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Fulltext Novel tools for the surveillance and control of dengue: findings by the DengueTools research consortium

Wilder-Smith A, Tissera H, AbuBakar S, Kittayapong P, Logan J, Neumayr A, et al.

Glob Health Action, 2018;11(1):1549930.
PMID: 30560735 DOI: 10.1080/16549716.2018.1549930

BACKGROUND: Dengue fever persists as a major global disease burden, and may increase as a consequence of climate change. Along with other measures, research actions to improve diagnosis, surveillance, prevention, and predictive models are highly relevant. The European Commission funded the DengueTools consortium to lead a major initiative in these areas, and this review synthesises the outputs and findings of this work conducted from 2011 to 2016. Research areas: DengueTools organised its work into three research areas, namely [1] Early warning and surveillance systems; [2] Strategies to prevent dengue in children; and [3] Predictive models for the global spread of dengue. Research area 1 focused on case-studies undertaken in Sri Lanka, including developing laboratory-based sentinel surveillance, evaluating economic impact, identifying drivers of transmission intensity, evaluating outbreak prediction capacity and developing diagnostic capacity. Research area 2 addressed preventing dengue transmission in school children, with case-studies undertaken in Thailand. Insecticide-treated school uniforms represented an intriguing potential approach, with some encouraging results, but which were overshadowed by a lack of persistence of insecticide on the uniforms with repeated washing. Research area 3 evaluated potential global spread of dengue, particularly into dengue-naïve areas such as Europe. The role of international travel, changing boundaries of vectors, developing models of vectorial capacity under different climate change scenarios and strategies for vector control in outbreaks was all evaluated.
CONCLUDING REMARKS: DengueTools was able to make significant advances in methods for understanding and controlling dengue transmission in a range of settings. These will have implications for public health agendas to counteract dengue, including vaccination programmes.
OUTLOOK: Towards the end of the DengueTools project, Zika virus emerged as an unexpected epidemic in the central and southern America. Given the similarities between the dengue and Zika viruses, with vectors in common, some of the DengueTools thinking translated readily into the Zika situation.
Fulltext Development of standard clinical endpoints for use in dengue interventional trials

Tomashek KM, Wills B, See Lum LC, Thomas L, Durbin A, Leo YS, et al.

PLoS Negl Trop Dis, 2018 10;12(10):e0006497.
PMID: 30286085 DOI: 10.1371/journal.pntd.0006497

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

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