Swine flu vaccines get first UK trial

Fergus Walsh | 22:23 UK time, Monday, 28 September 2009

Researchers in Oxford have started the first trial of Britain's two swine flu vaccines. Working with teams in Bristol, Exeter, Southampton and London, they are aiming to recruit 1,000 youngsters aged six months to 12 years. Although both vaccines are likely to get licensed in the next few weeks, none of the trials has taken place in Britain. Pandemrix (made by GSK) was approved by the European Medicines Agency on Friday, while Baxter's H1N1 jab seems likely to get approved this week.

http://www.swineflutrial.org/

This is the first time the vaccines have been used in the UK and the first comparative study of the jabs.

Professor Andrew Pollard from the University of Oxford is heading the research: "We are doing this trial to compare head-to-head the two vaccines which are going to be used in the UK against swine flu to see which one works best in children and which one is best tolerated. We are sort of in a race against time because we know the flu season is already started. We hope to immunise the children over the next 10 days or so.

The GSK vaccine is made using the traditional means of growing the virus in embryonated hens' eggs, before the virus is broken and deactivated. The Baxter vaccine is made in cell culture, so is suitable for those who have an egg allergy. The sort of side effects that are expected are sore arms and fevers. The information given to parents also lists rare side effects including Guillian-Barré syndrome which can cause ascending paralysis and even be fatal.

It's worth quoting here from the trial information: "Other very rare events that have been seen with routine flu vaccines include seizures and temporary bleeding disorders. In the past Guillian-Barré syndrome (a rare disorder of nerves) has been associated with flu vaccines but the relationship remains uncertain, with some studies suggesting a possible link but others not finding it. One large study in the UK found that influenza-like illness itself was associated with an increased risk of the Guillian-Barré syndrome but there was no link with the seasonal influenza vaccines, suggesting that vaccination might actually protect against the disorder by preventing flu."

What I take that to mean is that, if you have the vaccine, there is a remote, theoretical possibility that you could get GBS (as happened in the USA in 1976 with their swine flu vaccine), but you are more likely to get it as a result of contracting flu. So while it is impossible to rule out the risk of GBS from the vaccine, it is very remote, and this must be balanced against the very real and proven risks of complications from flu.

Weekly pandemic flu media update

24 September 2009

KEY POINTS

• The rates of flu-like illness and related activity have shown further increases in England.
• The flu-like illness rate in England from the Royal College of General Practitioners (RCGP) scheme increased to 16.2 per 100,000 in week 38. Most age groups saw an increase.
• This week, the antiviral collection numbers in the National Pandemic Flu Service have continued to increase and this has been seen in all age groups under 65. Once again, the biggest increase has been seen in the 5-15 year old age group with antiviral collections again doubling from 2,886 to 5,580.
• Interpretation of data to produce estimates on the number of new cases continues to be subject to a considerable amount of uncertainty. HPA modelling gives an estimate of 9,000 new cases in England last week (range 5,000 to 20,000).  This is the second weekly increase since week 30.
  This estimate incorporates data from National Pandemic Flu Service and GP consultations.
• Sharp rises in influenza activity in recent weeks are reported from the USA - concentrated particularly in school age children. Increasing activity has also been reported in a number of European countries, particularly France.

X-179A - Pandemrix - based on HA & NA - May 27 2009

A candidate reassortant vaccine virus (X‐179A) has been developed, using classical reassortment technology, from an A/California/7/2009 (H1N1)v virus, by the New York Medical College, New York, USA.


The haemagglutinin (HA) and neuraminidase (NA) sequences of the A/California/7/2009 (H1N1)v virus can be found on the public web site of GenBank via the following links:
HA gene sequence
http://www.ncbi.nlm.nih.gov/nuccore/227977171?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum

NA gene sequence
http://www.ncbi.nlm.nih.gov/nuccore/229396468?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum

EMEA homepage

European Medicines Agency has approved Pandemrix

Vaccines for swine flu by Fergus Walsh

Vaccines for swine flu

Fergus Walsh | 16:30 UK time, Friday, 25 September 2009

Plans to vaccinate millions of people in Britain against H1N1 swine flu have taken a step forward today. The European Medicines Agency (EMEA) has approved Pandremrix, manufactured by GlaxoSmithKline (GSK) [36Kb PDF].

A licence won't be granted until it's been approved by the European Commission, but that is expected in the next couple of weeks. GSK is one of two suppliers of pandemic vaccine to the UK, the other being Baxter. But its vaccine did not get approved today. The EMEA said that there had been an issue about the quality of the vaccine, but that they hoped to resolve that next week. The Baxter vaccine is not made using eggs, so it will be useful for those rare people with an anaphylactic reaction to egg.

The UK has contracts for up to 132 million doses of pandemic vaccine - enough for everyone in Britain to receive two shots. But early data suggests one jab may be sufficient. This is what the EMEA had to say on this:

"The Committee is currently recommending a two-dose vaccination schedule, at an interval of three weeks, for adults, including pregnant women, and children from six months of age. The Committee acknowledged that there are preliminary data suggesting that one dose may be sufficient in adults. The Agency is expecting further data from ongoing clinical studies over the coming months and these recommendations may be updated."

It should mean that Britain is on track to begin begin an immunisation campaign next month. Just a reminder of which groups will be vaccinated first. Here's the list, in order of priority:

• individuals aged six months and up to 65 years in the current seasonal flu vaccine clinical at-risk groups
• all pregnant women, subject to licensing considerations on trimesters
• household contacts of immunocompromised individuals
• people aged 65 and over in the current seasonal flu vaccine clinical at-risk groups

So how many people will that involve? Getting figures for the whole of the UK means contacting four separate health departments, which is why very often, you will see only the figure for England. My understanding is that the total is 11.45 million people for the UK (9m England; 1.3m Scotland; 0.75m Wales; 0.4m Northern Ireland). In addition, more than two million frontline health workers will be immunised in tandem with the above groups.

The government now has an agreement with GPs to vaccinate the at-risk groups. But this will take a huge amount of organisation, especially since the seasonal flu campaign will continue.

There are many questions which arise from the planned immunisation campaign, not least how big the uptake will be. NHS staff members have a very poor record of taking the seasonal flu jab, with only 16% uptake.

Many pregnant women may also be loath to have the jab and rather hope for the best that they don't get the virus, and that if they do, get it mildly. Pregnant women are at elevated risk of both catching swine flu and getting complications. In order to carry a child through pregnancy, the body's immune system is naturally suppressed.

The first person to die from complications of swine flu in June was a 38-year-old woman in Scotland who'd given birth prematurely. She had underlying health conditions. Andremember Sharon Pentleton? She got swine flu when six months pregnant and had to be flown to Sweden for specialist treatment. Fortunately, she is now recovered and her baby is due next month.

Both of those cases are extreme examples. The vast majority of pregnant women who catch swine flu will have a mild infection. But the expert advice is that they should be immunised. What is not clear yet is how early in the pregnancy it will be recommended and whether or whether it will be restricted to women who are in the second and third trimesters (that is, from three months onwards).

The final recommendation on timing rests with the Joint Committee on Vaccination and Immunisation (a sort of NICE for vaccines). I've been looking at the minutes of their meeting in August [63Kb PDF] and it gives an idea of what they are thinking on this:

"The committee supported the use of either vaccine once licensed in pregnant women. The committee noted that many women are advised not to take any kind of drug in their first trimester unless recommended by a medical practitioner. The committee advised that all pregnant women, including those in their first trimester, could receive the vaccine. Both swine flu vaccines are inactivated and there is no evidence that the foetus is at any risk when the mother is immunised with an inactivated vaccine such as the seasonal flu vaccine. Seasonal flu vaccines have been used for a number of years in the US with no evidence of harm. The committee noted that vaccinating pregnant women would not only provide benefit to them but also provide benefit to the infant, when born, through vertical transfer of maternal antibodies."

The JCVI also sees no reason why you can't have your pandemic flu jab at the same time as a seasonal flu vaccine. This is what they had to say on that:

"The committee advised that since the swine influenza vaccines are inactivated, they could be co-administered with all other vaccines including seasonal influenza and childhood vaccines. Vaccines should be given at separate sites, preferably in different limbs. If given in the same limb, they should be given at least 2.5 cm apart."

So what will the government do with all those extra vaccines, once the at-risk groups are immunised? My hunch is that they may decide to offer the jab to all children, not just to those who are at risk of complications. But that decision does not need to be taken now, and instead officials will wait to see how the virus behaves in the months ahead.

Pandemrix (pdf) data sheet

PRESS RELEASE
European Medicines Agency recommends authorisation of two vaccines for influenza pandemic (H1N1) 2009

Q&A from EMEA

Pandemrix (pdf) data sheet includes constituents & adverse side effects

Pandemrix @ Wikipedia


1. NAME OF THE MEDICINAL PRODUCT
Pandemrix suspension and emulsion for emulsion for injection.
Pandemic influenza vaccine (H1N1)v (split virion, inactivated, adjuvanted)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
After mixing, 1 dose (0.5 ml) contains:
Split influenza virus, inactivated, containing antigen* equivalent to:
3.75 micrograms**
A/California/7/2009 (H1N1)v-like strain (X-179A)
* propagated in eggs
** haemagglutinin
This vaccine complies with the WHO recommendation and EU decision for the pandemic.
AS03 adjuvant composed of squalene (10.69 milligrams), DL-α-tocopherol (11.86 milligrams) and polysorbate 80 (4.86 milligrams)
The suspension and emulsion, once mixed, form a multidose vaccine in a vial. See section 6.5 for the number of doses per vial.
Excipients: the vaccine contains 5 micrograms thiomersal
For a full list of excipients see section 6.1.



Adjuvant in Pandemrix (pdf) data sheet

• squalene
• DL-á-tocopherol
• polysorbate 80

Mass swine flu vaccination could begin within weeks

European Commission expected to rubber-stamp regulator's recommendations within days

• Comments (5)
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• Sarah Boseley, health editor
• guardian.co.uk, Friday 25 September 2009 16.23 BST
• Article history

A couple wearing masks kiss in Mexico City during an outbreak of swine flu. Photograph: Alfredo Estrella/AFP/Getty

Mass vaccination against swine flu could begin within weeks, following the approval of two vaccines by the European regulator today.

One of the two recommended for a licence by the European Medicines Agency (EMEA) is Pandemrix, the vaccine made by British company GlaxoSmithKline (GSK) which is under contract to supply the UK. The other is Focetria, made by the Swiss company Novartis.

The UK has also signed a contract with Baxter, but the EMEA said yesterday that it needed some information about its vaccine, called Celvapan. The agency hopes to be able to approve it next week.

The EMEA's recommendations go to the European Commission, which is expected to rubber-stamp them within days.

The approval follows an expedited procedure which was based mainly on mock-ups of how the vaccines were expected to behave if bird flu rather than swine flu had sparked a pandemic.

But the EMEA says it is satisfied that inserting the new strain into the vaccine "should not substantially affect the safety or level of protection offered".

It has asked manufacturers actively to investigate and monitor any side-effects from the vaccine "so that action can be taken as early as possible if a safety issue emerges". It points out that "as with all medicines, rare adverse reactions may only be detected once the vaccines are used in large numbers of people". The manufacturers have agreed to conduct post-licensing safety studies on 9,000 people for each vaccine.

GSK has said that volunteers suffered only very mild side-effects in trials, including headache, joint pain, muscle pain, pain and redness at the site of the injection, fever and fatigue.

A spokesman for the Department of Health said they planned to start vaccination in October, but were "still dependent on production and delivery of sufficient vaccine to start protecting people". Those most at risk because of their state of health will be prioritised.

Some countries, including China and Hungary, have already approved swine flu vaccines and begun vaccination, but these are variants of existing vaccines and will not protect to the same extent as a vaccine incorporating the pandemic virus strain.

The EMEA is recommending that people should be given two shots, at an interval of three weeks. It says it recognises there is evidence that one dose may be enough, and may change its advice later. The vaccines are approved for use in pregnant women and children over the age of six months.

The clinical trials on which approval was based involved more than 6,000 people for each vaccine, who received a version which was basically the same as the one to be rolled out, but originally contained an avian flu (H5N1) strain – which had been expected to cause a pandemic – instead of H1N1.

"Decades of experience with seasonal influenza vaccines indicate that insertion of a new strain in a vaccine should not substantially affect the safety or level of protection offered," said the EMEA in its statement.

Across the UK, 82 deaths have been linked to the virus, with 70 in England (up three in the last week), nine in Scotland, one in Wales and two in Northern Ireland.

Across England, the number of people being treated in hospital has risen by more than 50%, from 143 last week to 218 this week. Of these, 25 patients are in intensive care.

Swine flu cases almost double

Schools across the country have seen new outbreaks of swine flu as children returned to lessons this month, Government officials said.

 

By Rebecca Smith
Published: 5:00PM BST 24 Sep 2009

Liam Donaldson - Swine flu second wave starting as 66 schools suffer outbreaks in first weeks of autumn term Photo: ANDREW CROWLEY

There have been 66 reported outbreaks of the H1N1 virus in schools in England since the end of the summer holidays, Sir Liam Donaldson, Chief Medical Officer said.

In total there have been an estimated 9,000 new cases of the disease last week, almost double the previous week's total showing that the disease is now rising again, he said.

 

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Sir Liam said the H1N1 vaccines are expected to be licensed soon by the European regulators and that he would have 'preferred more breathing space' before cases started to rise this Autumn in order to get the immunisation programme in place.

Pregnant women, health and social care workers, people aged between six months and 65 years who have underlying health conditions and people living with patients who have compromised immune system will be vaccinated this year.

Early trials show that one dose may be effective but early data from tests in children suggest they may still require two doses for a full immune response, Dr David Salisbury, head of the Immunisation at the Department of Health said.

The World Health Organisation announced that several countries including Australia, China, Hungary and the US have already licensed vaccines for the pandemic strain of H1N1.

Japan and several countries in Europe will shortly follow, according to the WHO.

Dr Salisbury said other countries have different licensing procedures and other vaccines which has meant they have been approved earlier.

Sir Liam added that in some areas swine flu cases have risen at a slower rate than during the first wave in July and some test results suggest that a larger number of children may have been infected earlier this year but not shown symptoms.

This has given them some protection and they are not falling ill now.

The largest number of school outbreaks has been in Yorkshire and Humber, with 27 outbreaks, but Sir Liam said this is probably because the data collection there has been more stringent.

He added that were 'probably more (outbreaks) than that , that we have not heard about'.

The number of pupils infected in an outbreak will vary and it is not known how many children in total are involved in those outbreaks. Schools are not being closed any more when an outbreak occurs as officials say this causes disruption and does little to slow the spread.

Swine flu vaccine Pandemrix, from GSK, approved for use

The swine flu vaccine which will form the bulk of the British immunisation programme has been approved by European drugs regulators meaning it can be used within weeks.

 

By Rebecca Smith, Medical Editor
Published: 10:38AM BST 25 Sep 2009

Vaccinations of priority groups is due to start next month in Britain Photo: GETTY

European Medicines Agency has recommended that the GlaxoSmithKline vaccine, called Pandemrix, be authorised for use and the European Union now needs to rubber stamp the decision.

Vaccinations of priority groups is due to start next month in Britain with pregnant women, people aged between six months and 65 years with long-term illnesses, health and social care workers and people living with patients who have a compromised immune system being offered the jabs.

 

Related Articles

• Swine flu cases almost double

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• Swine flu: 'second wave on the way'

• Swine flu: one dose of UK vaccine effective

The vaccine will be licensed on a two-dose basis even though some early clinical trials had suggested that one dose may be sufficient in healthy adults.

The EMEA will monitor clinical trials on dosing and may update the recommendations at a later stage.

The British government has ordered enough vaccine from GlaxoSmithKline and Baxter, to provide two-doses for the whole population but will offer the vaccine to 13 million people in the priority groups first before deciding if it is necessary to offer the jabs more widely.

The Baxter vaccine is still going through the licensing procedure.

Sir Liam Donaldson said the second wave of the H1N1 virus is starting to take off since the schools went back and there were an estimated 9,000 new cases last week.

He said he had hoped for more 'breathing space' before cases took off again in order to get the vaccination programme in place.

The EMEA also recommended that the Novartis vaccine called Focetria be licensed.

The recommendation to license the vaccines was based on mock-up products using the H5N1 strain of flu which was extensively tested. The products then had the strain switched for the current H1N1 pandemic strain with further smaller scale trials.

This is how the seasonal flu vaccines are licensed every year and has proved extremely effective in allowing flu vaccines to be produced and licensed quickly, the EMEA statement said.

Further clinical trials in adults and in children are ongoing and more results will become available in the coming months.

A statement from the EMEA said: "As with all medicines, rare adverse reactions may only be detected once the vaccines are used in large numbers of people.

"The Agency has requested that vaccine manufacturers implement plans to actively investigate and monitor the safety of vaccines as soon as they are used across the EU, so that action can be taken as early as possible if a safety issue emerges.

" As part of this, the manufacturers have committed to carry out post-authorisation safety studies in about 9,000 subjects for each vaccine."

Fergus Walsh - One dose vaccine trials and more intensive care beds planned

Intensive care, and more on vaccines

Fergus Walsh | 11:32 UK time, Friday, 11 September 2009

Plans to double the amount of intensive care provision to deal with H1N1 swine flu cases have been outlined by health officials.

It's an acceptance that hospital critical care is likely to come under intense pressure when the next wave of swine flu comes.

The plans for England were outlined by Ian Dalton, National Director of NHS Flu Resilience.

They would see a doubling of the current 1,982 adult intensive care beds. There are 363 paediatric critical care beds which would also be increased substantially. Similar arrangements will occur throughout the UK.

A doubling of intensive care beds is no easy task, because of the need for specialist ventilators and other equipment.

Equally important are the highly-trained members of staff who work in critical care. So how will it be done?

More ventilators are being bought. Staff who currently work in other areas are being trained in critical care. Recently retired hospital workers will be placed on a reserve list to be called up if necessary. Critical care teams may be asked to work longer hours.

All these measures will help, but there is one other dramatic measure required to increase intensive care provision - cancelling operations.

As and when a huge peak of swine flu cases occurs, the NHS is ready to postpone as much planned surgery as required in order to free up intensive care beds.

This will free ventilators currently used in theatre as well as critical care beds used for patients recovering from cardiac and other major surgery.

This would be a temporary measure which would last for weeks rather than months during the peak of any outbreak.

The plans are based on the assumption that 2% of swine flu cases require hospitalisation, but this has since been downgraded to 1%.

Meanwhile, cases of swine flu continue to decline. There were an estimated 3,000 new cases in England in the past week, down from 4,500 last week and the rate of GP consultations stands at just 8.6 per 100,000.

In Scotland, where the schools went back first, there has been a slight increase in GP consultations to 43.9 up from 40.2, so this might be a very early indication that cases are about to rise.

The United States has seen a sharp increase in swine flu in recent weeks.

The Chief Medical Officer, Sir Liam Donaldson, has spoken in upbeat terms about swine flu. He said "we are tantalisingly close to being able to win the battle against the virus".

He explained that the current dip in cases meant that there was a real chance that they could vaccinate at-risk groups before the outbreak took hold again.

And more pandemic H1N1 vaccine trials results have been published, this time from Australia [Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine, New England Journal of Medicine].

The early results show that a single dose of the vaccine shows an immune response similar to that gained from seasonal flu jabs.

This is significant because it suggests that just one dose may be required to offer protection. All the worldwide planning to date on pandemic vaccines has worked on the assumption that two injections would be required.

The study involving 240 healthy adults aged 18-64 also found that the vaccine has a similar side-effect profile to that of seasonal influenza vaccines. The vaccine was produced by CSL in Melbourne.

Dr Alan Hampson, Chair of the Australian Influenza Specialist Group said:

"The study showed that a very high percentage of the adult recipients produced a good antibody response, which should provide a high level of protection, to a single dose of vaccine made by conventional methods and formulated at the usual potency. This is great news as it means that available vaccine supplies will go much further than might have been anticipated and that protection can be achieved with a type of vaccine that has a long history of safe and effective use."

Professor Robert Booy, Head of Clinical Research at the National Centre for Immunisation Research & Surveillance (NCIRS) at the University of Sydney said:

"This is indeed very encouraging and perhaps as good as we could have hoped for in that it appears only one dose of vaccination is required. It is important too that the safety profile is good. Results in children are keenly awaited."

This follows similar results from an early trial using a pandemic vaccine made by Novartis.

Results from trials involving the vaccines which will be used in the UK - being produced by GSK and Baxter - are yet to be published.

Swine Flu Vaccine Results - one dose only required

SEPTEMBER 11, 2009

HHS Celebrates Early Swine Flu Vaccine Results

by Jon Cohen

In an effort to assuage growing concerns about the swine flu pandemic, the U.S. Department of Health and Human Services (HHS) pulled out all stops today to broadcast the news that one dose of a vaccine against the novel H1N1 virus will likely will protect adults.

As HHS Secretary Kathleen Sebelius explained at a press conference this afternoon, the preliminary findings from clinical studies that one dose triggers a strong antibody response in adults “is critically important news.” Flanked by top officials from the National Institutes of Health, the Centers for Disease Control and Prevention, and the Food and Drug Administration, Sebelius noted that if two doses were necessary, as some had predicted, it would take longer to immunize the population and require more product. But she also emphasized that no data yet exist about how the vaccine works in children and pregnant women, two groups that remain at high risk for developing severe disease from the virus. And the timing of the vaccine's arrival remains a major concern, she said.

Anthony Fauci, head of the NIH’s National Institute of Allergy and Infectious Diseases, described early data from adult trials sponsored by his institute. In people ages 18 to 64 who received one of two different pandemic H1N1 vaccines, 80% to 96% developed a “robust immune response” 8 to 10 days after a single 15 microgram dose. People 65 and older did not respond as well, with only 56% to 60% reaching similar antibody levels. The new data mesh with data reported yesterday in The New England Journal of Medicine of trials conducted outside the United States.

The unusual high-level press conference to discuss preliminary results from clinical studies reflects the high level of anxiety in the country about the pandemic. The new information, Sebelius said, “shortens the window of worry, and more people can be protected much earlier.” It also means that the limited supply of vaccine, which will not start to arrive in the United States until mid-October, can be made available to more people in other countries more quickly.

Still, many experts say it appears that the pandemic may well peak in the United States in mid-October, before the vaccine arrives. “The models are based on assumptions,” said Fauci. “Certainly there could clearly be peaks before people get vaccinated, but there are other ways to mitigate the spread.” Anne Schuchat, head of the CDC’s National Center for Immunization and Respiratory Diseases, stressed that the virus pops up in different communities at different times. “We do believe that many prevention opportunities will be possible with vaccine, particularly now that we have this great news that protection might be possible in adults after that first dose,” said Schuchat.

US Vaccine may arrive just too late but only one dose needed

SEPTEMBER 11, 2009

U.S. Swine Flu Vaccine: Good News, Bad News

by Jon Cohen

An increasing number an influenza experts in the United States are worried that the wave of the swine flu epidemic that has started to hit the country may peak before a vaccine can do much good, a news storyin today’s issue of Science explains.

On 15 October, the U.S. government expects to receive the first batches of a vaccine designed to thwart the novel H1N1 virus causing the pandemic. But that is right around the time when many experts now think the spread of the virus may peak in the country. Given that it takes about 2 weeks to build immunity after vaccination and that there will be a limited supply for at least a month or more, the vaccine may have little impact in the United States this fall. “This potential mismatch in timing could significantly diminish the usefulness of vaccination for mitigating the epidemic and could place many at risk of serious disease,” predicted the President’s Council of Advisors on Science and Technology in a report the White House released on 24 August.

On the good news front, many researchers had worried that a vaccine against the novel H1N1 virus would require two doses to build substantial immunity—which would mean further delays in the time required to protect the population as well as twice as much product. But clinical tests of novel H1N1 vaccines published online yesterday by The New England Journal of Medicine show that a single dose can trigger high levels of antibodies in adults. No data are yet available for trials in children, who typically have much less robust immune responses to the seasonal influenza vaccine and require a second dose.

As another paper published yesterday, this one in Science Express, emphasizes yet again, widespread use of a vaccine could have a powerful impact against the H1N1 virus—if it arrived early enough and was widely used. Biostatistician Ira Longini from the University of Washington, Seattle, and his colleagues show that the vaccine would need to reach at least 70% of the population, starting with children first, to significantly impede spread. But Longini, a noted influenza modeler, also suspects that the pandemic now spreading across the United States as children return to school may crest in mid-October.

Longini and others note that this pandemic closely mirrors the one that hit the United States in the fall of 1957. If that occurs, Longini said in an e-mail note, “given the current vaccine production and distribution plan, we will be too late to have any effect on the epidemic.” That is precisely what happened with the vaccine effort in 1957.

With the novel H1N1 pandemic, the vaccine effort began almost immediately after the virus was isolated in late April. “In May, it seemed like we were in good shape with vaccine,” noted Longini.  “There seemed to be time.”  But now time seems to be running out quickly.

Early suppression of H1N1 with antivirals is crucial, When this flu is bad, it's very bad.

"Either you're off work a few days, or you go to hospital, often to the intensive care unit. There's no middle ground."

In the southern hemisphere, 15 to 33 per cent of hospitalised cases went to ICU in the past two months. "That's very high for flu," ... "When this flu is bad, it's very bad."

In these cases the virus rapidly destroys the lungs' alveoli, where gas transfer occurs, often causing acute respiratory distress syndrome (ARDS), which usually kills in half of all cases. ...  found that this past winter in Mauritius and New Caledonia, H1N1 caused ARDS 100 times as often as ordinary flu.

The direct viral damage inflicted on the lungs by severe H1N1 contrasts with SARS and bird flu, whose impact is mainly due to a runaway, body-wide immune response, ... This means early suppression of H1N1 with antivirals is crucial, which in turn requires spotting cases fast.

Who will get severe H1N1? Kumar is coordinating a multi-hospital study of severe H1N1 to find out, .. results suggest severity is linked to HLA, a genetic variation in immune systems. This could be why flu is worse in some ethnic groups.

(194 words, New Scientist max. 200)

Swine flu death estimate 'reduced by two-thirds'

The second wave of the swine flu pandemic will not be as bad as first feared, the Government's most senior doctor claimed as he lowered the death toll forecast by two-thirds.

Lucy Cockcroft and Martin Beckford
Published: 7:00AM BST 04 Sep 2009

Sir Liam Donaldson, the Chief Medical Officer, estimated that 19,000 people would die from the virus under the "worst case scenario", a significant drop from the figure of 65,000 given in July.

He said the revised estimations, calculated by Government scientists, were "assumptions and not predictions".

They are based on one in three people across Britain becoming infected, and do not take into account what impact the swine flu vaccine, due next month, will have.

one in three = 20,000,000 get swine flu and if 0.1% of these die then 20,000 die. The previous estimate assumed 0.35% would die.

Sir Liam also predicted that the second wave of the pandemic will hit Britain in about seven weeks, according to analysis of how the virus has spread so far.

He said: "We are very unlikely to see a peak before the second half of October, which is something we are very pleased about because we are expecting to be able to use the vaccine by then."

Figures show that cases of confirmed swine flu continue to drop, with only 4,500 diagnosed this week, down from 5,000 last week. Just over a month ago there was a high of 100,000.

There has also been a 26 per cent decrease in people consulting their GP with flu-like symptoms, while the death toll in the UK stands at 70.

The revised predictions came as a medical researcher accused world health authorities of making an "alarmist" response to swine flu, which only considered the worst case scenario.

Writing online at Bmj.com, Peter Doshi, a doctoral student at the respected Massachusetts Institute of Technology, said: "Experts are unsure that the 2009 pandemic will be any worse than seasonal flu.

"Officials responded to the H1N1 outbreak as an unfolding disaster.

"Measures were taken that in hindsight may be seen as alarmist, overly restrictive, or even unjustified.

"If the 2009 influenza pandemic turns severe, far exceeding the impact of seasonal influenza, early and enhanced surveillance may prove to have bought critical time to prepare a vaccine that could reduce morbidity and mortality.

"But if this pandemic does not increase in severity, it may signal the need to reassess both the risk assessment and risk management strategies towards emerging infectious diseases."

Employers are being warned not to underestimate the potential threat posed by swine flu, however, even though it has so far proved less catastrophic than at first feared.

The Chartered Institute of Personnel and Development (CIPD) and the Business Continuity Institute (BCI) issued joint guidance advising firms to prepare for up to half of their staff being off work for as long as a month this winter.

The organisations say that even if employees themselves remain healthy, they may be call in sick or request time off if their children's schools are closed or childcare providers fall ill.

Ben Willmott, senior public policy adviser at the CIPD, said:

 "There is a real danger that senior management teams ignore the threat to their business posed by a second and more serious wave of swine flu after seeing the first wave subside much more quickly than anticipated.

"The media and public hysteria sparked by the initial stage of the pandemic has created a 'cry wolf' effect where the temptation for business leaders is to ask what all the fuss was about and get on with the priority of competing and surviving in recession.

"Evidence shows that still only a minority of employers have an adequate contingency plan in place to deal with a flu pandemic, which is extremely worrying considering that staff absence levels could peak for some businesses at levels which will make business as usual extremely difficult. 

The CIPD and the BCI believe all businesses should plan for a worst case scenario where staff absence rates reach 50 per cent.