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FluTrackers Interviews David S. Fedson, M.D. - Meeting the Challenge of Influenza Pandemic Preparedness in Developing Countries

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  • #16
    Re: FluTrackers Interviews David S. Fedson, M.D. - Meeting the Challenge of Influenza Pandemic Preparedness in Developing Countries

    Keep up the good work, Sharon!

    For anyone looking at Dr. Fedson's research, just remember that it can be dangerous to take statins at the same time as fibrates:

    Gemfibrozil, when used together with the statin family of cholesterol-reducing medications, for example, lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), rosuvastatin (Crestor), and atorvastatin (Lipitor) increases the risk of a condition called rhabdomyolysis (muscle injury) which when severe can lead to kidney damage and seven death. Rhabdomyolysis may occur as early as three weeks or several months after starting combination therapy. The benefit of combining gemfibrozil with statins does not outweigh the risk of rhabdomyolysis.
    Here's the research article on Gemfibrozil Treatment of Severe Mouse Influenza:

    Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza


    We have shown that gemfibrozil, when administered i.p. on days 4 to 10 after exposure to virus, after the onset of illness, significantly increased survival in mice with severe influenza.

    Although gemfibrozil is as yet untried in human influenza, it could have two major advantages. First, it is already approved for daily human use, albeit by a different route, to lower plasma lipids and cholesterol (18, 23). Second, from our data, enhanced survival did not depend on giving gemfibrozil before the onset of illness, since treatment begun 4 days after exposure to virus, when mice were already sick and had lost weight, was effective. This implies that gemfibrozil has the potential to be a treatment rather than a preventative in human disease, allowing limited stocks of the drug to be focused where required in a pandemic. The idea that severe systemic inflammatory disease arises through overproduction of proinflammatory cytokines in influenza (6, 8) now also has general acceptance. This made it attractive to test the effects of gemfibrozil on influenza, a disease acknowledged to operate through these cytokines. No fibrate appears to have been previously tested against an infectious disease.

    Using anti-inflammatory agents against influenza is a recent suggestion, with Fedson proposing statins as a prophylaxis and treatment for an influenza pandemic (11, 12). While the concept has been gaining favor (20), no direct data are as yet available. Since the aim of this study was to find an agent useful in animals already sick from influenza, our initial trials included simvastatin at the human daily maintenance dose for lowering blood lipids. Unlike gemfibrozil, simvastatin had a negligible effect on sick animals under these conditions. Nevertheless, the use of statins in influenza, including as prophylactic agents, warrants closer examination, since the epidemiological data that support the protective effects of statins arose from sepsis patients who were already taking these drugs at the time they became ill (1).

    We also found that gemfibrozil gave some protection, in survival terms, against the severe systemic inflammatory illness that results from administering LPS (Fig. 3). This suggests that it could also protect against other similar inflammatory conditions as well as influenza. In addition, activity against LPS implies that at least a major effect of gemfibrozil against influenza is to inhibit inflammatory cytokines, not the virus. Nevertheless, the mechanisms by which gemfibrozil exerts the effects we have observed are yet to be elucidated. Our next priorities are to examine whether inflammatory cytokine production is inhibited and to determine if gemfibrozil has any direct antiviral action.

    Although the published mouse 50% lethal dose of gemfibrozil is 3,162 mg/kg for a single orally administered dose, and 300 mg/kg/day of gemfibrozil, given for 3 or 12 months, is well tolerated in rats (15), we are wary of extrapolating this to pathogen-infected mice without further study. Also, it is yet to be ascertained how outcomes of oral and i.p. dosages compare. As noted elsewhere (3), gemfibrozil reduces the production of inflammatory cytokines, molecules that are involved in the host response against pathogens as well as disease pathophysiology (6). The literature on the effects of anti-TNF agents in rheumatoid arthritis provides an example of this useful and harmful duality of inflammatory cytokines (22). This possibility in influenza will be examined in several ways, including further parallel studies using gemfibrozil against influenza and LPS toxicity. The LPS model is useful because it involves no cytokine-susceptible infectious agent and causes pathology only through excessive cytokine production.

    In summary, if these results translate to human infections, gemfibrozil may prove to be a readily testable and useful treatment for influenza, both in high-risk individuals with the currently circulating influenza virus strain and in any pandemic resulting from an antigenic shift in a subtype, including the current avian H5N1 influenza virus.


    • #17
      Re: FluTrackers Interviews David S. Fedson, M.D. - Meeting the Challenge of Influenza Pandemic Preparedness in Developing Countries

      hat tip Senior Moderator Fla Medic -

      Tuesday, May 19, 2009

      Swine Flu Vaccine Production Delayed

      # 3220

      Anyone who didnít see this one coming hasnít been paying attention.

      Swine Flu Vaccine Will Take Months, Health Officials Say

      By THE ASSOCIATED PRESS Published: May 19, 2009
      Filed at 7:06 a.m. ET
      GENEVA (AP) -- Drug manufacturers won't be able to start making a swine flu vaccine until mid-July at the earliest, months later than previous predictions, the World Health Organization said Tuesday.

      The disclosure that making a swine flu vaccine is proving more difficult than experts first thought came as U.N. Secretary-General Ban Ki-moon and WHO chief Dr. Margaret Chan met Tuesday with representatives from up to 30 pharmaceutical companies to discuss the subject.

      Health officials from around the world are attending WHO's annual meeting in Geneva this week to discuss the outbreak that has infected 9,830 people in over 40 countries, killing 79 of them.

      According to vaccine experts convened by WHO last week, swine flu virus is not growing very fast in laboratories, making it difficult for scientists to get the key ingredient they need for a vaccine, the ''seed stock'' from the virus.

      The flu experts said vaccine manufacturers will not be ready to produce a swine flu vaccine until mid-July at the earliest, the agency reported Tuesday on its Web site. Previously, WHO officials had estimated that production could start in late May.
      (Continue . . . .)
      The hope was that (and you need to insert a small miracle here) somehow vast quantities of H1N1 vaccine could be produced, and distributed in time for this fallís flu season.

      On May 9th, in A Vaccine Reality Check , I rattled off just a few obstacles that I felt could interfere with that timetable.
      • The virus could mutate over the summer or fall, possibly rendering any vaccine being manufactured now less protective (or even useless).
      • The virus may not grow well in eggs (that happens sometimes), reducing the amount of antigen that can be produced.
      • They could discover problems during the animal and human testing phase, which canít even begin until late July.
      • The much vaunted global manufacturing capacity may not be as high as some have projected.
      • People may need more than the standard 15 mcg flu shot to provoke an immune response, or need two shots, which would cut down on the number of doses that could be produced.
      • The logistics of delivering a (prioritized) vaccine to hundreds of millions of people (possibly in two shots a month apart) over a short period of time are tremendous.
      • And of course, there could be diplomatic wrangling over the sharing of vaccines with developing countries, or over the export of vaccine from the manufacturerís country until their needs have been met.
      Apparently #2 on my hit parade has already proven to be a problem; The virus isnít growing well in the lab.
      In this case, the seed stock for a candidate vaccine isnít growing well, which could prove problematic for mass production later on as well.
      All of these other problems are still in play, by the way.

      And if you follow the link to read the AP article, the estimates of our being able to produce 5 billion doses of vaccine are Ė to put it kindly Ė generous.
      The promise of a vaccine, Iím sure, mollifies a lot of fears.
      But the logistics of producing, and delivering a vaccine are enormous, and should not be underestimated.

      Better, I think, that we lower expectations on having a vaccine (and if we get lucky, hey, we can celebrate), than to make promises today that will likely crumble in the fall.

      The CDC, to their credit, has steadfastly refused to speculate on when, or how much, swine flu vaccine will be available.

      A course that is looking more prudent every day.
      "May the long time sun
      Shine upon you,
      All love surround you,
      And the pure light within you
      Guide your way on."

      "Where your talents and the needs of the world cross, lies your calling."

      ďIn a gentle way, you can shake the world.Ē
      Mohandas Gandhi

      Be the light that is within.


      • #18
        Re: FluTrackers Interviews David S. Fedson, M.D. - Meeting the Challenge of Influenza Pandemic Preparedness in Developing Countries

        > The CDC, to their credit, has steadfastly refused to speculate on when,
        > or how much, swine flu vaccine will be available.
        > A course that is looking more prudent every day.

        so we have to rely on the estimates of other organizations.
        ECDC,RKI,vaccine producers, etc.
        I'm interested in expert panflu damage estimates
        my current links: [url][/url] ILI-charts: [url][/url]