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I was daydreaming a bit this morning during a Gartner Group conference call on pandemic planning.  The speaker, Ken McGee, a VP of Gartner, was doing his usual excellent job of covering the situation. 

As I allowed my mind to wander, I came up with a metaphor for those of us whose mission it is to try and convince large numbers of people daily that a pandemic may be imminent.  I visualized a large symphony orchestra preparing to play something long and dramatic.  Perhaps an opera, or a Mahler symphony.  We'll use the opera comparison, as people may not be familiar with Mahler's symphonies, some of which required the construction of moveable sound baffles and entire rooms for extra musicians.  Besides, some of those had five movements, which destroys my metaphor.

But enough of Mahler.  Back to the metaphor.  Think of a pandemic as a kind of opera.  For our purposes, we'll call it an Opera in Three Acts, like Tosca or The Barber of Seville.  First, the orchestra shows up, begins to dress, grabs its instruments and occupies the stage.  This, collectively, comprises Phases One, Two and Three of the World Health Organization's numerically color-coded system deliniating where the world sits in regards to a pandemic.

During the end of Phase Three, the orchestra begins tuning its instruments and limbering up for the events that follow.  There is a delightful cacaphony of different strings, winds and brass, all playing their own little tunes, while the musucians are trying to adjust their instruments for humidity, temperature and environment.  This sound begins to build, and build, and build, until the conductor taps his baton on the music stand and the hall suddenly hushes. 

I believe we are at that exact moment with H5N1.  The room is hushed.  The orchestra is prepared and ready for what happens next.

What happens next, of course, is the Overture.  This is short and introduces us to the themes we will encounter during the opera itself.  What follows is the Opera in all its glory, usually spoken in foreign languages we wish we knew better (or knew at all), but the theme is universal:  Pain, suffering, heartbreak and usually, death. 

I cannot escape the feeling that the World Health Organization and the H5N1 virus itself may be preparing us for the Overture.  Look at the events of just the past week:  First, the WHO tells us that testing confirms the extreme likelihood of human-to-human (to human) transmission of H5N1 among four brothers last October and November in Pakistan.  If you look again at the onset dates, that conclusion was anectodal but strong.  Now it is confirmed.  And without saying specifically what changes (if any) in the virus itself may have occurred, the WHO speaks resoundingly about H2H in Pakistan, while revealing the confirmation of two other cases of H5N1 that had previously been undisclosed.  Give the WHO props for transparency but one demerit for tardiness.

Now, just today, the Chinese have come forward with conclusive evidence that the infection of a 24-year old Chinese man last November/December and the subsequent infection of the man's father was, indeed, another case of H2H.  As you might recall from my blog, Cones, umbrellas, Chinese fathers, and H2H, the Chinese were ready to explain the second infection as anything from both being exposed to common bird poop to the father chewing on the son's clothing while in hospital.  Here was a quote from a Chinese official:

Chinese health ministry spokesman Mao Qunan said Lu's infection was due to close contact with his son, but that the transmission was not technically "human-to-human".

"It has no biological features for human-to-human transmission," he told journalists.

Wrong!  Here is the Reuters story from today:

Chinese son likely gave bird flu to father: report

Mon Apr 7, 2008 6:32pm EDT

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - A 24-year-old Chinese man who died of bird flu in December passed the virus directly to his father in a rare case of human-to-human transmission of the virus, doctors reported on Monday.

Chinese officials had already said they believed the younger man infected his 52-year-old father, who survived, but genetic sequencing and other checks confirmed this was likely, the researchers said.

"In this family cluster of confirmed cases of infection with highly pathogenic avian influenza A (H5N1) virus in mainland China, we believe that the index case transmitted H5N1 virus to his father while his father cared for him in the hospital," they wrote in the Lancet medical journal.

H5N1 avian influenza is regularly breaking out in birds across Asia, the Middle East, Africa and Europe. It only rarely infects humans but has killed 238 out of 376 people known to have been infected since 2003.

Most have been directly infected by a sick bird, but in a few rare cases, one person appears to have infected another. These have been documented in Indonesia and, just last month, between two brothers in Pakistan.

Most have been among people who are genetically related and this also appears to be the case with the two Chinese men, the researchers said. Some experts believe there may be a genetic susceptibility to H5N1 infection.

The fear is that the virus will acquire changes that allow it to be passed from one person to another more easily. This could cause a pandemic that could kill tens of millions of people globally, so experts are carefully studying every case of transmission.

Yu Wang of the Chinese Centre for Disease Control and Prevention in Beijing and colleagues investigated the cases of the man and his son, who were diagnosed within a week of each other in December 2007 in Jiangsu Province.

They also tested 91 people the two men had come into close contact with. None of these people became infected.

The young man had a high fever, cough and watery diarrhea and his father nursed him intensively in the hospital.

The younger man died but his father got the flu drugs Tamiflu and rimantadine as well as serum from a woman inoculated with an experimental H5N1 vaccine and recovered.

"With the exception of occasional infection in health workers, all published incidents of possible or probable person-to-person transmission report transmission between genetically related individuals," Nguyen Tran Hien of Vietnam's National Institute of Hygiene and Epidemiology in Hanoi, and colleagues wrote in a commentary.

"Although this finding could be related to the intensity and intimacy of contact between family members, host genetic factors might also play a part in susceptibility to H5N1," they added. So anyone in close, prolonged contact with an H5N1 victim should get flu drugs just in case, they said.

Last week the World Health Organization said some human-to-human spread likely occurred when three brothers in Pakistan became infected with H5N1 last year.

The largest known cluster of human bird flu cases occurred in May 2006 in Indonesia when at least 7 family members died.

(Editing by Philip Barbara)

Interesting that the Chinese protocol entails the use of an M2 inhibitor, Rimantadine, in the course of treatment.  Also interesting that the Chinese experimented with the same serum that is now the basis for their new H5N1 trivalent vaccine, which I reported on yesterday.  Nice of the dad to "volunteer." 

The use of Rimantadine causes me to speculate the infection was Fujian, the strain Dr. Robert Webster and others discovered a couple of years ago.  I will rely upon others to correct me via comments if I am wrong.  The use of M2 inhibitors was pretty much rendered useless awhile back via the Chinese use of amantadine in the poultry vaccine for H5N1.  The virus mutated its way around amantadine as if it were an antiviral Maginot Line, and rendered the use of M2 inhibitors pretty much moot.

Perhaps Fujian H5N1 puts M2 inhibitors back into play. 

Someone out there, a poster on Flu Wiki or Flutrackers, is counting the number of suspected human clusters of H5N1,   I have lost count of the sheer number of human clusters that have occurred since 2003.  But I am betting that we are seeing a marked increase in these clusters.  

So the conductor is set at the podium; the orchestra has taken up its instruments; and the opera hall is hushed.

I'd find me a seat if I were you.  The overture to Phase Four is about to come.  This is gonna be one helluva show. And the fat lady's not gonna sing for awhile.