豬流感 與 Tamiflu 糖? (a note on Tamiflu Resistance)

Tamiflu by hongiiv

Since I was the last patient today, my doctor and I had some time to engage in a more detailed chat. Our wide ranging discussion covered not just eyes (where he is an ophthalmologist and surgeon) but many areas of medicine.

In one discussion thread, I described the swine flu (豬流感) panic in Hong Kong where one student in a school tested positive with swine flu and that lead to the whole school (or class?) being prescribed with Tamiflu.

Yes, I am blunt, I am describing this kind of prescription as Tamiflu Candy. Is the hospital authority a bit too cautious to prescribe Tamiflu so widely? Is the HK Hospital Authority taking wise risk in balancing the actual risk of Swine Flu with the risk of developing drug resistance to Tamiflu?

In the old days, HK doctors loved to prescribe antibiotics, the stronger the better, for things that antibiotics have absolute no effect. They went by the theory that patients asked for them, and the pills make the patients feel “better”, why not? And of course, they and their patients learned (?) some hard lessons when the bacteria became resistance to those over-used antibiotics!

I am hoping to create a series of blog entries and video chats with my doctor to talk about different areas in medicines. For example, do you think a 75 years old person having the blood pressure of a 20 years old person is good? Well, you will be very WRONG! My plan is to provide credible scientific reading materials and links alongside with the blog entries and videos. Arm the patients will solid medical researches and results so they can have well-informed discussions with their health care providers.

For the record, the following is a New York Times June 9th article “How a Mild Virus Might Turn Vicious” (emphasis added). I wrote my blog entry before I read this NYT article which express the same concern with Tamiflu resistance.


June 9, 2009
How a Mild Virus Might Turn Vicious
By Donald G. Mcneil Jr.

The swine flu virus is rapidly making its way around the world, but it has been relatively mild so far, causing only 139 confirmed deaths. Could it mutate into something more lethal?

Scientists looking at its genetic structure say there is no obvious pressure for it to do so — no reason for this virus to “want,” in the Darwinian sense, to kill more of its hosts.

It is already doing a near-perfect job of keeping itself alive by invading human noses and inducing humans to cough it from one to another, said Dr. W. Ian Lipkin, director of the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health.

“A really aggressive flu that quickly kills its host” — like SARS and H5N1 avian flu — “gives itself a problem,” Dr. Lipkin said.

But flu viruses are highly mutable, and anything could happen in the next two years, the time a new strain normally takes to circle the globe. After all, Spanish influenza began as a mild strain, then turned horrifically virulent, killing 20 million to 100 million people in 1918-19.

But Dr. Peter Palese, head of microbiology at Mount Sinai Medical School and part of the team that rebuilt that virus in 2005 from fragments found in old lung tissue, said that strain was a “once-a-millennium or once-every-10-millennia event — things like it don’t happen very often.”

Nor is it clear, he added, that viruses really “want” a particular outcome.

“For me, that’s too much anthropomorphic thinking,” Dr. Palese said. “Look, I believe in Darwin. Yes, the fittest virus survives. But it’s not clear what the ultimate selection parameter is.”

A mutation that confers lethality, he explained, may confer another advantage scientists have not pinned down.

The new virus has been described as “a real mutt” by Walter R. Dowdle, the former chief of virology for the Centers for Disease Control and Prevention, because of its unique mix of Eurasian and American swine, human and bird genes.

Flu chromosomes are quite simple — eight short strands of RNA that issue the genetic code for a grand total of 11 proteins. They break apart in a jumble inside cells they infect, and then they reassemble, picking up random bits of other flus, which makes the results unpredictable.

The current swine flu strain lacks several genes believed to increase lethality, including those that code for two proteins known as PB1-F2 and NS-1, and one that codes for a tongue-twister called the polybasic hemagglutinin cleavage site.

PB1-F2 appears to weaken the protective membrane of the energy-producing mitochondria in an infected cell, ultimately killing the cell. Specifically, it attacks dendritic cells, the sentinels of the immune system. Its lethality could be accidental — a protein good at killing sentries might just go on killing other cells once inside the fort.

All pandemic flus, including those of the Spanish, Hong Kong and Asian flus, make PB1-F2. So does the H5N1 bird flu. The current swine strain does not.

The NS-1 protein also maims the immune response by blocking interferon, an antiviral protein made by cells.

Very lethal bird flus also have the unusual cleavage site, which allows the hemagglutinin spike on the virus’s shell to split and inject its genetic instructions into different kinds of cells, like those in the lungs and the gut.

Such an addition to the novel H1N1 would be very dangerous. But because it has been found only in avian flus, it is unlikely to become a component of a human flu, Dr. Palese said. Even the 1918 virus, which was avian in origin, lacked it.

A much more likely change, scientists have said, is that the H1N1 swine flu will become resistant to the antiviral drug Tamiflu. A gene for Tamiflu resistance is now almost universal in seasonal H1N1 flus.

If that happens, the world’s Tamiflu stockpiles will be all but worthless, and doctors may have to switch to Relenza, which is a powder used with an inhaler, which makes it more expensive and harder to take.

Depending on the mutation, older antiviral drugs like rimantidine may be useful, but so much resistance to them developed in seasonal flu that they were largely abandoned a few years ago.

Dr. Palese was asked about another notion concerning likely mutations. There has been outrage at Egypt’s decision to kill all the pigs belonging to its Coptic Christian minority. It has been depicted as misguided and motivated by religious bigotry, because the “swine flu” is really now a human flu.

But Egypt is also in an especially dangerous situation. The new swine flu reached it just last week. The H5N1 avian flu has circulated in its backyard chickens since 2006, defying all eradication efforts. In the last year, dozens of H5N1 cases have been confirmed in toddlers, almost all of whom have survived — which led some experts to speculate that those are cases of a less lethal version of H5N1 that is better adapted to humans.

In that case, might it be wise to get rid of the country’s relatively small pig population, since pigs are “mixing vessels” that can catch both human and bird flus?

“I agree with the premise, if you really could eliminate an animal reservoir,” Dr. Palese said. “But the virus is out of pigs now — and it’s more important that those poor people have something to eat.”

This article has been revised to reflect the following correction:

Correction: June 10, 2009
An article on Tuesday about the potential for the swine flu virus to mutate into a more lethal form misstated part of the name of a research center led by one expert, Dr. W. Ian Lipkin, who said the virus was effective at keeping itself alive in its present, mild form. Dr. Lipkin is director of the Center for Infection and Immunity — not Immunology — at Columbia University. (The error also appeared in an article on Sept. 7, 2007, about a virus suspected in mass die-offs of honeybees.)


From Hong Kong , June 11, 2009 The Standard “Schools on edge“,

All Hong Kong’s primary schools, kindergartens and nurseries are facing closure today amid fears that a 16-year- old girl has become the city’s first non- imported case of human swine flu (H1N1). […]

A medical professor, who did not want to be named, said any decision to close schools would be more political than medical.

“From the medical point of view, it may not be necessary to close all schools if the disease can be contained and has not spread outside the school.

However, the government may need to play safe to avoid political risks,” he said.”But we understand the fear – if one local case is established, the first patient may have already spread the virus to 10 others in the community.”


Comments are closed.

%d bloggers like this: