Lab Confirmed Human Cases
of Avian Flu as of August 2005 view
Ominous signs are multiplying.
Last month, Europe's attention was gripped by the post-mortem
of a single dead seagull in the Finnish town of Oulu.
And in Russia's Ural mountains, authorities ordered
the slaughter of thousands of poultry after making a
troubling new finding: the avian flu virus is being
spread by migratory birds.
Flu surveillance these days is
a strange mix of the familiar and the frightening. On
the one hand, there are hopeful signs that this year's
batch of influenza vaccine may turn out to be a better
match than last year's A/Panama (H3N2)-like strain and
that, this time, suppliers will be able to meet demands
worldwide. On the other hand, there is growing fear
of a pandemic of deadly avian (H5N1) flu that will render
all such preparations meaningless.
"I'd be very surprised if we don't
see H5N1 in both Europe, and Japan and the Korean Peninsula
in the next few weeks," says Dr Henry Niman, developer
of the flu monoclonal antibody and founder of US biotechnology
Dr Niman says that as migration
spreads what he calls "wild bird flu" around the globe,
it becomes increasingly likely that these strains, rather
than the poultry strains of Thailand and Vietnam, will
be the source of a human pandemic that could take millions
"It's a numbers game. Until now
this wild bird flu has been mostly seen in thinly-populated
parts of Russia, Kazakhstan and Mongolia," he says.
"If we haven't seen human cases it may be because of
a lack of opportunity rather than any characteristic
of the virus. But it will get plenty of opportunity
as it moves into more densely-populated areas like Europe.
In fact, it's probably already there."
This year's vaccine mix contains an A/New Caledonia/20/99
(H1N1)-like strain, an A/California/7/2004 (H3N2)-like
strain, and a B/Shanghai/361/2002-like strain, or similar
equivalents. A/California (H3N2) began to overtake last
year's dominant A/Fujian strain in Canada and around
the world early this year, and is widely expected to
come roaring back this fall. Influenza B strains are
also becoming more common, especially in some European
countries, while Influenza A (H1N1) strains have remained
in the background.
Canada, which leads the world in
flu vaccinations per capita, is well stocked with almost
11 million doses of vaccine in public hands that's
enough to permit adding healthy children aged six to
23 months to the list of priority recipients.
The 50-million-dose shortfall in the US that led President
Bush to theatrically forego his flu shot last year is
unlikely to be repeated. Nonetheless, the Center for
Disease Control is taking no chances, delaying vaccination
of all but high-risk patients until October 24. One
category of people who made it onto the high-priority
list at the last minute was Hurricane Katrina survivors.
The potential for flu transmission among the displaced
But while the world seems reasonably
ready to face a normal flu season, it remains woefully
ill-prepared to face a catastrophic pandemic of H5N1
avian flu, which some WHO officials now describe as
"inevitable". Forty countries have now filed bird-flu
response plans with WHO. Unfortunately almost none of
them are in the part of the world where H5N1 is endemic.
"There may be some small restrictions
imposed in the early days of a pandemic," says WHO's
Dick Morris. "But they will fail, because infected people
won't yet be showing symptoms."
The world already appears to have
had a lucky escape this year when two Thai women were
apparently infected by a sick relative. One of the two
died. Dr John Oxford, a virologist and instructor at
Queen Mary's School of Medicine in London, says the
disease appears to have broken down "the final door".
"It sends a cold shiver down the
spine," says Dr Oxford. "This is a very important step
towards the conclusion that we all wanted to avoid
the spread of this virus from human to human."
If a pandemic begins in the next
year, Canada hopes to be able to produce a vaccine in
fairly short order. To get a jump on the virus before
the exact composition of the strain is known, researchers
at the National Microbiology Laboratory in Winnipeg
are working on "seed strain" or prototype vaccines.
The plan is to use these as a base
from which to customize H5 and H7 flu vaccines for a
specific outbreak. The government has contracted with
Quebec's ID Biomedical to maintain a production capacity
that should allow for vaccination of the whole population
within ten months.
STRAIN THAT ROARED
It's a good plan that keeps Canada's options open, especially
when compared with the slapdash preparations in the
US. But it does leave a gap between the initial outbreak
and immunization - a gap that Canada's 22.5 million
stockpiled doses of Tamiflu aren't going to cover. That's
only enough to protect the country's health professionals
for about two months. And that's assuming Tamiflu works,
which is far from certain.
Even at high doses, Tamiflu has
shown little prophylactic efficacy in trials involving
mice. An early and aggressive intervention with Tamiflu
after an outbreak among tigers at a Thai zoo failed
to save a single animal.
That hasn't prevented the growth
of a lucrative internet business in Tamiflu. Most sales
are going to the US. But there's little doubt that Canadian
doctors are writing prescriptions to allow friends and
family to build personal stockpiles. The number of Tamiflu
prescriptions written in Canada this year more than
tripled to 76,000.
Swiss drug maker Roche, the sole
manufacturer of Tamiflu, has committed to increase world
production eightfold by the end of 2006. New plants
are scheduled to open at several locations across the
United States. Nonetheless, supply will struggle to
keep up with demand.
"We are on a collision course to
panic," warns Dr Michael Osterholm, director of the
Center for Infectious Disease Research and Policy at
the University of Minnesota. "This drug which
has yet to really be demonstrated to have any clinical
impact on H5N1 infection is now going to become
product. The reality is going to come through that there
is only so much available."
Virologists say that to protect
the general population would require one antiviral dose
per person per day for two waves of infection
a tall order for even the richest of nations, and an
almost insurmountable challenge for the manufacturer.
But it now seems that an older, cheaper drug may offer
some protection against the strain of avian flu recently
detected in Russia. Amantadine is an off-patent drug
now used mostly for treatment of Parkinson's disease.
Dr Niman says that although the
Indochinese strains of H5N1 are clearly amantadine-resistant,
wild bird flu does not appear to carry resistant markers.
That's good news for Canada, which recently hedged its
bets by buying four million doses of the drug.
But Dr Niman cautions that the
usefulness of antivirals is so doubtful that the world's
best hope remains the aggressive development of a broad
range of vaccines, and the capacity to produce a lot
of them quickly in other words, the Canadian
approach. But more work also needs to be done on parental
strains, he add, to prepare for a pandemic that could
now come from almost any quarter.
"For the whole world to be putting
all its eggs in one basket, working on vaccines for
this one target strain that may or may not be the real
threat is an approach that I think is doomed to fail"
warns Dr Niman.