de Jong on H5N1 in Vietnam
difficulty differentiating H5N1 from seasonal flu and dengue fever
This conference is starting Thursday and looks really interesting. Some of the presentations include:
Importance of the receptor binding surveillance to detect the jumping of the host range of the highly pathogenic bird influenza virus (H5N1) into humans Yasuo Suzuki, College of life and health sciences, Chubu University, Aichi, Japan
Clinical and laboratory comparison of human infections with dengue, influenza or avian influenza a (H5N1) viruses in Indonesia Herman Kosasih, Naval Medical Research Unit #2 (NAMRU-2) Jakarta, Indonesia
An alternative neutralization assay for H5N1 influenza a virus using retroviral pseudotypes Nigel Temperton, MRC/UCL Centre for Medical Molecular Virology, University College London, London, United Kingdom
http://www.isanh.com/avian-influenza/index.php
Who is Herman Kosasih [from NAMRU-2]? I haven’t heard of him before.
And, what does that last presentation mean — An alternative neutralization assay for H5N1 influenza A virus using retroviral pseudotypes? Can anybody translate that into plain English? ;-)
Who is Nigel Temperton, for that matter? Never heard of him either, but his is one of 10 projects that recently got funding from the Medical Research Council (MRC) in the UK: http://www.mlwmagazine.com/story.asp?storyCode=2036291
Sure are a lot of bf researchers out there nowadays! Warms my heart. ;-)
If u ask me this disease should be pushed to the top of everybodies A. list fast. This is a race and we need the scientific world to take notice. Thinking out of the box is needed on this one. It’s a matter of life or death on a massive scale. The problem is it’s just to hard for most people to get their heads wrapped around the timeline of this threat and it’s deadly serious nature. When u discuss it with most people and mention Flu they think flu like in your average flu and cannot comprehend something more like EBOLA stampeding through their community. I use EBOLA as an example because it’s pretty close to the truth of what this thing does to people when it gets them in it’s claws. That gets their attention.
Glennk - Good comparison re the ebola. I just received the outline for the National Red Cross presentations and I am pleased to say that they are telling it like it is rather than sugar coating it. A Roanoke TV station had it on their news last night. Once these more localized public announcements are made, I think people will start coming out of the woodwork.
We are doing important groundwork, but we are not doing it alone.
I sent this letter to the organizers (no response). It summarizes the supplements found to have anti-influenza activities. http://home.san.rr.com/earlybird/antiinfluenza.doc I forwarded a copy to anon_22 in case the other recipient discarded it as spam. I really think without another source of anti-virals we need to use what we have. Both mullein and black elderberry have been shown to synergistically improve the effectiveness of amantadine.
Someone is giving a presentation about the using of pomegranate as an anti-viral. I did not include that because I could not find many references to that outside of 3 studies from Cuba.
I hope this is a productive conference for all.
Oh, duh! I’m being little slow-witted here. I think anon_22 is actually going to this conference — on another thread she said she was going to Paris and would be at a conference for the next few days. Must be this same one.
anon_22 – at 21:40 & 22:05 http://www.fluwikie2.com/pmwiki.php?n=Forum.TheHenryNimanControversyII
I hope she gets a chance to do more “on the spot” reporting! :D
Yes, she’s going to the conference.
Hi Theresa42,
I will try. Although I have several appointments set up so is may not be easy. Also, I have a whole lot of things from the other 2 conferences that I do still want to write about. So I might just give myself a bit of time to digest all that and compare different revelations and approaches etc.
OK, I’m not very coherent, Have to go. thanks
Ranchgirl – at 08:40
Can you provide alink for the Red Cross presentations?
anon_22 — Oh, hey - whenever you get the time! It’s just great that someone from FW is there. Will be very interesting to hear all of your reports. Thanks!
Interesting panel on BF vaccine, at the Paris conference today, describes it as “10 years away”, quotes Osterhaus, Fedson in the article from the BBC.
“Avian flu experts meeting in Paris have been told that a viable vaccine against the human form of the disease could take 10 years to develop… “
[snip]
“…According to Dr Fedson, who also worked for a number of years in the vaccine manufacturing industry, the vaccine produced from H5N1 was proving particularly difficult to grow.
It was also proving ineffective at stimulating an immune response that would give a person a good defence against bird flu.
He told BBC News: “Right now, worldwide, we can produce 300 million doses of seasonal flu vaccine, but it turns out that the H5N1 vaccine is so poorly immunogenic and replicates so poorly that… we could immunise globally, with six months of production, about 100 million people.
“From a public health point of view this is catastrophic,” the former professor of medicine at the University of Virginia School of Medicine, US, said. …”
[snip]
“…On the subject of a vaccine, he said: “If a pandemic were to happen tomorrow, we would not have a vaccine; at least not a vaccine with which we could vaccinate the European population or the American population - and we need a vaccine for the world.
“Basically, if we don’t invest now in suitable clinical trials, there will be a shortage of vaccine - if we have a vaccine at all.”
Governments were in denial about the potential danger and this was the root of the problem, according to Dr Fedson.
“If you look to the UK, France, the Netherlands and Italy (countries with companies that produce vaccine) - are any of the health authorities in these counties spending public funds on clinical trials of H5N1 vaccine? The answer is ‘no’.
“Not a single pound sterling is spent by the Department of Health in the UK on clinical trials - why is this so? Contrast this with spend on the Eurofighter for European defence, a weapon system no longer needed. Our priorities have got mixed up. Governments are feckless.”
[snip]
“…Commercial world
There was no point blaming the vaccine manufacturing companies, said Dr Fedson, who was at one time director of medical affairs at Aventis Pasteur.
“We’ve got to get away from the fantasy that pharmaceutical companies are charities - they make hard-nosed decisions about where they are going to make their profits.
“Some companies have sensed that by building supplies or stockpiles of pre-pandemic vaccine, they can make easy money by just selling millions of doses to governments - they don’t have to hire a sales force.
“They’re doing good business based on governments being fearful of what might happen if they are perceived to have done nothing.
“When governments say they have bought, say, eight million doses of pandemic vaccine, all they are doing is buying a bucket full of antigen, because we really don’t know how it is going to be formulated and there is no licensed, registered pre-pandemic vaccine in the world.
“They are hedging their futures.”
The First International Conference on Avian Influenza in Humans has been taking place this week at the Pasteur Institute in Paris. “
Ceredwin – at 06:41
Thanks for the update. We are looking forward to reports from everyone/anyone there. The question is did Fedson’s remarks refer to traditional egg-based vaccines only? I’d think the newer DNA technology would change that considerably over the next 4–5 years.
another question per the vaccine taking ten years.. are they talking constant production to reach a goal of giving every person on the planet an injection (which would take ten years) or are they talking, ten years to make an effective vaccine?
I am going to write up selected pieces from the 2 days, although I need to warn you that it may take a while, since I am having a number of houseguests/family for the next 2 weeks. 5 additional teenagers in the house makes for some interesting groceries shopping. :-)
Menno de Jong gave a good discussion of human H5N1 disease from the experience in Vietnam cases. Some main points:
1) Influenza H5N1 can be associated with multiple organ dysfunction:
2) Diarrhoea occurs in 40–70% of cases, initial symptom in some patients, GI infection?, consequences for infection control
3) Immunopathogenesis: evade host interferon response, induce cytokines
4) Cytokine-inducing capacity may be increasing from 1997 to now (Guan et al 2004 PNAS 101:21, p 8156–8161)
5) H5N1 and H3N2/H1N1 can be clinically indistinguishable (comparison of 18 H5N1 and 8 H3N2/H1N1 cases) - this can pose problems with diagnosis. Also co-circulation increases capacity for re-assortment
6) Summary of virology:
7) Fatal cases - No evidence of cross infection – all died from primary viral pneumonia
8) Tamiflu works - Good response even if treated late
8) Tamiflu works - Good response even if treated late
There won’t be enough to go around any time soon and, um, having only one treatment is a set up for drug resistence.
Grace RN – at 16:25 Am on the road without my computer. Will scan the Red Cross Q&A and link it up when I get back home.
Thanks for summary anon_22. More reason than ever to ramp up production of Tamiflu. Yeah, there’ll be drug resistant strains eventually, but it oughta buy some time. Should definitely be useful as a prophylactic for HCWs.
So, based on #6, this thing pretty much just goes wherever it wants?!? Blood, GI, lower lungs…
And I see something here that has been debated before---
Initial progression of lung disease despite effective suppression of viral load by treatment with oseltamivir
and
Tamiflu works - Good response even if treated late
Tamiflu (oseltamivir) may work well to kill, or lessen the effects of, the virus, but damage to the lungs could take place even with the administration of Tamiflu in time.
Am I reading that right?
Anon_22
Are they seeing full recovery from the bug??? If so how soon after intervention is the person able to return to full duties???
Are they seeing degradation in brain activity after recovery???
Are they seeing lost of any motor skills or strength levels after recovery???
Other than the H3N2/H1N1 mask, have they identified any other virus which may mask H5N1 and therefore make reporting more difficult???
Take your time on the answers, Understand you have a house full. Enjoy the day and your family.
Anon_451,
This was a presentation from de Jong from Vietnam 2004–5, 18 patients of whom 13 died. He didn’t say anything about the survivors.
“Other than the H3N2/H1N1 mask, have they identified any other virus which may mask H5N1 and therefore make reporting more difficult???”
No, but someone else from NAMRU did a comparison of dengue, ordinary flu, and H5N1 in Indonesia. I will write that up soon cos it’s pretty interesting.
BBB,
“Tamiflu (oseltamivir) may work well to kill, or lessen the effects of, the virus, but damage to the lungs could take place even with the administration of Tamiflu in time.”
He had a slide (which I can’t draw) of the viral load dropping very steeply straight after starting oseltamivir, but the chest x-ray was still progressin. This shows again that it may very well be host responses to viral replication that cause the most problems in ARDS, and not the primary viral infection.
This again illustrates something which can’t be emphasized enough, that the key aim of treatment is to get tamiflu in the system as early as possible.
Suzuki from Japan is advocating receptor binding surveillance: his concept is that we can use the glycan microassay (which basically uses a slide with various kinds of sialoside sugars to find out what the virus will bind to) to find out the receptor binding preference(s) of strains that we isolate, which will, according to him, give us an idea whether the virus is getting more and more efficient.
The question/doubt that I have with this approach is that the switch from 2,3 to 2,6 binding may be an important component of changes in transmissibility, but most likely there will be other factors, and good solid epidemiological data can also tell you a lot without necessarily needing such surveillance. I don’t know how expensive/difficult the tests are but such SURVEILLANCE will need to include fairly large samples on an ongoing basis for us to be able to detect a trend, and I’m not sure on the grand scheme of things whether that is the best way to spend the money or our efforts. It may make people so one-track minded that they miss other important clues along the way.
But then that’s just my opinion, and I’m not an expert…
Anon_22
I thank you for your answers. Looking forward to the post on other masking virus.
However; please spend some time with your family. That is far more important at the moment.
anon_22 is in the UK. This is not a holiday weekend there.
Melanie – at 20:52 It is still late Saturday night going in to Sunday. Anon_22 has a full house of guests for the weekend no matter how short. As you must know, family, no matter how much we may dislike them is still very important to all. My only desire was that Anon_22 be able to enjoy the family and not feel pressure to respond to some yoyo (me) on the Wike.
Thank you for letting me know where Anon_22 is at. It explains a lot on the timing of the post.
Best regards
anon_22 is pretty balanced about what she can and can’t do and we’ll get her reports and reflections when she can give them. She skyped with Dem earlier this evening (EDT) before he headed back to work, anon isn’t the only one with a wanky schedule.
anon_22: WHENEVER you get the chance, could you please add to your summaries exactly which cytokines are involved? As we all know, there are more cytokines than there are stars in the universe and many have multiple activities which often oppose the activities of other cytokines. Knowing which are believed to be the “major players” at this point could prove useful to further discussions. THANKS!!! :)
cytokines: I didn’t manage to get that from the slides, but I had a look at the PNAS study and it was in there, so perhaps someone can look it up.
H5N1 influenza: A protean pandemic threat. Guan et al PNAS 2004 vol 101 no 21 p 8156–8161
Herman Kosasih of NAMRU reporting on clinical and lab comparison of dengue, human flu, or avian flu in Indonesia:
H5N1 epidemiology in Indoesnia June 2005–2006
Summary: it is difficult to distinguish AI from other endemic infections during acute illness, causing delay in diagnosis and treatment. Poultry contact, shortness of breath, serial blood counts to track leucopenia, lymphopenia, and thrombocytopenia may be useful.
Notice it took an average of 7.9 days from onset of symptoms to H5N1 infection being suspected.
Hi everyone. Interesting discussion. Annon 22, you are doing fine work as is Melanie and DemfromcT as well as all the rest.
I just have a short comment to make. It seems like everyone (scientists regulators) need to have their ‘magic pills’ despite clear indications otherwise…
…I don’t think we are going to get our collective heads around the next, the coming pandemic until we come to terms with the fact that vaccines don’t work and anti-virals won’t work.
Even if they did. the supplies aren’t there anyway, so it appears that they continue to spend most of their time at these conferences talking about the grossly hypothetical that on a practical basis will not work.
They have had the tractor in this gear for nine years: it’s about time they change gears to one in which the solution have a half-a-chance of working or we are all ‘screwed’ literally and figuratively.
I hope this is relevant.
Quote from H5N1 influenza: A protean pandemic threat Guan et al PNAS 2004 vol 101 no 21 p 8159
Induction of Proinflammatory Cytokines in Primary Human Macrophages. The H5N1/97 viruses associated with human disease induced a massive proinflammatory cytokine response in primary human macrophages in vitro (9). To investigate whether the recent human H5N1 isolates have this phenotype, we compared viruses isolated from humans in 1997 (A/HK/483/97) and 2003 (A/HK/212/03 and A/HK/213/03) with a virus representing the parental A/Gs/Gd/96-like (H5N1) lineage (A/Gs/HK/437.6/99) and with other contemporary H5N1 reassortants isolated from poultry. The human influenza virus A/HK/54/97 (H1N1) and lipopolysaccharide were used as low and high cytokine inducers, respectively. As previously reported, the human H5N197 virus induced high TNF-a expression, whereas the human H1N1 virus (data not shown) and A/Gs/HK/437.6/99 induced low TNF-a expression (Fig. 2). Induction of IP-10 followed a similar pattern. Inactivation of the virus byUVirradiation reduced cytokine induction markedly (data not shown).
Among the recent avian H5N1 reassortants, A/Ck/HK/YU562/01 (genotype B) induced a low TNF-a response, A/Ph/ HKsv674.1502 (genotype X) induced an intermediate response, and A/Ck/HK/61.9/02 (genotype Z) induced a high response. GenotypesXand B induced intermediate-level expression of IP-10, whereas genotypeZinduced high-level expression of IP-10.A/HK/212/03 and A/HK/213/03 were high inducers of both TNF-a and IP-10 expression. The results of the mRNA assays were consistent with the results of the protein assays (data not shown). These findings suggest that the human H5N1 viruses of 2003 have a high cytokine-inducer phenotype like that of the 1997 human H5N1 isolates. The genotype Z virus isolated from poultry also shared this phenotype, and thus, the TNF-a-inducing phenotype appears to be related to pathogenicity in humans….
Whereas the precursor Gs/Gd/1/96-like H5N1 viruses (e.g., A/Gs/HK/437.6/99) were low inducers of TNF-a and IP-10 in this model, the A/HK/213/03 and aZgenotype virus (A/Ck/HK/61.9/02) were high inducers of both cytokines. The two 2003 patients with H5N1 disease had unusually high serum levels of IP-10 (20). The parallel between the cytokine induction phenotype in vitro and the pathogenicity of an H5N1 virus in humans is striking and may be pathogenetically relevant. The current dominance in chickens of the Z genotype, a high cytokine inducer, suggests that human infectionwith theseH5N1viruses may lead to clinically severe disease.
Anon22, I am happy to read that Tamiflu works against the virus. The patients still died very often, but that is like the saying “the surgery was a success but the patient died :) (sorry for the joke)
Did they mention which dosage they used ?
TIA!
Anon22, Thank you so much for carving out this update time when your schedule is exceedingly busy. I am also VERY happy to learn that tamiflu was found to be helpful and also wonder at what doseage and length of treatment course. Thank you!
de Jong did not mention dosage but Erik De Clercq from Belgium did. He said twice the normal dose ie 150mg twice daily for 10 days. And add probenecid if you have it. Go here scroll to 11:37 for that and increasing tamiflu efficacy.
I might also add that best results are when you can take it less than 48 hours from onset of symptoms. 24 hours even better. The data from Turkey, unpublished, using the standard dose of 75mg twice daily: those who died (4) started tamiflu on 8.5d from onset. 6 survived and their mean time from onset to start of tamiflu was 3.6 days. See this thread
Correction: de Jong did mention dosage for the vietnam cases, 75mg twice daily, ie standard dose. He just didn’t make any specific recommendations from that.
it is unclear from current recommendations whether it’s “double dose and probenecid”, or “double dose or probenecid”. it is also not established (see Tom DVM) that antivirals and vaccines don’t work, but that’s an old argument. ;-)
What Tom’s right about is that at the moment, we do not have enough.
Posted by Anon_22 at 19.53
8) Tamiflu works - Good response even if treated late
The guidelines for administering Tamiflu in the UK are
‘plans should assume that anti-viral treatment will initially be available for all patients who have
an acute influenza-like illness and fever (>38c)and have been symptomatic no more than 2 days
http://tinyurl.co.uk/3e69 (pdf doc)
so whether there is a good response or not when treated late, we will not get Tamiflu after 2 days of symptoms.
08:29,in a pandemic it will be different.
DemFromCt. Don’t just take my word for it.
“…the vaccine produced from H5N1 was proving particularly difficult to grow.”
It was also proving ineffective at stimulating an immune response that would give a person a good defence against bird flu.”
“Right now, worldwide, we can produce 300 million doses of seasonal flu vaccine, but it turns out that the H5N1 vaccine is so poorly immunogenic and replicates so poorly that… we could immunise globally, with six months of production, about 100 million people.”
“From a public health point of view this is catastrophic,”…
Dr. Fedson
see Ceredwin at 6:41
SolitaireUK,
well, the plans for the UK assume many fairytale scenarios (eg being able to deliver the medicine to 100% of the patients within 24 hours) so we can’t draw any conclusions from their recommendations at this point.
Tom, Dem, etc re tamiflu dosage:
I know you already know this but this is for everyone else as well :-) The problem is that there are no clinical trials to determine dosage(cos there haven’t been enough H5N1 patients that have been studied as part of a trial although the NIH is going to do that) so all dosage beyond the standard one is just extrapolation from animal data (re Webster) and anecdotal from folks actually treating patients.
Therefore, there is no ‘official’ recommendation on tamiflu dosage; the WHO in their guidelines stopped short of that, only saying that “There is currently no empirical evidence to suggest the use of a loading dose or higher doses of oseltamivir in patients with severe disease but increased doses and duration of treatment have been suggested as a strategy to reduce the risk for development of drug resistance.”
However, “Consistent animal data from three studies in mice indicate that high]dose oseltamivir treatment increased survival in this animal model.”
So if you are asking about official recommendation, then it is still the standard dose of 75mg twice a day for 5 days. If you are asking what is the best bet for an individual, I would speculate that it needs to be AT LEAST twice that for twice the duration. So I guess, whether you add probenecid to the standard dose or to the double dose depends on how much you trust the 150mg dose will do the job, and how much tamiflu you have, and whether the patient can tolerate the dose etc. Since I did hear from 3 physicians in Asia treating these cases speaking off the record that they would go for 4x the dose (didn’t mention duration or probenecid), I would guess the dose range could be 150mg twice daily, or 75mg twice daily plus probenecid, up to 150mg twice daily + probenecid, or 300mg twice daily at the high end.
But all this of course is evolving so I would suggest keep updating yourself on current thinking every now and then.
Tom DVM – at 09:41
I’m aware we ain’t got nothing now. Doesn’t mean Fedson’s right, doesn’t mean we won’t for 10 years, doesn’t mean newer vaccines won’t work. It does mean traditional egg-based technologies don’t cut it.
Tom,
I would say that overall NA inhibitors (tamiflu and relenza) do work, but like all other drugs, you cannot expect them to work for all patients at all times. If there is a pandemic right now, tamiflu would still be the best bet for any patient.
Vaccines are a different story. The hurdles are many and they don’t look like they will be solved anytime soon.
On a collective level, of course, then you have the issue of very limited supplies of both. But that is not a drug efficacy issue. We should separate these 2 discussions so newbies don’t get confused.
Dem at 10:05
I’m with you on keeping an open mind. Even if we have vaccines, antivirals, etc, there will still be a lot of people who won’t get anything. Therefore we should not dismiss things eg vaccines that are less than optimal but keep all possibilities open, as even small improvements in survival can make a big difference if you translate that to millions of people.
I think therefore we should lower our standards/expectations of these drugs/vaccines, and accept lower efficacy as better than nothing when we think of it as a global problem.
OK. I don’t think we are very far apart on these things.
Egg-based vaccines don’t work to this point…and the vaccine is not immunogenic…and there is no guarantee that the immune response is protective…and even if hypothetically the vaccine worked perfectly, we don’t have access to supplies that will make a difference to the susceptible population.
annon 22. Up until a little more than a year ago, anti-virals were the second component of the ‘magic pill’ that was going to save us from the pandemic. A group of scientists asked the world approx. a year ago to fund a worldwide public effort to produce a third generation of antivirals…the effort was led by Dr. Osterhaus…they were refused.
The dosage started out as a normal dose used in seasonal influenza…the dose is now by some estimates up to four times the dose. Where I come from when you have to keep increasing the effective dosage either the drug does not work in the first place or very soon it will be over-run with resistance making it completely ineffective. Add to that resistance has been picked up in at least two patients in, as you said, a small subset.
But we do have effective treatments…they just don’t make for exiting dialogue at conferences.
The pneumovax(sp)vaccine, to prevent secondary bacterial infections, makes sense from a public health point of view and would without doubt save millions of lives in a pandemic.
Broad-spectrum antibiotics, powdered oral electrolytes, oral anti-fever medication and oral prednisolone provides a therapy that is manageable that could be provided in an environment with no functioning healthcare system.
These treatments are all off-patent which means large stockpiles can be produced with minimum outputs of captial, increasing the effectiveness of limited captial resources.
The problem is, like in supplies during a war, there is a lag period to step-up production up to sufficient levels.
We can talk about antivirals and vaccines in the ten to twenty year time period…but we must prepare now for the real risk of a pandemic in the one to five year time period. If this occurs we will have nothing in the way of effective treatments and without doubt anarchy will result.
Anon thanks for update and all the info. It seems stocking up on Tamiflu is the way to go if you can get it. If research is right and it turns out that high doseages of Tamiflu plus other drugs will save people’s lives if given early enough then were probably screwed if this thing hits any time soon. Not near enough Tamiflu and only speculation on how to use it all add up to a massive inability to deliver. Even though we can see this coming from a mile away so could the US right before WW2. Hell, one guy even wrote a book detailing almost the exact scenario at Pearl Harbor. Meant crap it happened anyway and the military prepared for a Battleship war in the Pacific. I’m afraid the same thing is going to ahppen here. We probably have all the meds. Tamiflu, Relenza etc. we need to fight this but when the time comes we won’t have anywhere near enough nor will it be distributed and used fast enough by enough professionals and people at home to save many lives. Now that said, at the second wave of this just as happened at Pearl with the 2nd attack wave an hr. later we’ll be better prepared to fight this thing. The first wave is the one we will be absorbing tremendous loses. One thing that would really mitigate a 1st wave disaster if present research pans out is a super ramp up of Tamiflu . The US should allow a generic to be produced by every drug company that wants to make it fast and it needs to be pre-positioned for rapid deployment. Also, since it’s highly unlikely enough medical personnel will be available to provide it when needed some kind of public training and mass distribution might make sense. The Drs. might resist but this is a public health crisis not business as usual. It’s like when weapons are distributed to a population to stave off a known invasion. I hate to say it but that’s exactly what happened in Iraq. The population was armed even before we arrived and the insurgency afterwards was essentially pre-ordained by plan. Here though we need to get these meds. into the hands of as many people as possible train them so when they or their families get sick they’re ready. Millions would be saved, maybe? Unfortunately, what were likely to witness is a typically conservative and extremely slow reaction by hte authorites. There will be too little too late for millions as the medical pros. fight among themselves about what to do and are rapidly overwhelmed by a tidal wave of sick and dying patients. In short a disaster of epic porportions.
Tom,
“The dosage started out as a normal dose used in seasonal influenza…the dose is now by some estimates up to four times the dose. Where I come from when you have to keep increasing the effective dosage either the drug does not work in the first place or very soon it will be over-run with resistance making it completely ineffective. Add to that resistance has been picked up in at least two patients in, as you said, a small subset.”
I have to disagree. (But then you knew I would :-) )
The standard dose was recommended for seasonal flu at a time when H5N1 was not heard of. When you apply it to a different context, then it is reasonable to think the dosage might be different. There is a difference between a drug that does not work no matter how much you give it, and a drug that works when you find the right therapeutic range. So a strain that is resistant to amantadine, for example, would not work even if you give high doses of amantadine. But if it worked at high doses of amantadine (still as an illustration only) and not standard dose, then we would say that amantadine works for that strain but the dose has to be higher.
I agree about pneumovax and antibiotics and electrolytes etc. But when we are talking about definitive treatment of H5N1 infection, then we have to speak of antivirals.
So to clarify for any newbies etc:
Antivirals = specific drugs that either kill the virus or stop the virus from causing disease via replication
H5N1 vaccines = vaccines that you give ahead of time to induce a certain degree of immunity to the virus, ie not for treatment
pneumovax = vaccine to prevent pneumonia caused by pneumococcal bacteria, which is a common complication of severe inflenza infections.
antibiotics = drugs that kill or inactivate bacterial infections, reducing the mortality from bacterial infections secondary to the viral infection.
from anon_22 at 19:53 describing Menno de Jong’s comments about Vietnam 2004
That is not good. I wonder if this is true with the clades that have spread more widely.
I assume we will all get sick. Isolation is not practical and won’t get the bills paid (got lots of them, its the American way). I did have some hope (misplaced?) that if I just respond quickly with my anti-virals (herbs) that it will give us a chance to reduce viral spread. The next assumption is that a lower viral count will reduce the likelihood of cytokine disregulation. Treating pneumonia at home with limited resources (and teaching the public at large how to) is not easy. Air hunger sucks.
“Retain unwavering faith that you can and will prevail in the end, regardless of the difficulties, and at the same time have the discipline to confront the most brutal facts of your current reality, whatever they might be.” -Stockdale Paradox from Good to Great by Jim Collins.
Dr. Philip Thorpe’s lab at UTSW-MC/Dallas, Peregrine, NIAID(NIH), USAMRIID (U.S. BioDefense Res. Pgm.), and Tulane, Duke, & Utah-St Univ’s take dead aim on ALL ENVELOPED VIRUSES (ex: Hep/B+C, Influenza/Avian Flu, HIV, CMV, Pneumonia, Herpes, SARS, Ebola, Marburg, West Nile, Dengue, Lassa Fever) with Anti-Phospholipid Therapy (APT) agents, like Anti-PS/3G4/Bavituximab(formerly Tarvacin), which are “surprisingly effective in inhibiting the entry, replication and the spread of viral infections.” …Bavituximab is categorized as an ‘anti-phosphotidylserine immunotherapeutic’ -immunotherapeutics attempt to stimulate or activate the immune system to reject and destroy tumors or to respond to infectious agents.
4–24–2006: Tarvacin (chimeric mab 3G4) will henceforth be referred to by its generic name, BAVITUXIMAB, to avoid confusion with OSI’s anti-cancer drug Tarceva. New, separate trade names will be identified for BavituximabAC and BavituximabAV, “a process which has now begun”. http://tinyurl.com/jgav6 I’ve been following the progress of Peregrine’s bavituximab (formerly Tarvacin) since postings first appeared on Agonist and Current Events. The clinical data is impressive. There is hope, but it is not in vaccines for some years. Puzzles me why Bavi is not recognized more as the effect agent it is. ???
Peregrine’s Website: http://www.peregrineinc.com Bavituximab Anti-Viral: MOA: http://tinyurl.com/9emdh Clinical Trials Overview: http://tinyurl.com/d6mld Bavituximab Anti-Cancer: MOA: http://tinyurl.com/7kgfh Clinical Trials Overview: http://tinyurl.com/cn9xv PEREGRINE’S SRB - MEMBER PROFILES: http://tinyurl.com/c34ft EXPERT QUOTES/COMMENTARY ON BAVITUXIMAB’s MOA/POTENTIAL: http://tinyurl.com/nmdw4 FACT SHEETS (PDF) on Bavituximab/Cotara/Peregrine: http://www.peregrineinc.com/content.php?mi=MjI Informative Blog on Peregrine & Bavituximab: http://ybn.typepad.com/your_bunnys_nose Latest 10K 4–30–05 iss 7–14–05: http://tinyurl.com/ggro5 PR: http://tinyurl.com/hx8bk Latest 10Q 10–31–05 iss. 3–13–06: http://tinyurl.com/znpuo PR: http://tinyurl.com/k8rwy
annon 22. Just out of interest…
…they are currently losing 50% of those infected with H5N1; all recieving some form of intensive care in a hospital.
How do they know that 50% of those affected would have lived whether or not they were treated with antivirals…
Bavi’s clinical trials are promising. With H5N1 and other disease. I am puzzled that its story is not more well-known. I’ve been following Bavi (formerly tarvacin) since information was posted on Agonist and Current events. I think that there is hope, but at this time, not in vaccines. Would that the world direct its attention toward Bavi . . . . and put its support behind an effective medicine for avian flu etc.
unpathed: I went to Peregrine’s site and read the post about Tarvacin and it said it’s only in early trials as an anti-flu drug. What exactly are Bavi’s trials sbout and where could I read about them?
try this:
ClinicalTrials.gov provides regularly updated information about federally and privately supported clinical research in human volunteers. ClinicalTrials.gov gives you information about a trial’s purpose, who may participate, locations, and phone numbers for more details.
Tom,
“annon 22. Just out of interest…
…they are currently losing 50% of those infected with H5N1; all recieving some form of intensive care in a hospital.
How do they know that 50% of those affected would have lived whether or not they were treated with antivirals…”
Nobody can say whether any one patient would have lived, but if you take a larger group and see whether there is any correlation between survival and the use of antivirals, then you have some idea. So the fact that there is a big difference in the date of starting tamiflu for those who survived and those who didn’t (eg in Turkey) tells us that a) it is likely that the drug was one of the things that made a difference, and that b) timing of starting the drug is important.
Conversely, if you find that survival is the same whether they took the drug early or late, then you might say well maybe that didn’t make any difference.
Another example: The fact that H5N1 was not suspected in Indonesian patients till almost 8 days after the first symptoms (see post at 22:07) means that the high CFR in Indonesia may not necessarily be unique to the strain there (or it may be) but may just be consistent with the need for antivirals to be given very early to save lives.
Now, hypothetically, if we are getting data that a number of patients are dying DESPITE getting antivirals on day 2 or 3, then it’s time to revisit antiviral efficacy.
I for one,would like to thank all of you ‘experts’ who are clearly putting a lot of time and effort in updating this forum regarding Tamiflu, it would seem to me that the pendulum is starting to swing over to the area where it is likely that we will need to use more that the current ‘one dose per person’ if that proves to be the case, god help us, for it will surely blow out of the water the ratio of purchasing enough Tamiflu for 25% of the people in the UK.
To my of thinking it only re-enfores. That the best policy is “Isolation’.
Alan the Pom,
I agree with everything in your post!
Except that the UK government thinks ‘we are well prepared’ and there is no political will to even talk about this.
Or there may be some political will in making sure that we DO NOT talk about this.
Neither TB or GB has any political capital to open this can of worms, or at least that’s what they think, cos everything involves spending, and there’s no money anywhere, with all that the NHS black-hole has sucked in since GB decided to play Santa Claus.
So the 25% tamiflu myth is likely to be maintained unless some brave media types are willing to take them to task about it.
As a layman I am interested in learning more about Probenecid. Can someone explain how Probenecid is potentially helpful in reducing the effects of H5N1 when used in conjunction with Tamiflu. What are the suggested doses?
I am new to posting, but not to reading this forum, and would also like to extend my thanks to the many minds at work.
glennk, You might want to look at the Jeffries Conference webcast from last week. I signed in using Peregrine as company name, and I was able to view the webcast. Fascinating stuff!!!
here are a couple of probenecid links. Dr. Howton engaged us at Flu Wiki in an email conversation when it first occurred to him to suggest this.
Probenecid Could Stretch Tamiflu Supplies In A Pandemic
Doctors find way to double supplies of Tamiflu using WWII tactic …
Thank you for the sites. Very interesting…and a shame it has not been investigated more. It seems the first sustained clusters will be the first true study.
Probenecid looks promising for those who manage to get hospital care but for the great majority of us it’s not going to be worth a damn, nor will it be made available to the public for obvious reasons. The really sad fact we are all going to experience is that our (USA) expensive JIT healthcare system is going to collapse under the hammer blow this pandemic will deal it. The medical community and the Gov’t if it really gave two shits about the public health would immediately ramp up generic production of Tamiflu and Relenza make it available cheap for everyone with a public education program on how and when to use it. This would do 2 things save millions of lives and leave the hospitals for acute care situations. Anything else IMO is just so much mental masturbation. Instead what’s going to happen is a rush to the emergency room by masses of sick people. Maybe, I’m wrong but it seems atleast at this juncture The US Gov’t’s policy reduced to it’s bottom line is YOYOS (Your On Your Own Suckers!)
A question, just for clarification: The summaries here are from the Paris Conference? Thanks a lot annon, its very much appreciated.
T42, why did you title the thread with “Anti-Avian”? Is that a new word or was that the name of the symposium?
Mr White42 – at 02:45 - T42, why did you title the thread with “Anti-Avian”? Is that a new word or was that the name of the symposium?
Mr White — that was the name of the conference as given on their website — as far as I could see anyway:
Sorry hon, I thought that sounded odd. Thank you for the link.
Here’s another presentation that I thought was interesting. Seong from South Korea gave a presentation on ‘ANtiviral effect of catechins in green tea on influenza virus’. Before everyone rushes out to buy the tea, please note that research is still at the earliest stages, and it appears that oral intake does not produce enough serum level for antiviral activity. Sorry!
Green tea has been thought to have various health benefits for a long time, including possible role in prevention of cancer, cardiovascular and degenerative diseases etc. The active ingredients are called catechins.
In vitro studies were carried out using various assays, and it was found that catechins were powerful inhibitors of virus growth on plague formation, in MDCK cells, as well as inhibition of virus adsorption (attachment) to chicken RBC’s, etc. There were some effects on viral RNA synthesis and neuraminidase activity, but those were not as strong in the normal concentrations.
By altering the structure of the catechins molecules, researchers found that certain derivatives of catechins enhanced the main mechanism of inhibition of attachment to host cells. By acting on the first step of the viral replication cycle ie entry into cells, they are superior to NA inhibitors such as tamiflu or M2 inhibitors such as amantadine.
In addition, their effect appears to be irreversible, whereas both tamiflu and amantadine’s effects are reversible at high virus concentrations. Thus catechins would work better when there is a high virus titre.
The problem with these compounds is that they are extensively metabolized after oral intake, so that serum concentrations do not rise enough for antiviral activity. One way to go round that is possibly to create inhaled versions of the drugs.
The other problem is the lack of animal models. Apparently, trying to get mice to take any feed containing catechins is very difficult as they would not eat or drink, perhaps due to some anorexic effect of the compounds.
Still it may be something to keep an eye out for, and one can also speculate whether adding green tea leaves to poultry feed might reduce the incidence of AI, since avian infection is largely through the faecal-oral route.
bump for anyone interested in green tea
I already have a large cache of green tea, black tea…different herbal teas, grow some of my own teas…big tea drinker : )
My version of BB’s RWFK, except I have to act silly on purpose.
I’ll say it again, there is always seasonal flu somewhere. There is no reason alternative medicines cannot be put in clinical trial to test efficacy. If they don’t work alone maybe they work synergistically together or with existing anti-virals to stretch the supply. It should be done soon.
Fredness:
The problem other than profit is simply snobbery. Consider the Essiac cancer tea story. Last year I read a study by Duke University about taking flax oil and cottage cheese for prostate cancer. They followed subjects less than a month but the blood PSA tests dropped, and tumors shrank. They were like thrilled with this finding. Then the alternaltive people avalanched them with emails about a German scientist Budwig who discovered this and wrote the protocol fity years ago. Duke was stunned…how come no one was using it? It’s not glamourous and how can you bill someone for buying cottage cheese? Surgery anyone? Now that can be billed big time.
Could we disect this World Bank presentation (PDF)? I like slides 5, 9 and 10. In slide 9, what does 0.7%, 2% and 5% of GPD mean - I mean, what could we compare those numbers to? Also, is that supposed to be a short recession or a long lasting one?
Are there more presentations we might grab and look at (I mean from that Conference)?
expected GDP decline effect of the pandemic.
In the last image, they seem to assume a pandemic with 40million deaths.
World wide GDP-loss would be 3.2%, 1.8% due to preparation,
0.9% due to absenteism or health care, 0.4% due to mortality.
with 70 million dead, they assume 5% loss of world GDP. So, with 230million deaths (compared with 1918) it would be 16.4%.
Do they have an estimate which country’s currencies would collaps with 16.4 GDP-loss worldwide ? How much can USA handle ?
You will typically find that these scenarios are somehow avoided (why?) they are beyond “worst case”. Although, when you ask experts , if H5N1 goes pandemic, then the pandemic is expected very severe.
IMO these economic organisations are loosing credibility with their estimates.
lugon,
The full text of the World Bank presentation is here.
Bless Milan Brahmbhatt for putting his whole speech on the internet.
Two things I want to point out about his speech:
1. His approach to risk assessment for human pandemic, paying special attention to who he quotes. As an official of the World Bank, he couldn’t possibly have not quoted the WHO. But notice who are the other 2 that he quotes:
“The WHO observes that “Best case scenarios, modeled on the mild pandemic of 1968, project global excess deaths in the range 2 million to 7.4 million. Other estimates that factor in a more virulent virus, similar to that responsible for the deadly 1918 pandemic, estimate much higher numbers of deaths. Both scenarios are scientifically valid. The differences arise from the assumptions about the inherent lethality of the virus, which past experience has shown to vary greatly.” World Health Organization. “Avian Influenza: Assessing the Pandemic Threat.” January, 2005. WHO/CDS/2005.29. Other experts go further to argue that clinical, epidemiologic, and laboratory evidence suggests that a pandemic caused by the current H5N1 strain would be more likely to mimic the 1918 pandemic than those that occurred more recently, resulting in far higher death totals. Michael T. Osterholm. “Preparing for the Next Pandemic.” New England Journal of Medicine. 352: 1839–42. May 5, 2005.
“However one 1999 study of the United States calculated that a relatively mild epidemic similar to the 1968 epidemic could lead to between 100000 and 200000 deaths in the US, together with 700000 or more hospitalizations, up to 40 million outpatient visits and 50 million additional illnesses. Martin I. Meltzer, Nancy J. Cox and Keiji Fukuda. (1999). “The Economic Impact of Pandemic Influenza in the United States: Priorities for Intervention.” Emerging Infectious Diseases. Volume 5, No. 5. Sept.-Oct.
2. He had a very interesting slide showing effects from a) direct mortality, b) illness/absenteeism and c) efforts to avoid infection. It is very instructive to study the proportion of each and ask ourselves how we need to direct our mitigation efforts.
This was probably the most striking slide of his whole presentation, and notice that he used severe scenario.
It’s quite clear to me the guy is trying very hard to wake the world up. Whether anyone is listening is another story.
I’m surprised he used the severe scenario as well. Very sobering content. Anon 22 thanks for these great updates. BTW, what is the general mood level of the participants? Has the general mood affected you?
From link on World Bank Presentation - from anon_22 at 11:42:
“ In addition, a human pandemic may emerge not now but later, and not from H5N1 but from some different strain of flu virus. Other zoonoses and pathogens also continue to emerge. The general problem of global infectious diseases is going to be with us for a long time, and may get worse. “
Wish he could have elaborated more on this.
Commonground,
That territory has already been covered by Laurie Garrett, and it takes her many hundreds of pages to do it. Read The Coming Plague.
Anon: I read the WB analysis. Two interesting recommends. 1. Re-think JIT management philosophy..AKA for stockpile or go out of business when this hits. 2. “Lastly, there are a critical set of questions partially grounded in economics that need to be solved at the global level, including how best to foster R&D and innovation of new types of vaccines and anti-virals, how to foster rapid growth in manufacturing capacity for anti-virals and vaccines (the latter once a human pandemic strain has been identified) and how to establish adequate stockpiles of vaccines and anti-virals that would allow ‘rapid response’ to a pandemic outbreak. In recent years economists have been developing many creative new ideas about how to accomplish these objectives more effectively and cheaply than before. Some of these ideas now need to be taken off the drawing board and considered for implementation, at least in prototype forms.”
Leo7 – at 12:11 “I’m surprised he used the severe scenario as well. Very sobering content. Anon 22 thanks for these great updates. BTW, what is the general mood level of the participants? Has the general mood affected you?”
Well, scientists are good at not having moods, at least not in public. :-) However, there does seem to be a mixture of urgency and despondency from folks that I’ve spoken to. Remember that most of these people have dedicated a lot more of their time and effort than any of us on this forum, so they know full well what the implications are. And they have far more experience than they care to share of coming up against all sorts of obstacles including money or bureaucracy or politics.
In the series of conferences that I’ve been to, I have probably spoken to close to 100 people, all specialists of one type or another, from different countries. I have only met one person, who shall remain nameless, who think we are going to be fine.
Does that affect me? Not really, its not more nor less than what I expected.
glennk,
Your second point is what Fedson has been doing with vaccines and what he is trying to do now with statins.
I have to go right now, but I will come back and post some more about this.
glennk - at 12:53, being affiliated with a commerical roofing business, I also picked up on your first comment. It would really be costly to try and stockpile commerical roofing materials….you actually couldn’t, wouldn’t have enough room to store the stuff.
Re: “Probenecid Could Stretch Tamiflu Supplies” As a non medical person I need to yet again seek the opinion from you experts. IF and I say again IF Probenecid proves to be a useful drug to complement Tamiflu. What would the likely dose be. IE: if you had ten Tamiflu capsules would you need ten Probenecid capsules, and if it was found that you needed to double the Tamiflu dose to be effective, would you also need to double the Probenecid,and would they be taken at the same time. This is a “theoretical question”.
Re World Bank slides - why is 5% of GDP a lot? Is 0.7% a lot? What do we compare it to?
I can only imagine that 5% of GDP means maybe 50% of profits, or something like it. Someone please explain why this is such a bad thing? And excuse my ignorance?
Alan,
The standard dose of probenecid for adult for antibiotic therapy adjunct (to increase the availability of antibiotics) is 500mg 4X daily, and that is irrespective of the antibiotic dose. The same principle would apply for tamiflu. The first dose should be taken at the same time as tamiflu but the subsequent dose schedules are different, as probenecid needs to be taken 4x (at 4–6 hour intervals) daily, whereas tamiflu dose is every 12 hours.
GDP = Gross Domestic Product. This is the sum of all* economic activity in the US. It does not count ‘unmonetized economic activity’(selling a used car, paying the babysitter in cash etc.) It is was $12.486 trillion dollars in the US in 2005.
So a 5% loss would be $600 billion.
GDP in 2003 grew 2.7.%, 2004 grew 4.2% 2005 grew 3.5% 1Q of 2006 grew 5.6%
If we lost 5%, we would be in recession. A recession is generally recognized as three quarters of declining business activity.
For perspective, here is a brief summary of economic activity during the Great Depression:
The Great Myths of the Great Depression page explains just how bad that depression was:
Over the four years from 1929 to 1933, production at the nation’s factories, mines, and utilities fell by more than half. People’s real disposable incomes dropped 28 percent. Stock prices collapsed to one-tenth of their pre-crash height. The number of unemployed Americans rose from 1.6 million in 1929 to 12.8 million in 1933. One of every four workers was out of a job at the Depression’s nadir, and ugly rumors of revolt simmered for the first time since the Civil War.
Thanks, ssol. So, even if I don’t really see how bad 5% would be, would it make sense to look into emergency community currencies? just in case? Please go over there if you prefer not to clutter this thread.
anon-22, your post at 19.21
Many thanks, if it was not for you and others like you on this forum, we non-medical types would have some major problems. I come from a ‘Mechanical Enginering’ background, so I have no problems in assessing risks and sorting out any other non-medical issues. I just feel so frustrated that we all in our own way seem to have something to contribute in dealing with this coming BF threat, yet some how we seem unable to get together to pool our knowledge other than through this Forum Link. One again many thanks.
Closed to maintain Forum speed.