Greetings: Welcome to this Friday Letter Special Edition. With all of the
talk about anthrax and other bio-terrorist weapons, Gilder Biotech Report
editor Scott Gottlieb filed the following comments we thought you'd find
of interest.

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Dear Friday Letter Reader:

Over the last week I've been asked a lot of questions about how to protect
against smallpox -- a threat which seems to have a growing number of
people concerned. A friend who works with the CDC says some there believe
it may the bioterrorists' weapon du jour.

Given the lack of technical sophistication of this crowd, any smallpox
attack would likely consist of a dozen bioterrorists self-infecting and
then walking around the New York City subways. The simplicity of such an
action provides some opportunities to protect ourselves, including making
available some powerful antivirals, many of which came about during the
AIDS crisis.

First a little background on smallpox. The virus spreads from person to
person, primarily by tiny droplets expelled from the throats of infected
persons and by direct contact. Contaminated clothing or bed linens can
also spread the virus.

Patients spread smallpox primarily to household members and friends; large
outbreaks in schools, for example, were uncommon. This finding was
accounted for in part by the fact that transmission of smallpox virus did
not occur until onset of a rash. By then, many patients had been confined
to bed because of the high fever and lethargy caused by the early stages
of the illness. Secondary cases were usually restricted to those who came
into contact with patients, usually in the household or in the hospital.

The patient was most infectious from onset of rash through the first 7 to
10 days of rash. As scabs formed, infectivity waned rapidly. Although the
scabs contained large amounts of viable virus, laboratory studies showed
that they were not especially infectious, presumably because the virus
particles were bound tightly in the rash.

Infection starts after virus particles are implanted in the throat, nose,
or lungs. The infectious dose is unknown but is believed to be only a few
virus particles. After about two weeks, patients experience high fever,
malaise, headaches and backaches. Severe abdominal pain and delirium are
sometimes present. A rash that resembles chicken pox then appears in the
mouth and throat, face, and forearms, and spreads to the trunk and legs As
patients recover, the scabs break and turn into pitted scars.

Back as late as the 1970s, when the last cases of smallpox were reported
in the Western world, there were few treatments -- other than vaccination.
That has changed. There are at least half-dozen antivirals that are
believed to have efficacy against smallpox. Many of these can probably be
used as post-exposure prophylaxis.

Most of the studies with these drugs have been conducted in animals and
test tubes. There are a few human trials to draw on. I will focus on two
drugs: one because it's believed to be excellent, and could be available
in the time of a crisis. The second, while not as effective, is widely
available today.

The first is Cidofovir, an antiviral agent aimed at DNA viruses, developed
by Gilead Sciences (GILD). Cidofovir was tried against HIV, but didn't
work that well. First of all, it had to be delivered intravenously to be
effective. Also, it was toxic to the kidneys. So it was largely abandoned.
The drug, however, is still on the market for limited use in some
complications of AIDS, and there is laboratory and clinical data that it
would be very effective against smallpox.

The other drug is Rifampin, a mainstay in the treatment of tuberculosis.
While Rifampin lacks the potency of Cidofovir, it's widely available and
could provide some measure of post-exposure prophylaxis. It works by
blocking assembly of the smallpox virus. It's easy to get, and certainly
better than nothing.

All this is not to say anyone expects an imminent attack. But even a few
cases of smallpox would be catastrophic. For all the fear over anthrax,
it's still a one-time agent. It doesn't spread from person to person. To
catch it you need to come directly in contact with the spores. And the
first thing we do in the hospital is wash down the suspected victims.

The real test for our nation will come when a communicable disease like
smallpox crops up. Even doctors are petrified of the possibility. There
have been a lot of stories about the risk of a looming attack. Let's hope
it's just media hype.

--Scott Gottlieb, M.D.

Click here, https://www.gilder.com/biotech/biotechnewsSub.asp, if you'd
like to subscribe to the Gilder Biotech Report by Scott Gottlieb, MD

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