Swine flu is officially a pandemic. But don't worry ... not yet, anyway

Out of 30,000 global cases, only 145 deaths have been reported and development of a vaccine is well under way. But scientists will not relax: the virus could mutate and grow stronger over the summer - and what happens if it mixes with bird flu?

• Robin McKie, science editor
• The Observer, Sunday 14 June 2009
• Article history

It was the final surge in numbers that forced the World Health Organisation to act. With confirmation last week that swine flu cases had risen above 1,000 in Australia, it was clear the disease was now spreading freely around the world. Thousands of cases had already been reported in the United States, Mexico and Chile. Officials at the World Health Organisation simply had no choice. On Thursday, they announced swine flu had achieved pandemic status, the first strain of influenza to reach this mark for 41 years.

It seems an alarming prospect. Are we again set to face a disease that can kill millions as happened with the pandemics of 1918, 1957 and 1968? Margaret Chan, the World Health Organisation's director general, was confident, however. The disease is only a "moderately severe" risk, she announced. Out of 30,000 cases worldwide, only 145 deaths have been reported. Development of a vaccine - the world's main anti-flu weapon - is already under way while stockpiles of anti-viral drugs such as Tamiflu are also available, at least for developed nations.

It would be premature to assume complete security, however. Before the world vanquishes swine flu, many hurdles will have to be cleared. In particular, every stage of the development of a swine flu vaccine, our key hope of fighting the disease, could be disrupted, scientists warned last week. "We must be prepared for something that is more severe than is currently observed," said Dr Alan Hay, director of the World Influenza Centre, in London. "We cannot be complacent."

For a start, swine flu vaccine production is still at a very early stage. Indeed, the artificial strain that will form the core of a vaccine has only just been created, with researchers in Britain, Australia and the US having produced almost identical versions. These have only just been passed to pharmaceutical firms to see if they can quickly produce the vaccine on a mass scale.

The British version of the vaccine strain - known as RG121 - was created two weeks ago at the National Institute for Biological Standards Control near London. Like its US and Australian counterparts, it is made of bits of several flu viruses but specifically stimulates immunity against swine flu. Unlike swine flu, however, it can be grown easily in hens' eggs. Eggs are used throughout the drugs industry as incubators in which viruses - the basic components of vaccines - are grown.

"Hens' eggs remain the bulwark for vaccine production," said Professor Peter Dunnill, of the Centre for Biochemical Engineering at University College London. "It is a pretty ponderous business, however. Each egg has to be looked after carefully and you have to beware lest infections kill them off."

This point was backed by Dr James Robertson, leader of the team that created the RG121 strain. "Different strains behave differently in eggs and produce varying amounts of virus particles. In the case of our swine flu vaccine strain, we simply do not know yet how much virus you will get from each egg,

At present, pharmaceutical companies' estimates of the amounts of virus particles they will get from their eggs are optimistic. This could be a mistake, warn scientists, and companies could find they get less than a third or a quarter as many viral particles as they hoped for, a reduction that would, in turn, limit the number of vaccine doses available to the public.

Once viruses are extracted from eggs they are broken into pieces including bits of their protein coats. These protein pieces are important because they stimulate immune responses in humans and can be used to make a vaccine. "Coat proteins raise antibodies in the blood so that a person, coming across the real live virus, will be prepared to launch an immune attack against it," said Robertson.

But sometimes, it takes more than one dose of a vaccine to stimulate full protection. The current seasonal flu vaccine requires only a single shot but other vaccines require two inoculations, a point stressed by Dr Hay. "It may require two doses to provide significant immunity against swine flu," he told the Observer. And if a swine flu vaccine requires a double dose, this would also limit numbers of doses available to provide full protection as quickly as possible.

Even if viral production in eggs goes to plan, manufacturers such as GlaxoSmithKline will be stretched to meet demands and have decided to add chemicals known as adjuvants to their vaccines. Adjuvants stimulate immune systems and so reduce amounts of vaccine needed to create antibody protection in an individual. "We will be using adjuvants in our vaccines," said Stephen Rae of GlaxoSmithKline. "This will be the first time we have used them for a flu vaccine but we are confident they will work."

However, Professor Dunnill again warned that care should be taken with such predictions. "It remains to be seen if pharmaceuticals can rely on using adjuvants and still produce a single dose vaccine against swine flu," he said.

And then there is the issue of timing. At present, only a limited number of people have succumbed to swine flu in the UK with the Health Protection Agency putting the figure at 1,121 confirmed cases yesterday. But most scientists now predict a second wave of the disease is likely to strike later in the year. Exactly when and how it hits will have profound consequences for Britain, as Hay explained.

"The key issue is how the virus mutates in the southern hemisphere over the next few months during the winter there. That is far more important than its behaviour in the northern hemisphere during our spring and summer." The virus is more likely to spread through populations during the southern hemisphere in winter and the more it does so, the more it is likely to mutate, possibly into a new, more virulent form.

There is also the issue of the timing of that return. If a reinvigorated, more virulent forms appears late in the year, health and pharmaceutical workers could have enough time to prepare reasonable supplies of vaccine. "However, if it returns earlier in the year, in September, say, there is not much chance we will have enough vaccine ready by then," Dr Hay warned. "It is undoubtedly a problem. Certainly, there is no doubt the big issue here is time."

Should vaccine supplies be low when the second wave strikes, health workers will then face a problem of deciding which members of the public should be rated as priority targets. Health and utility workers, police and security staff, will be obvious choices. But selecting the elderly - a key choice for seasonal flu vaccine - as priorities for swine flu vaccines would be a mistake, Hay said. "Around 75 per cent of people who have succumbed to swine flu have been under age of 30 and very few have been over 60. It is very likely that people of 60 and above may well have some immunity."

Intriguingly swine flu is of the same basic type, called H1N1, as the virus that caused the 1918 pandemic, the world's worst outbreak of flu which killed up to 100 million people across the globe.

"That basic strain circulated round the world for another four decades until 1957 when it was replaced by a new type, known as H2N2, which was responsible for the Asian flu epidemic of that year," Hay said. In other words, people who were children or young adults before 1957 may well be carrying immune protection to an old virus that is a distant descendant of the 1918 flu strain and which is giving them protection against swine flu. Hence the relatively robust response of those over 60 to the current pandemic - though these individuals will still need protection from standard seasonal flu with vaccines that are now being stockpiled by pharmaceutical firms.

Vaccines are not our only protection against flu, of course. Anti-viral drugs - in particular, Tamiflu - block the spread of the flu virus between cells in the body and offer another line of defence against the disease. "Vaccines are our real hope but there is no doubt Tamiflu will help," said Dunnill. "But we should note resistance to the drug is spreading. The normal seasonal flu virus has acquired Tamiflu resistance over the past year and we will have to monitor, very carefully, how swine flu behaves. We cannot take the drug for granted, that is certain."

And finally scientists point to the disturbing scenario in which swine flu spreads to countries such as Indonesia and infects animals or humans who are already affected by bird flu. The latter disease is difficult to acquire but is highly virulent if caught. By contrast, swine flu is easy to pass on although, at present, it rarely produces serious symptoms. In a person who becomes infected by both strains, however, it is possible that there will be an exchange of genetic material resulting in the creation of an easily transmissible but highly virulent virus. "It is a nightmare vision which, fortunately, remains only a remote prospect at present," said Dunnill.

All these issues make it difficult for doctors and scientists to be certain how they will cope if swine flu, as expected, returns to Britain with renewed vigour later this year. Or it may return in a relatively non-virulent form and pharmaceutical companies may suffer no vaccine production problems. Alternatively, things could go wrong.

"We can anticipate many things and that, in the end, is all we can do," said Hay. "We must prepare as best we can for all these scenarios and then deal with the ones that unfold. It will probably be a long battle, however."