Pandemic May Require Cocktail of Drugs to Combat
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Our study suggests that stockpiling a single drug ... might not be sufficient if we are faced with a pandemic'
Steve Gamblin of the National Institute for Medical Research in London and other British bird flu experts warned this week that governments need to stockpile antivirals besides just Tamiflu (oseltamivir) because of evidence that a mutated strain of H5N1 is resistant to Tamiflu.
Consequently, a bird flu pandemic could produce strains that also are resistant to Tamiflu, which has been considered by public health authorities around the world to be the most effective antiviral for combating H5N1 and other bird flu infections in humans.
"What this research shows is that stockpiling any one drug to prepare for a potential H5N1 pandemic is unlikely to provide adequate cover," Gamblin was quoted saying, adding, "in order not to be outflanked by the virus, it will be necessary to have stocks of both existing drugs."
“Mutations arising which have a selection advantage are very quickly exploited [by the virus],” Gamblin said, noting, “our study suggests that stockpiling a single drug, oseltamivir, might not be sufficient if we are faced with a pandemic.”
In February, the World Health Organization (WHO) reported that some seasonal flu viruses – which in the US mutated into several strains authorities weren’t prepared for and which the season’s vaccines weren’t designed for – were growing resistant to Tamiflu. WHO pointed to a study which showed high levels of resistance to Tamiflu in parts of Europe.
In addition, WHO reported that Australia, Hong Kong, North America, and parts of Europe also reported finding seasonal influenza viruses that had developed resistance to the drug.
In North America, WHO found the main seasonal virus in circulation showed "elevated resistance" to Tamiflu.
WHO spokesman Gregory Hartl said the organization was surprised to see the high levels of resistance in the study, which focused on the A H1N1 viruses circulating last winter in Europe.
Tamiflu resistance is a growing concern among health authorities because it is the most effective antiviral against H5N1, the strain many virologists fear is the most likely bird flu to mutate into a human transmissible form, triggering a pandemic.
A preliminary survey by the European Center for Disease Control (ECDC) said that of 148 samples of influenza A virus isolated from ten European countries in November and December 19 showed signs of resistance to the drug.
WHO expert Dr. Frederick Hayden said “based on initial reports, it is not a global problem now but it is a global concern.”
WHO further said that it was not changing its recommendations that Tamiflu be used as the first drug to treat, prevent, and contain a pandemic flu.
But given that Tamiflu – which is not a vaccine and will not prevent sickness or death in all cases – is expected to be heavily administered, even as a prophylactic, during a pandemic - health officials are extremely worried that intense use will accelerate resistance.
Brit Oiulfstad, the pandemic influenza coordinator for the County of Los Angeles, told HSToday.us that she and other authorities “are concerned about … the current push for community-wide antiviral prophylaxis when the effectiveness for such long-term use (several times the duration of the recommended treatment period) has not been evaluated.”
Even the Centers for Disease Control and Prevention (CDC) community mitigation guidance cautions that “it is not known if influenza antiviral medication will be effective against a future pandemic strain.”
The federal government’s pandemic plan calls for “targeted antiviral prophylaxis … of disease clusters, administration of antiviral treatment to persons with confirmed or suspected cases of pandemic influenza and provision of drug prophylaxis to all persons in [an] affected community.”
Oiulfstad noted that heavy reliance on antivirals is “even more troubling when we are currently dealing with the effects of overuse/misuse of antibiotics.”
The government’s pandemic plan makes note of this concern: “CDC will work with state and local partners to monitor the development of resistance to antivirals … resistance may develop rapidly if these drugs are used widely.”
“Planning for antivirals is very complex as we are not certain that the current antivirals will be effective in whatever viral strain will be circulating,” Oiulfstad said. “However, planning for any pharmaceutical dispersal is good for other future events. In Los Angeles County, planning for antiviral use and distribution is going well as our overall goal is to use antivirals in medical settings to reduce serious illness and death among cases, not general prophylaxis.”
Oiulfstad added: “We do not know the effects of long-term antiviral use in a prophylactic setting. Therefore, we always consider that we must do no harm, and until we have some more answers, we proceed on those recommendations for prophylaxis with great caution. Until the science is in that shows that these drugs prevent illness, this seems to be the only reasonable way to approach the problem.”
According to the British researchers, while both H5N1 and seasonal flu could develop resistance to Tamiflu, the viruses appear to be highly susceptible to Relenza, another drug used as an antiviral for treating infected persons.
Gamblin said the best way to treat flu victims in the long term may be with three or four antivirals and a vaccine; whether the vaccine is one specifically designed for the strain of flu a person has contracted.
A new antiviral, peramivir, is under developed by Biocryst Pharmaceuticals. However, it must be injected and reports state it hasn’t performed well in clinical trials. Two older flu drugs are available but flu viruses have quickly developed resistance to them. They might, though, be useful in combination with use of several other antivirals as Gamblin suggested.
Meanwhile, a vaccine that could offer some protection from H5N1 and its mutations is being developed by Purdue University and CDC researchers.
The vaccine has been effective against H5N1 for a year or longer in mice, but it has not been tested in humans.
"In humans, we want a vaccine to be fully effective for at least a year," said Suresh Mittal, a Purdue virologist and professor of comparative pathobiology. "How long it will last in humans we don't know yet."
Last month, Sanofi Pasteur delivered to the US Department of Health and Human Services 38.5 million doses of a vaccine designed for an emerging strain of H5N1.
Although the only truly effective vaccine for a virus is the one that is made for a specific strain, some studies have suggested – and some scientists believe – that any H5N1 strain vaccine inoculation could provide some level of protection against another strain a vaccinated person is infected by.
