What’s the truth here? Woman throws up at the Pentagon parking lot. Says she just visited Africa. Then the story changed. Now they say she doesn’t have ebola and did not travel to Africa.
[quote]maverick88 wrote:
[quote]DrSkeptix wrote:
[quote]MattyG35 wrote:
Couldn’t find any literature on it, but what I did find (eg someone wrote it somewhere on the internet) was that the lifespan of antibodies is a few weeks, although I can’t verify whether this is accurate.
That would explain the antibodies still being present postinfection.
This had some values, although I don’t have time to make proper sense of it
Just trying to find some established information on whether or not antibodies remain in circulation for awhile after infection.[/quote]
Are you even asking the right question?
- Are the ebola virions blocked by native antibodies?
- Are the other mechanisms of recovery–antibody-dependent cell kill, T-killer cell–immunity-- more important?
- The elimination half-life of IgGs is generally 6 weeks, less with active circulating antigens (i.e., virions or fragment). What may matter is whether enough lymphocyte and plasma cell mass are activated to be continuously present and productive. (e.g., compare Hepatitis A curves to those of say, smallpox.)
- Why presume that the presence of convalescent antibodies renders the patient non-infectious? We presume so based on the African epidemics of the past, but the number of survivors are too few to achieve statisical certainty.
If people are waiting around for a magic vaccine to appear in a few months, to be tested, proven safe and effective…they had better have a back-up plan. Phone the Neptune Society for helpful ideas.
[/quote]
Does a persons health, age, etc. raise the likelihood of survival? Since most deaths have been in Africa is the mortality rate due to the poor health of those infected,.[/quote]
Health status is probably irrelevant. Remember how it spread in Africa: the healthy strong family members would clean and tend to the corpses, and catch it (with a mortality of 50-70%)
The paradox: in the hemorrhagic fevers, those that are healthy may be at the highest risk of morbidity and mortality; they have the strongest immune response–systemic inflammatory syndrome, or multiorgan failure–which overwhelms them before there is a chance for recovery. (Witness the recent bird flu epidemic, where the populations worst stricken were healthy young adults, pregnant women and children, and not the elderly.)
The Neptune Society provides for “pre-need” planning. Avoid the rush.
[quote]Aragorn wrote:
No, not at all. Notwithstanding the CDC stepping on its own dick, the public relations area you speak of is trying to do exactly that–prevent public panic. The media and the talk shows are doing the exact opposite and I. Cannot. Stand. It. The only thing worse than people who don’t trust experts is people who Panic and don’t trust experts. Do experts make mistakes, sometimes extremely damaging? Yes they sure do. Thalidomide anyone? But here’s the thing–these people work their entire lives to be extremely good at this one area, and the general public watches the Kardashians. Expertise needs to be respected even when disagreed with.
Speaking of politics though, not quite the same for politicians as say CDC infectious disease researchers (note the difference between “researcher” and “bloke on a plane with a badge”, because I’m doing it on purpose)[/quote]
Sorry Aragorn, with all due respect as I know you are more prepared to discuss this topic on a scientific basis than possibly anyone else here, I have to disagree with this. Maybe you just need a caveat to distinguish between the general public and other intelligent individuals that aren’t necessarily experts. Trust and respect for knowledge are two very different concepts. I give the utmost respect to those that have dedicated their lives to infectious disease research, but when it comes to my family and my life I am going to remain as skeptical as always, especially in a world where it is nigh impossible to find the difference between experts and those with an agenda.
I don’t think anyone, except for those potentially planning a terrorist attack, want to see this spread, but I would not at all be surprised to see many so-called experts deny what is obvious to them before admitting they aren’t as intelligent as they thought. I do not trust experts to simply say “I don’t know”, which in many cases is the most intelligent thing someone can say.
In this case I think the best solution is to follow Nigeria’s lead. It is well known that to date the only way to beat ebola is to let it extinguish itself. For that reason a flight ban from West Africa is the best way to prevent the spread of the disease, especially when you consider that even if the experts are correct, simple human negligence has proven that we are incapable of preventing the disease from spreading. The State Department can very easily work around bureaucracy issues when it comes to returning aid workers, but even then I have more concern for innocent Americans than those that knowingly took the risk of putting themselves at ground zero.
The last thing we need to do is send individuals into the middle of this.
I very well may be wrong, but that’s a key point. I can be 100% positive that I am unsure and take all necessary precautions, because of my acknowledged ignorance, to mitigate the risk of myself or fellow Americans contracting the disease, but I have no way of knowing when an expert is unsure and making suggestions based on political or career pressures.
[quote]DrSkeptix wrote:
Health status is probably irrelevant. Remember how it spread in Africa: the healthy strong family members would clean and tend to the corpses, and catch it (with a mortality of 50-70%)
The paradox: in the hemorrhagic fevers, those that are healthy may be at the highest risk of morbidity and mortality; they have the strongest immune response–systemic inflammatory syndrome, or multiorgan failure–which overwhelms them before there is a chance for recovery. (Witness the recent bird flu epidemic, where the populations worst stricken were healthy young adults, pregnant women and children, and not the elderly.)
[/quote]
So Ebola kills via a “cytokine storm” reaction?
[quote]SexMachine wrote:
[quote]DrSkeptix wrote:
Health status is probably irrelevant. Remember how it spread in Africa: the healthy strong family members would clean and tend to the corpses, and catch it (with a mortality of 50-70%)
The paradox: in the hemorrhagic fevers, those that are healthy may be at the highest risk of morbidity and mortality; they have the strongest immune response–systemic inflammatory syndrome, or multiorgan failure–which overwhelms them before there is a chance for recovery. (Witness the recent bird flu epidemic, where the populations worst stricken were healthy young adults, pregnant women and children, and not the elderly.)
[/quote]
So Ebola kills via a “cytokine storm” reaction?[/quote]
Yes, probably:
PLoS Negl Trop Dis. 2010 Oct 5;4(10). pii: e837. doi: 10.1371/journal.pntd.0000837.
Human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis.
Wauquier N1, Becquart P, Padilla C, Baize S, Leroy EM.
Author information
Abstract
BACKGROUND:
Ebolavirus species Zaire (ZEBOV) causes highly lethal hemorrhagic fever, resulting in the death of 90% of patients within days. Most information on immune responses to ZEBOV comes from in vitro studies and animal models. The paucity of data on human immune responses to this virus is mainly due to the fact that most outbreaks occur in remote areas. Published studies in this setting, based on small numbers of samples and limited panels of immunological markers, have given somewhat different results.
METHODOLOGY/PRINCIPAL FINDINGS:
Here, we studied a unique collection of 56 blood samples from 42 nonsurvivors and 14 survivors, obtained during the five outbreaks that occurred between 1996 and 2003 in Gabon and Republic of Congo. Using Luminex technology, we assayed 50 cytokines in all 56 samples and performed phenotypic analyses by flow cytometry. We found that fatal outcome was associated with hypersecretion of numerous proinflammatory cytokines (IL-1β, IL-1RA, IL-6, IL-8, IL-15 and IL-16), chemokines and growth factors (MIP-1α, MIP-1β, MCP-1, M-CSF, MIF, IP-10, GRO-α and eotaxin). Interestingly, no increase of IFNα2 was detected in patients. Furthermore, nonsurvivors were also characterized by very low levels of circulating cytokines produced by T lymphocytes (IL-2, IL-3, IL-4, IL-5, IL-9, IL-13) and by a significant drop of CD3+CD4+ and CD3+CD8+ peripheral cells as well as a high increase in CD95 expression on T lymphocytes.
CONCLUSIONS/SIGNIFICANCE:
This work, the largest study to be conducted to date in humans, showed that fatal outcome is associated with aberrant innate immune responses and with global suppression of adaptive immunity. The innate immune reaction was characterized by a “cytokine storm,” with hypersecretion of numerous proinflammatory cytokines, chemokines and growth factors, and by the noteworthy absence of antiviral IFNα2. Immunosuppression was characterized by very low levels of circulating cytokines produced by T lymphocytes and by massive loss of peripheral CD4 and CD8 lymphocytes, probably through Fas/FasL-mediated apoptosis.
So take aspirin?
[quote]pushharder wrote:
[quote]MattyG35 wrote:
So take aspirin?[/quote]
…and creatine.[/quote]
If hydration is important in weathering this cytokine storm, creatine might not be to hard of an idea
[quote]MattyG35 wrote:
So take aspirin?[/quote]
Sure.
It will make it easier to mop up the blood.
FWIW, my wife was told by another doctor friend that the three-drug cocktail for HIV knock Ebola back about 30%.
Not a cure, but slows it down such that a person has better odds if they start the drugs early.
Serious enough that we got ourselves a 5 person supply to sit around the house in the event things got scarce.
[quote]Jewbacca wrote:
FWIW, my wife was told by another doctor friend that the three-drug cocktail for HIV knock Ebola back about 30%.
Not a cure, but slows it down such that a person has better odds if they start the drugs early.
Serious enough that we got ourselves a 5 person supply to sit around the house in the event things got scarce.[/quote]
Uhh…citation, please. You may be seriously misinormed in this. Filoviruses ain’t retroviruses; but screwy things do happen, I suppose.
Is 30% viral reduction enough? No:
[i]
Antiviral Res. 2013 Sep;99(3):207-13. doi: 10.1016/j.antiviral.2013.05.017. Epub 2013 Jun 7.
A novel Ebola virus expressing luciferase allows for rapid and quantitative testing of antivirals.
Hoenen T1, Groseth A, Callison J, Takada A, Feldmann H.
Author information
Abstract
Ebola virus (EBOV) causes a severe hemorrhagic fever with case fatality rates of up to 90%, for which no antiviral therapies are available. Antiviral screening is hampered by the fact that development of cytopathic effect, the easiest means to detect infection with wild-type EBOV, is relatively slow. To overcome this problem we generated a recombinant EBOV carrying a luciferase reporter. Using this virus we show that EBOV entry is rapid, with viral protein expression detectable within 2 h after infection. Further, luminescence-based assays were developed to allow highly sensitive titer determination within 48 h. As a proof-of-concept for its utility in antiviral screening we used this virus to assess neutralizing antibodies and siRNAs, with significantly faster screening times than currently available wild-type or recombinant viruses. The availability of this recombinant virus will allow for more rapid and quantitative evaluation of antivirals against EBOV, as well as the study of details of the EBOV life cycle.
Published by Elsevier B.V.
PMID: 23751367 [PubMed - indexed for MEDLINE] PMCID: PMC3787978 Free PMC Article
Share on FacebookShare on TwitterShare on Google+
[/i]
Notice that viral protein is detectably replicated within 2 hours of infection…a weak inhibitor, or a bottle in the bathroom cabinet, is not going to help.
Nevertheless, here are three drugs which are weakly inhibitory:
[i]Antiviral Res. 2013 Jun;98(3):432-40. doi: 10.1016/j.antiviral.2013.03.023. Epub 2013 Apr 8.
Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses.
Chang J1, Warren TK, Zhao X, Gill T, Guo F, Wang L, Comunale MA, Du Y, Alonzi DS, Yu W, Ye H, Liu F, Guo JT, Mehta A, Cuconati A, Butters TD, Bavari S, Xu X, Block TM.
Author information
Abstract
Host cellular endoplasmic reticulum α-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure-activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses.
Copyright © 2013 Elsevier B.V. All rights reserved.
PMID: 23578725 [PubMed - indexed for MEDLINE] PMCID: PMC3663898 Free PMC Article[/i]
But here is some interesting in vitro data regarding, of all things, SERMs:
[i]
Sci Transl Med. 2013 Jun 19;5(190):190ra79. doi: 10.1126/scitranslmed.3005471.
FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection.
Johansen LM1, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehár J, Hensley LE, White JM, Olinger GG.
Author information
Abstract
Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)- and ex-US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections.
PMID: 23785035 [PubMed - indexed for MEDLINE] PMCID: PMC3955358 Free PMC Article[/i]
The original Ebola Zaire epidemic in 1979 was noted to be most prevalent and deadly among young women, particularly young pregnant women. Peter Piot, the Belgian who co-discovered the virus, attributed this, probably accurately, to shared needles re-used in a single pre-natal clinic (!). Who know…maybe estrogen makes it worse?
[quote]Jewbacca wrote:
FWIW, my wife was told by another doctor friend that the three-drug cocktail for HIV knock Ebola back about 30%.
Not a cure, but slows it down such that a person has better odds if they start the drugs early.
Serious enough that we got ourselves a 5 person supply to sit around the house in the event things got scarce.[/quote]
Uhh…citation, please. You may be seriously misinormed in this. Filoviruses ain’t retroviruses; but screwy things do happen, I suppose.
Is 30% viral reduction enough? No:
[i]
Antiviral Res. 2013 Sep;99(3):207-13. doi: 10.1016/j.antiviral.2013.05.017. Epub 2013 Jun 7.
A novel Ebola virus expressing luciferase allows for rapid and quantitative testing of antivirals.
Hoenen T1, Groseth A, Callison J, Takada A, Feldmann H.
Author information
Abstract
Ebola virus (EBOV) causes a severe hemorrhagic fever with case fatality rates of up to 90%, for which no antiviral therapies are available. Antiviral screening is hampered by the fact that development of cytopathic effect, the easiest means to detect infection with wild-type EBOV, is relatively slow. To overcome this problem we generated a recombinant EBOV carrying a luciferase reporter. Using this virus we show that EBOV entry is rapid, with viral protein expression detectable within 2 h after infection. Further, luminescence-based assays were developed to allow highly sensitive titer determination within 48 h. As a proof-of-concept for its utility in antiviral screening we used this virus to assess neutralizing antibodies and siRNAs, with significantly faster screening times than currently available wild-type or recombinant viruses. The availability of this recombinant virus will allow for more rapid and quantitative evaluation of antivirals against EBOV, as well as the study of details of the EBOV life cycle.
Published by Elsevier B.V.
PMID: 23751367 [PubMed - indexed for MEDLINE] PMCID: PMC3787978 Free PMC Article
Share on FacebookShare on TwitterShare on Google+
[/i]
Notice that viral protein is detectably replicated within 2 hours of infection…a weak inhibitor, or a bottle in the bathroom cabinet, is not going to help.
Nevertheless, here are three drugs which are weakly inhibitory:
[i]Antiviral Res. 2013 Jun;98(3):432-40. doi: 10.1016/j.antiviral.2013.03.023. Epub 2013 Apr 8.
Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses.
Chang J1, Warren TK, Zhao X, Gill T, Guo F, Wang L, Comunale MA, Du Y, Alonzi DS, Yu W, Ye H, Liu F, Guo JT, Mehta A, Cuconati A, Butters TD, Bavari S, Xu X, Block TM.
Author information
Abstract
Host cellular endoplasmic reticulum α-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure-activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses.
Copyright © 2013 Elsevier B.V. All rights reserved.
PMID: 23578725 [PubMed - indexed for MEDLINE] PMCID: PMC3663898 Free PMC Article[/i]
But here is some interesting in vitro data regarding, of all things, SERMs:
[i]
Sci Transl Med. 2013 Jun 19;5(190):190ra79. doi: 10.1126/scitranslmed.3005471.
FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection.
Johansen LM1, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehár J, Hensley LE, White JM, Olinger GG.
Author information
Abstract
Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)- and ex-US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections.
PMID: 23785035 [PubMed - indexed for MEDLINE] PMCID: PMC3955358 Free PMC Article[/i]
The original Ebola Zaire epidemic in 1979 was noted to be most prevalent and deadly among young women, particularly young pregnant women. Peter Piot, the Belgian who co-discovered the virus, attributed this, probably accurately, to shared needles re-used in a single pre-natal clinic (!). Who know…maybe estrogen makes it worse?
[quote]DrSkeptix wrote:
[quote]Jewbacca wrote:
FWIW, my wife was told by another doctor friend that the three-drug cocktail for HIV knock Ebola back about 30%.
Not a cure, but slows it down such that a person has better odds if they start the drugs early.
Serious enough that we got ourselves a 5 person supply to sit around the house in the event things got scarce.[/quote]
Uhh…citation, please. You may be seriously misinormed in this. Filoviruses ain’t retroviruses; but screwy things do happen, I suppose.[/quote]
Well, my source is my wife (an OB) who was talking to her friend (a surgeon in Dallas), and it is admittedly conjecture. But here:
[quote]Jewbacca wrote:
[quote]DrSkeptix wrote:
[quote]Jewbacca wrote:
FWIW, my wife was told by another doctor friend that the three-drug cocktail for HIV knock Ebola back about 30%.
Not a cure, but slows it down such that a person has better odds if they start the drugs early.
Serious enough that we got ourselves a 5 person supply to sit around the house in the event things got scarce.[/quote]
Uhh…citation, please. You may be seriously misinormed in this. Filoviruses ain’t retroviruses; but screwy things do happen, I suppose.[/quote]
Well, my source is my wife (an OB) who was talking to her friend (a surgeon in Dallas), and it is admittedly conjecture. But here:
[/quote]
Thanks!
There are no other published reports of lamivudine “working” in any context.
Dr.Skeptix, do you know if controlling the cytokine storm improves survival or not?
[quote]MattyG35 wrote:
Dr.Skeptix, do you know if controlling the cytokine storm improves survival or not? [/quote]
My personal experience is limited and relies on clinical judgment, general supportive measures–pressors, glucocorticoids naively, organ support, fluid managemnt–and time.
No tool has been “proven;” by the time the syndrome is recognized it is too late.
But:
Curr Top Microbiol Immunol. 2014 Sep 30. [Epub ahead of print]
The Role of Cytokine Responses During Influenza Virus Pathogenesis and Potential Therapeutic Options.
Teijaro JR.
Author information
Abstract
Aberrant pulmonary immune responses are linked to the pathogenesis of multiple human respiratory viral infections. Elevated cytokine and chemokine production “cytokine storm” has been continuously associated with poor clinical outcome and pathogenesis during influenza virus infection in humans and animal models. Initial trials using global immune suppression with corticosteroids or targeted neutralization of single inflammatory mediators proved ineffective to ameliorate pathology during pathogenic influenza virus infection. Thus, it was believed that cytokine storm was either chemically intractable or not causal in the pathology observed. During this review, we will discuss the history of research assessing the roles various cytokinesCytokines , chemokines, and innate immune cellsInnate immune cells play in promoting pathology or protection during influenza virus infection. Several promising new strategies modulating lipid signalingLipid signaling have been recently uncovered for global blunting, but not ablation, of innate immune responses following influenza virus infection. Importantly, modulating lipid signaling through various means has proven effective at curbing morbidity and mortality in animal models and may be useful for curbing influenza virus induced pathology in humans. Finally, we highlight future research directions for mechanistically dissecting how modulation of lipid signaling pathways results in favorable outcomes following influenza virus infection.
PMID: 25267464 [PubMed - as supplied by publisher]
Curr Top Microbiol Immunol. 2014;378:129-47. doi: 10.1007/978-3-319-05879-5_6.
Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule.
Oldstone MB1, Rosen H.
Author information
Abstract
Cytokine storm defines a dysregulation of and an excessively exaggerated immune response most often accompanying selected viral infections and several autoimmune diseases. Newly emerging and re-emerging infections of the respiratory tract, especially influenza, SARS, and hantavirus post considerable medical problems. Their morbidities and mortalities are often a direct result of cytokine storm. This chapter visits primarily influenza virus infection and resultant cytokine storm. It provides the compelling evidence that illuminates cytokine storm in influenza pathogenesis and the clear findings that cytokine storm is chemically tractable by therapy directed toward sphingosine-1-phosphate receptor (S1PR) modulation, specifically S1P1R agonist therapy. The mechanism(s) of how S1P1R signaling works and the pathways involved are subjects of this review.
Immunol Res. 2011 Oct;51(1):15-25. doi: 10.1007/s12026-011-8240-z.
Quelling the storm: utilization of sphingosine-1-phosphate receptor signaling to ameliorate influenza virus-induced cytokine storm.
Walsh KB1, Teijaro JR, Rosen H, Oldstone MB.
Author information
Abstract
Initial and early tissue injury associated with severe influenza virus infection is the result of both virus-mediated lysis of infected pulmonary cells coupled with an exuberant immune response generated against the virus. The excessive host immune response associated with influenza virus infection has been termed “cytokine storm.” Therapies that target virus replication are available; however, the selective pressure by such antiviral drugs on the virus often results in mutation and the escape of virus progeny now resistant to the antiviral regimen, thereby rendering such treatments ineffective. This event highlights the necessity for developing novel methods to combat morbidity and mortality caused by influenza virus infection. One potential method is restricting the host’s immune response. However, prior treatment regimens employing drugs like corticosteroids that globally suppress the host’s immune response were found unsatisfactory in large part because they disrupted the host’s ability to control virus replication. Here, we discuss a novel therapy that utilizes sphingosine-1-phosphate (S1P) receptor signaling that has the ability to significantly limit immunopathologic injury caused by the host’s innate and adaptive immune response, thereby significantly aborting morbidity and mortality associated with influenza virus infection. Moreover, S1P analog therapy allows for sufficient anti-influenza T cell and antibody formation to control infection. We review the anti-inflammatory effects of S1P signaling pathways and how modulation of these pathways during influenza virus infection restricts immunopathology. Finally, we discuss that combinatorial administration of S1P simultaneously with a current antiviral enhances the treatment efficacy for virulent influenza virus infections above that of either drug treatment alone. Interestingly, the scope of S1P receptor therapy reported here is likely to extend beyond influenza virus infection and could prove useful for the treatment of multiple maladies like other viral infections and autoimmune diseases where the host’s inflammatory response is a major component in the disease process.
Interesting, eh? But don’t get your hopes up: who knows if the benefit is specific to the action of influenza-like viruses on the vascular endothelium? See:
Virology. 2013 Jan 5;435(1):92-101. doi: 10.1016/j.virol.2012.09.039.
Dissecting influenza virus pathogenesis uncovers a novel chemical approach to combat the infection.
Oldstone MB1, Teijaro JR, Walsh KB, Rosen H.
Author information
Abstract
The cytokine storm is an aggressive immune response characterized by the recruitment of inflammatory leukocytes and exaggerated levels of cytokines and chemokines at the site of infection. Here we review evidence that cytokine storm directly contributes to the morbidity and mortality resulting from influenza virus infection and that sphingosine-1-phosphate (S1P) receptor agonists can abort cytokine storms providing significant protection against pathogenic human influenza viral infections. In experiments using murine models and the human pathogenic 2009 influenza viruses, S1P1 receptor agonist alone reduced deaths from influenza virus by over 80% as compared to lesser protection (50%) offered by the antiviral neuraminidase inhibitor oseltamivir. Optimal protection of 96% was achieved by combined therapy with the S1P1 receptor agonist and oseltamivir. The functional mechanism of S1P receptor agonist(s) action and the predominant role played by pulmonary endothelial cells as amplifiers of cytokine storm during influenza infection are described.
Be wary of results coming from a single author and his/her lab.
[quote]Powerpuff wrote:
- I’m a School Psychologist. You can’t make a lot of assumptions about the intelligence of a group of people who are so different from the normative sample for which these tests were designed. They are sooo different in terms of experience, culture, educational level, on and on.
[/quote]
Really, so what “normative sample” were the tests in Liberia designed? Or were the tests designed for Liberia? Keep in mind that the principle language of Liberia is English in your answer.
No offense, but I am going to take the detailed briefing by CIA Analysts tasked to AFICOM a bit more seriously over politically-correct statements by a school counselor somewhere in the USA.
The CIA factbook on West Africa is not even confidential; you can probably find it on the web. It’s very detailed and specific.
You can argue root-cause of their idiocy all day long – nature, nurture, lack of righteousness by Africans a pre-mortal existence (per your Brigham Young) or whatever. I don’t care about cause. I care about “are.”
And they ARE stupid.
[quote]tedro wrote:
Sorry Aragorn, with all due respect as I know you are more prepared to discuss this topic on a scientific basis than possibly anyone else here, I have to disagree with this. Maybe you just need a caveat to distinguish between the general public and other intelligent individuals that aren’t necessarily experts. Trust and respect for knowledge are two very different concepts. I give the utmost respect to those that have dedicated their lives to infectious disease research, but when it comes to my family and my life I am going to remain as skeptical as always, especially in a world where it is nigh impossible to find the difference between experts and those with an agenda.
I don’t think anyone, except for those potentially planning a terrorist attack, want to see this spread, but I would not at all be surprised to see many so-called experts deny what is obvious to them before admitting they aren’t as intelligent as they thought. I do not trust experts to simply say “I don’t know”, which in many cases is the most intelligent thing someone can say.
In this case I think the best solution is to follow Nigeria’s lead. It is well known that to date the only way to beat ebola is to let it extinguish itself. For that reason a flight ban from West Africa is the best way to prevent the spread of the disease, especially when you consider that even if the experts are correct, simple human negligence has proven that we are incapable of preventing the disease from spreading. The State Department can very easily work around bureaucracy issues when it comes to returning aid workers, but even then I have more concern for innocent Americans than those that knowingly took the risk of putting themselves at ground zero.
The last thing we need to do is send individuals into the middle of this.
I very well may be wrong, but that’s a key point. I can be 100% positive that I am unsure and take all necessary precautions, because of my acknowledged ignorance, to mitigate the risk of myself or fellow Americans contracting the disease, but I have no way of knowing when an expert is unsure and making suggestions based on political or career pressures.
[/quote]
Not at all Ted! I always like to hear your thoughts on matters at hand–they are invariably intelligent and interesting. I think my articulation of the matter suffered in my frustration frankly; I’ve been inundated with facebook posts and people around me that are simply out of their minds and I do believe I may have finally snapped :).
I am most certainly NOT saying to trust some nameless “expert” blindly when they tell you everything is alright, or this policy will do “x” or any such thing. I firmly believe in trusting your own instincts and discernment when it comes to you and your family, and this is one of many reasons I have so many problems with government as a whole and with certain arms of the gov’t specifically…However you hit the nail on the head with regard to “respect” for expert knowledge–that is what I was really getting at. Skepticism is one thing, but wholesale “they’re disinegnuous, empty suits, liars” nonsense is not skepticism; it is something else entirely.
I hear this all day long and it absolutely infuriates me because what it points to is not “independent thought” on the part of the person saying these things but in fact a sort of thought process that says “my opinions on the matter are just as important and valid as theirs”. This is not the case. Everyone is entitled to hold his or her own opinions but they are NOT entitled to equal weight until they have earned it.
There is a very fine article entitled “The Death of Expertise” on thefederalist website, and although the author makes a number of mis-steps with articulation I think the context and overall point of the article extremely accurate and essentially what I was getting at here. At any rate I agree with you here certainly.
Where I do not agree with you is on our response to ebola. If we can find a workable travel restriction that still allows aid workers and others to be able to easily transfer and help on the front lines AND come back I am all for it. However, although ebola will burn itself out in time, I believe the cost in human suffering is too much to pay to allow that. And further it does not matter how the travel bans work because as was noted earlier in this thread only the immediate prior connecting flight is tracked–many people may be able to flee, infected, and take a flight here from say, Egypt or Europe, and pass the ban while still bringing in infection to us.
This is more likely to happen the more people are infected with the virus. The only way to ensure nothing is brought in to the USA is to end the epidemic. There are millions of people at risk and the longer it spreads the more likely it is to mutate into an even more virulent strain which would pose an even greater risk. I view it as imperative to cut down on the infected host pool as much as possible for many reasons rather than just letting it “burn out”.
You said, “I very well may be wrong, but that’s a key point. I can be 100% positive that I am unsure and take all necessary precautions, because of my acknowledged ignorance, to mitigate the risk of myself or fellow Americans contracting the disease, but I have no way of knowing when an expert is unsure and making suggestions based on political or career pressures.” This is absolutely true and I agree thoroughly. Unfortunately the difference between you and many other people in the general public is that you can acknowledge you might have ignorance and they cannot and do not. This is why I say if one is going to question experts–and one should–one needs to do it with the knowledge of your handicap in their field. And do it respectfully (unless you have knowledge of fraud or intellectual dishonesty going on)
[quote]thethirdruffian wrote:
[quote]Powerpuff wrote:
- I’m a School Psychologist. You can’t make a lot of assumptions about the intelligence of a group of people who are so different from the normative sample for which these tests were designed. They are sooo different in terms of experience, culture, educational level, on and on.
[/quote]
Really, so what “normative sample” were the tests in Liberia designed? Or were the tests designed for Liberia? Keep in mind that the principle language of Liberia is English in your answer.
No offense, but I am going to take the detailed briefing by CIA Analysts tasked to AFICOM a bit more seriously over politically-correct statements by a school counselor somewhere in the USA.
The CIA factbook on West Africa is not even confidential; you can probably find it on the web. It’s very detailed and specific.
You can argue root-cause of their idiocy all day long – nature, nurture, lack of righteousness by Africans a pre-mortal existence (per your Brigham Young) or whatever. I don’t care about cause. I care about “are.”
And they ARE stupid.[/quote]
I have no idea what tests might have been used to test the intelligence of the Liberian people. I’m just saying that when you are dealing with an impoverished third world country where people have been living in very primitive conditions with a culture that’s incredibly different from our own, these measures we use in the US or other First World nations are not going to transfer easily. There are so many confounding factors at work, it would make meaningful comparisons very difficult.
Yes, their customs regarding grieving and funerals are obviously making things worse in terms of controlling the spread of the virus, as is a lack of education about microbes, stigma about the disease, superstition, and a host of other third world problems. If by stupid you mean ignorant, OK. But if West Africa is populated by people with the innate intellectual capacity of Forrest Gump, then I’d have to see what kind of data that’s based on.