Resistant virus prompts concern over second line of defence.
Bird flu has reached the edge of Europe, causing governments to increase their vigilance and boost stockpiles of the drug Tamiflu. But experts say that relying too heavily on one drug for protection in the event of a pandemic may be a mistake.
It was recently confirmed that the deadly H5N1 avian flu virus that has killed 60 in South-East Asia, and which experts fear will mutate and cause a pandemic, was responsible for the deaths of more than 1,000 birds in Turkey. An avian flu virus that has killed wild birds and poultry in nearby Romania is almost certainly the same strain, although this will not be confirmed until 15 October. In both countries, thousands of birds have been culled to prevent any further spread of the virus.
Speaking to a committee investigating the risk of a bird flu pandemic at the UK House of Lords, Jan Slingenberg of the UN's Food and Agriculture Organization (FAO) said there is "near certainty" that the Romanian cases are the feared virus. "The avian H5N1 virus has now entered Europe," he said.
In response, countries are stocking up on Tamiflu, the main anti-viral medicine recommended by the World Health Organization (WHO). Turkey has asked Swiss pharmaceutical company Roche Holding AG to provide 500,000 boxes of medicine. Romania is reportedly also trying to get hold of thousands of doses. Governments are stockpiling the drug for use if the H5N1 virus mutates to a form able to transfer between humans.
It's going to happen. Once you start using Tamiflu in large numbers, resistance will occur. James Robertson , National Institute for Biological Standards and Control, Potters Bar, UK
Tamiflu is currently effective against H5N1 in humans, but research published online by Nature suggests that this situation may change1. Analysis of H5N1 virus from a Vietnamese patient treated with Tamiflu found some viruses that were partially resistant to the drug. The patient recovered after a higher dose was given, and that partial resistance has emerged is not a surprise. But the work suggests that resistance may become a real problem that we need to consider more carefully.
"We don't know how frequently this kind of mutation can appear," says Yoshihiro Kawaoka, a virologist at the University of Tokyo in Japan and the University of Wisconsin, and lead author on the paper. "We are relying too heavily on Tamiflu; we need more drugs," he adds.
Ideally, he says, countries would continue to stockpile Tamiful. But there would also be a range of other drugs on hand to fight the flu virus, as a second line of defence. The one other antiviral drug currently known to be effective against H5N1, Relenza, was found to kill off the partially resistant virus discovered, but few countries have any reserves. Only Germany is storing it up in large quantities as part of its protection against a possible pandemic, although other European countries and the United States have some stocks.
Albert Osterhaus, a virologist at the Erasmus Medical Center in Rotterdam, the Netherlands, agrees that drug companies have been slow to develop antivirals that could be used to fight bird flu. He also noted that although it is a useful alternative to Tamiflu, Relenza has limitations.
"Tamiflu can be stored in bulk and has a long shelf-life, but Relenza is relatively difficult to stockpile," he says. Relenza must also be taken with an inhaler, making it potentially unsuitable for children and very ill patients. Both Kawaoka and Osterhaus agree that more drugs need to be developed.
James Robertson, a virologist at the National Institute for Biological Standards and Control in Potters Bar, the United Kingdom, agrees that Tamiflu-resistant H5N1 is likely to be a problem. "It's going to happen. Once you start using Tamiflu in large numbers, resistance will occur."
But he adds that the new research had found that the partially resistant virus in this case was not as dangerous as the normal H5N1. "The resistant ones that appear seem to be weaker viruses; they don't reproduce as well," he says. But a resistant virus could take on a second mutation, he notes, that would help it to thrive.
Improper use of the drugs could also breed more resistant viruses. Kawaoka says that Tamiflu can relieve symptoms of human flu within two days, causing people to stop taking the drug early; this could encourage the growth of resistant viruses. "It is important to take a full five-day course of the drug to reduce the possibility of resistance," he says.
KawaokaY., et al. Nature advanced online publication, doi:10.1038/4371108a (2005).
National Institute for Biological Standards and Control, Potters Bar, UK
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Simonite, T. Researchers call for more bird flu drugs. Nature (2005). https://doi.org/10.1038/news051010-16