such as "Introduction", "Conclusion"..etc
May 6, 2009 — In a global influenza
pandemic, small stockpiles of a secondary flu medication – if used
early in local outbreaks – could extend the effectiveness of primary
drug stockpiles, according to research made available April 30 ahead of
publication in PLoS Medicine.
Many countries are investing in large stockpiles of a single drug,
oseltamivir (Tamiflu). But influenza viruses can become resistant to
antiviral drugs, and the widespread use of a single drug is likely to
increase the risk that a resistant strain will emerge. If such a strain
were to spread widely, the effectiveness of antiviral drugs in treating
infected patients, as well as their ability to slow the spread of a
pandemic, would be greatly reduced.
Using a mathematical model to represent the global spread of
pandemic influenza, an international team of researchers led by Joseph
Wu of the University of Hong Kong, and including collaborators in the
UK and the US, found that treating as few as only the first 1% of the
population in a local epidemic with a secondary drug rather than with
oseltamivir, could substantially delay the development of resistance to
oseltamivir. This reduction in resistance was predicted to benefit not
only local populations, but also those in distant parts of the world
where the pandemic would subsequently spread through air travel.
In the context of the currently emerging swine flu, the secondary
drug could be zanamivir (Relenza), the only other approved drug to
which the new H1N1 strain has been found to be susceptible.
This strategy is predicted to be effective because it delays use of
the primary stockpiled drug until a certain proportion of the local
population (about 1.5% according to the model) has been infected with
virus that remains susceptible to the primary drug. With drug-sensitive
virus in the majority as people recover from infection and develop
immunity, only a minority of further infections are likely to be
resistant to the primary drug.
Technically, such a delay could be achieved by postponing the launch
of any antiviral intervention. However, because even a short delay
would mean denying antiviral drugs to people who would benefit from
them, the researchers instead propose the deployment of a small
stockpile of a secondary antiviral during the early phase of the local
The model, prepared before the current swine flu crisis, considered
two possible strategies, "early combination chemotherapy" (treatment
with two drugs together while both are available, assuming that
clinical trials show such a combination to be safe for patients) and
"sequential multi-drug chemotherapy" (treatment with the secondary drug
until its stockpile is exhausted, then treatment with the primary
drug). While either strategy could be effective in principle, only the
sequential strategy would be practical in responding to the currently
emerging H1N1 swine flu, because the safety of combining zanamivir with
oseltamivir (for combination therapy) is not established.
After simulating the impact of these strategies in a single
population, the researchers then introduced international travel data
into their model to investigate whether these two strategies could
limit the development of antiviral resistance at a global scale. This
analysis predicted that, provided the population that was the main
source of resistant strains used one of the strategies, both strategies
in distant, subsequently affected populations would be able to reduce
the consequences of resistance, even if some intermediate populations
failed to control resistance.
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