Dr. Mack's presentation to the CDC June 19-20, 2002.
The following transcript is very important to save in your documents
since the CDC website has removed the transcripts of June 19-20, 2002
COMMITTEE ON IMMUNIZATION PRACTICES
Atlanta Marriott Century Center
The verbatim transcript of the Meeting of the Advisory Committee on
Immunization Practices held at the Atlanta Marriott Century Center,
Atlanta, Georgia, on June 19 and 20, 2002.
NANCY LEE & ASSOCIATES
Certified Verbatim Reporters
P.O. Box 451196
Atlanta, Georgia 31145-9196
(This is pgs 139 to 166 of the transcript In the original, the
lines are double spaced with irregular page placement. Emphasis
added is mine.
PLEASE PASS ON!! S. Tenpenny,
........Dr. Tom Mack is our next speaker.
DR. MACK: I wasn't aware of the mandate that I had and I made the
arrogant assumption that you might actually be interested in my opinion
about the three questions that are open to you, and so I'm going to give
it. I will try and deal with the request, as well.
As you probably know, I'm at the University of Southern California School
of Medicine. I've been out of the smallpox game for roughly 40
years. My credentials include probably spending more time working
up population-based outbreaks of smallpox than virtually anybody ever
has. We spent three years in Sheikhupura district in Pakistan and
worked up 121 outbreaks, which we estimated were roughly 85 to 90 percent
of all the smallpox that occurred in that population of a million or so
people. And the experience contrasts somewhat with a lot of the
other series because population-based outbreaks include small outbreaks
that never result in any hospitalization, and individual importations
which never result in any cases coming to the attention of
So in the Pakistan study, this is roughly a situation where more than a
quarter of the people were unvaccinated. It tends to be villages of
from two to 20 to 100 crowded compounds, 1,000 to 5,000 people. Any
given village received an importation maybe once every ten or 15 years,
so these were people who were not familiar with everyday smallpox.
And in essence, there was really no medical or public health care, and
there are a variety of political and historical reason for that, which we
can go into, but the import of it is that there really was no
You heard several references to my review of the European
experience. I'd like to reiterate that this was -- these
experiences were in essentially susceptible populations with physicians
who were unfamiliar with the disease, media and communication skills much
less than today, and the standard of living actually substantially less
than today in both Europe and America. So in my opinion,
the propensity for spread in both these circumstances is substantially
greater than it would be in the United States
You're going to hear more about vaccinia. I'm not going to
spend any time on that. I just want to point out the last word in
this slide, which is VIG. I haven't heard that phrase mentioned
today. To me, it should be an extremely important
consideration in all of your deliberations because in the absence of VIG,
any extensive vaccination would be extremely dangerous.
I'll try and skip data slides because you've seen many of them
already. This just reiterates the effectiveness of past
vaccination, and in this case it demonstrates that the severity of
disease was affected.
This is the study that was previously referred to by the Russian
gentleman who tried to vaccinate people who'd previously had smallpox,
demonstrating that the history of severity was an important determinant
of whether or not he could get vaccination takes, irrespective of the
interval since the case occurred.
Okay, the trade-off is with smallpox, and I'd just like to
point out that not only is it a nasty syndrome, but the case fatality
is probably less than is usually advertised.
And the reason for that is that most series are heavily loaded with
children. If you look at the age-specific case-fatality rate, it's
much lower among adults. And so I would estimate that if we had an
importation today in the adult population, the case fatality would
probably be around ten to 15 percent.
It does have a truly terrifying pathognomonic appearance, and that's one
of the characteristics that would make control much easier. Again,
as has been mentioned, there's acute illness during a brief period of
infectiousness. There are no reservoirs or vectors.
There is a finite half-life in the
environment. And most importantly, there's a big
-- one to two -- one to three-week interval between generations in which
activity for surveillance and containment takes place. And by
and large, transmission within social limits is what occurs, not within
the population at large. And these, by and large, cannot be
sustained. In fact, were there no smallpox eradication
program, my guess is that smallpox would have died out anyway, it just
would have taken a lot longer.
Now a few slides to show you what it actually looks like. That's
hemorrhagic smallpox. This lady was actually not vaccinated, she
just has sparse disease. But you can see that the characteristics
of the lesions are just the same.
This is a girl at three days of rash. I don't think anybody could
pick up that that is smallpox without an awful lot of experience.
This is the same girl at seven days.
This is also a man at three days. Unfortunately, I didn't have a
slide of him, but he died with very rapid confluent smallpox, and you can
detect that it's going to be confluent from his appearance
I'll go over these slides because they've been shown before.
In 27 percent of the cases in Sheikhupura, there was no
transmission at all. Another 37 percent, only one generation.
Now we're talking about a place where there really was no care
given. The mean length of the outbreaks was six weeks.
That's roughly three-plus generations, so a few of the
outbreaks were longer. We could detect the source.
Virtually all the people we could identify as introducers, even though
sometimes we came upon the outbreaks substantially late. In other
words, most people knew where they got smallpox. It wasn't a matter
of their having gotten it on a train or gotten it in an unknown
The top figure here shows the distribution of cases in the same compound
as an introducer, showing essentially the incubation period variation,
and it does correspond to what's been known before, one to three
weeks. The lower one shows the distribution of cases in other
I would point out that when one is looking at attack rates, they're
always confounded by the nature of the social arrangement. A
compound in west Pakistan is very different from a compound in west
Africa. The people are much more closely in contact, and so the
attack rates here were much higher than they were in west Africa, and I
daresay also in Madras because the living arrangements are very
different. And the definition of what constitutes a unit for study
is very different.
This has been referred to in the past. Twenty-seven percent,
again, no transmission. Thirty-five percent, only one or two
indigenous generations. Even with the hospitals, no more than six
generations. The largest generation was 20
This is an illustration of the effect of temperature and humidity on the
occurrence of disease. This represents the seasonal distribution in
Sheikhupura, almost the same figure we derived from seasonal distribution
in east Bengal. During the dry season, the cases are much more
effectively transmitted than during the wet season. And in fact,
it's not just a function of population movement, but it's actually a
function of virus survival. If you just look at the last two figure
on this graph, there are three times as much effectiveness of
transmission to other compounds in the period when the increase in
incidence was occurring than when it was decreasing.
Okay. What do we expect if there were a terrorist
introduction? I would expect a small number
of cases. I don't think suicide dissemination is a very
likely possibility because of the severity of the disease. I think
that airborne spread would be relatively inefficient and I
don't think very many cases would occur, and that's just giving
you my personal opinion.
The danger would be from release within a close space, like an
airplane. Then there might be several -- a substantial number of
cases, but they would all share a common experience and probably could be
identified. Cases would be florid because we're an
immunosusceptible population, by and large. People would be
aware of exposure after the initial diagnosis, and I think dissemination
from the individual cases would probably be relatively
The key to any introduction would be, as has been mentioned,
surveillance. I think initial recognition would be the most
important single factor. Identification and follow-up of contacts,
obviously. Isolation of known and probable cases, preventing
admission to hospitals and opening separate facilities, and then
vaccination of likely contacts.
Initial recognition, to me, awareness of the possibility of the disease,
is vastly more important than the details of how to distinguish it from
chickenpox. I don't like to see posters with lots of fine
print. I like to see a poster with a really big picture, and that
would make people aware that the possibility exists. And when they
saw that, they'd run to the books and they'd learn what they could
otherwise see on posters. Large subtleties will seep through
afterwards, just as they did with the anthrax situation.
And by large photographs, this is the kind of photograph that I would
like to see on a big poster. These are the classic lesions.
That could not be any other disease.
Now very early, it's difficult. But after a few days, there's not
going to be much likelihood of error. There will be the occasional
case modified by vaccination. But if there's only one case, what
worries? There'll be subsequent cases and they'll be much more
likely to be diagnosed. So we may miss some if it were to occur,
but we won't miss very many.
That's the flat variety that was referred to earlier. Contact
identification. Personnel. We don't need vaccination, we need
personnel. If smallpox were to come to Los Angeles
tomorrow, the more cases we'd expect, the more people we need prepared,
and that -- those people may come from San Francisco, they might come
from Atlanta, they might come from Michigan, under ideal
I would like to think of the fire-fighting as a model for how to deal
with a smallpox outbreak. People might be prepared in every
locality, and then be gathered together when necessary. The more
public exposure, the more people are needed, for obvious reasons.
Availability of protected personnel to me is vastly important, and that
would mean field epidemiologists, lab people and care providers,
designated people. And I would suggest that older and foreign MD's
who were previously vaccinated ought to be given priority.
Multi-locality Federal cooperation is really advantageous.
Most important determinant to the eventual number of cases is
whether or not somebody gets put in the hospital. And
everything should be done to prevent that, and the most
important thing is initial recognition. That depends on the state
of alertness and familiarity with the possibility of the syndrome.
And a dedicated facility need not be large, but better small and
agreed-upon than large and contentious. I don't know whether you
people have had such discussions in your localities, but we certainly
Populations requiring separate vaccination policy. See, I didn't
know those three questions, but I anticipated them. Vaccinating
those expected to implement control, those known exposed to a case or an
exposed person, those not so exposed but at risk of work place exposure,
and members of the community at large.
With respect to the first, I think this is very essential that there be
designated individuals who are vaccinated in advance, with VIG available
and with screening for those at risk for complications. Oops, I
think I missed one. That's all right. Yes, that was my
This is the people who are actually exposed. Now I was asked to
speak about post-exposure vaccination a few minutes ago. There's
not much to say about it. I can give you the little bit of data
that I have. It isn't very good data. I expect that
post-exposure vaccination does make a difference. I
don't know exactly, on a day-specific basis, how that difference
changes. I would certainly want to be vaccinated myself, and I
would want to vaccinate my relatives. I would also think about
passive immunization and chemotherapy, of which I know nothing -- the
latter, at least. But we would do whatever we could.
We're going to have to expect, if there is an importation, that there are
going to be people we do not identify who have already been exposed, so
we'd better prepare for it.
These are figures that have already been shown -- no, that's not.
That's not true, sorry. The last two columns compare post-exposure
to no vaccination. You can talk yourself into there being a
difference, if you wish. My guess is there is, but I couldn't
convince any biostatistician of it. Similarly, nine out of 19 who
got post-exposure vaccination were affected, compared to one out of
three. Can't make a big case out of that. And by the same
token, 12 out of 16 versus 26 out of 27. If you put all these
numbers together, you might or might not get statistical
significance. They would be heavily confounded by a variety of
circumstances which are not under control, so I wouldn't want to say we
have strong evidence that it works, but it should be done
I have the opinion that doctors and emergency room workers
should not be vaccinated a priori, as a category. I
think that is true because the likelihood of their being exposed, even
under circumstances of importation, is very, very small.
And I also think that that will eventually become mass
vaccination, whether we want it to be or not. They will be
concerned about their families. There will be people
making decisions who have not thought through the risk issues.
Policemen and firemen and everybody else who potentially
might be exposed under a contingency will demand equal treatment and I
don't think it'll work.
Unexposed community members have negligible risk. There
is a substantial risk from a vaccine, as you'll hear in a moment.
It is the single most dangerous live vaccine. We
would still need to vaccinate and identify contacts. We would need
personnel and resources for surveillance rather than mass
vaccination. That protection will not be
maintained. It will gradually wane and we'll have to do it again
The informed consent that you would have to prepare to vaccinate somebody
in the public, if it's honest, would have to say that the dangers
would exceed the benefits. And even if you
fudged those words in such a way that you were happy and thought it would
be convincing, an awful lot of people who ultimately might be exposed
would not be convinced. You'd have to go back again anyway.
So I don't think it would work and I don't think it would be
If people are worried about endemic smallpox, it
disappeared from this country not because of our mass herd
immunity. It disappeared because of our economic
development. And that's why it disappeared from Europe and many
other countries, and it will not be sustained here, even if there were
several importations, I'm sure. It's not from universal
So if I were the New York health czar, knowing a case would get on the
subway, I would rather have the money to prepare field workers than to
give mass vaccination. The first unnecessary death from a
vaccination complication would result in more, not less, smallpox
transmission because people who needed the vaccination under that
circumstance would refuse it. The presence of partial herd immunity
would not lessen work and might lead to complacency.
So my views on the three questions are obvious. I would choose
option one for the first one. I would choose option two for the
second one. And I would emphasize the inclusion of local people
because CDC cannot respond quickly enough, and there will become -- when
the difference between the second or third post-exposure day and the
sixth through the seventh post-exposure day might be important. And
under option -- number three, surveillance, surveillance,
surveillance. It's not ring vaccination, it's surveillance.
Vaccination is a subsidiary issue. Thank you very much.
DR. MODLIN: Thank you, Dr. Mack.