The pathogenesis of dengue

Whitehorn, James; Simmons, Cameron P.

doi:10.1016/j.vaccine.2011.07.022

Cited by 208 publications

(185 citation statements)

References 113 publications

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“…When a febrile person (≥3 y old) was identified, written informed consent was obtained from adult participants or the parents of participants <18 y of age. Assent was obtained from participating children (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Blood was drawn at the time of case identification (acute sample), followed by a convalescent blood sample 14-21 d later.…”

Section: Discussionmentioning

confidence: 99%

“…Dengue virus (DENV) is caused by any of four closely related, but antigenically distinct and genetically diverse, virus serotypes (DENV-1, -2, -3, and -4), which are transmitted by day-biting, peridomestic Aedes mosquitoes, primarily Aedes aegypti (6). Incompletely understood immunological interactions among serotypes that can enhance disease severity (7)(8)(9) have hampered the development of effective, commercially available vaccines. A recent trial of a promising vaccine candidate demonstrated only partial (<33%) protection (10).…”

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confidence: 99%

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House-to-house human movement drives dengue virus transmission

Stoddard

Forshey

Morrison

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

433

404

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Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti, local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vectorborne pathogens, especially the importance of human movement, will lead to improvements in disease prevention.infectious disease | spatial epidemiology | arthropod-borne virus | emerging infections | disease ecology D engue is a mosquito-borne viral infection prevalent in the tropics and subtropics with an incidence and range that have increased substantially over the last three decades (1-4). The incidence of severe, life-threatening disease (dengue hemorrhagic fever or DHF) is also on the rise (5). Dengue virus (DENV) is caused by any of four closely related, but antigenically distinct and genetically diverse, virus serotypes (DENV-1, -2, -3, and -4), which are transmitted by day-biting, peridomestic Aedes mosquitoes, primarily Aedes aegypti (6). Incompletely understood immunological interactions among serotypes that can enhance disease severity (7-9) have hampered the development of effective, commercially available vaccines. A recent trial of a promising vaccine candidate demonstrated only partial (<33%) protection (10). Effective antiviral therapeutics are also not available. Thus, despite nearly a century of research, the only tools presently available to combat dengue target mosquito populations, mostly with insecticides and larval source reduction. In current practice, these tools are most often only partially effective (11). Although new vector control approaches are under development (12), innovations in dengue-control approaches are constrained by our limited understanding of virus-transmission dynamics and its drivers. In particular, the role of human movemen...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

House-to-house human movement drives dengue virus transmission

Stoddard

Forshey

Morrison

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

433

404

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“…Experimental wells were set up containing 1 3 10 4 labeled DC cocultured with 1 3 10 5 gd T cells (E:T ratio of 10) in 96-well roundbottom plates. After 2.5 h, 20 ml supernatant was collected and mixed with 200 ml europium solution, and the fluorescent signal was detected using a VICTOR 3 Multilabel Plate Reader (PerkinElmer). Maximum release of TDA was determined by treating BATDA-loaded DC with lysis buffer (PerkinElmer).…”

Section: Delfia Eutda Cytotoxicity Assaymentioning

confidence: 99%

“…The majority of DVinfected patients with clinical symptoms develop dengue fever without attendant complications, but 1-5% of patients develop lifethreatening severe dengue infections that are characterized by thrombocytopenia, bleeding tendency, capillary leak, shock, and end-organ damage (2). The immune response to the virus, other host factors, and viral determinants are thought to influence the severity of DV infection (3). Cellular immune responses against DV, ab T cell responses in particular, were studied carefully by several groups who sought to identify immune correlates of protection or disease severity (4).…”

mentioning

confidence: 99%

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Tsai

Liong

Gunalan

et al. 2015

The Journal of Immunology

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Little is known about the cellular mechanisms of innate immunity against dengue virus (DV) infection. Specifically, the γδ T cell response to DV has not been characterized in detail. In this article, we demonstrate that markers of activation, proliferation, and degranulation are upregulated on γδ T cells in PBMC isolated from individuals with acute dengue fever. Primary γδ T cells responded rapidly in vitro to autologous DV-infected dendritic cells by secreting IFN-γ and upregulating CD107a. The anti-DV IFN-γ response is regulated by type I IFN and IL-18 in a TCR-independent manner, and IFN-γ secreting γδ T cells predominantly expressed IL-18Rα. Antagonizing the ATP-dependent P2X7 receptor pathway of inflammasome activation significantly inhibited the anti-DV IFN-γ response of γδ T cells. Overnight priming with IL-18 produced effector γδ T cells with significantly increased ability to lyse autologous DV-infected dendritic cells. Monocytes were identified as accessory cells that augmented the anti-DV IFN-γ response of γδ T cells. Lack of monocytes in culture is associated with lower IL-18 levels in culture supernatant and diminished production of IFN-γ by γδ T cells, whereas addition of exogenous IL-18 restored the IFN-γ response of γδ T cells in monocyte-depleted cocultures with DV-infected DC. Our results indicate that primary γδ T cells contribute to the immune response during DV infection by providing an early source of IFN-γ, as well as by killing DV-infected cells, and suggest that monocytes participate as accessory cells that sense DV infection and amplify the cellular immune response against this virus in an IL-18–dependent manner.

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“…There is approximately 50 to 100 million infections reported each year, of which 500,000 cases were severe and potentially life-threatening (31,32). The causative agent for dengue disease is an icosahedral, enveloped virus that contains a single-stranded positive sense genome (31).…”

Section: Introduction On Denguementioning

confidence: 99%

Phyllanthus Sp a Local Plant With Multiple Medicinal Properties

Sd¹,

Yq²,

Sh³

2014

JUMMEC

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The plants of the genus Phyllanthus (Euphorbiaceae) are distributed in most tropical and subtropical regions of world. This plant has been long used as a traditional medicine to treat problems such as stomach, intestinal infections, kidney and urinary bladder disturbances, diabetes, and hepatitis B. There has been considerable interest in these plants in recent years. This review discusses the antiviral and anticancer aspects of Phyllanthus species. Scientific studies have demonstrated that extracts and purified isolated compounds (flavonoids, lignans, phenols, and terpenes) obtained from these plants possess antiviral effects against herpes simplex (HSV) and dengue virus infections (DENV). These observations are associated with the disruption of essential proteins needed during viral cycle, thus halting the viral replication. In addition, the Phyllanthus species have also been shown to exert inhibitory effects against selected cancers types. In these studies anti-proliferative, anti-metastatic, anti-angiogenic effects and induced apoptosis of human cancers cell lines were observed. These may be explained by the disruption of multiple survival pathways and differential protein expression. CONLCUSION:As a conclusion, tThe Phyllanthus plant possesses multiple medicinal properties, including antiviral and anticancer activities which may potentially be used as a medicinal source for many disease locally.

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The pathogenesis of dengue

Cited by 208 publications

References 113 publications

House-to-house human movement drives dengue virus transmission

House-to-house human movement drives dengue virus transmission

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Phyllanthus Sp a Local Plant With Multiple Medicinal Properties

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