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With the flu vaccination campaign beginning this week, Professor John Oxford makes a personal

plea for tougher action against

this global threat

Influenza is a sinister two-faced virus with a pandemic face and an epidemic side. There is no reason to suppose that during this coming winter we will see, for the first time in 36 years, flu in its global-sweeping and human-culling pandemic mode. But if we do, the world community will encounter a very nasty shock because we are ill-prepared.

There are some worrying signs that the pandemic ogre virus is starting to wake up. Most virologists now think that flu in its pandemic mode, which swept the planet three times in the last century, is poised to strike again.

It is a so-called emergent microbe. Emergent viruses are naturally bird or animal viruses but given an opportunity and some chance genetic mutations, they will jump the species barrier and transfer to humans. We have seen this phenomenon with SARS, a novel coronavirus probably native to the Asian civet cat or rat and also, of course, with chicken influenza A (H5N1).

This summer, chicken influenza emerged yet again and killed three people in Vietnam while millions more chickens had to be culled. I know there is a natural scepticism here. Probably more Vietnamese die each day from burns and traffic accidents. But the concern is that all these great flu pandemics started with one individual.

Who should be vaccinated?

This year will see attention switching to the younger members of the at-risk group. The advertisements featuring Sir Henry Cooper have been a driving force to persuade the over-65s into the doctor's surgery, alongside encouraging words from the nurse and doctor.

But many younger patients also need to recognise that they are vulnerable. These include people with asthma and diabetes and people with chronic heart or kidney conditions of all ages. Pregnant women are an important group recognised as vulnerable in the US, but not quite within the vaccination sights yet in the UK.

It must also be acknowledged that the Americans are rather good at preventive medicine. Why choke up the hospital casualty department in the winter with flu patients, they muse, when a simple dose of vaccine costing £5 or so will prevent this catastrophe? In their country doctors will be busy vaccinating 60-year-olds and a proportion of 55-year-olds as well. I predict that sooner rather than later the UK will join the US and Europe to include 60- to 64-year-olds in the flu campaign.

But what about doctors and nurses themselves? Can they not spread flu to vulnerable patients or become ill themselves and so join the casualty list? Of course they can. The Department of Health has had an uphill struggle to persuade hospital staff to volunteer for flu vaccines.

The main problem is high staff turnover, but the GP's surgery works as a more cohesive group. To my mind the entire health care team in GP surgeries should be vaccinated, including the receptionists. In the worst winter surgeries will be awash with flu virus. In fact this year my PhD student hopes to test a pilot flu detector system in a GP's surgery to see if we can measure the amount of virus there.

What's in this year's vaccine ­

and what of the future?

Attention to the yearly epidemics of flu will repay us manifold when we face the next great pandemic. This assertion is underpinned by simple mathematics. If doctors can achieve the target of vaccinating each year most of the 10-15 per cent of our community at risk of serious illness, hospitalisation and death, we can be assured that flu vaccine production will be maintained at a high level.

This year 15 million doses of a trivalent flu vaccine containing B/Shanghai/361/2002; A/Fujian/411/2002 (H3N2) and A/New Caledonia/20/99 (H1N1) will be made in eggs for the UK immunisation campaign. In the UK this production is predominantly carried out at the Chiron plant near Liverpool and equals, in theory, 45 million doses of a monovalent pandemic flu vaccine.

In other words the UK does have the production capacity to produce enough vaccine in a pandemic situation to protect almost the entire population. But would there be enough vaccine produced quickly enough? The answer is probably No.

If a new pandemic flu virus arose this summer in Vietnam we could expect it on our doorstep within weeks. A new vaccine virus takes nearly a year to formulate and therein lies a huge problem. But two vaccine producers in Europe (Baxter and Solvay) have confronted the issue and have invested in new plants to produce a novel type of flu vaccine, bypassing the old fertilised hen's egg which has, in reality, done us proud over the last half century.

Now the technique is to grow flu in stainless steel deep fermenters on monkey or dog kidney cells in much the same way as rabies or polio vaccine virus is grown. This will speed production and cope with a huge surge in demand, as during a pandemic year. These new mammalian cell culture flu vaccines should reach the doctor's surgery for next year's flu season, but not this year.

A few years further down the road are a clutch of genetically modified (GM) flu vaccines whereby the crucial NA and HA protein spikes of the virus have been inserted into a so-called replicon containing predominantly genes of adenovirus, or more exotically, Venezuelan Equine Encephalitis virus.

These new generation vaccines are neither dead nor living but in between. They have been designed by molecular biologists to undergo a single and restricted replication cycle only in human cells. They are likely to trigger a powerful immune response in the upper airways, just where it is needed to combat an alighting flu virus.

Flu antivirals

Distinguishing flu from flu-like illness is a challenge for GPs (see box above). Once a diagnosis is made, the possibility of flu antivirals comes into play. These include the older M2 blockers such as amantadine and the new anti-neuraminidase drugs like oseltamivir. Personally I feel they have a key place in the yearly battle with flu, and also have a totally reassuring role in a pandemic. I do consider that flu is a crippling disease and many victims, particularly the over-70s, take a year to recover and, of course, some never really recover.

To my mind the deterioration of an active elderly person into a frail dependent individual should be of more concern that mortality itself.

Predictions

So what will happen this winter? None of us knows for certain. But one thing is crystal clear, like the rain and the sun, flu visits our shores every year and we will view one or other side of the face of a killer virus. Come Christmas the virus will be spreading in the community.

I can think of nothing more comforting than the fact that by such time most of those at risk will have been vaccinated (the vast majority of them in general practice) and that a store of antivirals is at hand waiting to be used rather than just sitting idly in a chemical factory. With the mortality figures mounting, as they did over the Millennium winter, it was a bad start to a new century.

Surely the 15 per cent of susceptible people in our community deserve better than that?

John Oxford is professor of virology at Queen Mary's School of Medicine, University of London

Infant deaths in 2003

Last year's flu outbreak is best described as traumatic because a number of children died both here and in the US

This was caused by the Fujian virus that was not included in last year's vaccine because it did not grow well in the laboratories

They've managed to get Fujian in this year's vaccine and so we hope such as tragic beginning to the flu season will not be repeated this year

How to diagnose flu

Flu is easy to diagnose once the outbreak has started. Once GPs know flu is in the area they are likely to make a correct diagnosis in 80 per cent of patients

But when the flu outbreak has not yet started, it is much harder to diagnose

Using the following triad of symptoms should enable GPs to make an accurate diagnosis in seven out of 10 cases

THE BIG 3

1 Rise in temperature

2 Aches and pains all over the body, including the head

3 Respiratory symptoms, eg cough

The other two secondary symptoms to look for are:

i) Rapid onset of symptoms

ii) The patient wants to go to bed

References

1 Hammond, JAR; Rolland, W & Shore, THG, 1917, Purulent bronchitis: a study of cases occurring amongst the British troops at a base in France, Lancet, 2, 41-45

2 Barry JM, The Great Influenza Viking, USA, 2004

3 Welliver et al, 2001, Effectiveness of Oseltamivir in preventing influenza in household contacts, JAMA, 285, 748-754

4 Galbraith et al, 1969, Protective effect of amantadine on influenza A infections in the family environment, Lancet, 1026-1028.

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