# 3432
Updated (see bottom)
For the third time this week we are hearing of another case of Oseltamivir (Tamiflu) resistance in the novel H1N1 virus. The other two reports came from Denmark and from Japan.
While three scattered cases in different parts of the world hardly constitute a trend, this is a reminder that not all novel H1N1 viruses are identical. We are beginning to see some variations, or mutations, in this virus.
Most will be evolutionary dead ends, or will have no appreciable affect on the virus.
The concern is, that out of millions of infections, a biologically `fit’ mutation could emerge that changes the dynamics of the pandemic. It could be something like Tamiflu resistance, or an increase in virulence, or perhaps an increase in transmissibility.
Here is the Hong Kong health department’s press release (Hat Tip IronOreHopper on Flutrackers).
Detection of human swine influenza virus resistant to Tamiflu
Friday, July 3, 2009
Issued at HKT 17:01
A spokesman for the Department of Health (DH) said the department's Public Health Laboratory Services Branch (PHLSB) today (July 3) detected a strain of human swine influenza (HSI) virus which was resistant to oseltamivir (Tamiflu).
The virus was identified during PHLSB's routine sensitivity test of HSI virus to oseltamivir and zanamivir, the spokesman said.
"This is the first time Tamiflu resistance in HSI virus found in Hong Kong," he said, adding that similar cases were also reported in Denmark and Japan.
"Tests showed that this strain is sensitive to zanamivir (Relenza)," he said.
The virus was isolated from the specimen taken from a 16-year-old girl coming from San Francisco. She was intercepted by Port Health Office at the Hong Kong International Airport on June 11 upon arrival.
The girl was then admitted to Queen Mary Hospital for isolation. She was tested positive to HSI but opted not to take tamiflu. She had mild symptoms and was eventually discharged upon recovery on June 18.
The spokesman noted that PHLSB conducted routine sensitivity tests on specimens taken from confirmed HSI patients.
"This is the only Tamiflu-resistant strain so far among some 200 HSI samples tested in Hong Kong. Further tests are underway," he said.
Hong Kong has maintained an antiviral stockpile of both Tamiflu and Relenza.
The case will be reported to the World Health Organization (WHO), the spokesman said.
He reiterated that Hong Kong had an intensive influenza surveillance system on antiviral resistant influenza viruses.
"We will closely liaise with WHO and overseas health authorities and monitor the global development of antiviral resistant HSI virus," he said.
Two things notable about this case.
First, the girl was intercepted at the Hong Kong Airport, after flying in from the United States.
Second, and most importantly, she never took Tamiflu.
We’ve heard assurances that the first two cases `probably’ involved acquired resistance in the one detected individual, because they were taking the antiviral.
That is something that we know sometimes happens.
But in this case, the girl never took Tamiflu. Which leaves several interesting possibilities.
First, it is possible (but not terribly likely) that the mutation (almost certainly H274Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 274) spontaneously occurred in this one patient.
It would take an enormous stroke of luck to have detected `patient zero’ with this mutation from routine surveillance. Possible, but unlikely.
More likely, she was infected with a virus that already carried this amino acid substitution. Which infers there may be others carrying it as well.
Whether this mutation was caused by someone else who took Tamiflu, or whether it was simply a naturally occurring mutation, is something we may never know.
In any event, this highlights the need to check more samples for signs of resistance.
According to the last CDC FluView report, the CDC has tested 202 pandemic H1N1 isolates for antiviral resistance . . . which represents about 1/2 of 1% of the laboratory confirmed cases in the U.S., and an even smaller percentage of the actual cases.
Whether a third time indicates `enemy action’ (for you Ian Fleming fans out there) is something we will simply have to wait to see.
UPDATE:
Bloomberg News, in an article by Nipa Piboontanasawat and Jason Gale entitled: Tamiflu-Resistant Swine Flu Virus Found in Hong Kong has several interesting quotes.
By all means, follow the link to read the entire article.
First, from Malik Peiris, a world renown virologist from Hong Kong.
“Picking it up in a patient who was not treated is a cause for concern,” Malik Peiris, professor of microbiology at Hong Kong University, said in an interview. “One case doesn’t change the world, but if we are seeing more and more cases in patients who are not treated, then I think it would be more serious.”
Second, from Jennifer McKimm-Breschkin, an Australian virologist:
The case in Hong Kong indicates that the mutant virus is capable of being transmitted among people, said Jennifer McKimm- Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne.
“It’s very disturbing that, fresh into the human population, this one appears now to be able to retain fitness despite having the mutation and to be able to spread,” she said in a telephone interview today.
And third from Margaret Chan, Director-General of the WHO:
“Constant, random mutation is the survival mechanism of the microbial world,” WHO Director-General Margaret Chan said in an address to a meeting on the flu pandemic in Cancun, Mexico, yesterday. “Like all influenza viruses, H1N1 has the advantage of surprise on its side.”
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