Avian Flu Pandemic?

[Dymanic]

Anyone who doesn't think that such paranoid thinking can cause problems, look up the response to the feared "swine flu pandemic" of 1976. That flu was supposed to end the world as well, but it never happened. The US and many world governments got all scared and told everyone to panic (and they did) and the flu never happened. Billions upon billions of dollars were wasted and many lawsuits were filed.

In assessing risk factors, is it not perfectly reasonable to mesh likelihood and consequence?

In more than three decades of driving, I have never once been involved in an accident, yet I have spend thousands of dollars on auto insurance. Was that money wasted? If the state of California allowed me to do so, would you consider it prudent of me to dispense with auto insurance altogether? Last month, over a million residents of Houston -- at great expense --evacuated their city on the prospect of a direct hit from a major hurricane. Was that merely an exercise in paranoia? Given the same set of circumstances -- and considering that predicting the paths of hurricanes is prone to error -- would your advice be that they sit tight?

Ever heard of a Risk Assessment Matrix?

 

[Capsid]

Just got my flu jab!

This year's mix is 2 A strains and one B strain:

A/New Caledonia (H1N1)
A/California (H3N2)
B/Shanghai

I'm assuming that the more shots I have of whole inactivated vaccine then the more chance I have of generating an anti-M2 response which is conserved across all strains (including H5N1).

 

[Adrian]

In more than three decades of driving, I have never once been involved in an accident, yet I have spend thousands of dollars on auto insurance. Was that money wasted? If the state of California allowed me to do so, would you consider it prudent of me to dispense with auto insurance altogether?

How you value your own safety is of no concern to me. So... are you saying that the only reason you have auto insurance is that the government is making you? But this is off topic... back to the flu...

In assessing risk factors, is it not perfectly reasonable to mesh likelihood and consequence?

Last month, over a million residents of Houston -- at great expense --evacuated their city on the prospect of a direct hit from a major hurricane. Was that merely an exercise in paranoia? Given the same set of circumstances -- and considering that predicting the paths of hurricanes is prone to error -- would your advice be that they sit tight?

Ever heard of a Risk Assessment Matrix?

Hmmm...

You bring up the classical Risk Assessment Matrix, a very valid tool. Let's look at the risk formula that creates the plane that allows for the formation of the matrix:

Risk = Severity * Probability

Severity = (Loss/Loss Event)
Probability = (Loss Event/Unit Time or Activity)
Risk = (Expected Loss/Unit Time or Activity)

This equation does not "mesh" severity and probability. It is a relationship between the two, but they are individually calculated. The difficulty (as I pointed out in my previous post) is when the severity (which in this case could be very high) clouds the independant evaluation of the probability variable. I would argue that the RAM is not the only tool that should be utilized in objectively analyzing the situation. The RAM should be used in conjunction with a multivariate variable analysis to determine how much severity alters the percieved probability. Media hype can generate a cross-variable "bleed" effect where other variable is affected by the other. The only problem with using the RAM is that likelihood is so hard to predict in pandemic cases (read the Fineburg quote).

I would also recommend, even though people seem to have a violent reaction to this notion, a cost benefit analysis to determine the fiscal outcomes of various action plans that are formulated as a response to the disease. People always fall back on the "the value of human life is immesurable... blah blah blah". Economists haven't bought that crap for 50 years and we have plenty of models for valuation in such situations. Rough as it sounds, such valuations are necessary in formulating massive society effecting decisions. The decision to evacuate Houston would probably have been found as valid utilizing this technique, since the cost of evacuation were probably not as high as you are stating, but since I don't have the numbers I can't provide you with an opinion. In order to form an opinion on the decision I would need:

1. the error rate of hurricane path prediction
2. an estimation of the damage of the specific hurricane
3. the exact number of people evacuated
4. the cost of the evacuation
5. the real relative economic contribution of the geographic area
6. and time series values for economic recovery after a hurricane event of similar size and situation.

 

[drkitten]

I accept the sarcasm, but no I don't require that. I just require scientific proof.

Good enough for folk music, but not for science.

No. The WHO -- the professional scientists -- have accepted that human-to-human transmission has occurred, and has started operations on that basis.

It doesn't actually say that they have proof that they caught it from their patients.

No, it doesn't. It doesn't have to. They're specifically phrasing their reports to be maximally reassuring, as you might expect. Similarly, the FAQ does not ask "has human-to-human transmission occured?," but "does efficient human-to-human transmission occur?" (a question to which the answer 'No' can still be given.

Actually, here's another WHO cite:
http://www.who.int/csr/disease/avian_influenza/avian_faqs/en/index.html

Does human infection with H5N1 happen often?

No. Only very rarely. The first documented human infections with the H5N1 avian strain occurred in Hong Kong in 1997. In that first outbreak, 18 persons were hospitalized and 6 of them died. The source of infection in all cases was traced to contact with diseased birds on farms (1 case) and in live poultry markets (17 cases).

The human cases coincided with outbreaks of highly pathogenic H5N1 avian influenza in poultry. Very limited human-to-human transmission of the H5N1 strain was documented in health care workers, family members, poultry workers, and workers involved in culling operations.

Perhaps most significantly, the WHO has stopped that human-to-human transmission has not occurred. As recently as Feb 2004, the WHO was stating that "Bird Flu Not Transmitted By Humans." In more detail, "The World Heath Organization says the bird flu virus in Asia has not yet changed into a form capable of human-to-human transmission." They are no longer making that statement, instead focusing on "efficient" transmission.

If you look at the evidence, including the WHO's actions and statements, it's clear that the WHO scientists accept that H5N1 has been transmitted from human to human. They're even willing to go on record as identifying specific cases.

Anyone other than the Tobacco Institute would be convinced by this level of evidence.

 

[drkitten]

This equation does not "mesh" severity and probability. It is a relationship between the two, but they are individually calculated. The difficulty (as I pointed out in my previous post) is when the severity (which in this case could be very high) clouds the independant evaluation of the probability variable.

There is no "clouding of the independent evaluation" of the probability variable.

The WHO has said (and I have quoted), that a flu pandemic is inevitable and possibly imminent.

The WHO has satisfied itself that H5N1 is capable of being transmitted directly from one human to another, a key aspect towards a pandemic.

I would also recommend, even though people seem to have a violent reaction to this notion, a cost benefit analysis to determine the fiscal outcomes of various action plans that are formulated as a response to the disease.

Oddly enough, I agree with you. But the cost-benefit analysis you seem to prefer is deeply flawed by the exact reverse of the error you warn us about. You are specifically dowplaying the likelihood of a global pandemic in the teeth of the WHO's direct warnings, which means that the "benefit" from any active treatment will be reduced.

 

[Adrian]

If you look at the evidence, including the WHO's actions and statements, it's clear that the WHO scientists accept that H5N1 has been transmitted from human to human. They're even willing to go on record as identifying a specific "probable case of human-to-human transmission."

Probable = does not equal actual. Enough to be concerned, not enough for you to make statement like (and I quote you):

That's technically not misinformation. As I said earlier, there are confirmed cases (3?) of human-to-human transmission of this baby.

Maybe in your world "probable" equals "confirmed". Not in mine.

Perhaps most significantly, the WHO has stopped that human-to-human transmission has not occurred. As recently as Feb 2004, the WHO was stating that "Bird Flu Not Transmitted By Humans." In more detail, "The World Heath Organization says the bird flu virus in Asia has not yet changed into a form capable of human-to-human transmission." They are no longer making that statement, instead focusing on "efficient" transmission.

A very wise decision by the WHO. Since it seems "probable", to state that "Bird Flu Not Transmitted By Humans" would be incorrect. If there is a possibility, than one should not claim that it is a definite "no".

 

[Dymanic]

How you value your own safety is of no concern to me. So... are you saying that the only reason you have auto insurance is that the government is making you? But this is off topic... back to the flu...

Dude. It was a rhetorical question. A more generalized form of it might be: "do you consider any expenditure of money as wasted when spent on obtaining a degree of protection against a threat with an uncertain degree of probability of occurance?"

If you understand why I am not permitted to wait to obtain auto insurance until after I have had an accident, if you understand why public officials cannot wait until a hurricane actually makes landfall before issuing evacuation orders, then you understand why action to prepare for this pandemic cannot be deferred until after the virus has achieved sustained human-to-human transmissibility.

This equation does not "mesh" severity and probability

I won't argue that, but I will insist that the two are inseparable at the level of applying the results toward deciding what degree of protection is reasonable.

Media hype can generate a cross-variable "bleed" effect where [one] variable is affected by the other.

True enough, perhaps, if you are relying on sensationalist mainstream media as your primary source of data. I suggest that the microbiologists, virologists, molecular biologists, epidemiologists, and other experts who are estimating the likelihood variable as extremely high are relying instead on the best data available from their respective fields. Whether policymakers are able to objectively interpret the results is another matter, as is the question of whether their decisions will be based solely on those interpretations even if they are highly objective (I have occasionally had reason to suspect policy-makers of placing a higher priority on their future careers as policy-makers than on making policies they knew to be in the best interests of the majority concerned).

The decision to evacuate Houston would probably have been found as valid utilizing this technique, since the cost of evacuation were probably not as high as you are stating

Let's make sure #5 (the real relative economic contribution of the geographic area) fully encompasses the costs of shutting down thousands of factories, refineries, businesses, etc, and the resulting loss of production and revenues. Using a similarly inclusive approach, we might be able to arrive at an estimate for the average cost of a human life lost to flu based on an individual's projected productivity through the remainder of a lifetime (insurance companies do it all the time). We could then at least attempt a risk assessment using a RAM, and possibly avoid being labeled as either wide-eyed media credophiles or bleeding-heart do-gooders.

 

[drkitten]

Maybe in your world "probable" equals "confirmed". Not in mine.

So in your world does "documented" equal confirmed?

Very limited human-to-human transmission of the H5N1 strain was documented in health care workers

 

[Adrian]

Dude. It was a rhetorical question. A more generalized form of it might be: "do you consider any expenditure of money as wasted when spent on obtaining a degree of protection against a threat with an uncertain degree of probability of occurance?"

I know that it was rhetorical question. I don't answer rhetorical questions. I mock them, since they are usually just attempts to attack a viewpoint without relying on data.

If you understand why I am not permitted to wait to obtain auto insurance until after I have had an accident, if you understand why public officials cannot wait until a hurricane actually makes landfall before issuing evacuation orders, then you understand why action to prepare for this pandemic cannot be deferred until after the virus has achieved sustained human-to-human transmissibility.

I agree. I only have been questioning if human-to-human tranfer has actually happened and has been confirmed. Planning for disasters is important and is usually money well spent. I do have problems with expensive actions being initiated based upon generalities that have not been confirmed.

True enough, perhaps, if you are relying on sensationalist mainstream media as your primary source of data. I suggest that the microbiologists, virologists, molecular biologists, epidemiologists, and other experts who are estimating the likelihood variable as extremely high are relying instead on the best data available from their respective fields. Whether policymakers are able to objectively interpret the results is another matter, as is the question of whether their decisions will be based solely on those interpretations even if they are highly objective (I have occasionally had reason to suspect policy-makers of placing a higher priority on their future careers as policy-makers than on making policies they knew to be in the best interests of the majority concerned).

I know too many biologists to assume their objectivity. Even professional researchers are people and they have emotions. Thier emotions about the possibly catastrophic effects could cloud their ability to objectively collect the proper data.

Let's make sure #5 (the real relative economic contribution of the geographic area) fully encompasses the costs of shutting down thousands of factories, refineries, businesses, etc, and the resulting loss of production and revenues. Using a similarly inclusive approach, we might be able to arrive at an estimate for the average cost of a human life lost to flu based on an individual's projected productivity through the remainder of a lifetime (insurance companies do it all the time). We could then at least attempt a risk assessment using a RAM, and possibly avoid being labeled as either wide-eyed media credophiles or bleeding-heart do-gooders.

I would include the shutdown costs under #4, since they are resulted from making the decision to evacuate. They would be utilized during the cost-benefit analysis portion of the activity.

Project productivity of an individual that dies due to flu (I'm going to assume H5N1) becomes much more difficult to calculate. I was originally speaking of the Houston hurricane analysis, since one can evaluate a simple economic micro area (a city). If you want to apply it to the flu situation, it becomes much more complex. Say, we take the assumption that pandemic will occur and it is the big "doomsday" one with lots of people dying in many countries. One would have to look at the situation from a multi-nation macro position, which requires much more analysis and data (Globalization makes this more and more difficult every year). It still could be done...

My opinion boils down to three points:

1.) I just can't accept "probable" as meaning "definite".
2.) Until we have enough data to state that it is definite, we need to treat it as a "possible" or "probable" event and collect data in order to clarify our position in an objective and rational manner.
3.) We have to understand that our decisions have real costs and that riding the wave of fear and paranoia can have a real negative effect on society and many individuals.

That's all folks. Peace.

 

[drkitten]

My opinion boils down to three points:

1.) I just can't accept "probable" as meaning "definite".
2.) Until we have enough data to state that it is definite, we need to treat it as a "possible" or "probable" event and collect data in order to clarify our position in an objective and rational manner.
3.) We have to understand that our decisions have real costs and that riding the wave of fear and paranoia can have a real negative effect on society and many individuals.

Nothing is ever definite. It is technically only "probable" that the sun will rise tomorrow, but any rational observer would act as though the probability was indistinguishable from one.

I do not believe there is any rational ground for you assign any specific non-zero probability to the chance that human-to-human transmission of H5N1 has not occurred. if you disagree, then please tell me what that probability is, and on what basis you make that call.

Because, frankly, you're sounding more and more like a Tobacco Institute apologist insisting that there is no "proof" that smoking causes cancer.

 

[Adrian]

Nothing is ever definite. It is technically only "probable" that the sun will rise tomorrow, but any rational observer would act as though the probability was indistinguishable from one.

Wow... maybe you should read some Derrida, you might agree with him. I warn against that though, because I hear that it can rot your brain. I'm just an old-fashioned sort of guy that likes his reality the definite kind. I am holding three coins right now. That is definite. I am wearing contact lenses, also definite... hmmm...

I do not believe there is any rational ground for you assign any specific non-zero probability to the chance that human-to-human transmission of H5N1 has not occurred. if you disagree, then please tell me what that probability is, and on what basis you make that call.

I don't need a probability. No one has stated that the event has happend. I don't have to prove that what has not happened did not. The burden of proof falls upon the believer to prove that the event happened. No one has been able (or willing) to state as a fact that human-to-human transmission has happened and has been proven. At least, in sources I have read. I would love to read any other conflicting sources that anyone has available.

Because, frankly, you're sounding more and more like a Tobacco Institute apologist insisting that there is no "proof" that smoking causes cancer.

Not really. I am simply saying that telling other people that there have been 3 definite cases of human-to-human transmission is wrong when the sources only state that there has "probably" been some human transmission. You attempted this analogy before. It really isn't that effective, since it doesn't have much application in this instance (since I am actually siding with the proof... as it is actually written and not taking the words to mean more than they do). It would be much more effective to attack me on some emotional level like "it is clear that I don't worry enough about the living cost" or "I'm mean and pompous". Those comments would be childish, but much more applicable to the situation.

 

[Dymanic]

I know too many biologists to assume their objectivity. Even professional researchers are people and they have emotions. Thier emotions about the possibly catastrophic effects could cloud their ability to objectively collect the proper data.

I know too many non-biologists to assume their objectivity with regard to their ability to assess the objectivitiy of professional researchers.

Really, I tried to let this go, but it just kept bugging me. I think it was when I realized that this is essentially the same argument I have heard so many times from creationists, apparently convinced that the theory of evolution is a product of the fertile imaginations of scientists. My usual response to them is to note that the concept of observer bias has come up once or twice before in the history of science, and that because of this, modern science includes much cumbersome methodology dedicated primarily to minimizing this effect. In addition, among the human qualities to which scientists are also subject is a love of the playing of games of one-upmanship, and playing for blood. The creationist who supposes that those ideas that enjoy wide acceptance in the scientific community represent a closing of ranks on the part of scientists invariably has no concept of just how ruthless a playing field it is. There is a certain accepted format for the publishing of scientific findings, and it includes detailed descriptions of every step of a researcher's process. Among the human emotions to which scientists are subject is an innate fear of public ridicule, and since the publishing of scientific findings is an open invitation to that, this serves as strong motivation to the paying of close attention to details; if the author does not, someone else certainly will.

If you paid close attention to the details (instead of waving away mountains of painstakingly documented research as tainted by emotion-driven bias) you might find that although H5N1 has indeed been the subject of much recent attention due to its ability to infect humans, that ability is not the only reason for studying influenza viruses, that H5N1 is not the first avian influenza virus ever studied, and that much of the data which serves as the basis for estimating the likelihood factor as high emerges out of observations of the behavior of avian influenza viruses in both wild and domestic bird populations before 1997, when the first observed instance of bird-to-human transmission occurred.

http://www.cdc.gov/ncidod/EID/vol10no4/03-0396.htm
Take a look at some of the dates in the references listed there.

My opinion boils down to three points:

1.) I just can't accept "probable" as meaning "definite".
2.) Until we have enough data to state that it is definite, we need to treat it as a "possible" or "probable" event and collect data in order to clarify our position in an objective and rational manner.
3.) We have to understand that our decisions have real costs and that riding the wave of fear and paranoia can have a real negative effect on society and many individuals.

That sounds reasonable enough as far as it goes. Collecting more data is certainly part of the plan no matter what. But there's a difference between "fear" and "paranoia". I believe that the danger is real, and that the fear (while unpleasant) is, to the degree that it leads to productive action, an appropriate response (by way of contrast, there was a time in my life when I might have responded to ominous sounds coming from my car's engine by turning up the radio and lighting up a "doob"; but that was a long time ago). As for "definite", I am sure that my life today would be very different if I had been afforded that luxury at every important decision point (though I can't imagine that living it would have been nearly as exciting). Whether we decide to immediately start throwing huge gobs of resources at this thing or not, it's still a decision, and it's still a decision made on indefinite information. I do not disagree that there are risks accompanying either choice, but I don't accept "do nothing" as the default.

That's all folks. Peace.

Aw, c'mon. Not giving up on us, are you? We were just trying to give you a nice warm welcome to the forum!

 

[Badly Shaved Monkey]

Something has occurred to me that I have not thought through before with respect to bird 'flu. If H5N1 runs its course as an epidemic through the world's bird population would it be expected to effectively die out? In other words, is the aim to keep it away from people, by suppressing it in domesticated fowl, for long enough so that it goes its own way and disappears?

 

[Eos of the Eons]

there have only been 117 confirmed cases of the disease in humans to date, and 60 people have died from it.

http://www.spiked-online.com/articles/0000000CADBF.htm

I can find no confirmed cases of human to human transmission.

 

[Dymanic]

If H5N1 runs its course as an epidemic through the world's bird population would it be expected to effectively die out?

Wild bird populations may be expected to develop natural resistance to the virus, but that doesn't necessarily mean that the virus will have vanished.

is the aim to keep it away from people, by suppressing it in domesticated fowl, for long enough so that it goes its own way and disappears?

It depends on your priorities.

If poultry production is your first priority, suppressing the virus in domestic birds may be regarded as an end in itself. Among the measures you might consider is veterinary use of antivirals.

If minimizing the potential for an avian flu pandemic in humans is your first priority, the aim is to minimize the opportunities for the virus to swap genes with a strain already able to pass efficiently between humans. Among the measures you might consider is wholesale destruction of millions of domestic birds.

Just as is the case with most problems, it's hard to find solutions that are likely to make everybody happy.

The onset of the normal flu season in the northern hemisphere begins just about now, and as H5N1 becomes more widespread among both wild and domestic bird populations, the chance of the critical exchange of genetic material occurring in a co-infected host (it only takes one) increases with each passing day. Anything that reduces the chances of that will buy us some time, but the consensus among virologists is that it is pretty much inevitable.

Controlling the spread of the virus in wild bird populations is no longer a viable option. Ducks may not even develop symptoms.

It is no big surprise that among the first ideas that would occur to President Bush is the use of the military to enforce quarantines. That is, of course, laughably naive. In memory of a former president (one with a similarly stunning intellect), I hereby challenge the scientific community to develop the means to protect us from biological threats like this by covering our cities with big, airtight glass domes.

It seems to me like the best thing the average person can do is: wash your hands a lot this winter, try to avoid crowds, and buy a couple of big bags of beans and rice, maybe some extra canned food.

 

[Capsid]

http://www.spiked-online.com/articles/0000000CADBF.htm

I can find no confirmed cases of human to human transmission.

The only case where it might have happened is from a mother to child but even this is not certain. This is what I heard on BBC radio 4 on Thursday night. There was no immediate need for concern due to a definitive lack of evidence for human to human transmission.

 

[Dymanic]

http://www.spiked-online.com/articles/0000000CADBF.htm

I can find no confirmed cases of human to human transmission.

After reading the article you linked, I wonder whether you are in agreement with this statement:

"It is entirely correct and necessary that experts in the fields of medicine and policy should research and prepare for potential future disease pandemics, not least so that the rest of us don't have to spend our time fretting about such matters."

and whether, in light of the experience of the victims of the recent hurricanes, you would agree with this modified version:

"It is entirely correct and necessary that experts in the fields of meteorology and flood control engineering should research and prepare for potential future hurricanes, not least so that the rest of us don't have to spend our time fretting about such matters."

I say: Ask not what your government can do to protect you from this threat, ask what you can do to protect yourself.

I can find no confirmed cases of human to human transmission.

Define "confirmed".

If we wanted to know if the virus could be transmitted between rats, what we could do is take some rats, place them in an isolated environment until the maximum presumed incubation period had passed, then introduce a rat known to be infected with the virus. If the other rats came down with the flu, then rat-to-rat transmission would be confirmed (though a negative result would be less conclusive).

There is no theoretical barrier to performing the same experiment using human subjects. Any volunteers?

 

[Eos of the Eons]

After reading the article you linked, I wonder whether you are in agreement with this statement:


and whether, in light of the experience of the victims of the recent hurricanes, you would agree with this modified version:


I say: Ask not what your government can do to protect you from this threat, ask what you can do to protect yourself.


Define "confirmed".

If we wanted to know if the virus could be transmitted between rats, what we could do is take some rats, place them in an isolated environment until the maximum presumed incubation period had passed, then introduce a rat known to be infected with the virus. If the other rats came down with the flu, then rat-to-rat transmission would be confirmed (though a negative result would be less conclusive).

There is no theoretical barrier to performing the same experiment using human subjects. Any volunteers?

Confirmed, as in that both people weren't exposed to the chickens or other birds before one transmitted to the other. In all the cases, there is confimation that the people were in contact with the infected birds. There are no cases of human-human transmission. We would expect to see clusters of people who passed it onto each other if it were possible. We haven't seen that either.

We can live by fretting, or just be aware. I prefer to leave the anxiety and problem solving to those that can do something about it. There's no way I can make a vaccine for the human-human type virus. There's no way I can control how much vaccine is ready when they do discover the mutated virus. There's nothing I can do to protect myself if I end up being one of the first cases and there is no vaccine available to me to prevent my demise if I am one of the 50% that dies after contracting the disease.

So I choose to not worry so much, but try to be aware of the progression via unreliable news sources, and hopefully more reliable scientific documentation. Awareness is a good thing. I could try to avoid areas of outbreak. I'm not going to chew my nails in anticipatian of an outbreak though.

Protect yourself in any way you can, but there is only so much you can do. This is where awareness can be helpful.

Otherwise, we should support scientific advances so that those that CAN help us WILL be able to help us overcome diseases and natural disasters.

Protecting yoursefl from an airborne disease vs a devastating hurricane. Hmmm. I would try to not live in hurrican prone areas...and do that, I would try not move to a hurricane prone area. You can also have some sort of boat on hand to escape your home after the hurricane...and keep a store of canned food and bottled water to take on your boat. Try keeping your boat from blowing away during the hurricane...

I'm only going to worry about things (not hurricanes in my area) when they actually happen. I have a basement to hide from tornadoes now, so I feel a little better. Do what you can as an individual, but also support advances so that we can get help should we need it.

 

[HopkinsMedStudent]

I believe I can contribute something to this thread.

We just had a lecture given to our medical school class by one of the world's leading virologists who is an influenza expert. She has spent the past several months in Asia researching H5N1.

Basically, her take home point is that right now H5N1 is not a huge deal, but it has the potential to be one of the worst diseases the world has ever known.

The potential for danger is much higher than has even been postulated on this thread, because there are actually 4 target sites for mutation that would make H5N1 a superbug, capable of infecting cells across the whole body and not just respiratory epithelium. Normal influenza virus secretes hemagglutinin in a pro-enzyme form, meaning it requires activation by something else before a functional virion can be made. Specifically, it requires a serine protease that is made only by ciliated columnar cells that are found in our airways.

If H5N1 acquires one of those 4 prime mutations, it could infect any cell in the body. Dealing with normal flu is bad enough, but imagine how difficult it would be for doctors to treat if the virus could replicate in every tissue in teh body?

The other 4 mutations code for different virulence factors that would allow increased replication, reduced growth/latency checkpoints, and proteins that inhibit cytokines secreted by macrophages.

There are 2 concepts of genetic changes that apply in particular to influenza, genetic drift and genetic shift.

Antigenic drift happens every year, the hemagglutinin surface protein changes its protein makeup slightly every season. Our immune system uses the HA surface proteins as its primary antigenic "alert" system, triggering a cell mediated immune response (B cells, T cells). By subtly changing the surface architecture of HA every season, the virus ensures that previous immunity does not pass over to the next year. Thats why you have to get a flu shot every year.

As somebody else pointed out, the big problem with influenza that we dont have nearly as much a problem with in other viruses is the concept of antigenic SHIFT.

Antigenic shift is a lot more nefarious than antigenic drift. What happens is you have 2 reservoirs (birds, pigs) and an infected pool (humans). A pig gets co-infected by 2 flu viruses, a human version and a bird version. Each "pure" version of the virus has a bird/bird or human/human surface and core antigens, respectively.

When a pig cell gets co-infected by 2 flu virions, what happens is the segmented RNA genomes can reassort into a "hybrid" virion. The "hybrid" viron has the surface antigens of birds, but the core RNA thats infectious to humans. Thats very bad, because it means that if that hybrid virion infects humans, it will have avian surface antigens, which no human immune system has ever recognized before.

 

[Eos of the Eons]

Thats very bad, because it means that if that hybrid virion infects humans, it will have avian surface antigens, which no human immune system has ever recognized before.

See, we can fret about this, or just try to get on the actual mutated virus once it happens...if it happens. Just knowing the experts are aware of what can happen makes me feel more secure.