I wrote about the possible use of statins in pandemic influenza a little while ago here
Efforts are being made by David Fedson to organize workshops that would bring together groups of experts to explore the hypothesis that statins might be useful for treatment and prophylaxis of pandemic influenza. Here are a few points made by Fedson that I thought are well made and relevant to pandemic mitigation.
The Potential Global Impact of an H5N1 Pandemic. <snip> If a pandemic similar to the 1918 pandemic were to occur today, it would kill between 175 and 350 million people worldwide [1,2]. Because the case fatality rate of human cases of H5N1 influenza is 50 to 60%, a human pandemic caused by this virus could conceivably lead to a partial global population die-off. No one can estimate the probability that this will occur. No one can deny that it is possible.
The Inadequacy of a Vaccine Approach to Pandemic Control. Vaccines have been the mainstay for controlling seasonal influenza and are regarded as the primary intervention for controlling the next pandemic. A pandemic vaccine, however, will take many months to produce and producing an H5N1 vaccine will be especially difficult. <snip> There is little chance the supply of pandemic vaccine can be expanded significantly within the next 5–10 years. Supplies of antiviral agents will also be extremely limited.
Statins: a Possible Alternative for Treatment and Prophylaxis of a Pandemic. Because of the inadequacies of a vaccine approach to pandemic control, an effective alternative is needed. One possibility is to use medications that are already produced as generics and are available and affordable worldwide. Statins, the drugs used to treat high cholesterol levels and prevent heart disease, are one group of medications that could be considered [3]. The scientific rationale for this idea is based on their anti-inflammatory and immunomodulatory activities. Given as treatment or prophylaxis, statins might help to control the pro-inflammatory response that accompanies H5N1 infection. The public health rationale for using statins is their worldwide availability at affordable prices. In addition, they would be available on the first day of the pandemic.
Persuading Investigators to Explore the Statins/influenza Hypothesis. The statins/influenza hypothesis has been discussed with a wide range of investigators and health officials for more than three years. Several epidemiologists and clinicians have completed or soon will undertake studies exploring this idea using population-based clinical data sets. Persuading laboratory investigators to explore the statins/influenza hypothesis has been much more difficult. One way this could be done would be to bring together groups of investigators to explore the pros and cons of this idea.
Many investigators on both sides of the Atlantic would have much to contribute to a discussion of the statins/influenza hypothesis, especially in the following six areas of research relevant to the statins/influenza hypothesis:
If the workshop participants conclude that the statins/influenza hypothesis is worth pursuing, they would be asked to develop a research agenda that could quickly address the most important questions.
References
1. Fedson DS. Preparing for pandemic vaccination: an international policy agenda for vaccine development. J Public Health Policy 2005; 26: 4–29.
2. Fedson DS. Vaccine development for an imminent pandemic: why we should worry, what we must do. Human Vaccines 2006; 2: 38–42.
3. Fedson DS. Pandemic influenza: a potential role for statins in treatment and prophylaxis. Clin Infect Dis 2006; 43: 199–205.
David S. Fedson was formerly the Harry T. Peters, Jr. Professor of Medicine at the University of Virginia School of Medicine (−1995) and former Director of Medical Affairs, Europe for Aventis Pasteur MSD (1995–2002)
Several comments I want to make:
1) “a human pandemic caused by this virus could conceivably lead to a partial global population die-off. ”
Fedson is the only scientist I’ve met who is willing to say this publicly.
2) “The Inadequacy of a Vaccine Approach to Pandemic Control”
This coming from a vaccine expert.
3) The rationale for statins rests on 2 main pillars
4) “The statins/influenza hypothesis has been discussed with a wide range of investigators and health officials for more than three years.”
They just need to get their act together.
annon 22. Excellent thread concept!! Just what is needed, at least in my opinion. Thanks and hope you are feeling better.
Hope this is limited to the discussion of statins. If liver monitoring is a required part of the treatment, there is very little likelyhood that this would be possible during a pandemic.
There are many ways to get around this bug, we just have to get beyond the things that won’t work first.
Shoot…Hope this is not limited to the discussion of statins, vaccines and antivirals. Lets concentrate for a while on how to make other alternatives work effectively.
This is about efforts to find solutions that are
Janet posted this before I took this thread off for re-writing:
“Anon_22. Great input! Really important info. Thanks.
Does anyone have any idea what dosage level they are talking about? Any guesses on milligrams per day or over how long of a period, etc?”
Excellent!!!!!!!!!!!!!!!!
While you are at it, why not design a new type of healthcare system that might also be functional in a pandemic…the existing one won’t.
Tom DVM – at 11:50 “Excellent!!!!!!!!!!!!!!!!
While you are at it, why not design a new type of healthcare system that might also be functional in a pandemic…the existing one won’t.”
Yes, dream on…I might become omnipotent one of these days. LOL
Janet,
“Does anyone have any idea what dosage level they are talking about? Any guesses on milligrams per day or over how long of a period, etc?”
These are all things they need to work out. Hence the urgent need for research.
annon 22. You might become omnipotent, whatever that is some day, but we can design a system that can effectively deliver healthcare during a pandemic…and we should in concept on flu wiki because no one else seems to be doing much of a job, in my opinion.
I think the relevant authorities are still overwhelmingly in the ‘not going to happen’ camp…or more importantly in the ‘not going to happen under my watch’ camp.
/:0)
“Many investigators on both sides of the Atlantic would have much to contribute”
Just want to add that there are excellent investigators from Western Pacific, especially from Japan, who will have important input and will also be included.
Tom, this is a stupid question, so don’t laugh. What does /:0) mean?
The links for the references quoted above are:
emoticon: guy with a big nose looking at you, smiling. Tip your head to the left.
“guy with a big nose looking at you, smiling”
Yes, but what does it mean? As in what emotion does that represent?
Sorry, I’m a bit thick. Maybe I don’t have too many guys with big noses looking at me, yeah?
anon_22 – at 12:38
that you know of. /:0)
ok, this conversation is definitele degenerating. I plead guilty…
Hi annon 22. Sorry, am in and out today.
It’s nice to know that I am not the only one on this site that is “a bit thick”.
I had meant to add a smiley face to my post at 11:59 to show that although I was serious, I was not being unrealistic or super-serious about the subject.
/:0) is my interpretation of myself smiling.
By the way, I am really glad that you started this thread although we may be a little short-staffed at the moment to give it full consideration. If we can not have a full discussion now, I hope you re-introduce it in Sept.
Tom,
“By the way, I am really glad that you started this thread although we may be a little short-staffed at the moment to give it full consideration. If we can not have a full discussion now, I hope you re-introduce it in Sept.”
Sure, I hope there will be some progress by then.
annon 22.
1) If we hypothetically remove vaccine and antivirals from the equation how do we limit the effects of an imminent pandemic from H5N1 with a CFR of 10%?
2) Secondly, we hypotheitically remove a healthcare system as we know it today and redesign it so that it will be effective in the face of an emerging pandemic with a 10 % CFR…and we design it so that there will be no undue panic by the populace…
…in other words, even though the existing healthcare system does not exist, the replacement does not leave us feeling helpless but rather empowered to fight the pandemic and win…as in 1918.
If we answer 1) and 2), we will be empowered to face the enemy to the best of our colective abilities…
…and if we continue to rely on the status quo, we are ‘screwed’.
Possible solutions-
-Eliminate the guild socialism that is modern medicine. Allow anyone who wants to practice medicine do so, no license required. -Eliminate prescription laws. -Abolish the FDA.
Absent reforms as drastic as these, the next pandemic will provide sufficient justification for more serious reforms, some not so benign.
Well, it is easy, even normal for some, to imagine that when we get rid of our present system, we will have a better world.
That’s what all revolutionaries think. “Bring the whole system down. We will build it again from the ground up.” Without of course any solid ideas nor experience.
The result is often disaster, as we have seen too many times in the 20th century. Cambodia under the Khmer Rouge comes to mind.
Current institutions and regulations, however imperfect, often arose out of a very long process of trial-and-error, based on lessons learnt by others before us. We do not need to re-invent the wheel. Apart from anything else, we don’t have enough time, as far as pandemic mitigation is concerned.
We need to continually strive for improvements where we can.
Hi annon 22.
“Secondly, we hypotheitically remove a healthcare system as we know it today and redesign it so that it will be effective in the face of an emerging pandemic with a 10 % CFR…and we design it so that there will be no undue panic by the populace…”
The comment to remove the healthcare system was a metaphorical one. What I meant to say was that the existing healthcare system will fail or flat out collapse in a pandemic. I don’t know about your opinion but it is a sure thing to me…
…so the new system I was thinking of was a seizure of fast food take-out restaraunts with drive through windows. They could be used to dispense packages of medications to be administered at home with telephone back-up support by healthcare professionals…
…having healthcare advice immediately on the telephone of internet would decrease panic and fear responses by panicked citizens and take some of the added pressure off hospital emergency rooms.
If there was a place for the very sick to be given intensive care, the telephone, internet advisors could determine those at most need.
I didn’t mean to insult existing services, I meant to improve on them and assist them to stay up and running in a pandemic and at the same time prevent further casual contact by those seeking medicines (ie.standing in line-ups)
Tom,
I was responding more to LMWatBUllRun’s post than yours, but thank you for clarifying anyway.
Yes, I think the chance of a total system collapse is serious enough to be considered. I don’t know that we have good answers at this point. However, I think the more life-saving solutions we can offer for the world, the less stress there will be on the system.
Having a widely available drug as treatment would go a long way towards that.
annon 22. Agreed…However, if we are to have one widely avaliable drug as treatment, then we had better make sure it works…if not, then a wide range of supportive therapies would be appropriate in my opinion…then if one doesn’t work, there are others to ‘take up the slack’.
Tom, yes, yes, and yes.
Ok you folks are the really smart ones here and if I am out in left field just tell me to shut-up.
What about brown bags with things like:
Penicillin, Tetracycline , acetaminophen, aspirin and or other type drugs to help with the pneumonia, fever, aches and pains, sinuses problems etc.
These are things that could be put together by the Red Cross and after getting a history (allergies, age, weight that sort of thing) grab a bag that would meet the basic needs and move them out.
I know that only doctors or highly qualified nurses (yes nurses) should be making those type of calls but it may be a way to save many more then what would otherwise be saved.
Anon 451. Everyone’s bag will be different and that’s all right…so take out the aspirin (causes Reye syndrome especially in young children) and add oral electrolyte powders formulated specifically for the pandemic and our list would be pretty close…
…don’t tell anybody but I would also have oral prednisolone tablets in that bag as well.
Tom DVM – at 21:51 What is oral prednisolone tablets ?
Added the Aspirin more for the older adults as a blood thinner for heart support and to combat the fluid around the lungs. Any way that was in the old days may have changed and that is not good for those uses.
Anon_451,
All those other drugs are important but they are only good for supportive treatment. As far as we can tell, with the current mortality in H5N1 infections, I seriously doubt how much difference these will make for mortality figures from a public health point of view.
As I said before in a different thread, statins, in the context of pandemic flu, could be viewed in the same category as vaccines and antivirals.
Oh Oh Busted!!
Ok, prednisolone is a steroid that mimics natural steroid molecules produced by your body.
When you go into shock whether it is from a car accident, gun shot wound or from acute anaphylaxis (bee sting, food allergy), in effect holes are punched in your blood vessels, and plasma from your blood leaks into the area between cells…the end result is collapse due to decreased circulating blood volume and the resulting lack of oxygen supply to the tissues…
…prednisolone causes the blood vessel walls to repair themselves temporarily and increases blood volume and helps move stagnant fluid out of the tissues, reducing swelling etc.
I think it is a lucky thing that the drug that is given in intensive care situations (car accidents etc.) is also avaliable in an oral form that is also very effective.
annon 22 at 22:00 I agree.
annon 22. What will they have to do to prove that Statins are effective? Have they done testing in other mammals with H5N1 challenge?
Tom DVM – at 22:10 “annon 22. What will they have to do to prove that Statins are effective? Have they done testing in other mammals with H5N1 challenge?”
No to your second question.
What needs to happen is an opportunity for researchers from various fields to gather together to brainstorm a) whether there is a case for statin use in influenza, and b) what studies are needed to prove it one way or the other. That is what Fedson is proposing and working on, as described in my first post above. The six areas he outlined cover rather comprehensively the kind of data needed.
It seems a little screening in laboratory animals would’t take too long and should give an indication of preliminary efficacy. Then they could infect larger mammals…very carefully!!
Tom DVM – at 22:07 Good suggestion on the prednisolone. May help to repair the blood flow to the lungs in a bad case.
anon_22 – at 22:00 Your comments on the Satins is well worth the medical communities look. If they do work then that would be another weapon in you arsenal to fight with.
The drugs I was recommending would be more for the older folks (over 60 crowd) and those that may not have to bad a case of the flu. All I can see is the Tube at Piccadilly loaded with cots and you and your staff doing everything they can to keep people alive. Being able to send a few home with a bag full of drugs to fight a less severe case, may help you along.
Anon 451. As far as your comment on the aspirin goes…I guess if you were on aspirin as a prophylactic against heart disease then you would continue but it’s better to be taken out of the mix altogether when kids are involved because as far as I know, Reyes syndrome kills almost every child that gets it…maybe annon 22 could explain it better but it must be getting late in Britain.
In self defense, in relation to my comments on prednisolone…
…prednisolone is dispensed in emergency rooms in Canada to prevent the after-effects of bee stings in moderately susceptible individuals at a dosage of 50 mg/day for four days without any survelliance of any kind.
To make this a little easier to understand, here are some points from his paper Pandemic influenza: a potential role for statins in treatment and prophylaxis which lay out the logic in a different way.
In other words, dysregulation of proinflammatory cytokines appears to be the common pathway for clinical illness in human influenza infections in general, not just in H5N1.
Different viruses differ in the degree that they trigger this process, with H5N1 and the 1918 virus having been shown to be among the most potent.
In addition, human hosts can also have a wide range of this cytokine response, with those showing the most response having the highest morbidity and mortality.
If statins exert their beneficial effect on cardiovascular disease, for example, mainly by reversing this same mechanism, then they can be used in influenza to prevent, reverse, or reduce the degree of cytokine dysregulation which is the main culprit for severe disease and death.
annon 22. Seems like a pretty big “If” to me but I hope it works in the end…they don’t have to long to decide and then to bump up production so they had better get experimenting with laboratory animals…yesterday!!
Tom DVM – at 00:06 I second that opinion.
anon_22 – at 22:57 Is there anything the folks on the Wikie can do to help make it happen???
Anon_451 – at 00:29 “Tom DVM – at 00:06 I second that opinion.
anon_22 – at 22:57 Is there anything the folks on the Wikie can do to help make it happen???”
Well, at the moment, the main thing is to organize some workshops for the scientists to brainstorm on the issues listed above.
“If the workshop participants conclude that the statins/influenza hypothesis is worth pursuing, they would be asked to develop a research agenda that could quickly address the most important questions.”
As Fedson said, discussions about this in the medical community have been going on for 3 years. But no one has taken this on in a systematic way. WHO won’t/can’t do anything without data ie clear evidence of efficacy. Fedson tells me that the people who would be able to make the most valuable contributions are already identified. They would be the people most able to address the six areas listed above as well as any associated issues.
I guess what needs to happen is to find the funds to organize the workshops. He is envisioning probably one in Europe and one in the US, as this will be a bit more economical than trying to get everyone in one place.
Here is an interesting article from the JAMA Lipid-Lowering Therapy and In-Hospital Mortality Following Major Noncardiac Surgery, Lindenauer et al, JAMA. 2004;291:2092–2099.
Context Cardiovascular complications following major noncardiac surgery are an important source of perioperative morbidity and mortality. Although lipid-lowering medications are considered a key component in the primary and secondary prevention of cardiovascular disease, their potential benefit during the perioperative period is uncertain.
Objective To examine the association between treatment with lipid-lowering medications and in-hospital mortality following major noncardiac surgery.
Design, Setting, and Patients A retrospective cohort study based on hospital discharge and pharmacy records of 780 591 patients aged 18 years or older who underwent major noncardiac surgery from January 1, 2000, to December 31, 2001, at any 1 of 329 hospitals throughout the United States. Only patients who survived through at least the second hospital day were included. Lipid-lowering therapy was defined as use during the first 2 hospital days. Propensity matching was used to adjust for numerous baseline differences.
Main Outcome Measure In-hospital mortality.
Results Of the 780 591 patients, 77 082 patients (9.9%) received lipid-lowering therapy perioperatively and 23 100 (2.96%) died during the hospitalization. Treatment with lipid-lowering agents was associated with lower crude mortality (2.13% vs 3.05%, P<.001). In an analysis using matching by propensity score, 1595 patients (2.18%) treated with lipid-lowering medications died compared with 4158 patients (3.15%) who did not receive therapy or in whom treatment was initiated after the second day (P<.001). After adjusting for residual differences in the propensity matched groups using conditional logistic regression, risk of mortality remained lower among treated patients (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.58–0.67). Based on this adjusted OR, the number needed to treat to prevent a postoperative death in the propensity matched cohort was 85 (95% CI, 77–98) and varied from 186 among patients at lowest risk to 30 among those with a revised cardiac risk index score of 4 or more. In a further analysis using the entire study cohort and adjusting for quintile of propensity, a significant effect of treatment persisted (adjusted OR, 0.71; 95% CI, 0.67–0.75).
Conclusions Treatment with lipid-lowering agents may reduce risk of death following major noncardiac surgery. Clinical trials are required to confirm this observation.
Author Affiliations: Division of Healthcare Quality, Baystate Medical Center, Springfield, Mass (Drs Lindenauer, Pekow, and Benjamin); Department of Medicine, Tufts University School of Medicine, Boston, Mass (Drs Lindenauer and Benjamin); School of Public Health and Health Sciences, University of Massachusetts, Amherst (Dr Pekow and Mr Wang); Premier Healthcare Informatics, Premier Incorporated, Charlotte, NC (Dr Gutierrez).
2 reasons why this study is interesting:
bump
BUMP
Bumping for Anon_22
Bumb
bump - In my medicine cabinet.
bump
Revere’s post in Effect Measure has reminded me to come and update this one.
Funding for at least one workshop/conference has been identified, from private sponsors.
We are however running into difficulties finding an institution to co-sponsor for logistics and invitations etc. The ideal scenario is to hold one meeting in Washington DC and maybe if funds allow a second one in Geneva. Representatives from NIH, WHO, Gates Foundation etc will be invited to attend as observers (at no extra cost if it is held in DC), so that they can add their input and decide first hand whether they want to sponsor the research that will come out of the discussions.
I cannot believe the number of people who are saying “that’s a great idea, somebody should do something, but we are not the people to do it”.
OTOH, I just learnt from Dem yesterday that the definition of being an activist is to hear those kinds of responses. I never thought of myself as one till now….
We need this research. The children of the world deserve at least one attempt in getting this out. The CFR of H5N1 is so horrendous now, if statins are even moderately effective, we are looking at possibly millions of lives saved.
I know I have seen reports of anti-influenza activity from Erythromycin. I am guessing at these sources but I assume the citation was in PubMed. I really need to keep that treatment table current.
Sato K, Takahashi T, Okamoto S, Muranaka H, Okamoto T, Suga M. Action of EM703, a new macrolide derivative, on the lung that has been damaged by influenza virus Jpn J Antibiot. 2004 Jun;57 Suppl A:126–8. Japanese. No abstract available. PMID 16108615
Ninomiya K. Beneficial effects of macrolide antibiotics on children with influenza Jpn J Antibiot. 2003 Apr;56 Suppl A:84–6. Japanese. No abstract available. PMID: 14679754 [PubMed - indexed for MEDLINE]
Shiroki K. Anti-influenza mechanism of macrolide antibiotics inducing airway IL-12 production in murine influenza model Jpn J Antibiot. 2003 Apr;56 Suppl A:68–71. Japanese. No abstract available. PMID: 14679751 [PubMed - indexed for MEDLINE]
Am. J. Respir. Crit. Care Med., Volume 157, Number 3, March 1998, 853–857 Therapeutic Effect of Erythromycin on Influenza Virus induced Lung Injury in Mice full article
Missed one, although I can’t say that IL-12 is something we can find at the local drugstore. May be just one more piece of the puzzle in addition to statin use.
The protective role of interleukin (IL)−12 against influenza infection was assessed by analyzing the efficacies of orally administered clarithromycin (CAM) as an immunomodulator and intranasal administration of recombinant IL-12 in intranasally influenza virus-infected mice. In infected mice, CAM at 20 mg/mouse/day significantly elevated the levels of IL-12 and interferon- on days 2 and 3, respectively, after infection in the bronchoalveolar lavage fluid (BALF), but the levels in the sera were not affected. The levels of IL-4, −6, and −10 were not significantly affected in the sera and BALF. Corresponding with the local elevation of IL-12 level, CAM reduced virus yield and the number of infiltrated cells in the BALF, the severity of pneumonia, and mortality of the treated mice. The potential activity of CAM as an experimental immunomodulator was verified at a dose of 20 mg/mouse/day. Intranasal administration of the optimal dose (20 ng/mouse) of IL-12 on day 2 significantly reduced virus yield in the BALF after infection. The loss of body weight was significantly suppressed by IL-12 administration. The local elevation of IL-12 level at the optimal dose and timing in influenza infection was confirmed to be effective in alleviating the influenza infection in mice treated with the two different ways. Thus, the augmentation of IL-12 production or administration of supplementary IL-12 in the respiratory tract was essential in reducing virus yield in the early phase of influenza and may be crucial for recovery from influenza infection.
Closed to maintain Forum speed.