Urgent research is needed to test a cheap and widely available potential remedy for bird and pandemic flu. With H5N1 viral resistance developing to Tamiflu, the antiviral agent being stockpiled in the hope of saving lives in an influenza pandemic, urgent new approaches are needed. Statins could be the answer – but they need immediate animal and human research.

By Robert Walgate (December 05)

The H5N1 influenza A virus that causes bird flu can easily develop “high-level” resistance to the drug oseltamivir (Tamiflu) according to research in Vietnam, where most of the deaths from the disease have occurred so far.

An H5N1 influenza virus with a single amino acid substitution in neuraminidase antigen has been found in two of eight patients treated with the drug, conferring high-level resistance to Tamiflu, according to a Brief Report in the New England Journal of Medicine (22 December 2005, volume 353, pp. 2667-72).

“Where adjuvanted vaccines can’t be produced in sufficient volume, and with the Tamiflu story now showing we might need twice as much for twice as long as was thought, even before resistance develops, we’re quickly running out of solutions,” David Fedson told RealHealthNews today (22 December).

Fedson, a retired physician and vaccine policy specialist previously at Aventis Pasteur-MSD and before that a professor at the University of Virginia, has suggested testing the use of statins for treating the “cytokine storm” – creating extreme inflammation – which kills patients with severe influenza.

The global case is that statins are cheap – available generically or shortly to come off-patent – and simple to use. By contrast, Tamiflu and other antivirals are in short supply, extremely expensive for developing countries (around $15 a course), and must be administered within 24 to 48 hours of catching the ‘flu’.

In most situations of rural and urban poverty, therefore, antivirals are not likely to be a practical solution – just imagine pandemic flu in the slums of any giant Third World city. So with present strategies, the poor of the world are effectively condemned to death by an outbreak of pandemic flu.

The medical argument for statins as an alternative is that “flu kills by inflammation. Statins reduce such inflammation in cardiovascular disease, so why not in influenza?”

Fedson has been making this case for some time, but being retired and without an institution, he is having trouble making his voice heard. However, when RealHealthNews put the case for trying out statins to Margaret Chan, in charge of pandemic preparedness at WHO, she said “That’s a good idea!”.

She would consider testing statins in H5N1 patients (obviously under ethical circumstances – it would most likely be on compassionate grounds from those failing to respond to other treatments), but in fact there have been relatively few cases of H5N1 disease, she said, so such studies would be statistically weak.

“The rationale I’ve used is to examine the global need for something effective in a pandemic, where vaccines and antivirals are increasingly looking less likely to be helpful. The scientific rationale [for statins] is still circumstantial, but all that evidence points in one direction” – that they should work in influenza.

The signals for considering statins so far come from two epidemiological studies, one in Switzerland and the other in The Netherlands. ”In addition,” says Fedson, “there are clinical studies of statins in patients with pneumonia and another cytokine disregulation syndrome – bacterial sepsis.” Earlier experimental and clinical studies also “point in the direction that statins may be helpful in down-regulating the cytokine storm in serious influenza.”

Fedson meanwhile has been trying to drum up support for experimentation on the use of statins in animals such as ferrets – which are used as influenza models. Researchers at the Centers for Disease Control, Atlanta, and St Jude Childrens Research Hospital in Memphis may have taken up the challenge in the last three months, he says.

“We need data, and this means we need to enlist the support of investigators who could really nail this down,” Fedson told RealHealthNews. “If we get studies in a couple of animal models that show that cytokines are having a positive effect on the course of disease, then we’ll have real physiological and biochemical evidence.”

“We also have an astonishing lack of information on the clinical and molecular pathophysiology of ordinary influenza!” said Fedson. “In cardiovascular disease, people are climbing all over each other to look at the nuances of disease in individual patients. We have nothing like that for influenza.”

The global case for research on statins – and even influenza itself – seems very strong, and Fedson may now find his case strengthened by the new results on Tamiflu resistance – which suddenly bring the need for alternatives before the rich world, as opposed to the poor and neglected South. Perhaps we will now see a sudden change in attention to this research.