TORONTO - There is no evidence that Tamiflu-resistant viruses have spread beyond the walls of two hospitals where they caused clusters of cases among immunocompromised patients, the World Health Organization said Wednesday.
The Geneva-based global health agency said investigations into the outbreaks, in hospitals in Wales and the United States, have so far turned up no evidence the resistant viruses have spread from infected patients to the staff, to other patients in the hospitals or to the nearby communities.
"We're confident in saying that at the moment it looks to be limited, but ... it's a question of continually monitoring," said Charles Penn, an antiviral expert with the WHO's global influenza program.
The agency said in a statement that though the investigation is still underway, early results suggest the resistant viruses don't spread easily to healthy people, especially those following proper infection control procedures.
The two clusters involved eight patients in a hospital in Cardiff, Wales and four at Duke University Hospital in Raleigh, N.C., who were severely immunocompromised. Three of the patients in North Carolina have died.
It's known that people with severely compromised immune systems can develop drug resistance. In fact, about a third of the 96 cases of Tamiflu-resistant H1N1 viruses seen globally to date have been in this type of patient.
People whose immune systems are severely weakened can't shake infections, sometimes even with the help of drugs.
In the case of influenza, Tamiflu would help suppress replication of the virus in these patients. But the viruses that were able to evade the drug can develop resistance to it. And if a patient nearby is in the same shape, immunologically, the resistant virus could spread.
"It really reinforces that this patient group -- it's a small patient group -- is a very vulnerable group when it comes to influenza," Penn said of the outbreaks.
The WHO convened a meeting of experts last week to look at whether it should change its advice to doctors about use of the key drug.
In the end, it did not tell physicians to avoid using Tamiflu in this patient group. Only two antiviral drugs work against this strain of flu and such a recommendation would have been impractical.
But the WHO did urge health-care professionals treating these kinds of patients to watch and test for signs of Tamiflu resistance. It suggested higher doses and longer-than-normal treatment course would probably be needed.
Dr. Arnold Monto, an influenza expert from the University of Michigan, said he thinks the problem seen with severely immunocompromised patients suggests clinicians may need to look to combination therapy -- using two antivirals together.
That technique is used in treatment of HIV to lower the risk drug resistance will develop.
"I'm becoming a fatalist. If there's going to become a mutation that confers both resistance and transmissibility, it's going to happen a la Norway," Monto said. "But we don't have to tempt fate."
Monto was referring to the fact that in early 2008, what appears to have been a spontaneous mutation that conferred Tamiflu resistance arose and quickly spread globally in seasonal H1N1 flu viruses. The phenomenon was first spotted in Norway.
Penn said given the millions of courses of Tamiflu that have been used since the pandemic started, the 96 resistant viruses spotted is "a very low number." But like Monto, he said it cannot be assumed "it will stay like this forever."
The WHO told clinicians if severely immunocompromised patients remain ill with flu for prolonged periods, switching them to the other antiviral, zanamivir (sold as Relenza) should be considered. To date there have been no reported cases of H1N1 resistance to Relenza.
And if doctors decide to put nearby patients on antivirals to prevent them from contracting flu -- a measure known as prophylaxis -- they should use Relenza for those patients, the WHO statement said.
It also stressed that medical staff caring for severely immunocompromised patients and family members of the patients should be vaccinated against H1N1 to minimize the risk of infection.
