Scott McPherson's Web Presence

An excellent interview with one of Indonesia’s top influenza researchers reveals refreshing candor and focus. A tip of the cap to multiflusite poster AlaskaDenise for the link: http://www.thejakartapost.com/detail...218.H05&irec=4

Specifically, writer Emmy Fitri of the Jakarta Post sat down with Udayana University-based virologist and microbiologist I Gusti Ngurah Mahardika for a chat after the nation of 18,000 islands experienced its 103^rd confirmed human fatality from H5N1. This, sadly, was before the nation reported, in rapid-fire succession, its 104^th and 105^th deaths over the weekend.

Two excerpts are particularly worth highlighting. The first deals with Dr. Mahardika’s take on what we worry about with H5N1 and pandemics. I found it to be succinct and maybe we can all grab some new talking points from his words, since he is at Ground Zero:

Question : H5N1 mutated from a flu initially confined to birds, but can now infect humans. Is it possible to roughly predict how long it would take for this virus to mutate into a "pandemic" strain?
Answer: H5N1 itself is a product of natural evolution; an assortment of viruses from quails, geese, teal birds and wild birds found in Hong Kong. They meet at bird markets -- the perfect place for avian viruses to meet and mingle.

What we know is that it's still not easy for the virus to be transmitted from human-to-human, although it has proven that it can.
At present, human-to-human infections remain unusual, meaning that the flu has yet to acquire the full ability to be transmitted in this way. Perhaps it is still in the "trial and error" phase.

Are you saying there have been cases of human-to-human transmission of bird flu?
Yes, there have, but only a limited number of cases, like in early cases in Hong Kong (in 1997). What has made the avian influenza able to infect humans was mainly the presence of a genetic susceptibility in the human recipient.
We never can tell how long it will take for a virus to mutate into a pandemic strain, able to be passed from human-to-human. It could take a very long time or could come sooner than we thought.
We are also in the dark on whether the current H5N1 will be able to trigger a pandemic, or if it could happen with a mixture of H5N1 and other viruses -- we just don't know.
At least we can still hope, and buy time, while we brace ourselves for a pandemic.
What I see nowadays while we're buying time, instead of preparing ourselves for a worst-case scenario, people are making much ado about a (bird flu) vaccine (for humans) and a material transfer agreement for virus sharing.
These are really not necessary and ill-timed. We are wasting time over unimportant issues.

If bird flu is to be considered a natural disaster, perhaps it will be the only natural disaster humans have had time to prepare themselves for.

A second passage should be required reading for all:

As you once said, weather plays an important role in the emergence and re-emergence of outbreaks. Do we have weather-related studies to support prevention measures enforced here?
There are no studies specifically targeting bird flu but general knowledge is applicable not only for the bird flu virus but also other zoonotic viruses which thrive in highly humid conditions.
I don't think we need to put too much emphasis on this to justify what we already know -- I also believe that officials here, both at the agriculture and health ministries, must realize this also; they have data on the increase of outbreaks around this time. But unfortunately, we are not accustomed to being prepared, before trouble hits home.
We don't need rocket science for that. We need innovations and investment. Public campaigns must be intensified with the same warnings, and let people know what will happen if they don't heed the warnings.

Agricultural lifestyles, seen in densely populated urban settings like Tangerang, have a high risk of harboring diseases transmitted by animals. What is your comment?
I believe people know about bird flu -- at least they've heard of it. But we're talking about the Kampung Tengah livelihood. Why would people dare to sell a sick chicken or eat a sick chicken?
Our poverty and backwardness get in the way of us seeing better managed poultry and a clean and healthy environment. It should be easier done than said, now, with more and more fatalities. The government must be ready, at all cost, to remove poultry from housing areas, especially in crowded cities like Tangerang and Jakarta. At all cost -- otherwise it will be too late. (bold all mine)

“Too late”, of course, can be applied to both the poultry industry in Indonesia, as well as the human population everywhere. We should feel free to apply it to both. His criticsm of the Indonesian government’s ongoing tiff with the WHO should not be dismissed. Nor should his admonishment that a vaccine is not a magic bullet. I have maintained that fact over and over and over again, and I am grateful to see someone who has stared Death in the face to confirm this. Vaccines will come too late in the game to really help anyone. Antivirals may lose their ability to prevent or limit viral replication. As Dr. C. Everett Koop has said, we are fighting today’s (tomorrow’s) pandemic with the same tools we had 100 years ago.

I am in Heaven.  Jericho, the series even CBS could not kill by incompetent scheduling, makes its return tonight, Tuesday, February 12, 2008 at 10PM EST - on CBS. 

Long-suffering fans can rejoice that CBS thought enough of the fan revolt to order up seven new episodes.  And considering that the Writers Strike (I backed the writers all the way, natch) is just over, it means that Jericho (along with the Sarah Conner Chronicles) is about the only fresh drama on any network.

If you want a recap of Jericho, and why it is the most relevant show on television, just search this Blogsite using "Jericho."  You will get important plot information and maybe you won't have to cram for the season premiere.  Or, you can go to CBS.com and go to the phenomenal Jericho Website.

Basically, about two dozen American cities are radioactive dust.  Jericho, Kansas, is miraculously spared any real problems.  Then, Russian cargo planes drop Chinese-made generators and supplies to the townspeople.  The government has reconstituted itself in Wyoming.  The flag has dramatically changed (Where are the 50 stars?  WATCH THE SHOW!).  An influenza epidemic almost killed the mayor early in the season, and eventually he recovered -- only to die in a skirmish between Jericho and a warring nearby town.  And just as the two towns are about to square off in a nasty battle, the army -- somebody's army -- drops in from Nebraska.  Pity -- Hawkins was about to do something cool with that M-1 Abrams tank!  Who is Hawkins?  WATCH THE SHOW.

That's where Season Two picks up.  Jericho message boards are rumbling about a potential epidemic of a new virus, so flubies should enjoy the show.  Emergency managers and disaster recovery experts should enjoy the show.  Hell, everyone should enjoy the show!  So watch, please.  Especially those who get Nielsen stuff.

Now, for those of you who are fearful you'll miss American Idol:  CBS has decided to schedule the show at 10PM EST, so it does not run up against Idol!  So there.  Now you have no excuses left to see a series that was saved from cancellation by the tremendous fan passion.  And with only seven episodes, the producers have packed a ton of surprises and non-stop action into the show!

Here, read this review from Newsday:

http://www.newsday.com/entertainment/tv/ny-ettell5572872feb12,0,7256205.story

And be sure to buy the Season One boxed set:

It may not be as bad as 2004, but it is looking increasingly like this year's flu vaccine may have been as bad a repository of guesses as thinking the Baltimore Ravens and Atlanta Falcons were headed to the Super Bowl this past season.  Or perhaps thinking that Inspector Clouseau mixed the vaccine this year.

As you recall, last week I blogged on the appearance of A/H3N2/Brisbane-like Influenza A.  The location for that blog is: http://www.scottmcpherson.net/journal/2008/2/6/australia-gives-the-us-an-unwelcome-present.html .  To digest:

This past Southern Hemispheric flu season, an H3N2 substrain appeared and confounded the vaccine target Down Unda.  Now the virus has spread to the United States, which is bad because Brisbane-like was not known before the annual vaccine confab (please read my analogy to understand how that process works.  I guarantee you'll understand it!).  I use an easy-to-follow pro football analogy.

By the way, Antonio Cromartie had two interceptions in yesterday's NFL Pro Bowl, tying a record.

But I digress.  A Reuters story from last week confirms that this Brisbane-like H3N2 is playing havoc with doctors. 

WASHINGTON - The influenza vaccine given to Americans may not protect as well as expected, U.S. health officials said on Friday as the number of flu cases increased nationwide.

The U.S. Centers for Disease Control and Prevention said slightly more than half of the influenza virus strains reported to its surveillance system are not good matches against the strains included in this flu season’s vaccine.

The number of states reporting widespread flu activity jumped to 31 this week compared with 11 a week ago, the CDC said. But Dr. Joe Bresee of the CDC’s influenza division said there are no indications this flu season is worse than usual.

“Seasonal flu activity was slow to start this year but has increased sharply in recent weeks,” Bresee told reporters.

One measure officials use to gauge the severity of the season is the number of flu-related child deaths. Bresee said the CDC has heard of six U.S. children who have died from the flu, a relatively low number compared with recent years.

Flu viruses mutate and change all the time, so every year a different vaccine is created as officials predict which particular strains will circulate.

The vaccine is designed to protect against three influenza strains — two from Type A, an H1N1 and an H3N2 version, and one for Type B.

Bresee said about 30 percent of the overall strains of influenza in the United States may be a Type A strain that emerged in Australia called H3N2 A/Brisbane. It emerged too late to be included in the flu vaccine offered in the United States beginning in September and October. (Bold all mine)

But wait, there's more!  It seems that the WHO also missed the target -- almost Clouseau-like --  when it came to picking the right Influenza B virus, as well.  Continuing from the Reuters story:

The Type B strain chosen for this year’s vaccine also was not a good match for most of the B virus strains seen in the United States this flu season, Bresee said.

“While a less-than-ideal virus match between the viruses in the vaccine and those circulating viruses can reduce vaccine effectiveness, we know from past influenza studies that the vaccine can still protect enough to make illness milder or prevent flu-related complications,” Bresee said.

Bresee noted that decisions on the composition of the annual vaccine are made about nine months before it is made available to the public in the fall, and it is sometimes hard to know that far in advance which strains will circulate.

Flu vaccines take months to make.

And now for the trifecta!  Another mention of Tamiflu resistance to this year's flu:

Bresee also said some resistance is being reported to the antiviral drug Tamiflu, made by Switzerland’s Roche Holding AG and Gilead Sciences Inc of the United States. Of the viruses tested in CDC flu labs, 4.5 percent are resistant to the drug, Bresee said.

Influenza kills an estimated 36,000 Americans in an average year, and puts 200,000 into the hospital, the CDC said.

http://www.msnbc.msn.com/id/23075303/

This explains why, in spite of your dutifully-administered flu vaccine, you may wind up feeling a little like Chief Inspector Charles Dreyfus this flu season.

The current situation in South Asia:

Over half of Bangladesh's political divisions are overrun by H5N1 in poultry.  Bangladesh, India and Pakistan have all created "isolation wards" for what they assume to be an eventual stream of bird flu-infected farmers and cullers.  India and Bangladesh, two nations that are constantly feuding, skirmishing and even occasionally warring over disputed border territory, suddenly realize there is no border when it comes to H5N1 and begin cooperating with each other. 

India's culling attempts are insufficient to stop this latest and worst outbreak of H5N1 in poultry in the nation's history.  The virus may have spread to other states neighboring West Bengal -- plus one state not so close, specifically the port city of Chittagong.  Culling in states neighboring West Bengal is underway, now under mandate from the Congress of India.

Experts argue over whether there is, or is not, H5N1 now in human hosts.  And the WHO is trying valiantly to determine if this fertile human Petri dish of a region will spawn the Next Pandemic.

So to say the situation in the South Asian region is bleak is to say the 1972 Miami Dolphins were simply happy at the outcome of the Super Bowl.  In other words, a massive understatement of the situation.

Of course, there are suspected cases.  A few cullers in hospital in Kolkata (Calcutta); a few elsewhere.  There are legitimate concerns regarding the accuracy of the tests being administered to the suspected infected.  And that is one reason why the WHO is on the ground there, making sure that everyone does their due diligence. 

I can only assume that St. Jude (not the hospital -- I mean St. Jude, the Patron Saint of Lost Causes, and the saint the hospital is named for) is in the region, working overtime for the benefit of all.  Why?  The good news in the bad news is that, at least so far, there have been no confirmed cases of H5N1 in humans.  Considering the size of the poultry cull, which almost certainly will reach to tens of millions of birds in total between India, Pakistan, Bangladesh and Turkey, to not have detected H5N1 in humans so far is nothing short of miraculous.  And miracles are the province of the saints, right?

It's as good an explanation as any I can come up with, or have heard up to now.

Tamiflu resistance in seasonal influenza could thwart national pandemic plans

The cornerstone of most national pandemic preparedness plans revolves around the use of the antiviral drug Tamiflu, a neuraminidase inhibitor. Nations have been dutifully stockpiling the drug in massive quantities, keeping it in climate-controlled facilities guarded by armed military personnel.

But just as Hitler’s Wehrmacht took a Sunday drive around Belgium’s Maginot Line (pictured) in World War II, influenza appears to be ready to drive around the fixed fortifications of Tamiflu that have been constructed by national governments to combat an eventual influenza pandemic.

The Canadian Press’ Helen Branswell has written an excellent story on the sudden appearance of Tamiflu-resistant H1H1 across the European continent, as well as in Canada. The story appears at the bottom of the blog; but first, a little ru-ru (a punch line to a very, very funny joke).

We have known for years that H5N1 was slowly gaining Tamiflu resistance in some areas, most notably Egypt. We have also known that about 3% of Japanese seasonal Influenza B had shown some Tamiflu resistance.

What I don’t think we knew was that H1N1 was showing a markedly increased resistance to Tamiflu, and we did not know the CDC was actually tracking and cataloguing those resistance markers. Good for them; that is reassuring news. But if we are seeing a measurable, quantifiable increase in Tamiflu resistance in seasonal flu, we are doubtless able now to take a swag at the day that Tamiflu is no longer viable for influenza treatment of most – if not all – Type A influenzas.

Simply put: Tamiflu could go the way of Amantadine and Rimantadine, two antivirals that, once upon a time, went after the M2 protein outercoat of the flu virus, keeping it from dissolving  – until their effectiveness ran out and influenza A viruses became immune to the drugs.

The fact that Influenza A basically no longer responds to amantadine and rimantadine is unknown by a shockingly high number of American doctors, who apparently still get their updates on the effectiveness of medicine from the Saturday Evening Post. An excellent article from CIDRAP News details the unexplained continued mass prescription of M2-class antivirals to treat seasonal influenza by ignorant doctors – despite warnings from the CDC that such prescriptions are worthless. (Edited by me, the complete article can be found at: http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/jan2408antivirals-jw.html

Older flu drugs still used, against CDC advice

Jan 24, 2008 (CIDRAP News) – A recent survey suggests that about a quarter of primary care physicians (PCPs) were still prescribing older antiviral drugs for influenza during the last flu season, despite a federal warning to avoid them because of viral resistance, according to the Centers for Disease Control and Prevention (CDC).

In the survey of 730 physicians in four states, 26.4% reported prescribing amantadine or rimantadine to some patients in the 2006-07 flu season, according to the report in the CDC's Morbidity and Mortality Weekly Report. In January 2006 the CDC recommended that physicians stop using the two drugs because of high rates of resistance in circulating strains of influenza A.

The survey also showed that 69% of physicians ordered influenza tests for patients with influenza-like illness (ILI), and most of those ordered rapid antigen tests. Because rapid tests miss up to 30% of flu cases, the CDC says, physicians should exercise clinical judgment when using them.

Antiviral prescriptions
About 54% of the physicians reported prescribing antiviral drugs to at least some patients, with the rates ranging from 41.7% for pediatricians to 66.4% for family practice.

The most commonly prescribed antiviral by far was oseltamivir (Tamiflu), a neuraminidase inhibitor, used by 87% of the respondents. The two older drugs, amantadine and rimantadine, were prescribed by 17.8% and 8.7%, respectively. Zanamivir (Relenza), the other licensed neuraminidase inhibitor, was prescribed by 5.3% of the physicians.

Amantadine use was highest in New Mexico (43.2% of doctors), followed by Minnesota (16.6%) and New York (14.2%), the report says. Respondents in Connecticut reported the highest use of oseltamivir (94.7%), followed by those in Minnesota (90.2%), New York (85.8%), and New Mexico (70.3%).

In light of the findings on antiviral prescribing, the CDC article calls for more education efforts to make PCPs aware of current treatment recommendations. The report also says that pediatric patients treated with oseltamivir should be watched closely for signs of neuropsychiatric effects, such as hallucinations, delirium, or abnormal behavior. Such effects have been reported in a number of young patients in recent years, mostly in Japan.

Influenza testing
A large majority—69%—of the responding doctors reported using a flu test during the flu season. The use of testing ranged from 87.1% of the Minnesota doctors to 55.0% of those in New Mexico. Of those who ordered tests, 88.0% used rapid antigen testing, 18.8% ordered viral culture, and 6.3% ordered serologic tests.

The CDC says many rapid antigen tests for flu can be handled by nonlaboratorians in office settings, which may explain why many physicians choose them. "However, the benefit of obtaining results quickly must be weighed against the low sensitivities of the tests (70%-75%)," the report says. Consequently, "PCPs should use clinical judgment and check reports of weekly influenza activity from CDC and their individual state health departments to guide their clinical decisions."

OK, so we know we need to slap some New Mexican doctors silly, plus a few in New York and Minnesota. We also know that only 69% of doctors everywhere are actually testing patients for influenza. Most of the 69% served up the rapid test, which is only 70% effective at diagnosis. So what that means is that out of every 100 people who suffer flu-like symptoms, only 69 are tested, and of those, only 48 have reliable test results. Someone in statistics test me on this, please.

It also means there are gaping holes in surveillance in this nation, when it comes to – well, when it comes to everything. We’re not testing properly for influenza. We’re not testing for MRSA. We’re not testing for adenovirus, especially Ad14. No wonder, then, that a Tamiflu-resistant H1N1 might crop up without anyone noticing!

There has always been a hunch among flu researchers that, in exchange for Tamiflu resistance, there might be a corresponding drop in a Tamiflu-resistant flu virus’s ability to transmit person-to-person. A quid pro quo, a “You scratch my nose and I’ll scratch yours,” a get-along-to-go-along virus mutation.

But as Lee Corso would say, “Not so fast, my friend!” The study, reported so well by Ms. Branswell, suggests that Tamiflu-resistant H1N1 is just as virulent and just as communicable as regular H1N1. So throw that theory out the window!

It is also quite interesting that while Tamiflu is encountering resistance via the position H274Y genetic marker (on the HA strand of RNA), Relenza, another neuraminidase inhibitor, is not suffering resistance. We know Relenza is essentially worthless as a treatment for severe H5N1, because you cannot inhale the drug deeply enough into the lungs to be effective. But as I have maintained over and over again, Relenza will make a dang skippy prophylactic against bird flu!

Nations, therefore, would do well to try and determine the prophylactic Relenza dosage for first responders and law enforcement types, and think seriously about expanding their Relenza strategery, as well as using Tamiflu to treat ill essential workers.

Tamiflu and Relenza are the only arrows in the quiver today to fight an eventual influenza pandemic. Other antiviral trials have failed recently (Bio-Cryst). Despite suggestions that science and medicine look to other strands in the flu’s RNA nucleus for disruption of the virus, precious little research has been done on that topic to date.

It is abundantly clear that Tamiflu’s life expectancy as an Influenza A inhibitor is finite. How finite that is requires extensive research and extensive data-gathering. It also means extensive surveillance and sample-collecting. So those county and state health departments need to be ready to gear up for a pretty huge swabbing effort.

All this points back to a quote that Dr. C. Everett Koop, former Surgeon General of the US, said last year.  He said: "We're fighting today's pandemic with the same tools we had 100 years ago." 

How about we drop this pretense of finding magic bullets, and just get on with the task of teaching hundreds of millions of people how to wash their hands correctly, how to cough or sneeze into their arm or sleeve or tissue, and how to keep a respectable distance from strangers?  Teaching these simple items is the absolute most cost-effective thing we can do  today.  Vaccines will be late to the dance and not reproducable until we have ID'ed the pandemic strain.  Antivirals will be iffy, depending upon when the pandemic strikes and whether the virus might have reassorted with a Tamiflu-resistant strain of existing Influenza A (although Egypt's Tamiflu-resistant H5N1 hasn't reassorted with a human strain that we are aware of, yet we know it is being given Tamiflu resistance from somewhere). 

Tamiflu-resistant flu viruses found in Canada

Provided by: Canadian Press
Written by: Helen Branswell, Medical Reporter, THE CANADIAN PRESS
Jan. 29, 2008

TORONTO - Canada's National Microbiology Laboratory is reporting a high level of Tamiflu resistance among H1N1 viruses circulating so far this flu season in this country, one of a number of labs to see a phenomenon that is unsettling influenza experts.

Nearly 10 per cent of H1N1 viruses tested so far this year by the Winnipeg lab are resistant to the drug, a cornerstone of pandemic planning for many countries around the globe. In the past, fewer than one per cent of circulating human flu viruses were thought to be resistant to Tamiflu.

"That's quite a surprise," the lab's scientific director, Dr. Frank Plummer, said, noting the resistance mutation spotted in the Winnipeg testing is the same one that has been reported over the past few days from Norway, several other European countries and the United States.

Eight of 81 H1N1 viruses tested carry the H274Y mutation - one each from British Columbia and Newfoundland and Labrador, and six from Ontario. Plummer said that total includes one virus (from British Columbia) recovered from a child who is believed to have been infected in Sudan.

His surprise is shared by experts with the World Health Organization's Global Influenza Program, which convened a teleconference of about 50 scientists from leading influenza laboratories around the world Tuesday to try to get a handle on how far this virus has spread, how common it is in places where it is being found and what is driving the spread.

Dr. Frederick Hayden, a leading antiviral expert working at the WHO, said the resistance virus has been reported over a broad geographic range, both in terms of countries and within countries themselves.

"We do know that again within the countries that have the information, it's not just focal pockets. There are multiple sites, for example, within France or within Norway where this has been detected," he said from Geneva.

The United States has reported that 5.5 per cent of tested H1N1 viruses there are resistant to the drug. European countries known to have found resistant viruses include Norway, Denmark, France and the United Kingdom. Hayden suggested more countries have found these viruses, but said he wasn't at liberty to name names.

Perplexingly, Japan - the country that uses more Tamiflu by far than any other in the world - has not found any of these resistant viruses this flu season, Hayden said.

Reports worldwide still number in the "few dozens." But that is enough to send up red flags, especially given that in all of the cases where details are known, people who caught the virus hadn't taken Tamiflu.

It wouldn't be startling to see people who've used the drug shedding viruses that are resistant to it. Like antibiotic resistance, resistance to antiviral drugs can develop in people who use them, though rates of drug-triggered resistance are low with Tamiflu.

But it had been thought that viruses that acquired this H274Y resistance mutation would pay for that gain with a corresponding loss in their ability to transmit. The belief was that if they developed in someone using Tamiflu, they would be unlikely to infect contacts of that person and start to circulate more widely - in essence, that they would be too weak to compete with regular flu viruses in the race to infect human respiratory tracts.

These recent findings suggest the drug is more vulnerable to the development of drug resistance than had been previously thought, experts fear.

"This mutation is not going to affect the fitness of the viruses as much as we thought," said Jennifer McKimm-Breschkin, a virologist with Australia's Commonwealth Science and Industrial Research Organization in Melbourne.

McKimm-Breschkin was one of the scientists involved in the discovery of Tamiflu's competitor, Relenza. Though the two drugs are in the same class, Relenza is still effective against viruses with the H274Y mutation.

"We're now seeing the ability of this virus that we thought would not have the ability to compete (with unmutated viruses) spreading globally," she said, suggesting that doesn't bode well if H5N1 avian flu starts a pandemic. The same mutation creates Tamiflu resistance in H5N1 viruses.

Hayden said the appearance of resistant H1N1 viruses across such a broad expanse "does raise a lot of questions."

Dr. Joe Bresee, chief of flu epidemiology and prevention at the U.S. Centers for Disease Control, questioned Monday whether there was a true rise in the number of resistant viruses.

Bresee cautioned that increased influenza surveillance prompted by concerns over the H5N1 virus may be turning a spotlight on something that always existed but went unnoticed in the past.

Hayden disagreed, saying an international network of antiviral experts has been watching for this resistance pattern but it has only been found rarely.

"Basically it was present at very low frequencies, less than a half per cent. In most studies, (it was) not even detected. So I think this is a new phenomenon and one that we need to understand better."

He said work is already underway to try to catalogue cases and to sequence resistant viruses to see if their genomes hold clues to how the resistance arose.