A "cytokine storm" as the lethal element in H5N1 infection is back, not with a bang but a whimper. Maybe. Here's the gist, from the ever reliable Helen Branswell:
New research suggests successful treatment of the H5N1 avian flu virus requires targeting the virus, not the overwhelming immune response it triggers.The study, done in mice genetically engineered to lack critical immune system chemicals called cytokines, found these mice were as likely to die from H5N1 infection as mice armed with an intact immune system.
That suggests the activity of the virus, not the immune response it induces, is the main driver of the disease process, said the authors, from St. Jude Children's Research Hospital in Memphis, Tenn. (Helen Branswell, Canadian Press)
The paper, just published in the Proceedings of the National Academy of Sciences (PNAS) is interesting but not as conclusive as these statements suggest. Cytokines are chemicals important in local cell to cell signaling in the immune system. They are part of the alarm and coordinating instructions that tell different kinds of immune cells to start an action, stop an action or move to an area. There are a great many of them and we are far from learning how this intricate web of interlocking signals works and what might make it go so awry that it runs amok, much like a military unit that starts shooting up the place instead of performing in a disciplined fashion.
The authors infected mice deficient in the ability to make three cytokines (TNF-α, interleukin-6 and CC chemokine ligand 2). They are thought to be potentially important in the dysregulation that has been a prominent feature of a some H5N1 infections. Using three mice per group, the researchers examined mortality in mice deficient in each of these cytokines (one at a time) and found no difference in mortality from H5N1 infection. There is no mention whether there was any cytokine dysregulation in the normal (non-cytokine deficient) mice. They also did the same experiment using glucocorticoids (steroids that affect many cytokines broadly) with the same results. The conclude that inhibition of cytokines does not protect against H5N1 lethality and that targeting replication of the virus "may be preferable."
The numbers of animals were extremely small here, although it is clear there was no meaningful difference in the cytokine deficient and non-deficient mice. What I wonder about, however, is the idea that H5N1 lethality is monolithic. Virulence is a property of the virus, the host and the environment. People succumb to seasonal influenza but not all of the deaths are from the same cause. Sometimes there is acute respiratory distress syndrome with a primary viral pneumonia, sometimes a secondary pneumonia and sepsis, sometimes a severe bronchiolitis, etc. And sometimes there is evidence of a profound cytokine dysregulation. It is not clear what factors are involved in these differences. In some cases they may be host factors and in some cases differences in the virus. In this experiment we aren't given any information on the host response (we don't know the pathology in the mice, for example, that is whether there was any cytokine dysregulation of hypercytokinemia) in this single strain of laboratory mouse and an n=3; nor are we given information on the clinical course of the patient from whom the H5N1 viral isolate (A/Vietnam/1203/04) was obtained. Did the patient have evidence of cytokine dysregulation?
There is a clear bottom line here that is important. The actions of none of these three cytokines is necessary to the lethality of H5N1 this mouse model (which is probably a good model for human disease). Whether one or more might be sufficient under some circumstances we still don't know. Thus we think it is premature to write off the cytokine system as a target for treating patients who, for reasons we still don't understand, might have been catapulted into a disastrous dysregulation of their immune systems. By the time this happens it is no longer a question of preventing viral replication. That window is closed. The authors acknowledge this in the last sentence of the paper: "Thus, continued research on targeting host responses to H5N1 is justifiable."
This contrasts rather oddly with a statement earlier in the paper: "These results refute the popular paradigm that the cytokine storm is the cause of death during H5N1 infection." The only way I can see to reconcile these is to interpret the word "the" in "the cause of death during H5N1 infection" in a very strict way as in "the only cause of death (ever)," something which I don't think was part of the "popular paradigm."
My take: a very interesting paper, but overinterpreted.
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Revere, I read that PNAS paper and I was wondering about the steroid use on the mice. It apparently had little or no effects on the outcomes so the use of steroids is out too, or just dexamethasone?
Were they aiming at a possible improvement of the outcomes or to see if they could come up with a better treatment that might keep them or people alive long enough for the body to kick in and start fighting?
Or was it more of a debunking of the other mice studies?
Thanks Revere for bringing this paper to our attention.
What these data suggest to me is that lethal polymorphisms within the H5N1 genome are as big a problem as cytokine storm. Dr. Taubenberger's group has demonstrated that H5N1 strains contain many of the same lethal polymorphisms found in H1N1, the cause of the 1918 pandemic. These genetic segments are responsible for the virus's ability to attack extra-pulmonary organs including the brain, liver, heart, kidney, and blood coagulation system. It would be interesting for the article's authors to provide us with the postmortem results in these mice. My guess is that they would show multi-organ failure as is seen in many of the humans that have died with H5N1.
Since people possess immune systems they will not be protected from cytokine storm or multi-organ failure during infection with H5N1. Even it the immune dysregulation syndrome could be solved, something I think unlikely, the problem of lethal polymorphisms remains a considerable threat. This is, IMO, the point of the paper and why it is important.
Grattan Woodson, MD
Randy: All we can say from this study is that none of the three cytokines in this study singly is necessary for H5N1 lethality in these mice. The steroid results were meant to see if affecting multiple cytokines at the same kind was protective. Steroids have not been shown very effective in cytokine storm although there is equivocal evidence in humans about some. There were very few animals and no data on the pathology of in any of the animals, a curious omission in the paper which has a number of missing details.
Gratt: I am not so confident about any particular genetic signal with this virus conferring virulence. I know Taubenberger's results in 1918 H1N1 and they are certainly suggestive. But there are many more segments that might modulate or modify the effects of any particular polymorphism. But I agree that there are a variety of clinical courses, some but not all of which might involve cytokine dysregulation. One would not expect an immune deficient mouse to do well against a primary viral pneumonia but targeting a dysregulated cytokine system later in the course of infection might still be effective.
As I said, I think the authors have overinterpreted these results.
They gave 30 mg of cortisol to a mouse.
What they proved was that if you use astoundingly massive cortisol dose on a miniscule laboratory animal...it doesn't work.
However, I am not really too worried about the 'mice' in a pandemic...I am worried about my family and your families.
There is no alternative at the moment to moderate doses of prednisolone(ex. 50 mg)for short periods of time 5-7 days.
This is a massively overwhelming infection. Farm animal veterinarians treat these types of diseases all the time...find one and ask him/her their opinion.
They tried this experiment with SARS and proved if you give 2-3-4-5000 mg prednisolone per day intravenously it doesn't work real good either!!
At the moment you are losing more than 60% of your patients...so either we do something else or we hang our hat on Tamiflu and go home.
If you are not going to use an immune modulator used safely in extreme circumstances for more than fifty years...
...then with all due respect...where is your proven alternative...
...to answer my own question, there isn't one and I think we all know it!!
Randolph. Dexamethazone won't work...the only glucocorticoid that will work is prednisolone (with an l)
...and their ain't a snowball's chance in hell that statins are going to protect anyone against this bug.
Please read the following reference and then tell me that there is no place in a pandemic for the use of prednisolone at a total (out of pocket) cost for five days treatment of approx. 3 dollars and fifty cents.
Thank you...the reference is...
Methylprednisolone Infusion in Early Severe Ards.
Results of a Randomized Controlled Trial
Meduri et al
Chest 2007: 131; 954-63
Meduri et al are members of the Memphis Lung Research Program.
Tom: Why do you say statins wouldn't work? Just wondering. There are no trials for either statins or prednisolone in H5N1. They are also cheap and plentiful. Why so negative?
Tom DVM, I have been practicing medicine for 27 years and over that time the issue of do steroids improve the chances of patient survival in ARDS in people caused by a variety of etiologies has been discussed and reported ad nausea. As I recall the data, those supporting the use of steroids base their opinion on empirical observation reported in case studies primarily while those who oppose it base theirs on randomized controlled studies.
Having begun practice in the era when empiricism held sway and having to be dragged kicking and screaming into the new world of evidence based medicine which I now embrace, it is pretty obvious to me that steroids don't work well in these cases.
Also, there is not a wit of difference between dexamethazone, prednisolone, or hydrocortisone except for these agents mg-to-mg potency. The effects they have in the human and I presume animal body are exactly the same. Opinions to the contrary are again those based upon empiricism rather than science.
Submitted with the deepest respect for you and your contribution to the bird flu cause.
Your friend and fan,
Grattan Woodson, MD
Wa'll boys I think that they'll be trying everything and including Draino if it comes right now. I found a graph that I think it was St. Jude had done and placed it over the WHO graph for CFR's and ages. 1918 H1N1 graphed against 2007 H5N1 and with only a slight exception and I mean slight its a match. I dont know enough about the antigens except from the breakdowns over at GenBank. I can see patterns from H1N1 that are close matches with H5N1. Some of these I see also on H. Nimans webpage when he posts them up. I also see that when there is a jump of some kind and they finally get it up on either, you can see what for the lack of a better term is the creep.
It reminds me of that scene out of WarGames where the chick says, "Its got the codes, its going to launch." Chan really pissed me off yesterday with that veiledl load of crap re: 20% of the world is going to get it. So it really means now at 67% almost 40% and change of those will be gone. But dont worry they have it in hand... BIG jump from that 5% crap they were touting in January.
Hey, when you guys start talking about this in the doctors terms try to keep it fairly stupid for us weenies who took science only as an elective. I have to stop and get the first year of med school with the terms, and sometimes the body parts via Wikipedia or Grays. E.g. Cortisol is what fat people accumulate around their bellies or so the TV says when they are trying to sell weight loss drugs.
If you want that graph hit me on memphisservices@bellsouth.net
Tom, check this one out from 98. They were working on it then too.
Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA
Revere. Please excuse my momentary frustration. I do not believe in an abnormal immune response as the cause of the 'cytokine storm'
I have always believed, based on my experience, that in the case of H5N1 it depends on viral load and a super charged replication rate. This stimulates a normal immune reaction that produces a lot of 'cellular junk'. The consequences of direct viral destruction and removal of this circulating junk results in the cytokine storm.
Limiting the initial viral load would make all the difference between living and dying...although that is of course a generalization...as in even an inefficient mask is better than no mask etc.
Statins will not work, in my opinion, because this is a super-virulent virus and any minor effect will be overwhelmed...and I am not sure the epidemiological study was convincing.
Dr. Woodson. Thanks. I can only speak from my professional experience with these or similar viruses to SARS etc.
I tried cortisol and prednisone and dexamethazone...they had no or little effect and success rates were very disappointing.
I then tried prednisolone by intramuscular or subcutaneous routes in moderate to low doses...up to 250 mg/1500 lb.
...and thankfully, the treatment protocol worked beautifully. In these types of infections, a certain percentage will die from direct overwhelming virual infection in the first twenty-four to thirty-six hours. There isn't much you can do for those animals...however the prednisolone works on that second tier of patients who develop secondary bacterial infections etc.
I studied the pharmacology of glucocorticoids to explain the differences and I found that prednisolone does not have to be liver activated as prednisone does and I have always believed that dexamethazone was totally different (it didn't work at all).
So my studies indicate something a little different...in that prednisolone is unique and that is why it has been used specifically as an anti-shock anti-toxemia treatment.
Randolph. With prednisolone and other steroids you quickly run up against the law of diminishing returns.
I used a combination of prednisolone and anti-fever medications with the goal to have the animal weaned from the steroid to the anti-fever anti-inflammatory drug hopefully in five days and definitely by seven days.
After that you start to run into immunosuppression and if there is a secondary bacterial pneumonia you are sunk...better not to be on the steroid at all after seven days unless it is a few mg. per day...and I am not sure I would even do that.
The bottom line though is that a certain percentage will die no matter what you do in a very short period of time..a day or two...and for those patients all you can do is make them comfortable...in my experience.
Tom DVM states:
Statins will not work, in my opinion, because this is a super-virulent virus and any minor effect will be overwhelmed...and I am not sure the epidemiological study was convincing.
I ask respectfully:
Aren't the purpose of the statins to lessen the viral load and prevent it from being a death sentance and just a ball buster???
Tom: Lessening viral load and replication is probably a key goal (and antivirals are a tool here), but the role of statins or other cytokine/cheokine targets is to deal with the dysregulation and its lethal effects. Thus it is for when you have gotten in big trouble as a result of the virus. It doesn't attack the virus, granted, but like steroids is meant to lessen the effect. Your prednisolone also doesn't affect viral replication and it may make it worse because of its anti-inflammatory properties, so I don't understand your reasoning.
gilmore: no, statins aren't meant to affect the virus, which as far as I know, they don't.
Thanks Gilmore Revere.
I'm sure they must have a couple of other mice hanging around that they could use to conclusively tell us if 'statins' are effective or not.
Here is another reference of interest from beehiver...the best researcher I have ever met.
http://www.jimmunol.org/cgi/reprint/162/6/3527
Endogenous Glucocorticoids Protect Against Cytokine-Mediated Lethality During Viral Infection
"In conclusion, these studies have definitively established a protective role of endogenous glucocorticoid responses during a viral infection and identified the mechanism for mortality resulting in the absence of these responses. Thus, they show that glucocorticoids are key factors in regulating the delicate balance between protective and detrimental consequences resulting from immune responses to infections. By dissecting the individual components of the regulatory interactions between endocrine and immune systems, they further our understanding of pathways for defense against both infection and infection-induced cytokine disease."
Here is another beehiver reference:
http://www.jem.org/cgi/content/full/185/7/1185
Characterization of Early Cytokine Responses and an Interleukin (IL)-6-dependent Pathway of Endogenous Glucocorticoid Induction during Murine Cytomegalovirus Infection
According to my friend...it shows that one of the cytokines, IL-6 (interleukin - 6):
a) "induces production of natural corticosteroid as a 'natural' reponse to viral infection."
and b) "ACTH hormone is also involved in the cascade: IL-6 induces ACTH which induces corticosteroid."
The body responds to viral infections by increasing natural glucocorticoid levels...and human physiology is highly efficient and does not promote energy wasting processes during an infection...from my experience.
Stepping back from the PNAS article and H5N1 virus for a moment. There was research done in 1997 which helped to nail down the pathway of responses due to murine cytolomegalovirus (MCTV) infection through the various cytokines and hormones, to the final corticosteroid production. The study looked at the natural mouse responses and pathways (i.e., no drugs were delivered). The article is free access at http://www.jem.org/cgi/content/full/185/7/1185.
Title - Characterization of Early Cytokine Responses and an Interleukin (IL)-6-dependent Pathway of Endogenous Glucocorticoid Induction during Murine Cytomegalovirus Infection.
Part of what they found was that in this infectious cycle, IL-6 was a major player a pathway that INDUCED corticosteroid production. So...it implies that if the IL-6 cytokine is genetically knocked out in a mouse, (as in the PNAS study on H5N1 virus), it could significantly decrease a mouse's natural corticosteroid response.
They also found that this pathway involved ACTH
hormone: basically, IL-6 induces ACTH, which induces corticosteroid, which in turn lowers IL-6. There were a few additional steps involved, but that was the major feedback loop.
Additionally, the study took closely-spaced blood samples from the mice before and after infection time, to determine cytokine and hormone levels and when they peaked. And there were very clear peaks. In fact, an additional diurnal cycle of corticosteroid production was determined from.
The authors also stated that IL-6 is a major player in viral infections, and this has been acknowledged for H5N1 infection as well.
To my knowledge, there has been no similar careful research done to shine light on the cytokine and hormonal pathway(s) that occur after H5N1 infection, as well as the levels and timing of the peaks and valleys of those immodulatory substances. Until such groundwork on the pathways is established, it seems premature to perform the genetic "knockout" experiments as described in the PNAS article, along with the wide-ranging conclusions derived therefrom.
Such groundwork would also help to determine if glucocorticoid therapy would be helpful; which drug would be of most benefit; and if so, the dosage and timing of the drug. These details simply have never been carefully combed out in research efforts, without other confounding factors brought into play which could skew our thought process and analyses.
That is indeed unfortunate, because at this point in time it appears the need has never been greater. The research techniques are established, accessible, and possible.
Sorry about the bad url given above. You'll need to eliminate the period at the end of it:
http://www.jem.org/cgi/content/full/185/7/1185
beehiver: I think your points emphasize the point we and others have made about this paper. The interlocking effect of the cytokine system are yet to be worked out so the knockouts don't really tell the tale and the study was overinterpreted. The role of IL-6 in viral infections is a case in point. The CMV paper shows how there are interrelations with other cytokines that are important involving feedback loops, but trying to move from responses to CMV to H5N1 is a big leap and would have to be sorted out by some careful mechanistic studies. Meanwhile the clinical evidence for steroid efficacy in H5N1 is scant and not systematic but also not very encouraging, Tom's anecdotal testimony involving large animals notwithstanding. I understand he is drawing a distinction between prednisone and prednisolone and it is conceivable (although I don't think very likely) that this is a crucial difference. But at this point it has less support than the statin idea. I don't quite understand the resistance to that notion. I don't know if statins work or not. I'd like to see some study of it, however.
Revere. I agree completely.
Given the ongoing threat level and unique potential of H5N1, it seems it is time for a statistically significant (more than three mice) set of experiments to distill the subtle differences between all known and current treatments...
...then instead of continually speculating, we would have solid consistent results upon which to build a successful treatment protocol.
One addition in my treatment protocol eventually was spectinomycin. I remained convinced that this antibiotic had specific anti-viral activity...of course for unknown reasons as current belief is that antibiotics have no effect on viruses...
...so the study might also include a variety of antibiotics to test them as well for advantage with H5N1.
How about an article about the fundamental mechanisms of non-H5N1 cytokine storm--for which you can pretty much use 'multi-organ failure' as proxy--
http://www.urmc.rochester.edu/pr/news/story.cfm?id=1260
This would dovetail with an opinion I seem to share with Tom DVM, which is that the byproducts released due to cellular damage from the virus are what cause the 'cytokine storm', much the way dead skin left on a burn victim for more than a day can do, or tumor lysis can do in leukemia patients. If you put enough of what should be *inside* cells into the circulation by killing the cells, you wind up with a problem.
Lisa: The Rochester work says what we already know: that the cytokine signalling system is complicated and involves lots of interacting feedback loops. Whether the problem is products released from cellular damage, which is obviously what trauma does, or some devious mechanism of the virus, we still need to sort out. But I would point out that Tom is saying what seems to me two contradictory things. One, that the only thing that matters is viral load and replication; and two, that prednisolone, which doesn't target the virus but the cytokine signalling system or some part of it, is an effective therapy for early ARDS. If this is the case -- and I am agnostic on it -- then the statin strategy would also seem to have as much or more merit, since there are at least observational data to support it in the case of influenza, which there isn't for prednisolone.
I can't see that the Rochester trauma work supports the idea that it is products of cellular damage which is at work in influenza, since that work only examines the consequences of cellular damage. We know that the virus does interfere with interferon, so the question of viral action is still very much open. I think the authors of the PNAS paper have overinterpreted, but I also think that is true of Tom.
I lean against the use of steroids for ARDS.
I think it is valuable to look at what happens in cases of cellular damage in the absence of virus, and to compare that to what happens in the presence of virus.
One of the few cases to survive H5N1 infection *without* consistent western intervention was a young indonesian man treated with folk medicine by his father. The young man had a history of asthma which had previously been treated with a mixture that included cobra bile and other ingredients of unknown pharmacology (if any), but which featured red rice yeast as a major component--and this is what he was given to treat his lab-confirmed H5N1. I don't remember the gentleman's name but the timeframe was October/November 2006. Anecdotal, but still provocative for the potential utility of statins.
Lisa. As you and I well know, you can get lucky once...the person might have been a case that would get better without any treatment...maybe an epidemiological study with a couple of mice can prove that asthma provides protection against H5N1.
/:0)
Anyway, I still have to ask...if we cannot use low to moderate doses of an anti-shock-anti-toxemia drug that has been used safely for more than fifty years...then what is the alternative...
...the fact is that there is no alternative...Tamiflu doesn't cure anything and there is going to be no vaccine.
The whole point of this is to prevent ARDS before it becomes ARDS...the treatments are cheap and affordable (maybe 30 dollars per patient...
...if we treat proactively, we won't get ARDS.
In H5N1 infections with a collapsed healthcare system there will be no ARDS...they will die in the first 36 hours...
...It is the rest we want to save from secondary bacterial pneumonias and septicaemias. I know we can save these with no sequelae.
Timing is everything!!
Okay medical types. Whats the diff between prednisolone and prednisone. I looked it up chemically and I cant see that much difference as Revere says. I see the side effects are only different slightly, but what is the difference in the total effects?
Sent you an email last night asking for the graph you did MRK.
Our provider was changed three days ago and there are still problems throughout the community. We won't have email until Monday afternoon either.
>>Whats the diff between prednisolone and prednisone?
Prednisone is converted in the liver to prednisolone, which is the active form of the drug. Tom is the only person I've encountered who doesn't regard the two as functionally equivalent (barring liver problems).
On the subject of avian influenza and steroids, see my recent article.
We don't really know what killed the young during the 1918 pandemic. There are some very good descriptions provided by pathologists from post mortem examinations but they did not have all the tests and procedures available to us today back then. It is presumed that what they were seeing then was what we call today the ADULT RESPIRATORY DISTRESS SYNDROME (ARDS). What's more, if it was ARDS, and I think it was, the mechanism for it developing during N1H1 that has been called Cytokine Storm is also conjecture. ARDS seen in the ICU today has many causes not just viral infection. The condition is not a disease but a set of clinical signs and symptoms that are grouped together as ARDS. This is not new information but I just thought it might be a good time to remind us of this fact.
The mechanism of ARDS is not understood. There are a lot of theories and some may be on target for some of the reasons that this syndrome develops but off base for other causes. It is important to recall that ARDS has about a 50% CFR in patients treated today in a good hospital ICU by well-trained staff.
The mice studies quoted above show the importance of ENDOGENOUS glucocorticoid release during viral infection. It is really addressing one of the immune system's counter-regulatory aspects that are important for the maintenance of homeostasis or balance. This data does not address the use of pharmacologic doses of glucocorticoids administered EXOGENOUSLY to mice and their chances of survival. I think that these mice data are pertinent to the role of endogenous steroid release in response to human infection but IMO should not be extrapolated to the use of high dose exogenous steroid treatment during ARDS from any cause including H5N1.
Even the sophisticated tools we have today for evaluating patients and animals who develop the ARDS after infection with H5N1 have not provided us with a clear insight into its mechanism. It is my opinion that if this was known, then we might have a better chance of figuring out a treatment strategy for it. I am not saying that the Cytokine Storm mechanism is wrong. In fact I support it conceptually and think it is biologically plausible. It is my surmise that after THE H5N1 influenza virus infects a human host that is immune naïve; the virus has a very long time to reproduce within this tissue. When the host's immune system gets into gear, the lymphocytes, granulocytes, and macrophages go to town on the huge viral load present in the patient's tissues triggering the release of numerous cytokines in the process. The lung tissue is so infiltrated by virus that during the process of this massive immune response, the lung is damaged irreversibly. This damage, if this is how it occurred, would be consistent the clinical picture we call ARDS and result in the rapid death of the host. If this indeed is one of the influenza-related causes of ARDS and is also what happened in 1918 with H1N1, then it could also partially explain why people aged 15 to 45 had the highest death rates given that they would also have the best immune response. Younger children with a functioning thymus have immune tolerance that older ones loose when the establishment of cellular immunity is complete and this organ atrophies. (Maybe administering a recombinant thymus protein or two might be useful?)
The lack of a significant increase in death rates in people over 55 during the 1918 pandemic is a real enigma. Some speculate it was due to their having age related immune senesence and this factor protected them from Cytokine Storm. I doubt this explanation because if that was the case, then it might have reduced their risk of CS but certainly not from multi-organ failure induced by the lethal polymorphisms carried by N1H1. On the contrary, it would have increased their vulnerability to these viral factors. Others have suggested the only explanation that fits this observation without anomalies is that they were infected with a similar virus that circulated in the 1870-80 period. IMO, this reason fits the data best because it is only through some degree of immunity to N1H1 that these people would have been protected from both CS and multi-organ failure.
In the final analysis, as Revere points out, the key to preventing CS (and multi-organ failure) is to reduce the number of influenza viral particles that reproduce within the patient lowering his or her viral load to a level that can be managed by the human immune system without resulting is severe collateral damage. One way this is accomplished is by having some immunity to the virus before being infected. Another would be having an effective antiviral agent that could be administered early in the infection.
So, while it might be nice to work on the cause of CS and ARDS, the better approach is the one Dr. Osterholm suggested 2 years ago, funding a Manhattan-style pandemic vaccine Project that can rapidly take the virus that causes outbreak and scale up production of enough effective doses to provide adequate herd immunity for humankind. This means at least 2.5 billion effective doses. Only we in the advanced nations have the technology and capital to do this. The product of this research must be given freely to those in the developing and third worlds since it is essential to protect all of us, not just the rich. Global interdependence has become too important economically and socially. While we might be able to protect those in the advanced nations with a specific vaccine like this from the direct effects of the virus, if we fail to protect the other 87% of the world's population, the advanced economies will be crushed by secondary effects caused by the collapse of the economy society, and civil order within these other countries.
Grattan Woodson, MD
Doc-Good post. Now can you tell me how many people that you know who have prepared. There IMO will be no Manhattan style project because for the time being aint no reason to in their eyes. It will come soon enough.
I get laughed at and laughed at by people who are aware that I send people the information off of the news wires each day about BF. Graphs, pics, lungs and the really good no shit stuff like videos of how they go. The get a little more sobered up about it, but most still just sit like sheep waiting to be shorn.
Re: the rich helping the poor countries. On the moral front, I agree. On the other side of the coin I say they can go screw themselves. Why? Well in the face of a growing probable pandemic we have and are sending money in there like a bottomless pit. 500 million in recent history. Guess what? Very little of it went for culling, curing and preparations. They dumped a lot of it into Tamiflu and the dumb sons of bitches are feeding it to their poultry. So at what time will we take say 500 million and put it into preparations by our state and federal governments?
Not before Katrina hits is when. No one wants to raise taxes for it so its a slow plodding approach. Their out? We told you it was coming and with the NFP it shifts the responsibilty as it should to the states. The states had better wake up .
Also, if we take a 5% hit in the world we will shake the effects of that off within 5 years...eg. the Roaring 20's (McKibbin-Australia). Anything though past 8% and we got ourselves a problem. Our economy will be crushed automatically because of the infrastructure, not because of world economic society. It will be the US economic society. Few people mean few jobs, many survivors mean many jobs. We will blow through the supplies like an army with the suppliy lines cut. I would give it a month maximum and the cries are going to go out for help. There will be about three tiers of people that are worst hit and it would as they say start with the stockbrokers. What does a stockbroker know how to do? Next is the desk jockey. A truck driver will make loads more than say a stockbroker in under a year after it hits. Doctors being the first line that gets hit hard will be in short supply along with nurses.
We will have to do without a lot of things for a fairly long while but it will reach a state of equilibrium at 15% within 20 years. Our long term survival as a country could come into play at that number and without young people to fight a war or defend the nation it leaves only the nuclear option.
If indeed it were the 50% then it would take a century to recover as it did with the Black Plague. The population after that little pop took almost two hundred years to recover to the pre-plague dates.
Take a thread of line progression for everything in your life that you do, use or need. Figure out what will be needed and not needed and cover those bases of need. Everything else will go with the bathwater. Lets hope that the baby isnt in with it.
I dont discount what you are saying though. Its dead on the mark for whats going to happen. The poor countries can forget ever seeing any vaccine as we may well too. How each person prepares personally will determine the outcomes for communities. A fully prepared personal community will breeze through this like a French month long vacation. Outside in the cold of the NE or upper Mid-West its a death sentence regardless. Lack of food coupled with no heat for easily 30% of the nation and its bye-bye. I wouldnt want to be 200 miles inland during a Nor'Easter with no heat, water or food. Things would become primeval very quickly.
That is one scenario Randy, but not the only one.
The good Dr.'s points are well taken.
One thing about it...with more people on this great planet, we have more people looking for solutions! :-)
Cytosorbents Corp. recently received E.U. approval for a hemoperfusion cytokine removal filter. Approval was received prior to clinical study release (which according to the co. is soon to come)they are making indications that the study is very positive,no other product like this is on the market.
As an ICU nurse I am waiting for the study results as I always thought a reduction of cytokine storm and subsequent inflamation reduction would be positive in overall mortality rate reduction.