Reports from INSIDE the Singapore Conference

HERE'S ANOTHER ONE:

anon_22 – at 14:39

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

anon_22 – at 06:40

The Avian Reseroir How do low path (H5, H7) viruses become high path?

Will the high path h5n1 be perpetuated in the aquatic bird reservoir?

Historically, emerged strains do not go back to reservoir, there is already evidence that it has for h5. This is worrying.

Who or what spread the H5N1 virus? (1) in Asia (2) to Europe?

Initially, poultry industry. In Europe, migratory birds played some role, human major spread

European – at 06:45

I would guess they have seen all the “required” mutations in idetified sequences, but not in a single sample. The inference being that the more mixing of various strains there are the higher the chance of developing the “killer” H2H virus.

anon_22 – at 06:46

The Avian Reservoir

Reassortment was rampant during evolution of the Asian h5n1.

What selected the dominant Z genotype?

Did gene segments from H5N1 in domestic avian species contribute to the high transmissibility of the Qinghai H5N1 virus?

Genes from domestic species getting into wildbird species is a new phenomenon and worrying.

anon_22 – at 06:47

European, thanks.

<light-bulb goes up in head>

anon_22 – at 06:49

Gaps in Pandemic Preparedness

Inadequate link between animal and human surveillance as one key issue. Example of Thailand, several hundred volunteers did surveillance of every village, to pinpoint the exact problem, fighting cocks

Lack of co-opoeration between neighboring countries

Lack of strategy for the sotrag and distribution of antiviral agents

Lact of advanced provision in immunization strategies

anon_22 – at 06:51

Agricultural Vaccines

Agri vaccines, if used correctly, do they have potential to control /eradicate? - Webster thinks so

Problem, agricultural vaccines not standardised for HA antigen, not like human ones.

Poor vaccine will drive antigenic drift

Most of selection will be in duck under natural condition of long term shedding

anon_22 – at 06:57

Human H5N1 Vaccines

Why are H5N1 (A/Vietnam/1203/04) vaccines so poorly immunogenic?

H5N1 (A/HK/213/03) is a good antigen.

Why is there no correlation of protection with current H5N1 vaccines?

Studies on recombinant H5N1 vaccines in ferrets:
r.g/ A/Hon Kong/213/03 (H5N1)
Complete protection from homologous challenge
Cross protection from challenge with A/Vietnam/1203/04 (an extremely virulent strain)
#virus shedding reduced

1. weight loss
2. no virus in brain
3. no disease signs

anonymous – at 07:01

anon_22, thanks.


With the mutation he seems to mean single amino-acid replacements and each single of them occurred. But I don’t know, how he can know that that strain which he has in mind would cause a pandemic. Didn’t they always say: no one knows which strain can go pandemic ? Is that strain stable, reproducable, virulent ? And when they know the strain, can’t they make a vaccine ?

The reassortment, I hadn’t heard this. Where exactly did it happen ?

anon_22 – at 07:08

Webster – if we modify the HA, might get higher titre

Basis for pre-pandemic vaccine A/HK/213/03 complete protection from homologous challenge in ferrets even for worst strain A/Vietnam/1203/04

“We should be stockpiling this vaccine in hundreds of millions of does. We should be using it if we have a pandemic. If there’s a pandemic, and you were vaccinated with this vaccine, you will probably get sick, but probably not die.”

If we use a whole virus, recomb with N3, single dose , no disease, no shedding, ducks totally protected,

Current vaccine production: Limited capacity, need antigen sparing, etc, but whole virus vaccine will be its own adjuvant

“Whole virus is superb antigen. Historically, we took it apart cos it was toxic to children.” So you take a good antigen, break it apart so its not a good antigen, then fiddle around with adjuvants to make good antigen again? Doesn’t make sense. Now we can use recomination and substitute N3 and make the vaccine safe.

anon_22 – at 07:16

Human Pandemic Vaccines:

Many needs:

1. replace eggs with cell-based vaccine
2. new strategies - DNA, recombined, live attenuated
3. new adjuvants
4. new factories
5. liability and intellectual property issues (corral the lawyers)

anon_22 – at 07:20

Antivirals

• Neuraminidase inhibitors
• amantanes - A surprising no of strains 50% sensitive to amantadine, therefore use combination therapy. Should do studies now, on combination therapy.
• Urgent need to test other drugs eg ribavirin
• new classes of drugs required
• OTC – why don’t we make these medicines over-the-counter (ie no prescription)
  “Why is it not in people’s medicine cabinets, with instructions on how to use and how not, and when???”

anon_22 – at 07:21

Pandemic Preparedness Gaps

• between planning and implementation
• political will
• severity of infection
• reproductive number
• economic impact
• surveillance
• not enough planning
• Africa..!!

anon_22 – at 07:42

anon_22 – at 08:55