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Planning for an influenza pandemic

Experts from around the world attended a discussion meeting at the Royal Society, London, to discuss how to plan for an influenza pandemic. Antivirals, vaccines and diagnostic tests were discussed as were the problems associated with their use in practice. The meeting was held on April 25-26. Zoë Gross reports

An influenza pandemic could occur at any time and the best way to plan for one was effective management of annual epidemics, according to Dr Douglas Fleming, Royal College of General Practitioners, Birmingham.

However, there are a number of developments on the way, including new neuraminidase inhibitors, diagnostic tools and an intranasal vaccine.

New neuraminidase inhibitors
Diagnostic tools
Intranasal vaccine
Antivirals in practice
Supply issues
Previous pandemics

New neuraminidase inhibitors

Neuraminidase inhibitors were promising agents for use during a pandemic, said Dr Diane Young, RW Johnson Pharmaceutical Research Institute, US. A new neuraminidase inhibitor, RWJ-270201, for the treatment of influenza was currently in phase III clinical trials. RWJ270201 was effective against a wide range of influenza A and B strains both in vitro and in vivo and pharmacodynamic studies supported the potential for once daily dosing, she said. It was administered orally and was slightly more potent than oseltamivir and zanamivir.

Dr Warren Kati, Abbott Laboratories, Illinois, United States, said that another new neuraminidase inhibitor, ABT-675, had been discovered which exhibited uniform potent inhibition against A/N1, A/N2 and B strains of influenza. He said that ABT-675 was three to seven times more potent than oseltamivir and dissociated much more slowly from neuraminidase (on the surface of the influenza virus particle) than oseltamivir did. The compound, which was not cross-resistant with oseltamivir was still in preclinical trial stages and further results were expected later this year.

Diagnostic tools

A number of test kits which provided health care professionals with a diagnosis of influenza within seven to 20 minutes, depending on the test used, were now available, mainly in the US and Japan.

Dr Simon Tucker, Biota Holdings, Melbourne, Australia, said that the Flu OIA test (optical immunoassay technology) which provided a diagnosis of influenza A and B infection within 15 to 20 minutes, could be used by doctors at the “point of care”, benefiting patients through immediate appropriate intervention. The test used a variety of specimen types taken from patients' respiratory tracts. He said that the current gold standard was tissue culturing which could take weeks to confirm a diagnosis.

Dr Tucker told The Journal that he agreed that such tests had the potential to be used by pharmacists if there was a justifiable outcome, such as the ability to give zanamivir over the counter to patients who presented within 36 hours after the onset of symptoms and who tested positive for the virus. With the National Institute for Clinical Excellence guidance as it stood, use of these tests in the UK did not seem imminent.

However, commenting on pretreatment screening in doctors' surgeries, Dr Fleming questioned whether, based on UK consultations being limited to eight minutes, having patients with possible influenza sitting around in surgeries waiting for results was really what was wanted. Another participant at the meeting said that the cost of the test plus the cost of prescribing drugs such as zanamivir would also have to be taken into consideration.

Intranasal vaccine

An intranasal, cold-adapted, live, attenuated vaccine was currently in clinical trials and had the potential to significantly reduce the impact of influenza in both children and adults, according to Professor Robert Belshe, St Louis University health sciences centre, US. In a two-year study of children aged between 15 and 71 months, use of the vaccine, compared to placebo, resulted in a reduction in febrile illness, febrile otitis media and antibiotic use. In a study of its use in adults, the number of days of work missed because of febrile illness was reduced by 28 per cent and the number of days of antibiotic use was reduced by 45 per cent.

Antivirals in practice

Looking at the use of the antivirals, Professor Frederick Hayden, University of Virginia, US, said that both amantadine and rimantadine would be effective for the prevention and treatment of influenza A during a pandemic, even though the virus would still have the ability to mutate and spread. In terms of zanamivir and oseltamivir, he said that, although resistance was uncommon, neuraminidase inhibitors would also work in pandemic situations and viral transmission would be less than with amantadine and rimantadine.

Dr Joe Collier, editor, Drug and Therapeutics Bulletin, said that, so far, there was “no evidence of emerging resistance to zanamivir in a clinical setting”. However, it was very unusual not to get resistance and “the last thing that the licensing authority [in the United Kingdom] will do is make an antimicrobial available over the counter”.

He commented that otherwise healthy people who developed 'flu-like symptoms were currently advised to stay at home and take medicines obtained from pharmacies. He also said that the effects of zanamivir on treating the symptoms of influenza had not yet been compared with that of over-the-counter remedies such as paracetamol. The main difference between zanamivir and paracetamol, in terms of treating symptoms, was that zanamivir treated a cough whereas paracetamol did not. However, a cough remedy, for use in addition to paracetamol, could be bought over the counter.

Supply issues

Speaking about vaccine availability, Dr John Wood, National Institute for Biological Standards and Control, Hertfordshire, said that to plan for a pandemic, the time taken between strain identification and developing and producing vaccines needed to be reduced.

In terms of meeting supply demands during a pandemic, a participant said that drug companies could not be expected to make surplus supplies of products as the industry based figures on the previous year's sales.

Previous pandemics

There have been three pandemics over the past century and these occurred in 1918, 1957 and 1968 to 69. The worst of these was the Spanish influenza pandemic in 1918, which caused acute illness in 25 to 30 per cent of the world's population and resulted in 40 million deaths worldwide. Virologists have been expecting another pandemic since 1998.