Liberal use of antiviral may hamper H1N1 control

C&I Issue 9, 2009

The World Health Organization (WHO) has raised its alert level tophase 5, signalling an imminent pandemic, as swine flu (H1N1) has begun spreading between humans in Mexico, the US and now in the UK. Countries havebeen advised by WHO toactivate their pandemic preparedness plans, while companies manufacturing antiviral drugs or vaccine shave been told to ramp upproduction. With pandemic policies predicated on using the antiviral Tamiflu, and a vaccine months away,some are concerned that the liberal use of this drug will not only use up precious stocks before the virus becomes more virulent, butalso drive resistance.

As C&I goes to press, 21 countries have reported 1085 cases of infection. The majority of cases (590) and all but one of the 25 deaths are in Mexico, where the outbreak emerged.In the UK, there are 28 confirmed cases and 333 under laboratory investigation by the Health Protection Agency (HPA). Although there has been one death out of 286 confirmed cases in the US, the majority of infections outside Mexico have been mild. Never the less, the HPA says it is working to ensure that close contacts of patients who test positive are offered antivirals as a precautionary measure.It may, however, be more prudent to save the limited stocks of antivirals to treat illness, rather than attempt to contain the spread of the disease.At the moment, the virus seems contagious but not that dangerous.However, flu viruses are notorious for their rapid mutation, and previouse pidemics have sometimes followed a pattern of a first wave causing mildillness, followed by a second wave of greater virulence in the winter.

The UK has stockpiled enough of Roche’s Tamiflu (oseltamivir) to treat only half the population and some of that is now thought to be out of date. ‘It would certainly be unwise to blow the stock [of Tamiflu] to ringfence cases,’ says Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London,UK. ‘If we use up stock in that way we might regret it.’Giving antivirals prophylactically to prevent the start of an epidemic can be justified in the early stages,explains Openshaw, but once the epidemic has taken hold treatment must be more selective. Only those with the disease, and in particular those at risk of complications, should be given the drug. As well as beingwasteful, it is unwise to exposeotherwise healthy people to the riskof side effects, he says.

In addition, those infected willoften have only a mild form of the disease and will recover fully, leaving them with protective antibodies, Openshaw points out.

Another fear is that overuse of Tamiflu could lead to resistance. Peter Dunnill, a professor of biochemical engineering at UCL, UK, points out that prescriptions for Tamiflu are already up to 16 times higher than usual in the US – a perfect way to drive resistance.Indeed, scientists are very surprised how quickly seasonal H1N1 flu has become resistant to Tamiflu.

The only alternativeis GlaxoSmithKline’s Relenza (zanamivir),an inhalable antiviral that has a much smaller production run than Tamiflu and is more difficult to take.Meanwhile, a vaccine is likely to take at least another four months,as the process is still dependent on chicken egg technology – leaving those in the southern hemisphere, which is nearing winter, more vulnerable toa virulent strain. WHO has said thattests on the current seasonal vaccine against H1N1 showed that it was ineffective. Alternative approaches to vaccine production are quite irrelevant at this point, says Dunnill, because most are not yet approved for human use. And even when a vaccine is produced, only about 10% of the world’s population will receive it.

For those countries, such as Mexico, without access to a vaccine,there is growing evidence that statins may be of use. According to virologist David Fedson,epidemiological studies suggest that statins – which are readily available – may interfere with theinflammatory process in the lungsthat is associated with flu deaths.However, the flu community is notinterested in exploring this approach,says Dunnill. ‘It’s very irresponsible of WHO not to put resources into the testing of statins and related drugs[for this purpose]'

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