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It
has been reported recently that circulating flu strains have become
resistant to the popular antiviral medication Oseltamivir (trade name:
Tamiflu).
Because many companies have provided or are
considering providing Tamiflu to their employees in preparation for a
flu pandemic, Affiliated Physicians has received many inquiries
regarding the implications of this recent news.
Background and Education
There
are three strains of seasonal influenza viruses in circulation among
humans at this point. These include two influenza A subtypes
(H1N1 and H3N2) and one influenza B subtype.
For pandemic
purposes, we are only concerned about influenza type A because it has
multiple serotypes (subtypes) and mutates at a rate of 2 to 3 times
faster when compared to influenza B. Pandemics do not occur from
influenza type B.
Mutations:
Influenza A
mutates in two different ways: antigenic shift and antigenic
drift. Antigenic shift is the process by which at least two
different strains of a virus combine to form a new virus subtype.
For example, a pig may contract two different flu strains --- one from
a human and one from a bird. When the viruses infect the same
cell within the pig, the genes from the bird strain mix with genes from
the human strain to yield a new strain. That is Antigenic Shift.
Antigenic
drift is a continual process of genetic change among flu strains.
It is the natural mutation over time of known strains of
influenza. Antigenic drift results in a diminished immune
response among those that have been previously infected or immunized
because the virus has changed slightly.
The Current Situation
As
discussed previously, our current flu season is made up of the H3N2 and
H1N1 virus strains. Because we are at the very beginning of the
season and few cases have been reported, tests have been conducted on
only 84 active flu samples (from 3 states). Of those sampled, 73
were of the H1N1 serotype and 11 were of the H3N2 serotype. 72
out of 73 of the samples tested as resistant to Tamiflu and 11 out of
11 of the H3N2 samples tested as susceptible to Tamiflu.
This
tells experts that it is the virus strain, not the medication
(Tamiflu), that has changed. They propose that the cause of the
Tamiflu resistance is due to Antigenic Drift of H1N1.
This
information is further supported by evidence from Japan, which accounts
for approximately 75% of the world's Tamiflu use. If the
resistance were caused by the overuse of Tamiflu, one would expect a
high level of resistance in Japan. However, they have a very LOW
prevalence of resistance.
On the other side, Norway, which does not use a lot of Tamiflu, reported a 70% resistance to Tamiflu among their H1N1 strains.
Pandemic Flu Implications
The
current H1N1 resistance should not have any implications for pandemic
planning. Antivirals, including Tamiflu, can still be a very
valuable component of a pandemic plan. The current situation
does, however, illustrate just how quickly influenza viruses can
change. Some of those changes are small (antigenic drift) and
some are very big (antigenic shift). No one knows exactly what a
virus that causes a pandemic will look like when it makes the jump to
being easily transmissible from person to person.
The good
news is that we know that most strains of flu are strongly susceptible
to Tamiflu, including the current circulating strain of H5N1 (the one
we are most concerned about today).
The unfortunate news is that we don't know exactly what the next pandemic strain will be or when it will happen.
Andrew Shulman
Chief Operating Officer
Affiliated Physicians
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