Disease and economic burdens of dengue

Castro, Márcia C.; Wilson, Mary; Bloom, David E.

doi:10.1016/s1473-3099(16)30545-x

Cited by 133 publications

(131 citation statements)

References 70 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Infection by dengue virus (DENV), a positive-strand RNA virus belonging to the Flaviviridae family of viruses, has been recognized as one of the most important public health threats worldwide [1].…”

Section: Introductionmentioning

confidence: 99%

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

et al. 2018

View full text Add to dashboard Cite

Toll-like receptors (TLRs) are important sensors that recognize pathogen-associated molecular patterns. Generally, TLR9 is known to recognize bacterial or viral DNA but not viral RNA and initiate an immune response. Herein, we demonstrate that infection with dengue virus (DENV), an RNA virus, activates TLR9 in human dendritic cells (DCs). DENV infection induces release of mitochondrial DNA (mtDNA) into the cytosol and activates TLR9 signaling pathways, leading to production of interferons (IFNs). The DENV-induced mtDNA release involves reactive oxygen species generation and inflammasome activation. DENV infection disrupts the association between transcription factor A mitochondria (TFAM) and mtDNA and activates the mitochondrial permeability transition pores. The side-by-side comparison of TLR9 and cyclic GMP-AMP synthase (cGAS) knockdown reveals that both cGAS and TLR9 comparably contribute to DENV-induced immune activation. The significance of TLR9 in DENV-induced immune response is also confirmed in examination with the bone marrow-derived DCs prepared from -knockout mice. Our study unravels a previously unrecognized phenomenon in which infection with an RNA virus, DENV, activates TLR9 signaling by inducing mtDNA release in human DCs.

show abstract

Section: Introductionmentioning

confidence: 99%

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In addition to health care costs, dengue may impact tourism, as estimated for the neighboring island country of the Maldives (Bangert et al, 2018) and, at least conceptually, could affect development more broadly (Castro et al, 2017). Although uncertainty intervals remains wide, these latest estimates reinforce the health and economic benefits that India would realize if dengue were substantially controlled.…”

Section: Discussionmentioning

confidence: 95%

Economic burden of dengue illness in India from 2013 to 2016: A systematic analysis

Hariharan

Das

Shepard

et al. 2019

International Journal of Infectious Diseases

View full text Add to dashboard Cite

Objectives: This paper concerns a systematic analysis of dengue illness and costs in India from 2013 to 2016. A previous study for 2006-2012 found that that projected annual number of dengue cases (5.78 million) was 282 times the officially reported number (20,474), highlighting enormous uncertainty. Methods: This study updated primary data for India from 2012 to 2014 and synthesized the latest epidemiological and economic literature through 2018 using the country and global estimates. Results: The first empirically-based publication of dengue costs by country (in 2016) estimated India experienced 18,618,706 symptomatic dengue cases and 1602 deaths, and cost $1.51 billion in 2013. With a combination of increased incidence, more refined methods, and better data this 2018 study raised the latest estimates to 53,210,706 cases, 22,527 deaths, and $5.71 billion economic costs for 2016, representing increases over the previous publication of 186%, 1306%, and 278%, respectively. When consistent methods and data were used to compare 2013 to 2016, the corresponding changes were only +29%, À9%, and +12%, respectively over these 3 years. Conclusions: India's burden of dengue is substantially greater than previously estimated. Although uncertainty intervals remain wide, these latest estimates reinforce the health and economic benefits that India would realize if dengue were substantially controlled.

show abstract

“…Almost half the world’s population lives in at-risk areas across the tropics and subtropics, with an estimated 390 million infections and 96 million symptomatic cases per year (1). Dengue patients experience a range of symptoms including high fever, leucopoenia, maculopapular rash, retro-orbital pain, arthralgia and myalgia (2, 3). A minority of patients (approximately 500,000 cases per year) develop severe dengue, typified by cardiovascular complications such as plasma leakage (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…A minority of patients (approximately 500,000 cases per year) develop severe dengue, typified by cardiovascular complications such as plasma leakage (e.g. pleural effusion, oedema) and/or bleeding (haemorrhage) manifesting during defervescence that can lead to hypovolaemic shock, organ failure and death (2, 3). Fluid replacement therapy and other supportive treatments reduce the death rate, but there are no specific drugs to treat dengue and no diagnostic measure to predict the development of the life-threatening severe dengue (2-4).…”

Section: Introductionmentioning

confidence: 99%

A Critical Role for Perivascular Cells in Amplifying Viral Haemorrhage Induced by Dengue Virus Non-Structural Protein 1

Cheung

Mastrullo

Maselli

et al. 2020

Preprint

View full text Add to dashboard Cite

23Dengue is the most prevalent arthropod-borne viral disease affecting humans, with 24 severe dengue typified by potentially fatal microvascular leakage and hypovolaemic shock. 25Blood vessels of the microvasculature are composed of a tubular structure of endothelial cells 26 ensheathed by perivascular cells (pericytes). Pericytes support endothelial cell barrier 27 formation and maintenance through paracrine and contact-mediated signalling, and are critical 28 to microvascular integrity. Pericyte dysfunction has been linked to vascular leakage in 29 noncommunicable pathologies such as diabetic retinopathy, but has never been linked to 30 infection-related vascular leakage. Dengue vascular leakage has been shown to result in part 31 from the direct action of the secreted dengue virus (DENV) non-structural protein NS1 on 32 endothelial cells. Using primary human vascular cells, we show here that NS1 also causes 33 pericyte dysfunction, and that NS1-induced endothelial hyperpermeability is more pronounced 34 in the presence of pericytes. Notably, NS1 specifically disrupted the ability of pericytes to 35 support endothelial cell function in a 3D microvascular assay, with no effect on pericyte viability 36 or physiology. These effects are mediated at least in part through contact-independent 37 paracrine signals involved in endothelial barrier maintenance by pericytes. We therefore 38 identify a role for pericytes in amplifying NS1-induced microvascular hyperpermeability in 39 severe dengue, and thus show that pericytes can play a critical role in the aetiology of an 40 infectious vascular leakage syndrome. These findings open new avenues of research for the 41 development of drugs and diagnostic assays for combating infection-induced vascular 42 leakage, such as severe dengue.43 44 45 46 47 3 SIGNIFICANCE STATEMENT 48 The World Health Organisation considers dengue one of the top ten global public 49 health problems. There is no specific antiviral therapy to treat dengue virus and no way of 50 predicting which patients will develop potentially fatal severe dengue, typified by vascular 51 leakage and circulatory shock. We show here that perivascular cells (pericytes) amplify the 52 vascular leakage-inducing effects of the dengue viral protein NS1 through contact-53 independent signalling to endothelial cells. While pericytes are known to contribute to 54 noncommunicable vascular leakage, this is the first time these cells have been implicated in 55 the vascular effects of an infectious disease. Our findings could pave the way for new 56 therapies and diagnostics to combat dengue, and potentially other infectious vascular leakage 57 syndromes. 58 59 60 61 62 63 64 65 66 67 68 69 355 MR/R010315/1 to KM and a

show abstract

Disease and economic burdens of dengue

Cited by 133 publications

References 70 publications

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

Economic burden of dengue illness in India from 2013 to 2016: A systematic analysis

A Critical Role for Perivascular Cells in Amplifying Viral Haemorrhage Induced by Dengue Virus Non-Structural Protein 1

Contact Info

Product

Resources

About