Published Date: 2005-10-07 23:50:00
Subject: PRO> Influenza viruses, drug resistance (03)
Archive Number: 20051007.2924

INFLUENZA VIRUSES, DRUG RESISTANCE (03)
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Date: Thu 6 Oct 2005
From: ProMED-mail <promed@promedmail.org>
Source: Canada.com, Health News / Canadian Press, Thu 6 Oct 2005 [edited]
<http://www.canada.com/health/story.html?id=81201e24-9e91-4287-833b-
9da02ff083ac>

It appears a misunderstanding, not a mutation, is behind recent reports
suggesting the H5N1 avian flu strain is developing resistance to the drug
Tamiflu. The professor of pharmacology from Hong Kong University quoted as
warning of an emerging resistant strain of the virus says he was citing old
data, not new evidence, when he gave an interview last week. He was trying to
urge GlaxoSmithKline to reintroduce an injectable form of their rival flu
drug, Relenza. The resulting report suggested Tamiflu was becoming less
useful -- a claim that was widely repeated.
"My point is to emphasize on the introduction of injectable drugs. But they
use a headline 'Resistant H5N1 appears in Vietnam," Dr. William Chui, who is
also chief of the pharmacy service of Hong Kong's Queen Mary Hospital, said in
an interview. Chui says he was citing medical literature, including a recent
New England Journal of Medicine review article on human cases of avian
influenza that made reference to an H5N1 isolate from Viet Nam shown to be
partially resistant to oseltamivir, Tamiflu's generic name. That discovery was
made public in mid-May 2005 in the report of a meeting of experts the World
Health Organization convened in Manila to determine whether the pandemic risk
from H5N1 had risen. When the reports quoting Chui started to circulate, flu
experts around the world sent out urgent e-mails trying to find out who had
found new evidence of resistance. The flu community keeps close tabs on the
efficacy of these important drugs, known as neuraminidase inhibitors. They!
came up with a puzzling blank.
Except for that one partially resistant H5N1 isolate from Viet Nam, no
researchers have reported new discoveries of Tamiflu-resistant viruses
isolated from human cases of H5N1, both the WHO and Tamiflu's manufacturer,
Hoffman-La Roche, confirm. "There is a network of laboratories that has been
set up to follow antiviral resistance among influenza strains," says Michael
Perdue, a scientist in the WHO's global influenza program. "One of the first
things they look at (when they get new viral isolates) is the antiviral
sensitivity and resistance. And the papers that have been published thus far
have shown all the strains to be sensitive." That doesn't mean there might not
be evidence of resistance out there, being kept under wraps by researchers
pushing them through the publication pipeline of medical journals. Still,
Perdue thinks word might have gotten around. "There's no hard and fast rule.
But generally people let WHO know information like that. And we have not
heard."
Neither has Roche, which has stewed while reports have questioned the value of
their drug. Oseltamivir is one of only 2 drugs thought to be effective against
H5N1; Relenza is the other. Governments around the world have been rushing to
stockpile the easier-to-administer Tamiflu as a hedge against a possible
pandemic. (Tamiflu is sold in pills; Relenza is inhaled like an asthma
drug.) "We don't have additional (resistance) data so when we see articles
like this, we're as perplexed as everyone else," says Paul Brown, a vice-
president of Roche Canada and until recently global team leader for Tamiflu.
However, everyone, including Roche, expects some resistance to the drug to
develop if it becomes widely used. In fact, studies have shown just that in
Japan, the only market to date which has embraced Tamiflu in a serious way for
seasonal influenza. Antiviral researcher Dr. Frederick Hayden of the
University of Virginia says a recent study of Japanese children showed about
16 per cent developed resistance to the drug. "That's one in 6. So I would
anticipate that in H5N1-infected persons that the frequency would certainly be
no less," says Hayden, co-chair of an international network of scientists who
monitor for resistance to neuraminidase inhibitors. But even when resistance
develops, evidence suggests it may not spread easily. In the lab, viruses that
develop resistance to oseltamivir pay a price; they are less fit than non-
resistant viruses. That suggests it might be difficult for a resistant strain
of the virus to emerge and claim dominance over non-resistance strains. So !
far the evidence that resistance strains are less fit has been shown only with
human flu strains, Hayden says. But studies could and should be done to see if
the same holds true with H5N1 viruses, he insists.
[Byline: Helen Branswell]
--
ProMED-mail
<promed@prommedmail.org>
[Resistance is a relative term, and assessment of the reality of the emergence
of resistant virus needs to be evaluated in quantitative terms. For the
present this thread is cut, as there seems to be little evidence of the
emergence of avian H5N1 influenza virus exhibiting anything more than partial
resistance to oseltamivir in East Asia at the present time. - Mod.CP]

See Also

Influenza viruses, drug resistance (02): RFI 20051001.2878
Influenza viruses, drug resistance 20050930.2863
Avian influenza, human - East Asia (120): Viet Nam 20050901.2589
Avian influenza, human - East Asia (80): Viet Nam 20050519.1380
Avian influenza, poultry - China: antiviral treatment 20050621.1740
2004
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Avian influenza - Eastern Asia (93): WHO statement 20040716.1935
Avian influenza A (H5N1) virus, human vaccine prospects 20040125.0300
Avian influenza A (H5N1) virus, drug resistance 20040125.0298
2001
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Influenza virus, neuraminidase inhibitor resistance (02) 20010928.2372
Influenza virus, neuraminidase inhibitor resistance 20010926.2350
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