Two clusters of Tamiflu resistance in H1N1 patients probably don’t signal a change in the virus’s susceptibility to this key drug, the World Health Organization’s top flu expert said Thursday.
Dr. Keiji Fukuda said more investigation is needed of the clusters, discovered recently in hospitals in Wales and in North Carolina.
But the cases are in severely immunocompromised patients, a population known to be at risk of developing drug resistance if they are given antivirals or antibiotics for illnesses they cannot shake. A number of isolated cases of Tamiflu resistance have been seen so far in immunocompromised people.
As long as there is no sign the viruses are moving from these patients to infect people with healthy immune systems, there’s no reason to think there’s been a change in the virus, Fukuda suggested.
“What it points out is there needs to be a lot of vigilance taken with those groups of patients, but it probably does not have big implications for the overall pattern of spread or the overall patterns of illness in the general community,” he said from Geneva during the WHO’s weekly briefing on the H1N1 pandemic.
Evidence is mounting from clinicians around the world that the antivirals to which the pandemic viruses are susceptible are an effective tool if used properly, he said.
“But these clusters also point out that there are some unusual situations and people with severe immunocompromising conditions are the most susceptible people out there. So in the treatment of these patients we have to be ever mindful about how they are doing and how these drugs might be used.”
Since the emergence of the new H1N1 virus the WHO has been alerted to 75 cases of Tamiflu resistance worldwide.
Fukuda was less definitive about the public health implications of a mutation spotted by authorities in Norway which has potentially been linked to severe cases.
More investigation will be needed to clarify whether viruses with this mutation are more likely to trigger severe illness and whether the mutation is showing up in a growing percentage of the pandemic viruses, he said.
“And the question is whether this mutation ... suggests that there is a fundamental change going on in viruses out there or whether there is a turn for the worst in terms of the severity? And I think the answer right now is that we are not sure.”
The mutation, at position 222 on the hemagglutinin protein on the virus’s surface, has been spotted in a number of countries. But while the cases in Norway were seriously ill, in other places people with the mutated virus have had only mild disease. And it’s known that the mutation isn’t seen in all severe and fatal cases.
Fukuda also addressed investigations in Canada into anaphylactic reactions in people who have received the pandemic vaccine.
He said the fact that Canadian officials were able to spot a potential problem with one lot of vaccine and were able to halt further use of vaccine from that lot is a sign of a surveillance system working as it should.
Vaccine manufacturer GlaxoSmithKline and Health Canada haven’t yet determined why six people who were vaccinated from that batch developed a severe allergic reaction called anaphylaxis. In total, Canada has confirmed 24 cases of anaphylaxis in people who have received the H1N1 vaccine.
The reaction, which can be fatal if untreated, triggers a combination of skin, cardiac and respiratory symptoms including the swelling of tissues in the airways that can compromise breathing. It is treated with adrenaline, generally administered via the EpiPen devices carried by people with severe food and insect sting allergies.
Anaphylaxis does occur from time to time after vaccination, but it is rare. And six cases from a lot of 172,000 doses of vaccine is a higher than expected rate. But Fukuda said it could turn out there is nothing wrong with the vaccine in the lot in question.
He said to date 40 countries have started to vaccinate against the pandemic virus and the side-effect profile is like that of seasonal flu shots.
Fukuda said that while there appears to be a levelling off of pandemic flu activity in some places in the Northern Hemisphere, it is too soon to say activity has peaked.
“I think the take home message here is that we need to expect to see continued activity for at least some number of weeks in the Northern Hemisphere before we see a definitive downward turn.”
He also suggested an unusual case of repeat infection reported in the United States will likely turn out to be a rare event.
The U.S. Centers for Disease Control has confirmed that a West Virginia pediatrician caught the pandemic virus in August and then again in October, an unexpected finding. Generally speaking the antibodies developed in the first infection should have protected the doctor against reinfection for longer than a few months.
Fukuda said with influenza, most people who are infected are immune to the specific subtype for a couple of years, on average.
“And so it is unlikely with the pandemic virus we are dealing with a completely new phenomenon in terms of protection,” he said. “There are always some exceptions to rules but it is unlikely that this is a very broad phenomenon. So I would be surprised if we hear about many cases such as this.”