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Addressing the Complications of Ebola and Other Viral Hemorrhagic Fever Infections: Using Insights from Bacterial and Fungal Sepsis.

Hellman J - PLoS Pathog. (2015)

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine Faculty, Biomedical Sciences and Immunology Programs, University of California, San Francisco, San Francisco, California, United States of America.

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Research on Ebola virus (EBOV) has focused on preventing and controlling the infection using vaccines and antiviral therapies... Given the long-term challenge of the current epidemic and the likelihood of future outbreaks of viral hemorrhagic fevers caused by the filoviruses, including EBOV and Marburg virus, efforts should also focus on developing therapies to reduce the deadly complications of infection with these viruses... This Opinion argues that the wealth of knowledge about bacterial and fungal sepsis (herein referred to as “classical sepsis”) should be used to inform the development of adjunctive therapies to improve the outcome of EBOV and other viral hemorrhagic fevers... Infection of monocytes, macrophages, and dendritic cells leads to acute inflammation... Early activation and subsequent massive apoptosis of T-lymphocytes is associated with fatal outcomes in EBOV... Described below are strategies that have been studied in classical sepsis and could be applicable to sepsis caused by EBOV and other viral hemorrhagic fevers (Fig 1)... However, this approach is highly speculative, as high IL-6 levels have not yet been proven to mediate fatal outcomes of EBOV... Furthermore, although high cytokine levels correlate with fatal EBOV, paradoxically, an early robust pro-inflammatory response is associated with better outcomes in EBOV infection... The endocannabinoids, another class of endogenous lipids, have received attention recently for their ability to modulate inflammation... The availability and safety of plant-derived cannabinoids suggests that, if effective, they could be viable treatment options... Statins have inflammation-resolving properties and have been proposed for EBOV... However, some recent meta-analyses of RCTs have failed to show a survival benefit for statins in classical sepsis... The proteins VE-cadherin, Slit, Robo, Angiopoietin 2, and TIE2—all involved in maintaining the endothelial barrier—are being explored as therapeutic targets in classical sepsis and are potential targets in EBOV... Combined treatment with statins and angiotensin receptor blockers, which each have endothelial stabilizing effects, has also been proposed to treat the vascular leak associated with EBOV... Although we are encouraged by the reduction in the current EBOV epidemic, recently, cases of EBOV have been reported again in Liberia, and it is likely that there will be future outbreaks of EBOV and other viral hemorrhagic fevers.

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Related in: MedlinePlus

Potential approaches to sepsis caused by viral hemorrhagic fevers based on insights from classical sepsis.The schematic outlines potential approaches to reducing the downstream complications of the viral hemorrhagic fevers, based on what is currently known about the pathophysiology of EBOV sepsis and the state of the art of classical sepsis research.
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ppat.1005088.g001: Potential approaches to sepsis caused by viral hemorrhagic fevers based on insights from classical sepsis.The schematic outlines potential approaches to reducing the downstream complications of the viral hemorrhagic fevers, based on what is currently known about the pathophysiology of EBOV sepsis and the state of the art of classical sepsis research.

Mentions: Described below are strategies that have been studied in classical sepsis and could be applicable to sepsis caused by EBOV and other viral hemorrhagic fevers (Fig 1). Recognizing that some of these strategies will not be feasible in resource-limited areas, it would nonetheless be reasonable to move forward with preclinical and clinical studies to further characterize the pathophysiology and develop approaches to reduce the complications of EBOV sepsis.


Addressing the Complications of Ebola and Other Viral Hemorrhagic Fever Infections: Using Insights from Bacterial and Fungal Sepsis.

Hellman J - PLoS Pathog. (2015)

Potential approaches to sepsis caused by viral hemorrhagic fevers based on insights from classical sepsis.The schematic outlines potential approaches to reducing the downstream complications of the viral hemorrhagic fevers, based on what is currently known about the pathophysiology of EBOV sepsis and the state of the art of classical sepsis research.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591006&req=5

ppat.1005088.g001: Potential approaches to sepsis caused by viral hemorrhagic fevers based on insights from classical sepsis.The schematic outlines potential approaches to reducing the downstream complications of the viral hemorrhagic fevers, based on what is currently known about the pathophysiology of EBOV sepsis and the state of the art of classical sepsis research.
Mentions: Described below are strategies that have been studied in classical sepsis and could be applicable to sepsis caused by EBOV and other viral hemorrhagic fevers (Fig 1). Recognizing that some of these strategies will not be feasible in resource-limited areas, it would nonetheless be reasonable to move forward with preclinical and clinical studies to further characterize the pathophysiology and develop approaches to reduce the complications of EBOV sepsis.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine Faculty, Biomedical Sciences and Immunology Programs, University of California, San Francisco, San Francisco, California, United States of America.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Research on Ebola virus (EBOV) has focused on preventing and controlling the infection using vaccines and antiviral therapies... Given the long-term challenge of the current epidemic and the likelihood of future outbreaks of viral hemorrhagic fevers caused by the filoviruses, including EBOV and Marburg virus, efforts should also focus on developing therapies to reduce the deadly complications of infection with these viruses... This Opinion argues that the wealth of knowledge about bacterial and fungal sepsis (herein referred to as “classical sepsis”) should be used to inform the development of adjunctive therapies to improve the outcome of EBOV and other viral hemorrhagic fevers... Infection of monocytes, macrophages, and dendritic cells leads to acute inflammation... Early activation and subsequent massive apoptosis of T-lymphocytes is associated with fatal outcomes in EBOV... Described below are strategies that have been studied in classical sepsis and could be applicable to sepsis caused by EBOV and other viral hemorrhagic fevers (Fig 1)... However, this approach is highly speculative, as high IL-6 levels have not yet been proven to mediate fatal outcomes of EBOV... Furthermore, although high cytokine levels correlate with fatal EBOV, paradoxically, an early robust pro-inflammatory response is associated with better outcomes in EBOV infection... The endocannabinoids, another class of endogenous lipids, have received attention recently for their ability to modulate inflammation... The availability and safety of plant-derived cannabinoids suggests that, if effective, they could be viable treatment options... Statins have inflammation-resolving properties and have been proposed for EBOV... However, some recent meta-analyses of RCTs have failed to show a survival benefit for statins in classical sepsis... The proteins VE-cadherin, Slit, Robo, Angiopoietin 2, and TIE2—all involved in maintaining the endothelial barrier—are being explored as therapeutic targets in classical sepsis and are potential targets in EBOV... Combined treatment with statins and angiotensin receptor blockers, which each have endothelial stabilizing effects, has also been proposed to treat the vascular leak associated with EBOV... Although we are encouraged by the reduction in the current EBOV epidemic, recently, cases of EBOV have been reported again in Liberia, and it is likely that there will be future outbreaks of EBOV and other viral hemorrhagic fevers.

No MeSH data available.


Related in: MedlinePlus