Flu Science for Dummies 2

and of course the first comment

has to be, bump for visibility!!  LOL!



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sat Jul 25, 2009 at 23:35:46 PM UTC

Second Wave?

Are the increases of cases in Mexico, up to 700%, a possible sign of a second wave? Jon C

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by: JonC @ Sun Jul 26, 2009 at 03:34:03 AM UTC

Hmm, that's an interesting question

It's usually hard to tell except retrospectively, cos absolute numbers are unreliable.  Rather it's the variation in the trend over time that will tell us something.  

The UK ILI chart, for example, is significant cos of the very obvious rise, and that different regions are experiencing the same thing.  It also depends on the consistency of surveillance over time.

Tracking a flu outbreak is very difficult because a) the symptoms are non-specific and can be very mild b) cases double so quickly, in 2-4 days, such that no one is able to test or confirm anything for sure c) by the time you see the data, the real situation on the ground is already different.

Also, waves are highly local.  Even within one country, different regions can experience it at different times.  The synchronous rise in the UK is less typical but probably a reflection of the amount of people mixing that happens.  Or, the cynical me would also say, maybe some of them are well people seeking to get their hands on tamiflu!!  LOL

Such are the pitfalls of epidemiology.



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sun Jul 26, 2009 at 04:54:07 AM UTC

[ Parent ]

Not UK: England

That figure is just for England (and Wales maybe?), not for the UK as a whole. It's interesting to note that the situation in Scotland is different. How different is a bit hard to tell because the Scottish data is a week behind, but even so, looking at
http://www.documents.hps.scot....
shows a striking difference. At the beginning, though, many of the early UK cases were in Scotland.

Scottish schools broke up in the first week of July, English ones not until last week. Funny, that.

But of course it won't do to assume the difference is schools - what else could it be? Not population density or mobility: east central Scotland, including the capital Edinburgh, is still almost spared, despite having some of the earliest cases, and many thousands of people commute on packed trains across the country daily between badly affected west and the east. Temperatures? A bit lower here than in the south of England, but only a few degrees, and not consistently. Humidity? We've had a fair bit of rain in the last weeks, but probably the midlands have too... What else? Policies - school closures and Tamiflu - were pretty much in sync between England and Scotland, although decided separately. Just chance? probably the most likely explanation!

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by: Mathematician @ Sun Jul 26, 2009 at 08:53:26 AM UTC

[ Parent ]

probably all of the above

and applied in heterogeneous ways across different parts.  And, you are right, it's England and Wales.  I'm just so used to writing UK I forgot to make the distinction.



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sun Jul 26, 2009 at 08:58:41 AM UTC

[ Parent ]

what about multiple seeding?

Like Heathrow is the busiest international airport in the world.  There may just be a lot of index cases.  But I'm speculating, as I'm not sure how much effect multiple seeding would have.



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Sun Jul 26, 2009 at 09:00:37 AM UTC

[ Parent ]

Yes, plausible n/t

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by: Mathematician @ Sun Jul 26, 2009 at 10:20:25 AM UTC

[ Parent ]

I agree that chance is probably the deciding factor

but there might be social differences - more interactions between families and friends; less cough etiquette and hand hygiene; different commuting habits; smaller classrooms and places of work.

Might there also be an element of racial mix? Are some races more vulnerable to the virus and do the cities with the most cases have a higher percentage of those people? I don't see any pattern internationally.

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by: UK - Bird @ Sun Jul 26, 2009 at 13:25:53 PM UTC

[ Parent ]

could be, but

looking at each of those factors in turn (I've lived in both England and Scotland for decades) I don't see that any of them are good candidates for having explanatory power. Edinburgh and Glasgow just aren't all that different from similarly sized English cities.  

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by: Mathematician @ Sun Jul 26, 2009 at 13:54:13 PM UTC

[ Parent ]

decline since 2000

to the UK-people :

what do you think is a possible reason for the decline
in flu-activity in the UK since ~2000 ?

http://www.hpa.org.uk/web/HPAw...

2009 was an exception, we had a pandemic, but it was still better than
an average year before 2000

find the reason and let's all apply it !

ask experts for their subjective
panflu death expectation values
and report the replies

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by: gs @ Tue Jul 13, 2010 at 03:54:08 AM UTC

[ Parent ]

Two questions...

... 1. We don't seem to worry that the 'normal' seasonal influenza viruses will mutate, so why are we so worried that AH1N1 could mutate to become more virulent?

2. A friend of mine (male, 35, fit & healthy, good diet etc) came down with swine flu a couple of weeks ago and was floored by it. Vomiting & diarrhoea for days, delirious, fever, crippling muscle cramps, terrible cough & "razors in my throat". Most reports seem to be of a much milder illness - why would someone so fit with no risk factors become so ill?

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by: Fanny Adams @ Sun Jul 26, 2009 at 16:23:30 PM UTC

I'll leave one to the experts

any flu produces a wide spectrum of disease so that your friend could just have been unlucky..I had flu last Winter and two years before that.. both unpleasant but with the earlier bout I was in bed over a week and took months to get over it.. my husband is rarely ill but I find that when he is ill, it floors him too...

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by: coldethyl @ Sun Jul 26, 2009 at 17:40:15 PM UTC

[ Parent ]

mutation

I'm certainly not an expert, but I will take a stab at #1.

I believe there is always worry about flu mutating, drifting and/or re-assorting.

The increased concern with pandemic flu is simply a numbers game.  No resistance (novel flu) = more cases = more chances to create a new, nastier viral stew.

The worry for years with H5N1 was that it would mix with a seasonal flu that would give it a better ability to spread human to human, without dampening the CFR.

The worry every year with seasonal flu is that it will change significantly from the vaccine, making the vaccine less useful.

So, the concern has always been present, it is just more pronounced with the unchecked spread of a novel virus.  The more times you roll the dice, the more likely you will roll snake eyes.

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by: kristikaylene @ Sun Jul 26, 2009 at 17:49:21 PM UTC

[ Parent ]

I'll also take a stab at those questions :-)

#1 There is always a chance of seasonal flu mutating into something worse but it is mitigated by the probability that most people have had something similar which might give them some immunity. This means that less people should catch it and less people should experience severe effects. But there are no guarantees, after all H5N1 in birds mutated from a low pathogenic version. Swine flu also has new elements from both pig strains and a bird strain, they haven't been studied and who knows what affinity they might have for other genes from circulating flu viruses in birds and pigs. Some of the genes in the swine flu might not be fully adapted to humans yet and what will happen as they adapt might make the virus worse. Also swine flu has some of the signs of the 1918 flu. It attacks deeper in the lung, it attacks younger people in higher numbers than seasonal flu, it invades parts of the body not normally affected (GI tract) so it already raises red flags. The worry is that it could retain those unpleasant features while aquiring some other attribute that makes it more deadly.

#2 I think that this is the billion dollar question. What makes one person fall deeply ill and not another.

A lack of defences against flu in general?

Some weakness that is not obvious or permanent?

A poor intital immune response to the flu which enables it to invade deeper and in more numbers in the body?

A larger intitial dose of the virus.

An over reaction by his body?

A co infection (eg strep A)?

A feature of the virus?

Fate?

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by: UK - Bird @ Sun Jul 26, 2009 at 18:31:13 PM UTC

[ Parent ]

mutations

1. maybe more severe (higher CFR)
2. maybe more contagious (in the same situation, say 1 teacher sneezing on 20 students, a virus can infect 2 or 5 or 10)
3. resistant to antivirals

Not that I think #2 can be tested in real life, where spread depends on what we do, not just on the bug's features [1].

But I think we will know about #1 if different enough, and about #3.

[1]: sorry, geeks, couldn't resist!

You arm yourself to the teeth just in case.  You don't leave the gun near the baby's hand.

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by: lugon @ Sun Jul 26, 2009 at 18:37:02 PM UTC

[ Parent ]

difference between seasonal and pandemic

I think there are 2 main differences between seasonal and pandemic.

1) More than one wave per year in a pandemic, as opposed to one wave each year with seasonal flu.  Things are just faster and it's harder to predict when the next wave will hit us.

2) Also, the selection rules are different:

In a pandemic situation, most people have no specific immunity, so mutations compete and _maybe_ the nastier wins.  This mechanism would select the more aggressive.  The one that multiplies faster so that sneezes are more powerful so to speak.  At least that's my non-expert understanding.

This doesn't happen with an old virus, where people do have immunity, it's not so easy to find a new person that can be infected, and the most patient wins.  The one that lets the person walk around while infecting others.  The least aggressive clinically.  Again, my non-expert understanding.

Real experts, please chime in!

You arm yourself to the teeth just in case.  You don't leave the gun near the baby's hand.

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by: lugon @ Sun Jul 26, 2009 at 18:42:31 PM UTC

[ Parent ]

Why we are worried that Pandemic H1N1 could mutate to become more virulent?

There are at least three main reasons that I can think of to  be concerned that this H1N1 will MIGHT become more virulent.  

1) Influenza A is an RNA virus and RNA viruses make a lot of mistakes when they replicate - see http://www.epidemic.org/theFac...  When Influenza A does this it is called drift - http://www3.niaid.nih.gov/topi... Now most drift (like most mistakes)  is going to make the virus less well off but sometimes a change or series of changes make a virus more virulent or more contagious. Seasonal viruses have been drifting for a long time in humans but this new virus has not been recently circulating and may offer more surprises. This is the first reason we are concerned.

2) All Influenza A viruses at one point mutated from the same virus (thousands of years ago)  - see  http://mbe.oxfordjournals.org/... and the pieces are interchangeable (much like identical puzzles). So if a single cell in a person or animal gets infected with the two different Influenza A viruses at the same time, the progeny virus can have pieces of both.    This is called shift - See http://www3.niaid.nih.gov/topi...  Again since this virus is infecting lots of people there is a much bigger chance for a recombination to occur. This is a second reason to be concerned (and a reason to get the seasonal flu vaccine).

3) History. The 1918 pandemic started out a lot like this one with milder spread in the Spring and Summer (see Dr. Reed's lecture - http://www.cdc.gov/iceid/webca...   and/or  Dr. Taubenberger's and Moren's article http://www.cdc.gov/ncidod/EID/... ) but then got worse.  We don't know if the 1918 H1N1 mutated between summer and fall or if environmental conditions were responsible, however either way the effect was more virulence.

History is pretty scary BUT back in 1918 we did not have any antiviral agents, and we did not have vaccines. We didn't even know that viruses existed let alone know the genetic structure. In addition we were in World War 1.There were massive troop movements in the summer and little or no information being exchanged between enemies at war. (It was called the Spanish Flu because only Spain, which was not at war, released information.) And even since 2002 (when I first saw Dr. Reed's lecture) we have learned a great deal. There are now scientists through out the world working and unprecedented cooperation. So worried may not be the right word.  We are anticipating the possibility of a more virulent H1N1 and as a result preparing for the possibility because of shift, drift and history.      

 

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by: Public_Health_Networker @ Sun Jul 26, 2009 at 23:21:57 PM UTC

[ Parent ]

Thank you...

for posting the information and links.  I suspect we have, or will have, lots of folks seeking information.

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by: Okieman @ Mon Jul 27, 2009 at 03:25:57 AM UTC

[ Parent ]

Check out the drift in H3N2

Actually, genetic drift of the seasonal influenzas is always a big concern.

The vaccine for the upcoming flu season is designed to protect against three virus strains: A/Brisbane/59/2007 (H1N1), A/Brisbane/10/2007 (H3N2), and B/Brisbane/60/2008. These choices were made months ago, and the vaccine has already been produced.

Unfortunately, there is a new variant of A/H3N2 circulating in the southern hemisphere that the vaccine offers little or no protection against. See http://www.google.com/hostedne...

CDC says "Increased proportion of H3N2 virus isolates are testing as very low reactors to vaccine strain - Reactivity up to 32-fold down vs. A/Brisbane/10/2007"

Seasonal H3N2 tends to be a more severe disease than seasonal H1N1.

If this becomes widespread, we could have a situation where the seasonal vaccine doesn't work against the dominant H1N1 (which would be the novel H1N1 A/California/07/2009), or against H3N2.  

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by: JerryH @ Sun Jul 26, 2009 at 23:54:54 PM UTC

[ Parent ]

H1N1

I thought H1N1 was replacing seasonal viruses in the Southern hemi.

Tell the truth

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by: Goju @ Mon Jul 27, 2009 at 01:16:06 AM UTC

not in Australia

2/3:1/3

and all expectations are for multiple circulating viruses.

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by: DemFromCT @ Mon Jul 27, 2009 at 01:20:39 AM UTC

[ Parent ]

Is the novel H1N1

regarded as a genetic drift or a genetic shift?

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by: ssal @ Mon Jul 27, 2009 at 02:27:44 AM UTC

it's probably a combination

of drift and shift, that happened in an as-yet-undetermined host - probably either human or swine.



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Mon Jul 27, 2009 at 15:13:00 PM UTC

[ Parent ]

Thank you ...

... to everyone for your answers. Amazing.

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by: Fanny Adams @ Mon Jul 27, 2009 at 10:45:53 AM UTC

This is a great thread. Thank you

So... basically weather as well as pure chance will determine the possibility of the severity of a possible second wave. The effect of this wave will be felt by John/Jane Q. Public based upon the readiness or lack thereof of the governments/medical community and the effectiveness of a possible vaccine and its production timing. I feel like I'm betting the farm in Vegas. I guess we will see what will happen. Jon C  

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by: JonC @ Mon Jul 27, 2009 at 11:31:12 AM UTC

There's always another layer of complexity

waiting behind each summary we write, of course. ;-)

I'd add that we as individuals can do a number of things:

- We can look at our aims in this.  I personally feel the aims are just 2.  Keep essential things running as best we can while reducing transmission as best we can.  The cut-off point for what's essential, and how to do it, vary greatly depending on severity.

- We can learn how transmission works and what our role in this is.

- We can learn how our local community works and see how we can improve the, erm, pandemic experience.  See if we can help each other with mundane tasks so that trasmission will be made more difficult while we do things for each other (for pay or not).

So more than "betting the farm" we can, and should if you ask me, be working a bit to improve our personal and cooperative odds.  Nobody said we had to be fair with a virus!

You arm yourself to the teeth just in case.  You don't leave the gun near the baby's hand.

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by: lugon @ Mon Jul 27, 2009 at 11:43:09 AM UTC

[ Parent ]

Future

I guess I am just saying that nobody really knows what will happen. There are just too many veriables. I have always prepared for the worse and hoped for the best. My coworkers think I'm a nutjob, but it is worth it because one good, smart young man listened and researched and is prepping. Jon C

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by: JonC @ Mon Jul 27, 2009 at 11:54:00 AM UTC

Transmission, pathogenicity, virulence and vaccines

Revere is writing an excellent blog explaining all this here



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...

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by: SusanC @ Mon Jul 27, 2009 at 16:38:22 PM UTC

pubmed/medline

is someone else regularly checking the influenza
articles at pubmed
http://www.ncbi.nlm.nih.gov/en...
or
http://www.hubmed.org/search.c...

~56000 artices in total, ~100 new per week

I usually check all the headlines, ~10% of the abstracts
and some full articles. But uually I don't read full articles,
even abstracts are often too long.

I feel that there is no source of good summaries here,
authors want us to read the whole article/abstract
headlines are often misleading

e.g. when there is an important issue in the headline
and you hope to get some insight about that question
in the article, then often the article is only about,
why that question is important and what is being
done or suggested to examine it

e.g. vaccination :
how well does the vaccine work
vs. are people accepting it  

ask experts for their subjective
panflu death expectation values
and report the replies

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by: gs @ Tue Jul 13, 2010 at 04:45:59 AM UTC