Friday, August 21, 2009

Recommended use of antivirals - WHO

"Healthy patients with uncomplicated illness need not be treated with antivirals" WHO

Recommended use of antivirals

Pandemic (H1N1) 2009 briefing note 8

Related link:

WHO Guidelines for Pharmacological Management of Pandemic (H1N1) 2009 Influenza and other Influenza Viruses
20 August 2009

21 AUGUST 2009 | GENEVA -- WHO is today issuing guidelines for the use of antivirals in the management of patients infected with the H1N1 pandemic virus.

The guidelines represent the consensus reached by an international panel of experts who reviewed all available studies on the safety and effectiveness of these drugs. Emphasis was placed on the use of oseltamivir and zanamivir to prevent severe illness and deaths, reduce the need for hospitalization, and reduce the duration of hospital stays.

The pandemic virus is currently susceptible to both of these drugs (known as neuraminidase inhibitors), but resistant to a second class of antivirals (the M2 inhibitors).

Worldwide, most patients infected with the pandemic virus continue to experience typical influenza symptoms and fully recover within a week, even without any form of medical treatment. Healthy patients with uncomplicated illness need not be treated with antivirals.

On an individual patient basis, initial treatment decisions should be based on clinical assessment and knowledge about the presence of the virus in the community.

In areas where the virus is circulating widely in the community, clinicians seeing patients with influenza-like illness should assume that the pandemic virus is the cause. Treatment decisions should not wait for laboratory confirmation of H1N1 infection.

This recommendation is supported by reports, from all outbreak sites, that the H1N1 virus rapidly becomes the dominant strain.

Treat serious cases immediately

Evidence reviewed by the panel indicates that oseltamivir, when properly prescribed, can significantly reduce the risk of pneumonia (a leading cause of death for both pandemic and seasonal influenza) and the need for hospitalization.

For patients who initially present with severe illness or whose condition begins to deteriorate, WHO recommends treatment with oseltamivir as soon as possible. Studies show that early treatment, preferably within 48 hours after symptom onset, is strongly associated with better clinical outcome. For patients with severe or deteriorating illness, treatment should be provided even if started later. Where oseltamivir is unavailable or cannot be used for any reason, zanamivir may be given.

This recommendation applies to all patient groups, including pregnant women, and all age groups, including young children and infants.

For patients with underlying medical conditions that increase the risk of more severe disease, WHO recommends treatment with either oseltamivir or zanamivir. These patients should also receive treatment as soon as possible after symptom onset, without waiting for the results of laboratory tests.

As pregnant women are included among groups at increased risk, WHO recommends that pregnant women receive antiviral treatment as soon as possible after symptom onset.

At the same time, the presence of underlying medical conditions will not reliably predict all or even most cases of severe illness. Worldwide, around 40% of severe cases are now occurring in previously healthy children and adults, usually under the age of 50 years.

Some of these patients experience a sudden and very rapid deterioration in their clinical condition, usually on day 5 or 6 following the onset of symptoms.

Clinical deterioration is characterized by primary viral pneumonia, which destroys the lung tissue and does not respond to antibiotics, and the failure of multiple organs, including the heart, kidneys, and liver. These patients require management in intensive care units using therapies in addition to antivirals.

Clinicians, patients, and those providing home-based care need to be alert to warning signals that indicate progression to a more severe form of illness, and take urgent action, which should include treatment with oseltamivir.

In cases of severe or deteriorating illness, clinicians may consider using higher doses of oseltamivir, and for a longer duration, than is normally prescribed.

Antiviral use in children

Following the recent publication of two clinical reviews, [1,2] some questions have been raised about the advisability of administering antivirals to children.

The two clinical reviews used data that were considered by WHO and its expert panel when developing the current guidelines and are fully reflected in the recommendations.

WHO recommends prompt antiviral treatment for children with severe or deteriorating illness, and those at risk of more severe or complicated illness. This recommendation includes all children under the age of five years, as this age group is at increased risk of more severe illness.

Otherwise healthy children, older than 5 years, need not be given antiviral treatment unless their illness persists or worsens.

Danger signs in all patients

Clinicians, patients, and those providing home-based care need to be alert to danger signs that can signal progression to more severe disease. As progression can be very rapid, medical attention should be sought when any of the following danger signs appear in a person with confirmed or suspected H1N1 infection:

  • shortness of breath, either during physical activity or while resting
  • difficulty in breathing
  • turning blue
  • bloody or coloured sputum
  • chest pain
  • altered mental status
  • high fever that persists beyond 3 days
  • low blood pressure.

In children, danger signs include fast or difficult breathing, lack of alertness, difficulty in waking up, and little or no desire to play.

________________________________

[1] Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials. Shun-Shin M, Thompson M, Heneghan C et al. BMJ 2009;339:b3172; doi:10.1136/bmj.b3172
[2] Prescription of anti-influenza drugs for healthy adults: a systemic review and meta-analysis. Burch J, Stock C et al. Lancet Infect Dis 2009; doi:10.1016/S1473-3099(09)70199-9

Flu drugs 'not needed' in healthy

Tamiflu is the main antiviral being used in the UK. The World Health Organization has said healthy patients who catch swine flu do not need to be treated with Tamiflu.

Antiviral drugs should be used in patients who are severely ill or those in high-risk groups including the under fives and pregnant women, it said.

The cost of the drug and the potential for resistance were taken into account by the expert panel.

But the UK government said it was taking a "safety first" approach by offering antivirals to everyone.
A spokesman for the Department of Health said they would keep the policy under review.
The UK has stockpiled enough antivirals - the mainstay of treatment until a vaccine becomes available - to cover half the population.
They are being offered in England to anyone who has the symptoms of swine flu - in many cases through the national pandemic flu helpline.

Minimising the number who take the drug is a good idea
Dr Chris Smith, Cambridge University
Wales and NI flu deaths

In the last week almost 46,000 courses of antivirals were handed out in England.
It is not the first time prescribing of antiviral drugs has come under scrutiny.
Earlier this month research suggested that the drugs should not be used in children because they rarely prevent complications but yet carry side effects.
Infections in England are continuing to fall with an estimated 11,000 cases last week compared with 100,000 a month ago.
There have now been 61 deaths across the UK - 56 of those in England.
Experts expect to see a big surge in infections in autumn when flu viruses traditionally start to circulate more widely.
Mild illness
In updated guidance, the WHO said most patients infected with the pandemic virus continue to experience typical influenza symptoms and fully recover within a week, even without any medical treatment.
So it said healthy patients with uncomplicated illness need not be treated with antivirals, which include Tamiflu and Relenza.
High-risk groups, who should receive treatment include infants and children under five, the over 65s, nursing home residents, pregnant women, and patients with chronic conditions such as asthma or diabetes and those with reduced immunity such as people with HIV.
And patients who initially present with severe flu or whose condition begins to deteriorate should also get the drugs as quickly as possible.
The report also called for more research into the safety of Tamiflu given its widespread use in the UK, Australia and the USA.
Dr Christ Smith a virologist at Cambridge University said when the virus first emerged little was known about how dangerous it would be and how best to treat it.
"We now know it's no more severe than seasonal flu for which we don't make Tamiflu available for healthy members of the general population.
"No drug is without side-effects, and it is expensive.
"Minimising the number who take the drug is a good idea."
But a Department of Health spokesman said: "We believe a safety-first approach of offering antivirals, when required, to everyone remains a sensible and responsible way forward.
"However, we will keep this policy under review as we learn more about the virus and its effects.
"WHO state that 40% of severe cases worldwide have been in previously healthy children and adults and that serious cases should be treated immediately.
"This emphasises the need not to become complacent about the mildness of the illness and the reasoning behind a precautionary policy."

Vaccination, antivirals and some respite


Fergus Walsh | 12:04 UK time, Thursday, 20 August 2009
After several weeks' absence, I was delighted to see that the discussion has continued at Fergus On Flu. I haven't read all your comments yet, but I am really pleased that the blog has become established as a forum for discussion on an issue that now appears only sporadically in the media.
Swine flu virus multiplication from an animation sequence by the Novartis pharmaceutical companyI had a very good break - and encountered no H1N1 swine flu - and then filmed some news stories, so I have not been on holiday all this time! Many thanks for your kind wishes and for continuing the conversation.

A few issues which emerged while I've been away:
• First, vaccination policy on H1N1 swine flu. The decision to immunise those with existing medical problems, pregnant women and healthcare workersthis autumn was no surprise and had been widely predicted. Holding back from a wider immunisation campaign at this stage is interesting. Limiting the vaccine to at-risk groups will still create a huge logistical problem for the health service which will also be immunising the elderly and the vulnerable this autumn. I anticipate some public confusion about who is eligible for what.

• Another interesting development concerned the study about antivirals and children. This questioned the policy of giving Tamiflu or Relenza to otherwise healthy children who catch the H1N1 virus. The research suggested that the side-effects outweighed the benefits, but was based on seasonal flu, not on H1N1 swine flu. It seems to me that the research raises important issues, but is not a definitive study or the final word on whether antivirals should be available to all.

• Finally, as many had hoped, the incidence of flu has dropped sharply in August. This gives the NHS - and us all - some respite. The question now is: when will cases start to rise? I suggest looking to Scotland, where children are heading back to school well before those in England and Wales (see also BBC Northern Ireland's Flu meeting ahead of school start). If Scotland experiences a sudden increase in cases in the coming few weeks, then a similar surge can be expected elsewhere in the UK.

Only one in ten people complaining of flu actually have swine flu


Only one in ten people calling the flu helpline actually have swine flu, experts have said, as the number of cases of the disease in England drops further.

Liam Donaldson:
Britian's Chief Medical Officer Sir Liam Donaldson 'second wave of swine flu impossible to predict' Photo: REUTERS
Sample testing of people suspected of having the H1N1 swine flu bug have shown that only 10 per cent actually have it.
Testing everyone is not feasible now as there have been hundreds of thousands of cases over the summer and random samples are being tested to check if the disease is changing in any way or whether resistant to Tamiflu is emerging.
Last month 24 per cent of suspected cases tested were positive for H1N1 and the drop has raised speculation that skivers are using swine flu as an excuse to call in sick to work during the warm weather.
Earlier this month businesses warned that workers are using swine flu as an excuses to extend their summer holidays and were taking advantage of the flu line.
Justin McCracken, chief executive of the Health Protection Agency, said: "We see this every year, as the number of cases comes down so we see the samples of swabs that test positive comes down."
The number of cases of swine flu being diagnosed has dropped from a peak of 110,000 in the week beginning July 23rd to 11,000 last week.
Sir Liam Donaldson, Chief Medical Officer, added: "Even when you have a lot of flu around it (the proportion of positive tests) is around 50 per cent."
Overall calls and web hits to the National Pandemic Flu Service have dropped also but there Mondays are consistently the busiest day of the week, even though the service runs at weekends.
Sir Liam Donaldson, Chief Medical Officer, pointed out that Mondays are traditionally the busiest day for GPs as people hold off contacting health services over the weekend.
GP consultation rates about flu have now dropped below baseline levels, used to monitor seasonal flu activity, but this does not mean that swine flu has gone away, Sir Liam said.
He said there were 263 people in hospital at 8am on Wednesday and 30 of them were in intensive care. "This is very exceptional at this time of year, to have people with flu in hospital and in intensive care.
"Seeing a declining pattern doesn't mean it has completely gone away."
The total number of deaths associated with swine flu was confirmed at 54, up from 44 last week. This does not mean ten people died in a week, rather that investigations into whether the death is linked to swine flu have now been completed.
The under fives remain the age group most likely to be admitted to hospital.
Sir Liam said a second wave of swine flu is expected but that it is 'almost impossible' to predict when this will happen.
He said during the 1957/8 pandemic when the first case was reported in June, slightly later than in this flu outbreak, and the largest peak was in September with cases rising sharply after the schools went back. There was a second smaller peak at Christmas and the New Year.
However during the last pandemic, in 1968/70, when the first case was found in Britain in August, there was a peak in the Spring of the following year and then a very large peak at Christmas of the second year.
Sir Liam said the swine flu outbreak could behave like either of these pandemics or do something different.
He added that in Australia, where the winter flu season is coming to an end, swine flu has behaved much like ordinary seasonal flu in the pattern of cases, although there has been more severe cases in younger people than normal.
Vaccinations are due to begin in October and people in the priority groups, which include pregnant women and those with serious underlying health conditions, will be contacted by health officials once the immunisation is ready.
The vaccines, being supplied by GlaxoSmithKline and Baxter, are in trials at the moment.
Frontline health and social care staff will be offered the vaccine.

Weekly pandemic flu media update - 20 August 2009, by HPA



20 August 2009
KEY POINTS
  • This week there has been a further reduction in the rates of flu-like illness and related activity.
  • Weekly GP consultation rates continued to decrease over the last week in England.  
  • The majority of cases continue to be mild. There is no sign that the virus is changing. It is not becoming more severe or developing resistance to anti-virals.
  • 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 11,000 new cases in England last week (range 6,000 to 25,000). There has been a decrease in estimated number of cases in all age groups and in all regions.
    This estimate incorporates data from National Pandemic Flu Service and GP consultations.