Epidemiology of dengue: past, present and future prospects

Murray, Natasha Evelyn Anne; Quam, Mikkel; Wilder-Smith, Annelies

doi:10.2147/clep.s34440

Cited by 545 publications

(473 citation statements)

References 69 publications

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“…Distinct from the hepaciviruses and pestiviruses that are not arthropodborne, the flaviviruses are transmitted by mosquitos and ticks. Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes (DENV1 to -4) and has had a major impact on global public health (2)(3)(4).…”

mentioning

confidence: 99%

Identification of a Pyridoxine-Derived Small-Molecule Inhibitor Targeting Dengue Virus RNA-Dependent RNA Polymerase

Colby-Germinario

Hassounah

et al. 2016

Antimicrob Agents Chemother

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The viral RNA-dependent RNA polymerase (RdRp) activity of the dengue virus (DENV) NS5 protein is an attractive target for drug design. Here, we report the identification of a novel class of inhibitor (i.e., an active-site metal ion chelator) that acts against DENV RdRp activity. DENV RdRp utilizes a two-metal-ion mechanism of catalysis; therefore, we constructed a small library of compounds, through mechanism-based drug design, aimed at chelating divalent metal ions in the catalytic site of DENV RdRp. We now describe a pyridoxine-derived small-molecule inhibitor that targets DENV RdRp and show that 5-benzenesulfonylmethyl-3-hydroxy-4-hydroxymethyl-pyridine-2-carboxylic acid hydroxyamide (termed DMB220) inhibited the RdRp activity of DENV serotypes 1 to 4 at low micromolar 50% inhibitory concentrations (IC 50s of 5 to 6.7 M) in an enzymatic assay. The antiviral activity of DMB220 against DENV infection was also verified in a cell-based assay and showed a 50% effective concentration (EC 50 ) of <3 M. Enzyme assays proved that DMB220 was competitive with nucleotide incorporation. DMB220 did not inhibit the enzymatic activity of recombinant HIV-1 reverse transcriptase and showed only weak inhibition of HIV-1 integrase strand transfer activity, indicating high specificity for DENV RdRp. S600T substitution in the DENV RdRp, which was previously shown to confer resistance to nucleoside analogue inhibitors (NI), conferred 3-fold hypersusceptibility to DMB220, and enzymatic analyses showed that this hypersusceptibility may arise from the decreased binding/incorporation efficiency of the natural NTP substrate without significantly impacting inhibitor binding. Thus, metal ion chelation at the active site of DENV RdRp represents a viable anti-DENV strategy, and DMB220 is the first of a new class of DENV inhibitor. D engue virus (DENV) belongs to the family Flaviviridae, a group of enveloped positive-sense single-stranded RNA viruses that includes the genera Hepacivirus (prototype, hepatitis C virus [HCV]), Flavivirus (prototype, yellow fever virus), and Pestivirus (prototype, bovine viral diarrhea virus) (1). Distinct from the hepaciviruses and pestiviruses that are not arthropodborne, the flaviviruses are transmitted by mosquitos and ticks. Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes (DENV1 to -4) and has had a major impact on global public health (2-4).Infection with any of the DENV serotypes may result in a wide spectrum of clinical symptoms ranging from a mild flu-like syndrome (known as dengue fever [DF]) to the most severe forms of the disease, which are characterized by coagulopathy, increased vascular fragility, and permeability (dengue hemorrhagic fever [DHF]). The latter may progress to hypovolemic shock (dengue shock syndrome [DSS]) (3, 5). Among the four serotypes, DENV2 is the most prevalent on a global scale, followed by DENV3, DENV1, and DENV4 (6). Dengue is endemic in over 100 tropical and subtropical countries, and the global incidence of dengue has grown ...

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confidence: 99%

Identification of a Pyridoxine-Derived Small-Molecule Inhibitor Targeting Dengue Virus RNA-Dependent RNA Polymerase

Colby-Germinario

Hassounah

et al. 2016

Antimicrob Agents Chemother

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“…Globally, dengue cases continuously increase due to various factors such as viral evolution, climate change, human mobility, and settlements [16,17]. In the last decade, research funding on dengue arisen [18].…”

Section: Discussionmentioning

confidence: 99%

Ten-years trend of dengue research in Indonesia and South-east Asian countries: a bibliometric analysis

Maula

Fuad

2018

Global Health Action

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Background: Dengue fever is a mosquito-borne viral disease with high incidence in over 128 countries. WHO estimates 500,000 people with severe dengue are hospitalized annually and 2.5% of those affected die. Indonesia is a hyperendemic country for dengue with an increasing number of cases in the last decade. Unfortunately, the trends of Indonesian dengue research are relatively unknown. Objective: This research aimed to depict bibliographic trends and knowledge structure of dengue publications in Indonesia relative to that of South-east Asia (SEA) from 2007 to 2016. Methods: Bibliographic data were collected from PubMed filtered by Indonesia country affiliation. The annual growth rate of publication was measured and compared with neighborhood countries in the SEA region. Network analysis was used to visualize emerging research issues. Results: About 1,625 dengue-related documents originated from SEA region, of which Indonesia contributed 5.90%. The publication growth rate in Indonesia, however, is the highest in ASEAN region (28.87%). Total citations for documents published from Indonesia was 980, with an average of 14 citations per publication and h-index of 16. Within the first five years, the main research topics were related to insect vector and diagnostic method. While insect vector remained dominant in the last five years, other topics such as disease outbreak, dengue virus, and dengue vaccine started emerging. Conclusion: In the last 10 years, dengue publications’ growth from Indonesia in international journals improved significantly, despite less number of publications compared to other SEA countries. Efforts should be made to improve the quantity and quality of publications from Indonesia. The research topics related to dengue in Indonesia are in line with studies in SEA. Stakeholders and policy makers are encouraged to develop a roadmap for dengue research in the future.

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“…Globalisation with increasing interconnectivity, ecological habitat encroachment, socioeconomic changes, climate change, virus evolution, and urbanisation all drive dengue transmission intensity [75]. We studied the relative contributions of putative drivers for the rise of dengue in Singapore: population growth, climate parameters and international air passenger arrivals from dengue endemic countries, from 1974 to 2011 [76].…”

Section: Specific Objectivesmentioning

confidence: 99%

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

Wilder‐Smith

Tissera

AbuBakar

et al. 2018

Global Health Action

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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.

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Epidemiology of dengue: past, present and future prospects

Cited by 545 publications

References 69 publications

Identification of a Pyridoxine-Derived Small-Molecule Inhibitor Targeting Dengue Virus RNA-Dependent RNA Polymerase

Identification of a Pyridoxine-Derived Small-Molecule Inhibitor Targeting Dengue Virus RNA-Dependent RNA Polymerase

Ten-years trend of dengue research in Indonesia and South-east Asian countries: a bibliometric analysis

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

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