. Its application was studied in-silico and in-vitro and assays were optimised for use in a portable diagnostic workflow. Dengue transmission in remote settings was further investigated through serological surveillance studies estimating force-of-infection (FOI) and using satellite-derived environmental data in predictive mapping. Results: The observational study demonstrated the potential improved diagnosis and surveillance of dengue with molecular tests. The qualitative study defined a need for faster, more accurate, remote-connected, serotype-specific tests which can be operated outside laboratories. The literature review identified LAMP assays with high analytical and diagnostic performance. In-silico and in-vitro experiments optimised these with a 25-minute incubation duration and translated them into a lyophilised, colorimetric format. Serological surveillance studies measured high dengue FOI in Timor-Leste which is spatially heterogenous and closely associated with environmental factors, demonstrating the need for enhanced surveillance systems. Conclusion: Significant advances were made in the molecular and serological diagnosis of dengue which may enhance surveillance in remote areas. Spatial variation in transmission was characterised across a previously unstudied region.