New Tamiflu-resistant bird flu cases stir fears

时间:2019-03-02 10:10:04166网络整理admin

By Shaoni Bhattacharya Fears have been raised over more evidence suggesting that the deadly H5N1 avian influenza can mutate into strains resistant to the frontline flu drug Tamiflu. Two more patients with drug-resistant bird flu have been documented by researchers in Vietnam. The two patients, of eight studied, died from H5N1 influenza A, despite treatment with Tamiflu (oseltamivir) having been started early in one of them. The first case of Tamiflu-resistant bird flu was reported in October 2005 . Although the case raised alarm, some scientists noted at the time that in becoming resistant to Tamiflu, the H5N1 virus also seemed to become less virulent. In addition, ordinary human flu with such a mutation rarely goes on to cause a new infection in another person. “Becoming resistant to this class of drugs seems to impose a fitness penalty on the virus,” Frederick Hayden of the University of Virginia, US, an expert in antiviral drugs, told New Scientist at the time. But the first case was only partially resistant, whereas the new cases show high-level resistance to Tamiflu. And the first case had also received the drug for preventative purposes, once daily. The two new cases received the full therapeutic, twice-daily dose. “Furthermore, although the patient with partially resistant virus ultimately received oseltamivir at therapeutic doses and survived, both of our patients died,” writes the team led by Menno de Jong and Jeremy Farrar at the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam. “This frightening report should inspire us to devise pandemic strategies that do not favour the development of oseltamivir-resistant flu strains,” says Anne Moscona at Weill Medical College of Cornell University, New York, US, in a perspective accompanying the new study published in the New England Journal of Medicine. She warns that individual stockpiling of Tamiflu by people at home could be “potentially dangerous” as this is more likely to lead to people taking insufficient doses or stopping their course of drugs prematurely, which can allow the surviving flu virus to develop drug resistance. The researchers in Vietnam found that in the two patients with resistant strains of H5N1, the virus had undergone a change in a gene which codes for a protein called neuraminidase. This change means that it is much harder for oseltamivir to bind to the virus and block neuraminidase’s function. Neuraminidase enables the virus to release copies of itself from an infected cell. The team also found that in patients who went on to survive bird flu, the viral load became undetectable during treatment – this was not the case in the patients who died. This suggests that the emergence of Tamiflu drug-resistance “may be associated with clinical deterioration”, say the researchers. However, the emergence of drug resistance is unsurprising. The team notes that up to 18% of children who receive Tamiflu for human flu develop drug-resistant flu strains. “When a virus becomes resistant to oseltamivir, in theory that virus will be less virulent. It won’t be as fit,” Farrar told the BBC television programme Panorama on 18 October. “I don’t share that optimism. These organisms are fantastically able to adapt.” He added: “I think as soon as we apply widespread use of oseltamivir, we will start to see resistance developing inevitably, and I think we do have to pay attention to drugs other than oseltamivir.” Other scientists have cautioned against alarm. “Whenever you use any kind of drugs, antivirals or antibiotics, you expect to see resistance develop. Finding some resistance is not necessarily alarming,” said Keiji Fukuda, an expert at the World Health Organization’s global influenza programme, speaking to Reuters. Journal reference: New England Journal of Medicine More on these topics: