The H5N1 strain of influenza - often referred to as bird flu - is first known to have jumped from chickens to humans in 1997. Since 2004 it has ripped through poultry and wild bird populations across Eurasia, and had a 53% mortality rate in the first 147 people it is known to have infected. Health authorities fear this strain, or its descendent, could cause a lethal new flu pandemic in people with the potential to kill billions.
Flu has been a regular scourge of humanity for thousands of years. Flu viruses each possess a mere 10 genes encoded in RNA. All of the 16 known genetic subgroups originate in water birds, and especially in ducks.The virus is well adapted to their immune systems, and does not usually make them sick. This leaves the animals free to move around and spread the virus - just what it needs to persist.
But sometimes a bird flu virus jumps to an animal whose immune system it is not adapted to.
On August 10, 2007, executives from 11 of the country's leading financial services institutions came together in New York City to participate in the Executive Roundtable Series: Advanced Pandemic Planning for Financial Leaders.
In September of 2006, the WHO released a statement admitting that the assumption that the H5N1 virus must relinquish much of it's lethality in exchange for greater transmissibility simply wasn't based on fact. That it might attenuate, or it might not.
By this time, of course, pandemic planning had already adopted the 2% CFR as the `worst-case'. What we end up with, of course, is anybody's guess.
And over the past year we've learned that the H5N1 virus isn't just a `bad flu', it attacks multiple organs of its victims, and while Egypt has driven down the mortality rate to about 30%, it remains near 88% in Indonesia.
...what is unusual is that a Chinese health official is talking in such stark terms about a potential pandemic, less than one year before the Olympics in Beijing.
Models based on previous pandemic influenza outbreaks in China, and taking into account current conditions across the populous nation, forecast 177 million to 197 million Chinese people infected, with predictions ranging between 460,000 and 6.95 million deaths if China is hit by a flu pandemic now, Feng Zijian, director of the emergency treatment office of the China CDC told the 2007 Conference on Flu Vaccination and Training for Community Health Center Doctors, held in Guangzhou, the Guangzhou Daily reported.
Experts at the conference emphasized that the risk of pandemic-level influenza outbreaks has been increasing since 2003. "Around the globe we are seeing a greater number of bird flu outbreaks, each one enhancing the risk of bird flu, an influenza A strain virus, being transmitted to humans," Zhong Nanshan a member of the Chinese Academy of Engineering, who is well known for his work in SARS treatment, said.
The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.
Flu biology: receptors, Part 1
Category: Bird flu * biology
Posted on: October 16, 2007 5:22 AM, by revere
The need for better information about the science of avian influenza is urgent. But science is a slow process, or at least slow relative to an urgent time scale, even in times of rapid advances in technology. Even so, while we are waiting for the other shoe to drop, we continue to learn and unlearn about the influenza virus. One major gap has been understanding where humans have cells with receptors for bird flu viruses. A new paper published online last week in The FASEB Journal is finally providing some information. As usual, it is both informative and confusing. To understand what it is and is not saying we'll need to do a little review of the biology. We'll do this in two parts. The second post, tomorrow, will provide details of the FASEB paper (FASEB is the Federation of American Societies for Experimental Biology).
First a review:
Host cells (in this case, human cells) don't usually sit around naked. They've got clothes on. We explained this in excruciating detail in a series of posts earlier... Here's a short recap. The raw cell surface (its bare skin, so to speak, the cell membrane lipid bilayer) is clothed with a "lawn" of hairy protein threads sticking from and through it. The proteins are decorated with complex sugars (collectively called glycans) and the combination is called a glycoprotein. The sugars can be of different kinds and can be attached in different ways. Thus cells that would otherwise look pretty much the same when naked (a bag made of cell membrane) can look very different when clothed. This is an interesting biological tactic, so let's pause for a minute to consider it (just for fun).
All cells have the same genetic endowment, encoded in their DNA. What makes one cell different from another is its ability to turn some of the genes that make proteins on or off in various combinations. The genes make proteins by translating the code sequence into an amino acid sequence. A protein is just a bunch of amino acids strung together. Since there are a lot of genes there are a lot of possible combinations, too, most of which are non functional or never used. But what's left is more than enough to produce lots of different kinds of cells, even though they are all starting with the same inventory of genes. They employ the same genes but in different ways.
It turns out that's only a fraction of the information space available to cells. People don't (usually) sit around naked either. We wear clothes. Our choice of clothes is usually not genetically determined but responds to things that occur in and around us. I'll just leave it at that. And just like people after they are born, cells can put on all sorts of clothes. The change in appearance from wearing a different set of clothes is called post-translational modification. It occurs without any change in the genetic sequence or its expression by translation into proteins. Adding complex sugars to proteins produces the most abundant source of post-translational modifications we know of, enormously increasing the "information space" available to a cell. What does this have to do with pandemic influenza?
The different sugars that decorate the proteins on the cell surface and the specific way they decorate that surface are the ways that things outside the cell tell one kind of cell from another. This ability is biologically important. It is the way other cells or hormones, for example, are able to interact with a particular cell. But pathogens, like viruses, bacteria and fungi have co-evolved to exploit those same recognition markers for their own purposes, just like a burglar uses a window you use to look out or provide fresh air to get in. In particular,the influenza virus looks for cells with a specific sugar attached in a specific way, and when it encounters it as it is randomly floating around, it sticks to it, initiating further processes which result in the virus being taken into the cell. The glycoprotein the virus sticks to is called the receptor (as is the part of the virus that sticks to it).
The sugar the flu virus sticks to is one of a family of sugars with 9 carbons called a sialic acid. Sialic acid is bigger than glucose or simple sugar but smaller than the 12 carbon table sugar. The latter, however, is really two smaller 6 carbon sugars stuck together while sialic acid is a single sugar. While sialic acids are sometimes found on their own in nature, they are usually found attached to other sugars which in turn are attached to proteins to make glycoproteins (that is, they are articles of cell clothing). You can look in the earlier posts whose links are above for an explanation of the terminology, but the short version is this. Flu viruses from birds like sialic acids that are attached via something called an a2,3Gal linkage, while those more adapted to humans stick to sialic acids attached through an a2,6Gal linkage. Think of it as one liking cells with blue shirts and another liking cells in red shirts (no political implication intended). The assumption together with some supporting evidence has been that birds have cells with a2,3Gal and humans with a2,6Gal, which explains why bird viruses infect birds and usually not humans and vice versa. Pigs, it turns out, have both kinds of cells in their tracheas (windpipes), which gave rise to the "pig as mixing vessel" story of pandemic flu emergence.The pigs get co-infected and the bird and human viruses mix, producing hybrid new combinations with human liking receptors but bird infection characteristics. Presto. Pandemic. Except it doesn't seem to be that simple.
The underlying assumptions are two: that humans don't have a2,3Gal receptors in their respiratory tract or anywhere else accessible to an avian flu virus; and that without the matching receptor there won't be an infection. Neither of these seems to be true. Taking the second one first, we know that a2,3Gal liking virus can infect cells with a2,6Gal receptors, although they probably do this less easily.But maybe not, in some cases. The other assumption is also in question because we don't really have good information about what sialic acid linkages appear on human cells and which ones.
In the next post I'll give some details on this crucial question from the FASEB paper by Yuo et al.
Exactly how Indonesia's latest victim of avian flu, a 12-year-old-boy, came in contact with the H5N1 virus remains a bit of a mystery.
Of course, he is not alone.
Despite the insistence of authorities that it requires close contact with an infected bird, and that the virus is exceedingly difficult to contract, over the past couple of years we've received scattered reports of people sickened who had no such apparent contact.
While Indonesian authorities insist that the only route of infection is bird-to-human, they obviously aren't looking very hard to find any other vectors. In fact, some of the official explanations, tying a victim to infected fowl, have been pretty thin.
In reviewing general patent law principles, the authors state that naturally occurring substances that are not altered by human interventions are not considered patentable. "Hence, a wild flu strain as such would be inherently unpatentable--put simply, it cannot be seen as an 'invention', the fit subject matter of a patent," the report says.
The authors, while not making definitive legal assessments, highlight several observations. Among them:
Early, open publication of the gene sequence of a newly isolated flu virus strain would preclude patent protection, but would facilitate broad-based research and development.
Sequencing a gene using regular laboratory techniques is not likely to be considered inventive or nonobvious enough to warrant a patent.
Unless there is a clearly disclosed and defined new and useful function, most countries deny patent protection for gene sequences.
Initial searches did not find any patents for wild viruses, though there were several for newly engineered genetic materials such as synthetic virus-like particles (VLPs), methods of producing them, and vaccines produced from them.
Patent rights are not absolute. For example, many national patent laws allow researchers to use patented inventions for certain purposes related to research but not to commercial application.
The 10-year-old girl was treated at the Arifin Achmad hospital on Saturday and died less than 12 hours later.
A doctor at the hospital said local tests indicated that the girl had bird flu, but samples from her body were to be sent to Jakarta for testing to confirm the cause of death.
UPDATE
This case is confirmed as positive. The child's 17 yr old aunt, Riri, had just died of the same symptoms
at another hospital, but no testing had been done.
"It gets really problematic for them to link the case back to chickens when it's the aunt who just died with the same symptoms.
Apparently Riri died at the hospital very quickly, before they could even get her into isolation. That demonstrates virulence. And now we again are confronted with the spectre of multiple HCWs in multiple hospitals who had no idea they were treating H5N1, both in the case of Riri and Gozi.
Riri was at Instalasi Gawat Darurat (IGD) RSUD, Gozi was at RS Santa Rosa and RS Arfin Achmad. Everybody except the HCWs at RS Arfin Achmad (an H5N1 reference hospital) likely treated them without taking the proper precautions..."
Over the weekend, 10 year old Gozi Sultia Ningsih died of a confirmed H5N1 infection. Her 17-year old aunt, Riri Rianti, also died after being hospitalized on October 11, but, incredibly, no samples were taken for analysis. Just how, in perhaps the most bird flu-ridden province in Indonesia, can no samples be taken of a young girl with suspected H5N1 symptoms?! This is beyond the imagination of any competent medical professional or layperson.
This fact is not lost on the central government in Jakarta, which is growing increasingly frustrated with the inability of local medical authorities to observe suspected human H5N1 protocols. The exasperation is clearly noticeable in the quotes from Dr. H Djuharman Arifinof, chairman of the Dewan Perwakilan Rakyat Daerah (DPRD), or Regional Council of Representatives, representing the Riau district.
Same Case, Another Update
Hard to say what is true, but very suspicious for many reasons.
Indonesia is now saying this case is negative.
We are still left to wonder why no samples were taken from the little
girl's aunt, who was only a child, herself at age 17.
We also know that patients can have repeat negative tests and only
have a positive at autopsy. This has occurred in other countries, but no
autopsies are performed in Indonesia, and we will never know for sure.
The Indonesians are loathe to report "clusters" of cases. That we do
know. If both cases had been tested and were positive, then a cluster
would be noted, and much attention drawn to that area. So now we have
a suspected case, but no proof, and a suspicious case declared negative
after first being reported as positive in this very secretive country.
The four-year-old girl died on Monday after being admitted to hospital two days earlier, health ministry spokeswoman Lili Sulistyowati said by telephone.
The girl, who had been suffering from fever, died after being transferred to Persahabatan hospital in Jakarta.
Officials were still investigating the case, but four chickens had previously died in the girl's neighbourhood, another official at the ministry's bird flu centre said.
Tensions between Riau and Jakarta, news media turn nasty
The recent flap over whether ten-year old Gozi Sultia Ningsih actually died of H5N1 avian influenza or "regular" fever rages on, and will not be resolved until the WHO weighs in with the final word. However, that has not stopped officials from demanding that surveillance be stepped up in the region.
And it has, with the disclosure that no fewer than eleven (11) children from Gozi's immediate neighborhood (photo) have been taken in for testing and observation. The eleven began displaying flu-like symptoms. It started with seven children...
indigo girl
5,173 Posts
Microbiological Threats to the Financial Sector and the Global Economy
http://www.flutrackers.com/forum/showpost.php?p=104615&postcount=1
On August 10, 2007, executives from 11 of the country's leading financial services institutions came together in New York City to participate in the Executive Roundtable Series: Advanced Pandemic Planning for Financial Leaders.
Charles Schwab
ChicagoFIRST
Citigroup
Fidelity
Goldman Sachs
Lehman Brothers
NASDAQ
Northern Trust
Morgan Stanley
UBS
Visa
Their conclusions:
http://www.flutrackers.com/forum/showpost.php?p=104616&postcount=2