Influenza

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.

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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.

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  ThePharmYard as follows:

Influenza - Disease overview

Oseltamivir - Drug review

Influenza - Improving practice (UK)