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In this morning's post, I said it might be a matter of hours before Indonesia reached a grim milestone.

that was not a tough prognostication, regrettably: The AP reports that the 20-something woman who died Sunday has, indeed, died from H5N1.  Here is the story:

Indonesia Reports 100th Bird Flu Death

By ALI KOTARUMALOS – 2 hours ago

JAKARTA, Indonesia (AP) — Indonesia, the nation hardest hit by bird flu, has recorded its 100th human death as the virus picks up speed across Asia.

Health officials are bracing for more possible outbreaks during the upcoming Lunar New Year, when massive numbers of people and poultry are on the move.

In Indonesia, the H5N1 bird flu virus killed a 9-year-old boy and a 20-year-old woman from the outskirts of Jakarta, said Joko Suyono of the National Bird Flu Center.

The boy fell ill Jan. 16 and died Sunday in Jakarta after testing positive, Suyono said. The woman developed symptoms Jan. 19 and died in a hospital.

Two other Indonesians in their 30s, who also tested positive, were being treated in the capital, Suyono said.

Indonesia has recorded nearly half of the 222 human deaths from bird flu detected worldwide since the virus began decimating poultry stocks in late 2003.

Bird flu typically flares during the winter months, and a number of countries have recently reported fresh outbreaks in poultry.

India has recorded its worst-ever outbreak, and officials are scrambling to slaughter birds to try to stop the virus from spreading into Calcutta, where 14 million people live.

More than 1.6 million birds have been slaughtered since mid-January, state Animal Husbandry Minister Anisur Rahman said Sunday.

On Sunday, skittish officials in neighboring Bangladesh ordered the halt of all egg and poultry imports from India.

China lifted a bird flu quarantine in Xinjiang province on Sunday after 35,000 birds were slaughtered following a December outbreak, the official Xinhua News Agency reported.

Health officials in China and Vietnam have urged more strict controls to keep the virus from spreading during the upcoming Lunar New Year festivities.

Bird flu remains hard for humans to catch, but experts fear the virus could mutate into a form that spreads easily among people. So far, most human cases have been traced to contact with sick birds.

Associated Press writers Margie Mason in Hanoi, Vietnam, and Manik Banerjee in Calcutta, India, contributed to this report.

http://ap.google.com/article/ALeqM5h4z_Ugpa0UYwp7CmJNz0feyeHGbQD8UEUK800

Let's face it:  It's gonna be a long 2008.

My favorite punching bag, OIE's head Bernard Vallat, has been conspicuously silent since things went to Hell in a handbasket regarding the global spread of H5N1 a few weeks ago.  Maybe he has been reading his own organization's daily reports of the culling of what is now more than a million Indian chickens.  Or maybe he has been reading about the collapse of the West Bengal poultry industry.  Or maybe he has read the words of prominent virologists who said Vallat's statements were "naive and dangerous -- and widely acknowledged as such among vaccinologists."

That should also serve notice to Dr. Paul Offit, who recently boasted to New York Times' correspondent Donald G. McNeil that, in essence, H5N1 would never go pandemic.  In McNeil's recent fair and balanced article, titled "A Pandemic That Wasn't But Might Be," 

Dr. Paul A. Offit, a vaccine specialist at Children’s Hospital in Philadelphia, was one of those who, he jokes, “dared to be stupid” by bucking the alarmist trend in 2005.

“H5 viruses have been around for 100 years and never caused a pandemic and probably never will,” he said.

But Dr. Offit said he backed all preparedness efforts because he expected another pandemic from an H1, H2 or H3, the subtypes responsible for six previous epidemics, including the catastrophic one in 1918.

“What I worry is that this has been a ‘boy who cried wolf’ phenomenon,” he said. “When the next pandemic comes, people will say, ‘Yeah, yeah, we heard that last time.’ ”

http://www.nytimes.com/2008/01/22/science/22flu.html

Now, I am not personally aware of any record of H5 viruses being typed at all prior to 1959's Scotland discovery.  And if scientists are still divided about what caused the 1890 pandemic --was it an H2 or H3 virus, or something completely different? -- then I don't think Offit can flatly state that H5 has been circulating over the past hundred years.  Don't get me wrong:  I respect Offit, and am currently reading a copy of his book Vaccinated, which chronicles the amazing life of Dr.Maurice Hilleman (see my post, titled Will H2N3 reassortant prove Maurice Hilleman correct? ).

But I respect Dr. Gregory Poland more.  Dr. Poland (pictured) is one of the world's leading vaccinologists -- a peer of Offit's -- and basically runs the vaccine program at the Mayo Clinic.  He is also a world-class expert on the emergence of the H5N1 virus, and is deeply concerned with emerging world events.  You might also recognize Dr. Poland from his appearance on this past summer's BBC docu-drama "Pandemic."  Believe me, he had some choice words for Monsieur Vallat's recent comments about H5N1 being "stable" and H5N1 pandemic fears being "overblown"!! 

I wish someone would ask Dr. Poland for his opinion of Dr. Offit's claim that H5 has been around for a hundred years and will never go pandemic.  Maybe H5 has been around for a thousand years!  How long a virus has been festering in the intestines of flying birds is irrelevant.  It is how long the virus has shown a proclivity for human tracheas and lungs -- that is the question.  And for humanity, H5 in humans -- as far as anyone knows for certain -- has only been around for eleven years.  Not a hundred.  And not a thousand. 

It is like saying that the SARS virus has been hanging around in the blood of civet cats for a hundred years, so why worry?  let's ask the 8,000 people who caught SARS in 2003 -- minus the 800 or so who died -- ask them if it mattered that SARS was no biggie for 99 of those 100 years.

I also appreciated the remarks of Dr. Mike Osterholm, standard bearer in the fight against what he has coined "Pandemic Fatigue." Osterholm, also in the NYT article, "noted that the H3N8 flu found in horses in the 1960s took 40 years to adapt to dogs, but that since 2004 it has spread to kennels all over the country."

Influenza smoulders.  It finds its own way, and on its own timetable. 

Offit belongs to that group of people who believe that only H1, H2 and H3 viruses will ever cause a pandemic -- the theory of recycled pandemic strains of influenza.  Personally, as I mentioned earlier, I am not sure if anyone can say with any degree of certainty that H1, H2 and H3 have caused any more pandemics than the three that have been positively typed by researchers.  After all, influenza has only been typed with certainty in the past fifty years or so.  How anyone can say that these three strains were responsible for 1832, even 1847 or 1890, without supporting genetic material, is a stretch.

Offit's claim in the book about Hilleman is that Hilleman was able to find H2 antibodies in elderly people who lived through the 1890 pandemic.  Therefore, Hilleman claimed (and Offit parrots), the 1890 pandemic must have been an H2 strain.  The 1900 outbreak was an H3, reckoning by the 68-year clock Hilleman/Offit claimed exists (I can find no evidence of a 1900 pandemic, bu the way).  Using that 68-year calculation mechanism, the pandemic of 1847-48 would have been H1.

But wait!  Adding 68 to 1847 equals 1915.  Close enough; let's run with it. And if we know that the 1918 pandemic was an avian flu that jumped straight to humans (we do), as Dr. Jeffrey Taubenberger of the US Armed Forces Pathology Lab genetically proved (with an assist by Dr, Johan Hultin, one of the Unsung Heroes of influenza research), then wasn't that a novel virus?  Wasn't that something that had never been seen before?  Unless that jump had happened before then as well.

So what does this do to the Hilleman/Offit theory if it turns out that this adaptive mutation route is really the cause of the more lethal pandemics, and reassortment , while being a pandemic incubator as well, actually is the more prevalent yet the less likely to kill?  I'll tell you what it does.  It kills it Black Flag Dead.

It is hard to imagine any situation anywhere in the world knocking India off the Bird Flu Radar.  But it has happened.  And it is our old friend Indonesia that has caused the temporary shift in global bird flu attention.

While much of the world's attention (as well as my own attention) was focused on the events in West Bengal, quietly the situation in Indonesia was worsening as well.  But while there are no confirmed human cases of H5N1 in India to date, the exact opposite is happening in Indonesia, where no less than three people have tested positive for H5N1 in the past week -- and a fourth test is probably a fait accompli.

This sudden increase in H5N1 cases and deaths makes it literally a matter of days -- maybe hours -- before Indonesia reaches the 100-death level from H5N1.  That is a distinction that the country certainly does not want, but cannot avoid.

From today's Reuters wire:

Indonesia boy dies of bird flu, making death toll 99

JAKARTA, Jan 28 (Reuters) - A 9-year-old Indonesian boy who had tested positive for bird flu died on Monday, the health ministry said in a statement, taking the country's death toll from the deadly disease to 99.

There have also been reports of scores of Indonesians being sent to hospital with bird flu symptoms.  Fortunately, and as is usually the case, most people test negative for H5N1 and are sent home.  After all, Indonesia is a regular Wal-Mart of infectious disease, including dengue, chikungunya, malaria, you name it.  And thousands of people are afflicted and die annually from the aforementioned maladies.

But it's the H5N1 positives -- and the location of the positives -- that tell the complete story.  As you can see from the (above) excellent map of Indonesian human H5N1 cases maintained by intrepid flu poster Dutchy, there are areas where H5N1 is not just indigenous in poultry -- the disease has taken a liking to infecting humans in significant numbers as well,

The four new human cases are distributed as follows:  One from East Jakarta; one from West Jakarta; one from Tangerang, which has been the subject of several of my posts over the past few months; and one from West Java. 

What also appears to be happening is that the Case Fatality Rate in Indonesia seems to be inching higher. 

In the meantime, Vietnam has also reported a new case of H5N1 -- and death -- in a 32-year old male, located about fifty miles northwest of Hanoi.  Fujian H5N1 (Clade 2.3 or 2.3.4, if you prefer) is suspected. 

In the meantime, India is importing enough Tamiflu to make Roche's quarter, and there is absolutely no end in sight to the infestation of poultry in the region, which includes neighboring Bangladesh.  China is culling birds again by the tens of thousands, and Thailand and Turkey are again reporting infestations of H5N1 in poultry. 

When the media reports began to appear, talking about the "milder" bird flu situation, I think many of us scoffed openly at any insinuation that H5N1 was receding from either the bird population or the potential for pandemic.  Now, in just a few weeks, H5N1 has absolutely exploded back upon the world scene. 

The report -- carried here and elsewhere, regarding the illness of more than 2,300 people in the epicenter of the H5N1 outbreak in Birbaum, West Bengal, India -- has led to the establishment of a Tamiflu blanket over cullers working within the entire Birbaum area.

Media reports, filtered by Dr. Henry Niman, indicate that sick cullers are receiving Tamiflu -- and the application of the antiviral has been extended to cover otherwise healthy cullers.  The commentary can be found at:

http://www.recombinomics.com/News/01250801/Birbhum_Cullers_Ill.html

If this is accurate, this is the second-largest Tamiflu blanket in history.  The largest Tamiflu blanket that anyone outside the WHO is aware of, occurred in August, 2006, in four rural Indonesian villages in West Java.  This followed the death and funeral of a young girl.  When twenty people who attended that funeral fell ill and several died, more than 2,000 surviving villagers were given Tamiflu as a preventative.  That story, which originally appeared in the New York Times and was written by Donald G. McNeil, Jr., can be found at:  http://www.iht.com/articles/2007/02/14/news/flu.php?page=2 .

The issue has spilled over again into neighboring Bangladesh.  It is safe to say that, by any yardstick, both governments have, for the moment, lost containment of the H5N1 virus -- if they had any pretense of containment at all.

Finally, the virus is on the outskirts of Kolkata (Calcutta), one of the largest cities in the world.  Kolkata has an estimated population of more than five million people, making it one of the most densely populated cities in the world.  To paraphrase Sinatra, if the disease can make it there, it can make it anywhere.  Perhaps this is why there are some 12,000 courses of Tamiflu in the region as we speak, according to the Ministry of Health and Family Welfare. Also according to the Ministry, another 10,000 courses of Tamiflu capsules, 100 bottles of Tamiflu syrup (for children?) and five ventilators are in transit.

India is digging in.  It could be a long siege.

Intrepid readers:

My last post, titled "This is how a pandemic might begin..... 2,300 complain of fever in Birbhum, West Bengal :, is now accompanied by a companion piece -- about the sudden and totally unexpected deaths of more than 100 goats, in the same area.

From today's Times of India, just a few moments ago:

Flu panic rises as goats drop dead

25 Jan 2008, 0223 hrs IST,Caesar Mandal,TNN

This is serious stuff, even if it is unrelated to avian influenza.  Note the speed with which the landscape has changed in just the past twenty-four hours.  Note that it feels like we have been talking Indian H5N1 for weeks, when really the stories just started coming in ten days ago. 

This is how the start of a pandemic will make its presence known to us.  A few scattered media accounts, unconfirmed and unsubstantiated at first; then, suddenly, more and more specific reports will appear.  Finally, and with a crushing blow, the outbreak will happen.  And this is why we must continue to remain vigilant.  Because if H5N1 has crossed the species barrier again, and gain a foothold in Indian goats as well as wild birds and poultry, we will have another endemic reservoir of avian flu -- this time, located in the second most populous nation in the world.  And H5N1 will have significantly increased its chances of going pandemic.

As Dr. Henry Niman is fond of saying:  H5N1 does not read press releases.  His commentary is located at:

http://www.recombinomics.com/News/01240804/Birbhum_Goats.html