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Influenza
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Medical Opinion - Influenza
Published 17 November
2004 This Editorial has been written by the specialist
opinion leader, Allan H Young, Professor of Psychiatry, Royal Victoria
Infirmary, University of Newcastle and published in the latest issue of the
serial publication, Drugs in Context.
Influenza is a global
disease which imposes a huge medical and economic burden inevery country of the
world. The UK is no exception with one caveat - the virus is probably monitored
and tracked more in the UK than any other country around the globe. Over the
years, GPs have played a leading role in estimating the quantitative impact of
influenza. This started with the pioneering work of William Pickles in the
Wensleydale villages and continued with Edgar Hope-Simpson in Cirencester. Now
the torch is held by Douglas Fleming at the Royal College of General
Practitioners Unit in Birmingham. Certainly, the disease predominates in
primary care, with an estimated 95% of cases being seen and treated by GPs. In
an epidemic year, attack rates can affect up to 15% of the entire population.
The virus is unique in having two faces - global pandemics and yearly
epidemics. Both are a threat to us in the UK. However, the past 3 years have
been exceptionally quiet for influenza over the usual winter epidemic season.
Everyone has breathed a sigh of relief - but how long will this last? Over the
millennium winter, some 20,000 deaths were recorded in the UK from pneumonia
and bronchitis precipitated by influenza. Epidemics are never far away and the
elderly are particularly vulnerable, often ending up in casualty departments
with shortness of breath. This soon leads to a breakdown in the normal hospital
routine, as it did in the winter of 1999-2000.
We have recently seen a
magnificent Department of Health-led advertising campaign with the retired
boxer, Sir Henry Cooper, highlighting influenza as a serious disease and
encouraging the over 65s to request the influenza vaccine. We also know that an
encouraging word from the practice nurse or doctor can be vitally important in
motivating patients to receive vaccination. In some regions, well over 70% of
the at risk group (the over 65s, asthmatics and diabetics of any
age, persons with chronic conditions of the kidney or heart of any age) have
received vaccine. In the US, individuals over 50 years are predicted to be at
extra risk of serious complications and hospitalisations and are targeted for
vaccination. However, vaccination is only one element of the public health
fight back against influenza, although it does remain the cornerstone of our
strategy.
A decade ago, the front page of a scientific journal
announced the discovery of the first designer flu drug - a
neuraminidase inhibitor. The data emerging worldwide during the following years
have fulfilled early expectations.
Neuraminidase inhibitors such as
zanamivir (Relenza®) and oseltamivir (Tamiflu®) were shown to block all
known influenza A and B viruses in cell culture and animal models, and were
also shown to alleviate symptoms in patients and reduced viral spread in
families. Remarkably, by using genetic analysis, it has been shown that these
drugs would have been able to block even the 1918 Spanish influenza. Despite
these successes, the medical and scientific communities are still grappling
with the practical issue of how to administer the drug quickly, as to be fully
effective a neuraminidase inhibitor must be used within 48 hours of the onset
of symptoms. This conundrum needs to be solved and primary care will be at the
forefront of this. However, these agents are currently much more widely used in
Japan, the US and Australia than in the UK.
There is also good news on
the drug resistance front. Influenza viruses resistant to the action of
neuraminidase inhibitors emerge only rarely and appear to be genetically and
biologically crippled. Such drug-resistant viruses are thus less
virulent and less able to infect. There is every indication that neuraminidase
inhibitor-sensitive influenza viruses will predominate and not be superseded by
drug-resistant viruses. We appear to be safe from the MRSA
(methicillin-resistant Staphylococcus aureus) saga!
The next
decade will hold some serious threats from influenza. Thirty-six years have
passed since the last great world outbreak - the so-called Mao Tse Tung or Hong
Kong influenza of 1968. There was a comparable gap after the great Spanish
pandemic of 1918 until the Asian influenza of 1957. The Spanish flu - in
spite of a killing power unprecedented in the world of infection before or
since - is often regarded as the forgotten pandemic. Similarly, the
millions who died in the subsequent two outbreaks of the 20th century, although
within living memory, are in danger of being forgotten. To my mind these great
outbreaks can only ever by dealt with if the yearly influenza epidemic problem
is solved. At present we are practically powerless against the pandemic threat
because we do not stockpile neuraminidase inhibitors like oseltamivir or the
older M2 blockers like amantadine (Lysovir®). Like the influenza vaccine,
these drugs take time to synthesise in quantity, and, moreover their synthesis
can be complex. Should chicken flu (H5N1) emerge from south-east Asia
this year and arrive here we would be powerless to act for at least a year
whilst vaccine is made and stocks of neuraminidase inhibitors synthesised. The
use of a stock of neuraminidase inhibitors during the first wave of infection
would be a priceless public health asset in much the same way as the UK
government has stockpiled smallpox vaccine for emergency use. But a future
pandemic of influenza is virtually guaranteed, whereas very few public health
specialists anticipate a spread of smallpox either caused deliberately or as a
re-emerged monkey pox.
Ideally, the coming years will see GPs
prescribing more of the new anti-influenza drugs in primary care, both in
treating the most vulnerable patients and in preventing virus spread in
families and elderly residential homes. As well as providing their year-to-year
care, the community will be reassured that there is a cohort of GPs with very
practical experience of treating influenza. Even if the big one
keeps away for years it will come eventually.
Further reading
Fleming DM, Zambon MC, Bartfelds AI et al. The duration and magnitude
of influenza epidemics. Eur J Epidemiol 1999; 15: 467-73. Hope-Simpson RE.
Protection against Hong Kong influenza. BMJ 1972; 4: 490. Pickles WM,
Burnet FM and McArthur N. Epidemic respiratory infection in a rural population
with special reference to the influenza A epidemics of 1933, 1936-7 and 1943-4.
J Hyg 1997; 45: 469. Stuart-Harris CH, Schild GC and Oxford JS. Influenza:
the virus and the disease. London: Edward Arnold, 1985. Von Itzstein M, Wu
WY, Kok GB et al. Rational design of a potent sialidase based inhibitor of
influenza virus replication. Nature 1993; 363: 418-23.
Read more about Influenza -
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For more information, you can
download a free-of-charge
Quick Reference Guide to the Oseltamivir in Influenza
issue of Drugs in Context which is designed to give you an insight into
the numerous key points of information and practical guidance contained in each
issue, via carefully selected quotations taken directly from each part of the
publication.
Electronic versions (PDF) of the individual parts of this
issue of Drugs in Context are available for purchase at
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