Posted on 09/10/2006 4:09:38 PM PDT by blam
Bird flu triggers high and sustained virus buildup, cause of severe disease
15:13:05 EDT Sep 10, 2006
Canadian Press: HELEN BRANSWELL
(CP) - The severe disease that H5N1 avian flu provokes in people appears to be caused by the virus's ability to replicate at unusually high levels for a prolonged period - an overwhelming assault that triggers a massive and devastating immune system response, a new scientific paper suggests.
Interrupting that process before it reaches the tipping point is critical, say the authors of the article, who based their observations on detailed study of 18 H5N1 patients in Vietnam.
But experts unrelated to the research wonder whether the current anti-flu arsenal - mainly neuraminidase inhibitors such as Tamiflu - is equipped to do that job.
"The question I worry about is whether treating patients now with neuraminidase inhibitors may be very much like shutting the barn door after the horse is already out," said Dr. Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota.
"I don't know that. But we've got to find that out."
The World Health Organization is in the process of setting up a research network across countries afflicted with H5N1, in the hopes that joint studies will answer questions like the one Osterholm poses.
Dr. Frederick Hayden, an antiviral expert who heads the effort, said the first task will be to investigate whether different dosing regimes for Tamiflu might achieve better results.
As well, the group hopes to look at whether a flu drug that could be administered intravenously would be more effective at combating H5N1 infection. Injectable forms of two drugs - peramivir and zanamivir - are in development.
"A potent parenteral (injectable) agent ... is really needed and will give us the ability, I hope, to more rapidly control replication in patients with these kinds of severe infections," Hayden said.
The paper, to be published Monday in the journal Nature Medicine, is the first detailed record of the disease process or pathogenesis of H5N1 in humans. The observations are based on 18 H5N1 patients who were treated in Vietnam during 2004 and 2005. Thirteen of them died.
The researchers charted the way H5N1 replicated in those cases and how their immune systems responded. The massive amounts of virus generated triggered production of excessive levels of some chemokines and cytokines, chemicals used to attract white blood cells - the body's cleanup crew - to the site of infection.
This hyperactive immune response - called a cytokine storm - actually does more damage than it sets out to fix. And scientists aren't clear on how to suppress the damaging parts of that process without disabling the immune system's ability to fight the virus.
Lead author Dr. Menno de Jong suggested the key is early treatment with antivirals, perhaps combined with drugs that modify the immune response.
"The paradigm 'Hit hard and hit early' which has been used for treatment of HIV-AIDS in the past may well be very true for the treatment of avian flu," said de Jong, a physician and virologist with Oxford University's Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City.
"Considering the likely role of the immune response in causing damage during the later stages of infection, it obviously makes sense to think about the use of anti-inflammatory or immune-modulatory treatment," he said in an e-mail interview.
"However, we still know relatively little about which part of the immunological cascade is best targeted and how to target this."
The director of the U.S. National Institutes of Allergy and Infectious Diseases said more needs to be known about the way the virus interacts with a human host. That could shed light on when antiviral drugs would have maximum impact on replication and the cytokine storm phenomenon, Dr. Anthony Fauci said in an interview.
But finding that optimal point may not be easy, he suggested, because influenza replication typically peaks as people are becoming symptomatic and the immune response is already kicking into gear.
"To me that's almost a catch-22," Fauci said.
"Because if you know the person is infected and has virus replication only when they become symptomatic, then depending on how long that peak lasts, will you or will you not be able to have a substantial impact on it by (administering) antivirals?"
Osterholm for one is pessimistic on that count, suggesting neuraminidase inhibitors like Tamiflu may be better suited to preventing H5N1 infection rather than treating the ensuing disease once it's apparent someone is infected.
If that's true, he advocates stockpiling the drugs to protect health-care workers and keep hospitals operational during a pandemic rather than using the drugs for treatment, as the pandemic plans of many countries - including Canada - currently stress.
De Jong's paper also clearly underscores the differences between the disease provoked by H5N1 and that caused by human flu strains.
It notes, for instance, that swabbing the pharynx to look for virus is a more effective way to diagnose H5N1 than taking a nasal swab. With human flu strains, the reverse is true.
The researchers also found traces of the virus in the blood and rectum of critically ill patients. While that could be a hint the virus replicates in organs outside the respiratory tract and the lungs, it isn't proof positive, de Jong said.
Autopsies of H5N1 patients would needed to determine that, he and others said. But because of cultural objections, autopsies have been performed on fewer than a handful of the 143 people known to have died of H5N1 so far.
I suspect that by the time the flu becomes human-transmissible, we will have some answers.
By then those answers may not do us much good. I've seen casualty estimates for my County in the neighborhood of 300 to 700 dead depending on various factors.
Personally I think those are low, but what do I know.
L
Thanks, blam.
Anti virals attack the virus, but ,at least according to these studies, it is not the actual flu that kills you, but the body's response that produces burnout. There must be some way of testing this. One historical and undeniable fact is that the 1919 Spanish Influenza had its greates toll from the young and healthy. 12 year olds would show symptoms in the morning and die before nightfall while older folks would get sick and recover. Maybe supressing the immune system to the level of a 50 yr old would be worth a look.
Maybe. But, at 62 I don't feel safer.
Some of the birds interviewed in Alaska have bird flu, but not this variety.
I'm several years behind you, but my kid is 21 and the record of the Spanish Flu on adolescents and young adults was horrendous. If they were to treat the immune reaction in the same way that they treat an immune reaction during transplant procedures they may find a palliative. I know this doesn't allay any fears, but maybe the times call for unorthoox solutions
"It is also possible, although unproven, that some people might simply be born with receptors more amenable to the virus. That theory has been offered before by epidemiologists noting that, even in villages where all the chickens are sick, human outbreaks tend to cluster in families.
I have successfully suppressed my immune system to the level of a 50 year old, done gradually over the past 50 years. So far, so good.
Well I imagine that someone is going to pump a lot of prednisone into some sick folks and we will see if suppressing the immune system is as important as maintaining an immune system fight against the virus.
"Some of the birds interviewed in Alaska have bird flu, but not this variety."
Smart birds.
Did you ever get the feeling someone is trying to kill us? LOL IF it's not terrorists, it's Bird Flu or something else. I'm wondering if God's trying to get our attention! ;o)
bump to follow.
I had some thoughts along that line today when I first saw the headline about an earthquake in the Gulf Of Mexico today, lol.
I wondered about that too. My brother lives in the Mobile, AL area and I'm going to have to ask him if he felt it.
I live in Mobile too. I didn't feel it.
Oh, OK. That's good to know. He actually lives in Daphne, which I think is a suburb of Mobile. Do you know where that is? He and my sister in law were just out to NM for a visit, and he asked me to come visit them. I told him I would one of these days. Of course, I've been telling him that for 3 years now. lol
New Nutrient-Based Approach Shows Promise Against Deadly Bird Flu Symptoms
Clinician and Researcher Dr. Tim Guilford is investigating a promising new treatment for bird flu, which has potential for substantially reducing the mortality rate associated with H5N1 infections.
Dr. Guilford explains his strategy in layman's terms during interview with Dr. Shoshana Zimmerman of Bird Flu Beacon.
Los Altos, CA (PRWEB) June 6, 2006 --
One of the main causes of concern about H5N1 Avian Influenza (bird flu) is that approximately 1/2 of the confirmed cases have died. Experts attribute this mortality rate to an unfortunate immune response called a "cytokine storm."
This often fatal side-effect is triggered when a virus gets past the frontline defenses and the immune system over-reacts. Dr. Guilford likens this occurrence to urban warfare, in which the weapons used to take out the enemy also inflict heavy civilian casualties.
"Without instructions to back off, the immune system not only destroys the virus but the tissues around the virus, causing such acute respiratory distress (ARDS) that the immune system can readily kill the infected individual as well as the virus."
Describing the process in somewhat more clinical terms, Dr. Guilford says, “In a pandemic virus like H5N1 the body releases TNF (tumor necrosis factor) from immune and epithelial cells to help kill the virus.
However, the virus produces a protein that causes the energy producing mitochondria of the cell, located in the cell’s nucleus, to become suddenly sensitized to TNF.
This causes the mitochondria to break down and release substances that trigger rapid cellular death. While fighting a virus, excessive TNF can simultaneously attack cellular membranes and intercellular biochemical machinery.
When enough of these mechanisms are compromised in the lungs, Acute Respiratory Distress Syndrome (ARDS) occurs, and it is ARDS that can lead to death from bird flu.”
Dr. Guilford notes the need to both strengthen the body's frontline defenses and to inhibit the damaging effects of a large-scale release of cytokines.
He points out, “There is accumulating evidence indicating TNF is modulated by antioxidants in normal tissues, especially the antioxidant called reduced glutathione.
People with acute respiratory distress syndrome have been tested to be low in reduced glutathione in lung fluid.”
These findings have put Dr. Guilford onto the trail of a potentially effective treatment for the disastrous effects of H5N1 infection.
He is currently investigating the use of liposomal encapsulated reduced glutathione to maintain normal glutathione levels.
He says, “Medical research to date has previously focused primarily on stopping replication and proliferation.
However, if glutathione can be shown in clinical studies to modulate the cytokine storm, it will prove to be an effective and inexpensive approach to dealing with viral infections.
Currently, we have very few medical tools for the cytokine storm, and this approach appears promising.”
# # # Contact Information
Mead Rose
eHealth Institute, LLC
408-469-0127 Page 1/1
If you have any questions regarding information in these press releases please contact the company listed in the press release. Please do not contact PR Web. We will be unable to assist you with your inquiry. PR Web disclaims any content contained in these releases. Our complete disclaimer appears here.
And this paper goes into other Glutathione applications as wellGlutathione production/supplementation/stimulation--note item 9 Glutathione helps suppress the Tumor Necrosis Factor which triggers the cytokine storm, iirc, and production of glutathione can be stimulated by the use of turmeric (curcumin).
Descriptions of the 'Spanish Flu pretty much describe the symptoms of a Cytokine Storm in the patients who succumbed most rapidly, which explains why that particular flu killed so many healthy younger people.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.