Dengue: Update on Epidemiology

Wilson, Mary; Chen, Lin H.

doi:10.1007/s11908-014-0457-2

Cited by 50 publications

(49 citation statements)

References 78 publications

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“…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 dramatically in recent decades (7).…”

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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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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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“…During 2006 to 2010 in India 19.7% positivity of dengue was reported, highest 46.5% positivity during this period was found in 2010. In 2012 in pacific islands 4% people were infected by dengue and during FIFA world cup events in Brazil in 2014 rate of dengue virus infection was 31%, report was published in 2015 (Garg, Garg, Rao, Upadhyay, & Sakhuja, 2011; M. E. Wilson & Chen, 2015). In 2008, Institute of public health sciences reported the geographical distribution of dengue fever and the overall number of confirmed dengue patients was closely similar to present study 54.94% (Tahir et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Frequency of Dengue virus Infection among Febrile Patients of Lahore

Malik¹,

Javed²,

Wasim³

et al. 2017

GJHS

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Background: Dengue virus infection is one of the major global public health problems. The infection usually occurs with clinical manifestations ranging from an asymptomatic or mild febrile illness as classical dengue fever to the potentially life-threatening illness, dengue hemorrhagic fever and dengue shock syndrome. The objective of the current study was to observe the frequency and diagnosis of primary or secondary dengue viral infection among individuals in Lahore city, Pakistan.Methods: Study subjects were identified for the presence of dengue diagnostic markers including NS1 antigen, IgM and IgG antibody. The dengue specific antigen NS1 was detected by immonochromatography, while dengue specific antibodies (IgM and IgG) were measured through ELISA.Results: Total 98 (56%) out of 175 febrile cases were found infected by dengue virus. From total 98 confirmed dengue cases, NS1 antigen was detected in 59 (60.20%), IgM antibodies were present in 74 (75.51%) and IgG antibodies were detected in 40 (40.81%) individuals. Statistical analysis reveals correlation of NS1 antigen and IgM antibody among dengue patients with significant P-value (P < 0.01). Results indicated that 58 (59%) were infected by primary infection and 40 (41%) were infected by secondary infection. The most effected age group was 21-30 years (51.02%) and least effected age group was <10 years (3.06%). Males were observed higher in number 61 (62%) as compare to females 37 (38%). Overall, the frequency of dengue virus infections were 56% among undifferentiated febrile patients in Lahore city, Pakistan. Conclusion:Dengue is found endemic in city population with increased incidence in monsoon and post monsoon. Constant vigilance of patients and dengue vector control awareness programs among public and health care officials could support in combating dengue.

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“…Aedes albopictus (Skuse) is a potential urban vector of dengue, chikungunya, and Zika viruses (Derraik and Slaney 2015, Wilson and Chen 2015). Container‐inhabiting mosquitoes such as Ae.…”

Section: Introductionmentioning

confidence: 99%

Bromeliad targeted foliar treatments with Aqualuer^® 20-20 for hot spot mitigation using three hand sprayers against Aedes albopictus (Diptera: Culicidae)

Bibbs

Crosier

D’Amato

et al. 2018

Journal of Vector Ecology

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Bromeliads serve as a key environmental resource for Aedes albopictus (Skuse) in some peridomestic landscapes and are not addressed through conventional source reduction. As an alternative, three handheld sprayers were evaluated in point‐source applications of permethrin to bromeliads in Saint Augustine, FL. Each machine was screened for its utility in point‐source harborage treatments, while we simultaneously evaluated bromeliad‐focused treatments for reducing Ae. albopictus egg abundance in bromeliad plants. Semi‐field tests against caged Ae. albopictus produced 100% mortality at 24 h with each sprayer. Three field sites were assigned to each machine and a control, and bromeliad residual applications of Aqualuer 20‐20® were assessed through egg surveillance using ovitraps both within and beyond 30 m of the treated bromeliad harborage. The treatment decreased Ae. albopictus egg abundance across the field sites for three weeks post‐treatment with no significant differences among the equipment. Functional differences among machines, such as automated pressure control or leak guards on the nozzle, depend on the accessories that offer the greatest logistical benefit to the user. The field results suggest bromeliads are a viable target for harborage treatments. Selective treatments to bromeliads could offer a possible solution to containers that homeowners refuse to eliminate.

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Dengue: Update on Epidemiology

Cited by 50 publications

References 78 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

Frequency of Dengue virus Infection among Febrile Patients of Lahore

Bromeliad targeted foliar treatments with Aqualuer^® 20-20 for hot spot mitigation using three hand sprayers against Aedes albopictus (Diptera: Culicidae)

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Dengue: Update on Epidemiology

Cited by 50 publications

References 78 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

Frequency of Dengue virus Infection among Febrile Patients of Lahore

Bromeliad targeted foliar treatments with Aqualuer® 20-20 for hot spot mitigation using three hand sprayers against Aedes albopictus (Diptera: Culicidae)

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Product

Resources

About

Bromeliad targeted foliar treatments with Aqualuer^® 20-20 for hot spot mitigation using three hand sprayers against Aedes albopictus (Diptera: Culicidae)