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**AlaskaDenise** · May 4, 2006, 01:39 AM

Re: Reporting from the Lancet Asia Forum

Good information. I did not know children had a higher viral load. Is that per weight or total count? It almost sounds as if they will recommend child tamiflu for the entire shedding period... interesting.

Of the surviving 3.6 onset date tamiflu patients, I wonder what was the extent of their lung damage?

Thanks to anon_22!

**Snowy Owl** · May 4, 2006, 01:50 PM

Re: Reporting from the Lancet Asia Forum

http://www.fluwikie2.com/pmwiki.php?....NewsItemsMay4

All thanks to anon_22
anon_22 – at 14:39

Hi all, Webster did an extremely important presentation today on ‘Gaps in pandemic preparedness.’

The comments on ‘you will get infected, you’ll get very sick, but you probably won’t die’ had to do with his suggestion to make a whole virus pre-pandemic vaccine, using the A/HK/213/03 strain, recombined with N3. He said that they did a study with ferrets using this vaccine provided complete protection from homologous challenge, including the extremely lethal A/Vietnam/1203/04.

The ‘minimum of 10 mutations to go h2h’ comment: needed at least 3 HA, 2 for PB2, and at least one of each of the others. “The mutations are all out there, but the virus hasn’t brought it together, like ducks in a row.”
<hr> In other news, I am coming down with ‘flu-like symptoms’ and I have a 12-hour flight tomorrow, so I need to stop trying to do everything in one go, it being 3 am here. I’ll post some more tomorrow and thanks for your support.

anon_22 – at 14:53

The problem of autopsy had to do partly with the necessity for BSL3+ facilities, because of the high risks involved. This was pointed out by one ?Singaporean doctor with experience in this.
A lot of countries in Asia and Africa would not be able to afford that.

**AlaskaDenise** · May 4, 2006, 04:55 PM

Re: Reporting from the Lancet Asia Forum

based on all I've read about cross-reactive immunity, Websters' comment " ... make a whole virus pre-pandemic vaccine..." sounds worth the effort. If we can't have a "perfect" matched vaccine, any that would stop death and severe disability need to be utilized. We may have to live with "only" a very very bad case of flu.

.

**GaudiaRay** · May 4, 2006, 06:25 PM

Re: Reporting from the Lancet Asia Forum

Originally posted by AlaskaDenise

based on all I've read about cross-reactive immunity, Websters' comment " ... make a whole virus pre-pandemic vaccine..." sounds worth the effort. If we can't have a "perfect" matched vaccine, any that would stop death and severe disability need to be utilized. We may have to live with "only" a very very bad case of flu.

.

Webster: >?you will get infected, you?ll get very sick, but you probably won?t die?

To me, the operative phrase is "you probably won't die". That's cute.
Not it.
I was a guinea pig for the first H5N1 vax test. I won't be for this one. One to a lifetime. After it's perfected, I'll happily be in round two, with the adjuvant, but first go around on a probably won't die is not this person.

**Snowy Owl** · May 5, 2006, 04:54 AM

Re: Reporting from the Lancet Asia Forum

anon_22 ? at 22:08

Also, a completely off-the-record discussion with some clinicians of one Asian country that had been treating H5 patients revealed that they have a internal consensus for tamiflu dosage that is 4x the recommended dose. ie 300mg twice daily for adults, taken minimum 10?14 days.
WARNING: This is NOT tested, not officially sanctioned, there are no safety profiles, so please apply all health and professional disclaimers that you (or lawyers!) can possibly think of.

anon_22 ? at 22:24

Malik Pereis, quoting De Jong (no reference yet):
The viral load (total amount of virus in patient) in seasonal flu rises sharply after infection, peaks at around 48 hours, then delines steadily.
For H5N1, there is a scattered range of peak viral load which is later than the 48 hour for seasonal flu, to about Day 5. This means that the window for treatment with oseltamivir is wider.

Data from ?Thailand, also discussed by Pereis, gave the median date of start of treatment with tamiflu for survivors as 4.5d and for fatal cases as 9 days.

There is therefore sufficient ground to give tamiflu even if the drug is started after the first 48 hours.

Of course, results are better the sooner you start. The viral load profile also warns against stopping too soon.

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**Snowy Owl** · May 5, 2006, 04:58 AM

Re: Reporting from the Lancet Asia Forum

anon_22 – at 05:47

Here are my thoughts on the transmission dilemma: it depends on the incubation period. If the incubation period is long enough eg 5 days, then it might be worth attempting more stringent infection control measures. Lets’ say one person A is sick. B is the carer. C & D are teenage children.
If you don’t try infection control, you are likely to have B, C and D all get sick at the same time, and A has not recovered enough to care for all these sick people (assuming A recovers, which is likely if you are middle aged and have tamiflu), and everyone will be worse for it.

If you take very stringent precautions, and B gets infected but not immediately, lets say on day 3. Add 5 days incubation, B gets sick 8 days after A. There is more chance that A is in some sort of shape to care for B, ie the two can isolate themselves together away from the children, who will only deliver meals and stuff to the door but not enter the room.

If one of the children then gets infected, again after 3 days, showing symptoms on Day 16, there is a even higher chance that A can provide some care.

The shorter the incubation, the less this will work.

The longer you can keep from being infected, the better this will work.

I think…

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**Snowy Owl** · May 5, 2006, 05:45 AM

Re: Reporting from the Lancet Asia Forum

anon_22 ? at 06:36

Robert Webster?s presentation at the Lancet forum is IMO important enough to be reported here in detail on its own thread.

Title: Identifying the gaps in pandemic preparedness

He gave his opinion on these gaps, how to think about them, and what needs to be done. Stuff in quotation marks are quotes, as far as my notes tell me. The rest are synopsis of what he said. Stuff in italics are my comments/additional thoughts. ? is where I?m not sure if it?s exactly what he said.

Three Major Gaps:

1 - Will H5N1 acquire consistent h2h?

There has been family clusters, may be some genetic link there. There are those who say, ?It?s been around 10 years, won?t happen? Webster says ?I?ve worked with flu all my life, this is the worst virus I?ve ever seen.?

DON?T BE COMPLACENT

In chicken, the virus goes to brain, causes disease, together with systemic collapse. ?We have never seen an h5 or h7 doing what it can do in a mammal what it?s been doing in chicken.?

He estimates that the virus needs ?miminum 10 mutations? to go h2h, 3 in the HA gene, 2 in ?PB2, probably 1 mutation in almost every gene segment. ?All the mutations are out there, but the virus hasn?t got them yet, they are not lined up like ducks in a row yet.?

I wonder what he means exactly by ?all the mutations are out there??

2 - ?We don?t know anything about transmissibility?

Monotreme, that was my point at your CFR/lethality rate thread
This also echos what Fouchier said, that we know a lot about the nucleotide determinants of virulence, we know next to nothing about the determinants of transmissibility. This may be because these studies are harder to do?

They (Webster) did a Pig to pig study ? first pig infected and had a lot of virus in respiratory tree, but second pig did not catch it despite high exposure.

?Give us 5 years, we will understand more?

Pathogenicity: likely to be polygenic, and include host genome interactions.

3 - Lack of autopsy report ?

Calling for more autopsies, but these are limited by many factors, cultural, religious, political, as well as insufficieny of resources, eg the need for BSL3+ facilities.

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**eladdie** · May 5, 2006, 09:53 AM

Re: Reporting from the Lancet Asia Forum

I wonder what he means exactly by ?all the mutations are out there??

I took it to mean that someone has sat down and said,

If these 10 specific mutations occured simultaneously, then the human race would be deep sixed.

Then someone else said, Let's look at the published (and secret) gene bank sequences to see if they have been found.

They probably found all 10 mutations in the sequence databases.

Just not all at the same time in the same isolate.

Thus, they are all out there, just haven't gotten together yet for a

Party.......

BTW

HAPPY 5 de Mayo!!!!!!!!!

**Shannon Bennett** · May 5, 2006, 10:39 AM

Re: Reporting from the Lancet Asia Forum

"All mutations are out there." Well if nothing else then this puts paid to all of those naysayers who insist it is unlikly to lead to h2h.

**Snowy Owl** · May 6, 2006, 05:10 AM

Re: Reporting from the Lancet Asia Forum

05 May 2006

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anon_22 ? at 07:42

Richard Horton, Editor of Lancet, gave a fine short inspiring speech at the end. I cannot reproduce the whole speech, but portions captured by my notes (with the rest paraphrased from memory), are here, Bold type = my emphasis

This virus has been neglected and misunderstood. We all agree that there is lack of info, rsponse plans have holes.

Post-sars, some policymakers are over confident. They say we?ve got it figured out. Well, they haven?t.

WHO has a role in holding others up to accountability. It is not good enough to say countries have their problems etc.

We have to help the WHO.

Pandemic flu should be #1 in G8 summit agenda (coming up soon).
Private sector has shown extraordinary agility, but that is not enough.
We all seem to agree we do not have effective national plans, regional plans, resources, vaccines, anti-virals, surveillance,

We all know that this is the single biggest challenge humanity has faced, will face, for generations. It?s not enough to agree in this room.

We need to go out of this room and say it outside, loud and clear.

None of us are saying this loudly enough.

Need to follow through ? non-pharmaceutical interventions, social distancing, closing schools, who will get the vaccines first.

These need to be debated in the media right now.

We may have only 12?18 months at most.

It is not just a challenge, it is an predicament of extra-ordinary proportions

We hope that our worst fears won?t be realised, now we must go home and make sure that they won?t.

**Snowy Owl** · May 6, 2006, 05:15 AM

Re: Reporting from the Lancet Asia Forum

06 May 2006

anon_22 ? at 02:33

hey guys, just walked in the door from the airport and guess what?s the first thing I do? Yep, check out what y?all been saying :-)

Dem, I didn?t manage to stay awake throughout the whole conference so if someone else mentioned amantadine, I?ll have to look up the notes.

Anyhow, Webster appears very encouraged and is very emphatic that we need to do studies asap on combination treatment. We don?t know if it will work, but we have to be careful not to get fixated on one or two headline-catching treatments and forget there are lots that needs research (and research $$$). We may not have a pandemic for another five years, and in five years time we may have far better treatment opions if we keep doing everything.

**Snowy Owl** · May 7, 2006, 05:26 AM

Re: Reporting from the Lancet Asia Forum

anon_22 ? at 08:55

Patch,

?Was there anyone at the conference, that cared to speculate on a more optimistic scenerio? And if so, were any reasons given??

Unfortunately, no.

In comparison to when I met them in January, a couple of them seem more convinced/resigned that this is going to happen.

John Oxford in January was far more jolly and saying well, we don?t know if it?s going to happen and treating the whole (Jan) conference more like an academic topic, more like let?s discuss virology rather than what are we going to do.

Now it?s more like a cause, like he is trying to galvanise people to go out and convince others. It?s very subtle and if you are not a fellow Brit you probably wouldn?t notice. But I do.

The other one who I met a couple of times since January was Martin Meltzer. I was quite surprised at the extent to which he is now telling people to prepare, because that wasn?t my impression even a couple of months ago, where again he was more professorial and talked about statistics(!) and policymaking in general, and wasn?t as animated when I asked about pandemic preparedness.

Now there seems to be a tinge of heaviness, sort of feeling the weight of the responsibility, if you know what I mean.

In his presentation, the sentences I quoted before were repeated clearly and emphatically.

And his last slide says:

Conclusions:
What to do? ?Take home message??
Plan, Plan, Plan
Prepare, Prepare, Prepare
Practice, Practice, Practice

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**Snowy Owl** · May 7, 2006, 05:35 AM

Re: Reporting from the Lancet Asia Forum

anon_22 ? at 09:39

Monotreme, I think its an overall thing. Do you not feel that yourself? That the more you think about it the less you can convince yourself that it?s going to be ok?

anon_22 ? at 16:26

Jane,

?Did Martin Meltzer of CDC (health economist) really say the economic effects of pandemic would be mainly on the tourist industry and a rebound would occur in 1 or 2 quarters, (so most people don?t have any worries??)?
Dem is right in that everyone hears/remembers whatever it is that they want to hear. Or what they think they are able to understand.

No, he didn?t say the economic effects of pandemic would be mainly on the tourist industry.

There was a slide from ?Citibank: Global Portfolio Strategist: Avian Flu, Nov 2005′ which was apparently an investment analyst presenting risks to their clients. It basically showed ?buy? ?sell? recommendation columns eg on the ?buy? list internet commerce, freight delivery, etc and on the ?sell? list air travel, malls, tourism etc. It was one of several used to demonstrate overly simplistic assessments of macro-economic impact and how they carry little correlation between numbers ill, death, and econ impact, because these models do not take into account epidemiology.

On the slide Meltzer had circled the word ?tourism? and put in stars and ?Why??, as part of the discussion of his point. Whoever reported it must have taken a look at the whole set of slides, found the only one that looked vaguely similar to other ?economic impact? reports that you see from ?economists?, and decided that was the theme of the presentation.

Forgetting to report, of course, that the slide was clearly labelled Citibank, and not CDC Meltzer.

Here?s a lesson if we ever need one of being very careful with stuff that you read.

anon_22 ? at 16:36

Meltzer demonstrated how economic impact can/should be approached from many different angles, none of which carry straight-forward answers:

Days lost and value
Cost of medical care + days lost
Illustration of impact on sector of economy
Macro economic aspects
Policy options and implications
What can businesses do to plan and prepare?

In other words, what answer you get depends on what questions you ask. Asking a well-constructed question gives you slightly more useful answers. Some questions give you completely useless (or unusable) answers.

anon_22 ? at 16:41

Oh, and the ?rebound would occur in 1 or 2 quarter? thing?
I found it.
2 slides from ADB (Asian Development Bank) estimated reduction in GDP. On the side there is a remark which says ?Assumed: 2 quarters of economic contraction?.
As in, ?these numbers are based on the assumption that there will be 2 quarters of economic contraction?. Not ?the market will rebound after 1 or 2 quarters?.
Duh!
Anybody still have confidence in the finance pages in the papers please raise their hands?

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