a good read today and factual

Article in todays 'the australian'
Science races bird flu clock
Leigh Dayton
October 29, 2005
THERE'S unwelcome news for regular flu sufferers anxious to refill prescriptions for the bug-busting medication Tamiflu. Join the queue. Australia has contracted a serious case of bird flu panic, and the worried well have cleaned out stocks of the antiviral drug known in science circles by its chemical name of oseltamivir.

According to the manufacturer of Tamiflu, the Swiss pharmaceutical giant Roche, chemists' shelves won't be ringing up sales again until next month. A second shipment is expected at the end of December, said local spokesperson Rita Corrente.

Further, anyone hoping to get on the Tamiflu waiting list without a prescription will be disappointed. Earlier this month the National Drugs and Poisons Schedule Committee rejected a proposal to make it available from pharmacists over-the-counter.

Aside from the wait, a trip to the GP, and the $50 price tag for a pack of 10 capsules, virologist Steve Wesselingh says there's another reason why people hoping to protect themselves from bird flu should hold off, leaving Tamiflu for those at high risk of catching old-fashioned but dangerous human influenza A and B. At least for now.

"Tamiflu or other antivirals can be utilised to prevent or to treat infection, but in terms of preventing infection you need to be taking it at the time you're exposed," says Wesselingh, director of Melbourne's Macfarlane Burnet Institute for Medical Research and Public Health. He adds the obvious: "That's difficult to predict."









Wesselingh's point is particularly apt given that there's no evidence that Australians - human or avian - have contracted either of the potent strains of the avian H5N1 influenza A virus found in east Asia and parts of eastern Europe. The overseas body count remains low. As of October 24, the World Health Organisation (WHO) reports 121 people in Indonesia, Vietnam, Thailand and Cambodia have contracted the virus, probably from handling infected birds. Sixty-two have died.

Although the immediate health risk is small, the race is on to build-up a national stockpile of Tamiflu as well as Relenza, a second - and Australian-designed - drug that restricts the replication of influenza in an infected person. Should the worst strains of H5N1 build resistance to Tamiflu, Relenza promises to be an unexpectedly vital second line of pharmaceutical defence.

That's a distinct possibility, cautions the WHO. Of all the 15 subtypes of avian influenza H5N1 mutates the fastest and has a "documented propensity to acquire genes from viruses infecting other animal species".

Add it up: strains of the most worrisome subtype of bird flu are predisposed to develop the ability to not only infect people in close contact with animals, but to be transmitted easily from person to person. Worse, when it comes to H5N1 we humans are "naive", Wesselingh points out.

"That means our immune systems will give us no immediate protection against the virus." According to Wesselingh, it takes about two weeks to develop disease-fighting molecules called antibodies. "That means you're going to get very sick from influenza for the first few days to a week," he explains.

Researchers worldwide are racing to design a vaccine able to prevent infection in the first place by priming the immune system to kill the invading virus. But why is it taking so long to stock up the national medicine chest and crank out what many think is little more than a fancy version of the vaccine available for each year's battle with the flu bug?

The glib answer is, "politics and profits". Although international epidemiologists, virologists, medical providers and the WHO have warned for decades that the planet could at any time be hit by a deadly new strain of influenza - akin to the Big Ones of 1918-1919, 1957-1958 and 1968-1968 - national leaders have until now remained reluctant to spend the money.

Kay McNiece, a spokesperson for the Commonwealth Department of Health and Ageing, says the Government has contracted for 3.9 million courses of antivirals, mostly Tamiflu but also Relenza. "The minister is looking into buying more Relenza," she says.

Until this new surge in demand for antivirals, drug companies chased dollars primarily in so-called "lifestyle drugs" such as Prozac and Viagra. Little effort and funding was given to vaccine research, with notable exceptions such as Australia's Melbourne-based CSL Ltd.

The consequence is that development has been left largely to small teams of government-funded scientists like the Australians who developed Relenza. As today's Weekend Australian Magazine shows, that can be a long and often soul-destroying experience.

With minimal attention accorded to slow-sellers like Tamiflu - Roche sold only about two million courses worldwide in 2001 - there's been no push to make manufacturing more efficient. Case in point: the spice star anise. A wild variety of the humble plant contains the "adjuvant", a vital ingredient Roche uses to boost Tamiflu's effectiveness.

Until bird flu hit the headlines it mattered little that production of Tamiflu was limited by the availability of star anise, sourced in China only from March to May. Now, Roche has synthesised the active ingredient New Scientist magazine reported this month. That leaves only Cipla, the Indian manufacturer of a generic version, at the mercy of Mother Nature.

Both Roche and GlaxoSmithKline, the manufacturer of Relenza, are now cranking up production. GlaxoSmithKline has even announced plans to reopen a Melbourne production facility shut in 2000. Gearing up production, though, means just that. It takes months to get packets of tablets rolling off the production line in quantity. What's more, experiments with mice published in July suggest that the current dose may not be enough to save patients infected with a highly virulent strain of bird flu.

The fact that some strains of H5N1 avian influenza are so lethal - even in birds - has also slowed the development of a vaccine, notes University of Melbourne virologist Lorena Brown. "In poultry infected with highly pathogenic strains of H5N1, the virus can infect any cell in the animal's body, not just the lungs," she says.

The bottleneck, notes Brown, is that the virus kills cells within the eggs used to grow the virus in production. While CSL won't reveal details of how it's sidestepped this problem, Brown says the solution is a sophisticated process of genetic engineering called reverse genetics. It involves fiddling with the "H", or hemagglutinin, part of the virus's coat so that it's less toxic. By the way, the "N" stands for neuraminidase.

Over at CSL, spokesperson Rachel David says experts have jumped the genetic hoops and have a candidate vaccine against samples of H5N1 provided by the WHO. Two weeks ago they began the first clinical trials with 200 healthy human volunteers at two sites in Melbourne and Adelaide. If all goes well, she predicted that so-called Phase Two clinical trials may be ready to go in early February.

From there? "We'll compile a dossier for the Therapeutic Goods Administration, the Australian regulator," David says, optimistic that due to the urgency it will give the thumbs up or thumbs down quickly. Judging by experience from its conventional flu vaccines, David says it should take just six weeks to get the production lines rolling.

Under the best-case scenario, it would take three months to produce the 40 million doses required to immunise the Australian population. Then everyone can relax, especially the usual suspects who come down with garden-variety flu despite their annual flu shot. At least, they'll know that Tamiflu will be back on the chemist's shelf, nestled neatly beside packs of Relenza.

PS -at least the scaremongering has got some good results, instead of ignoring the scientists and others, we now have at least plans in place to protect the general public.
And all looking very promising for BTA sp for the next couple of years.
cheers