>I'm trying to visualize what's going to happen if/when H5N1 mutates to a
>person-to-person-transmissible virus.
>
>One image I have is of a very rapid spread because nobody has any existing
>immunity. i.e. Lots of people that we have contact with going about our daily
>business are going to be coming down with it.
Yes. Flu is very contagious. Many people will be exposed, many of them
will become ill, and some will become seriously ill.
>Given that, if somebody became infected and lived; it seems like they would
>still be encountering other infected people on a fairly regular basis after
[quoted text clipped - 6 lines]
>to additional courses of the antiviral drug in order to survive subsequent
>re-infections?
You develop immunity to a specific flu strain when you're exposed to
it. This immunity should protect you for some time (years) against
that strain, and give you some resistance to related ones. It's not a
lifetime immunity, but it works reasonably well in the short run. This
is independent of whether you recover with or without the help of
antiviral drugs.
Flu vaccines probably don't give you as good or as long-lasting an
immunity as actually getting the flu, but they are good enough to be
the difference between getting ill or not getting ill, or getting a
mild case instead of a serious case for most people. Also note that if
enough people are vaccinated, there won't be enough susceptible people
to spread the virus, so most people will end up never being exposed to
it. This is called "herd immunity" -- susceptible people are
surrounded by immune people who can't infect them. It's the best
method to protect the most susceptible: the chronically ill and the
elderly, who don't develop strong immunity from vaccines, and are most
likely to become seriously ill or die from even the annual outbreaks of
relatively mild influenza strains. It's also the best method to
protect a population from any serious disease, since no vaccine is 100%
effective. This is how smallpox was eradicated, and how most childhood
diseases were reduced to near insignificance in developed countries.
Note that while a pandemic could be disastrous, it's not the end of the
world. The WHO keeps records of laboratory confirmed cases, and as of
22 September, there have been 115 cases and 59 deaths in almost two
years. That sounds horrific until you realize that probably well over
a billion people have been exposed to the virus, and only those sick
enough to be hospitalized, and identified as potential victims of avian
influenza would be tested. When there was an outbreak of avian flu in
Hong Kong in 1997, with similar mortality rates, poultry workers were
tested and about 10% of them had antibodies for H5, without having been
seriously ill.
The World Health Organization has been doing a great deal to avert
pandemics. If this strain doesn't jump the species barrier, it will be
due to their efforts, and if it does, there will likely be "only"
millions rather than tens or hundreds of millions of deaths, due to
intense surveillance and early development of vaccines. As a
background, the 1918-20 pandemic killed about 50 million worldwide, and
about 70,000 people die of flu annually in the US. The brief SARS
epidemic a few years ago demonstrated both the effectiveness and flaws
in emergency plans, which stood up very well for that less contagious
but more virulent disease with no vaccine or effective treatment.
If it's your own health, and that of your friends and family that
concern you, note that most deaths will be in poor countries, where
chronic malnutrition and chronic illness from malaria, tuberculosis and
AIDS, poor and crowded living conditions and limited resources for
public health measures will make an epidemic harder to control and much
higher in mortality rate.
Note that a lot of the above is my opinion, which likely isn't worth a
lot since I'm not a medical worker, an immunologist nor an
epidemiologist. If you want more authoritative information, I suggest
the WHO web site, www.who.int, especially the sections on avian
influenza and pandemic preparedness.
(PeteCresswell) - 25 Sep 2005 19:36 GMT
Per bae@cs.toronto.no-uce.edu:
>Flu vaccines probably don't give you as good or as long-lasting an
>immunity as actually getting the flu
Thanks for the detailed response. "Herd immunity" was a new concept to me.
But It still begs the question of whether somebody who is coming down with the
flu and takes an antiviral gains immunity.
I can see it both ways:
- Either the person's immune system has time to be stimulated and produce the
requisite antibodies... or
- The antiviral does something to the virus so quickly that the person's immune
system doesn't get enough time to identify the virus and produce antibodies.
Given somebody who is very much at risk - as opposed to someone young and in
good health, this would seem to be a critical issue when it comes to a pandemic
and antivirals. In the first case, a single course of the antiviral could
save the person. In the second case, just a single course would only buy time
until the person became re-infected.

Signature
PeteCresswell
(PeteCresswell) - 25 Sep 2005 20:01 GMT
Per bae@cs.toronto.no-uce.edu:
>If you want more authoritative information, I suggest
>the WHO web site, www.who.int, especially the sections on avian
>influenza and pandemic preparedness.
I'm working my way through the WHO web site.
One issue I haven't found addressed yet: "Why not mix avian flu vaccine in with
the seasonal flu vaccine now being produced?" I'm guessing there's at least a
lead time issue in that last I heard they were still trying to figure out how
much of the stuff is needed for a given immunization.

Signature
PeteCresswell
(PeteCresswell) - 26 Sep 2005 01:01 GMT
Per (PeteCresswell):
>"Why not mix avian flu vaccine in with
>the seasonal flu vaccine now being produced?"
Just found something in one of the WHO articles that seems to explain part of
it.
Flu vaccine is produced by inoculating chick embryos with the disease.
H5N1 kills the embryo...
Partial clip from http://www.who.int/csr/disease/influenza/H5N1-9reduit.pdf:
-----------------------------------------
"The challenges are even more formidable for a highly lethal avian
virus like H5N1.Although a few companies are moving towards
cell-culture production technologies,fertilized chicken eggs are
the standard medium for the growth of virus for use in influenza
vaccines,and will remain so in the near future.Highly pathogenic
H5N1 kills chicken embryos and must therefore be modified.The
preferred method for doing so uses the technology of reverse
genetics to remove lethal genes..
Reverse genetics involves patented technologies,and this raises
issues of intellectual property rights.Industry knows how to
manage these issues,but the consequences of doing so may be
reflected in the price of the vaccine.In Europe,a vaccine produced
using reverse genetics is considered a genetically modified
organism ;the resulting safety concerns introduce additional
biosafety requirements for manufacturing facilities.Upgrading
of facilities to meet these higher standards is possible but costly
and cannot be done rapidly."
-----------------------------------------

Signature
PeteCresswell
bae@cs.toronto.no-uce.edu - 26 Sep 2005 16:39 GMT
>Per bae@cs.toronto.no-uce.edu:
>>If you want more authoritative information, I suggest
[quoted text clipped - 7 lines]
>lead time issue in that last I heard they were still trying to figure out how
>much of the stuff is needed for a given immunization.
As you posted later, they don't have a good vaccine yet, but apart from
that, there's no point in vaccinating the general population until the
disease actually appears. It's a considerable expense and some risk
for no real benefit.
Also note: if or when a human transmissible form arises, it will almost
certainly be due to exchange of genetic material between the avian
virus and a human virus in a person (or pig) infected with both. This
new form may be somewhat different antigenically, and may be better
addressed by a different vaccine. Note that one of the preventative
techniques the WHO is implementing is to vaccinate people involved in
destroying infected flocks against all the local human flu strains in
hopes of averting, or at least delaying the development of a
human-contagious form. Once a vaccine is developed, the logical people
to receive it will be those exposed to infected poultry, or to the
virus in other forms, such as laboratory workers involved in developing
or preparing vaccines.
Regarding your previous post: treating people who have already shown
symptoms with antivirals shouldn't have much effect on their ability to
raise antibodies against the virus, AFAIK. Many of the symptoms of flu
such as fever and malaise are due to the immune system taking action
against the virus. Giving antivirals to people who have been exposed
but haven't yet developed symptoms is often a good idea for their
individual health, and I don't know how much it would affect their
ability to develop immunity -- I suppose if given early enough, e.g.
within minutes of a laboratory accident, it might prevent significant
response. Using antivirals as a preventative for people who have not
been exposed is generally a bad idea. Not only does it promote the
development of drug-resistant strains, but no drug is free of side
effects and undesirable effects on at least some people, especially if
given for a substantial length of time. Vaccines (and in appropriate
situations, quarantines) are usually a far better method of protecting
a population. The SARS epidemic of a few years ago was stopped by
quarantine of patients and those exposed to them, but influenza is much
more contagious than SARS.
Of course, all this depends on a lot of factors. Is there a good
vaccine? It's not always possible to develop a good one -- cholera and
HIV are notorious examples. How serious is the disease? Nobody
reputable is going to recommend everybody go on antivirals for months
to prevent the common cold. How dangerous is the vaccine, relative to
the seriousness of the disease and the probability of catching it?
Vaccinating the general population for smallpox was stopped once it was
essentially eradicated from an individual country, and rare imported
cases were controlled by "ring vaccination" -- vaccinating everyone who
came in contact with the patient, everyone who came in contact with
those people, and out another layer or two, because smallpox vaccine
can occasionally have serious side effects. How contagious is the
disease? How easily are cases identified? For how long before symptoms
appear can the patient spread the virus to others?
Again, I have no credentials as an immunologist or epidemiologist, and
you should take the WHO's word over mine.
(PeteCresswell) - 27 Sep 2005 01:30 GMT
Per bae@cs.toronto.no-uce.edu:
>Also note: if or when a human transmissible form arises, it will almost
>certainly be due to exchange of genetic material between the avian
>virus and a human virus in a person (or pig) infected with both. This
>new form may be somewhat different antigenically, and may be better
>addressed by a different vaccine.
I got the same message from WHO's documents except that there seemed tb a
recommendation to vaccinate some subset of the populace with some sort of
H5-generic vaccine as a first step. I don't understand the ins and outs of
that... but that that's what they said.
Given
- that the 1957 pandemic covered the world in something like six months,
- the exponential increase in airline travel since then, and
- the lead time necessary to produce/distribute a vaccine;
the vaccine route sounds pretty much hopeless for the first wave.
Extrapolating from what I've read so far it seems like the initial pandemic will
cover the world in a month or less.
One hope would be that if it results from a rearrangement event - as opposed to
adaptive mutation - that the rearranged genes won't be as lethal as the current
H5N1 and we'll all get some residual immunity built up without too many excess
deaths over and above the current 30,000-70,000 (depending on who you talk to)
per year in the USA.

Signature
PeteCresswell
Bob - 27 Sep 2005 03:38 GMT
>Per bae@cs.toronto.no-uce.edu:
>>Also note: if or when a human transmissible form arises, it will almost
[quoted text clipped - 24 lines]
>deaths over and above the current 30,000-70,000 (depending on who you talk to)
>per year in the USA.
All of the above. All that bae posted and all from WHO are parts of
the general picture. And so are your concerns.
It is so very important that the situation is monitored carefully, and
the first hints of a human-transmissible virus be recognized. Acting
fast at the source is important -- to at least slow if not stop the
virus spread.
If there was an effective vaccine against the virus as we currently
recognize it, there might be serious consideration of using it in
advance, at least with some populations. There is work on developing
such a vaccine, but so far success has been limited. Better that the
work is at least in progress than that nothing was happening.
bob