Posted on 11/16/2006 2:40:06 PM PST by blam
Bird Flu Mutations Likely to Trigger Pandemic Identified
Thursday, November 16, 2006
By Daniel J. DeNoon
Either of two simple bird flu virus mutations could trigger a deadly pandemic, Japanese scientists warn.
Both mutations already have popped up in humans infected with the H5N1 bird flu virus.
They've been seen in bird flu viruses isolated from two people in Azerbaijan and from one person in Iraq, according to the Japanese scientists. Neither mutation has been seen among the more than 600 H5N1 viruses isolated from birds.
The two human mutations give the bird flu virus the ability to attach to human cells. It's the kind of mutation seen early in the 1918, 1957, and 1968 flu pandemics, warn Shinya Yamada of the University of Tokyo and colleagues.
Fortunately, the H5N1 viruses carrying these mutations do not appear to have caused any outbreaks of human-to-human transmission.
But these mutants seem capable of replicating in humans -- "an essential indicator of pandemic potential," the researchers report.
Flu viruses attach to receptor molecules on the outside of cells that line the airway.
(Excerpt) Read more at foxnews.com ...
Some of the people in Indonesia who have gotten it apparently didn't get it from birds. Also Niman says that the specs for the flu bird have in Indo isn't the same as the version people are getting. I'm a worse than layman so if you want to know about these details check the sites I've read. Unless you want to continue to think that the threat is imaginary, in which case be my guest.
http://www.fluwikie2.com/pmwiki.php?n=Forum.NewsReportsForNovember16
Bird Flu Finding a way to Evolve?
ScienceNOW Daily News 16 November 2006
“The H5N1 virus, better known as bird flu, may have a way of becoming more dangerous to people. Researchers have identified two mutations in a surface protein of the virus that enable it to bind more easily to human cells. Watching for these mutations in viruses isolated from people could provide early warning of the emergence of a virus with pandemic potential.
Avian and human viruses differ in the types of receptor proteins they recognize. This has made human H5N1 infections thankfully rare—so far, there have been only 258 cases in 10 countries (ScienceNOW, 9 February). Key to this discrimination is a protein known as hemagglutinin—the H in H5N1—which is tailor-made to bind to receptors on bird cells. It is thought that an avian influenza virus will only be able to infect people efficiently if the hemagglutinin protein mutates in a way that facilitates its binding to human cell receptors.
To search for such mutations, an international team led by Yoshihiro Kawaoka, a virologist at the University of Tokyo and the University of Wisconsin, Madison, screened viral samples collected from both birds and humans. This enabled the researchers to zero in on two single amino acid changes on the hemagglutinin molecule, each of which enables the virus to bind to human receptors. A structural analysis of these proteins found that the two amino acids are located in positions on the molecule where they could be involved in binding to host cell receptors. Both mutations were isolated from humans infected with the virus and were not present in any of more than 600 avian isolates checked, the group reports today in Nature.
Previous work indicates that the human cell receptors the mutated H5N1 could target are present in the upper respiratory tract. This sets the stage for the virus to be spread among humans through coughing and sneezing, says Kawaoka.
“It’s an important finding because it shows the possible molecular and structural basis for differences in viral attachment patterns,” says Thijs Kuiken, a pathologist at Erasmus University in Rotterdam, the Netherlands, who has been studying how the H5N1 virus crosses the species barrier. But he is cautious about the implications for a pandemic. “The fact that the virus attaches to a particular receptor on a cell does not immediately mean that it can replicate in that cell,” he says.
Kawaoka agrees that additional mutations are probably needed for the virus to acquire pandemic potential. “The problem is we don’t know how many steps away a pandemic strain is,” he says.”
http://tinyurl.com/y53ad8
Number 7, leaning away from stockpiles to health care workers & first responders is interesting. Any idea what the logic on that is?
Cheer up. I was 22 years old in 1968 and I recall nothing at all of any unusual flu threat. I think this is just more shabby reporting.
Okay, my last post for the night:
(FW is up and running again.)
http://www.fluwikie2.com/pmwiki.php?n=Forum.NewClusterInEgypt
Four Suspect H5N1 Patients Hospitalized in Suhaj Egypt Recombinomics Commentary November 16, 2006
The university hospital in Suhaj detained 3 children and a factor for the suspicion of their injury by the bird flu epidemic and they are Faten Ahmed Shawqi, its sister Manar and Shaimaa and their neighbour Mohamed Al Sayed “a worker” the child and the worker was injured by a pneumonia and a sharp descent in the heart and lost the awareness -
The above translation desscribes four suspect H5N1 bird flu patients hospitalized in central Egypt. Two patients are already unconcious, and the cluster includes three siblings and a neighbor.
Clusters in Egypt are cause for concern. The HA from a recent fatality had M230I, which matches all three seasonal flu’s (Influenza A H3N2 and H1N1 as well as Influenza B. The change creates five consecutive amino acids (QSGRI) that match the receptor binding domain of infleunza B, raising ocnerns of increased human-to-human transmission.
(Additional link on FW.)
I welcome links! I do not claim that the threat is imaginary. I do claim that over-reliance on a human vaccine as the only available solution is much too narrow. Basic hygiene, rapid detection (an effective public health system), and avoiding politically correct "paralysis" works in containing public health threats. Some successful programs in the western world were leprosy, plague, rabies, smallpox, typhoid, polio, rubella, rubeola, tuberculosis, tetanus, hepatitis, syphilis, and malaria; to name a few. It would be irresponsible to demand a global effort at the development of a human vaccine for H5N1 while people are still living with fowl and hogs in their homes in Asia. Kind of the equivalent to taking the handle off of the community water pump. Do not even get me started on whether AIDS or HIV carriers should have been quarantined for public health reasons. I am sure that Typhoid Mary was a nice person, and her "rights" were more important than other human lives.
I really know nothing, am merely copy'n'pasting what I found on that website.
That said, my "gut" feeling is that:
A. It's not true and they are merely saying that so first responders aren't hassled for their meds.
or
B. The antivirals don't do squat so it doesn't matter.
The logic against stockpiling for a mutating strain is pretty simple: do not spend money and resources on a what-if.
From Richard Krause at the NIH, regarding 1976 flu:
"Throughout the spring and summer, we monitored carefully for swine flu elsewhere in the world, particularly in the Southern Hemisphere, where it was winter. We received only scattered reports of an occasional case of swine flu in farmers in the Midwest, and controversy raged as to what the next steps should be. Should the vaccine be stockpiled? The argument against stockpiling was strong: the vaccine had to be given before the potential epidemic occurred in September and October, and we were racing against time. Initially, Albert Sabin insisted the vaccine should be given to children when school began in September 1976. Yet some experts preferred a "wait and see" approach."
Flu Wiki has an agenda. May I recommend some sites that do not prey on emotion and hysteria?
http://www.jhsph.edu/flu/index.html
http://www.cdc.gov/search.do?action=search&queryText=avian+flu&x=14&y=10
http://www.haverford.edu/biology/edwards/disease/viral_essays/warnervirus.htm
Thanks, will check them out. I assume none of them have agendas.
Oh, a gov site. I'm sure that has no agenda too.
AFAIAC, everyone has an agenda. Some agendas are prettier than others.
Sorry I'm being snide. I've been reading about this for about two years and if anyone says that there is no danger, it's an agenda, we're more modern now, etc etc, I shake my head in disbelief.
Extremely good article. Thanks for posting, Blam.
Many interesting H5N1 stories on the web tonight. Thanks for the links, little jeremiah (aptly selected screen name, BTW!).
Thanks for the pings, Joe.
To sum up:
Two alternative genetic changes have been identified by Japanese researchers, either one of which would lead to efficient H2H transmission. Both changes are relatively simple, and the logical conclusion is that efficient H2H transmission is certain to occur at some point in the future. (This could explain Tommy Thompson's speech in Seattle a few days ago stating that an H5N1 pandemic was certain to occur.)
Rumors abound that WHO is about to move H5N1 from stage 3 to stage 4. My bet is that even if WHO does this, the public and MSM will just yawn. The natural assumption is that the time to go from stage 3 to stage 4 is likely to be the same as that required to go from stage 4 to stage 5, so most people will think the next stage is years away.
Unfortunately, that is faulty logic. It appears that the remaining genetic changes that must occur for efficient H2H transmission have been identified, and they are minor compared to the changes that have occurred already.
Dr. Niman noted that very little further change is needed at this point, and that mortality has not declined thus far in spite of the significantly greater changes needed to get this far. He concluded from this that there is not much reason to believe that mortality will decline from the current 50%+ to the less than 2% currently being used in planning models.
It appears we already have at least two known cases of people with H5N1 variants that include the genetic changes thought to be needed for efficient H2H transmission. Whether uncontrolled H2H transmission actually occurred is not known for certain, but it seems likely that it did NOT. (Otherwise I suspect we would be having a different discussion...)
I'll spend a while poking around the web for more info, but this seems to be a lot of food for thought already.
I chose my screen name precisely for that reason. "Little" because I am but an insect compared to previous messangers. And I've gotten into a lot of trouble for carrying a message that some (many?) people don't want to hear.
Truth is truth and must be served, if we want to really live.
Been checking your first link, and they have some dubious info, for a start - they state that 40 million died in the 1918 flu. Also that people should have two weeks of supplies on hand. That's pretty minimal, although it's nice they're advising something.
I guess you like those websites since they're not all "raw" like FW. I'll keep reading, but tomorrow.
Here is some good stuff. Note that research on H5N1 began in 1961, with cats.
H5 infects humans and has healthy reservoir in water Aves spp.. Both low- and high-pathogenic strains exist, depending at least partly on the amino acid sequence at the cleavage site in HA1/HA2. Detection of an H5 subtype of influenza A in a human should always arouse a very high level of suspicion that the case was caused by the H5N1 strain of avian influenza, particularly in a country with ongoing outbreaks of H5N1 in poultry. H5N1 is the only strain within the H5 subtype that has ever been shown to cause disease in humans. The next influenza pandemic: lessons from Hong Kongref.
Epidemiology :
The Netherlands : on Mon Mar 15, antibodies against H5 LPAI were detected also in ducks at a farm in Lopik in the central province of Utrecht : although the virus could not be isolated, the government decided not to take any risk and thus ordered the culling of all 800 ducks. On Mar 19 some 1000 birds (442 ducks, 531 chickens, 5 turkeys, 9 geese, and 77 doves) were culled at a farm in Steenbergen (in the southern province of North Brabant), which had links to a farm in Lopik. The source may have been 2 shipments of a total of 2500 ducks from France : 5 other farms, which also received ducks from the 2 shipments, are still under investigation. On Mar 20 99 birds (34 ducks, 35 chickens, 3 turkeys, 3 geese, and 24 doves) were culled in a farm located at Liempde, province of North-Brabant
Canada : on 18 Nov 2005 a duck on a farm in Abbotsford in the Fraser Valley east of Vancouver, south western British Columbia tested positive by RT-PCR. On Jun 2006 4 domestic goose (purchased about 6 weeks before from a local co-operative) died in western Prince Edward Island and one tested positive for an H5 avian influenza virusref
Subtypes :
H5N1 subtype
First isolated from Sterna hirundo (common terns) in South Africa in 1961ref. it was probably transmitted by Odontophoridae infected with H9N2, Anser spp. infected with H5N1, and Anas spp. infected with H6N1 from Continental China to Gallus gallus in Hong Kong markets, and then to humans. Researchers introduced the H5N1 virus into the airways of 3 cats and 3 other cats were fed an infected chick. Finally, 2 cats were exposed to the virus by being placed in the same cage as the 1st 3 cats. The cats soon showed signs of disease: raised body temperature, decreased activity, and labored breathing. All developed severe lung disease. One cat died after 6 days of infection. The study authors also tested the effect of another type of influenza virus, H3N2, which most commonly causes flu in humans. Cats exposed in the same way to this virus did not develop disease. During H5N1 virus outbreaks, domestic cats are at risk of disease or death from H5N1 virus infection, either due to feeding on infected poultry or wild birds, or due to contact with infected cats. The role of cats in the spread of H5N1 virus between poultry farms, and from poultry to humans, needs to be re-assessed. Cats may form an opportunity for this avian virus to adapt to mammals, thereby increasing the risk of a human influenza pandemicref. Anyway it could not be passed between humans. Due to Asp92=>Glu in NS1, virus is resistant to IFNs and TNF-a.
Epidemiology (see also under veterinary medicine : avian influenza). One of the 2 strains, or clades, of HA that emerged since 2003 made people sick in Vietnam, Cambodia and Thailand in 2003 and 2004, while the other caused the disease in people in Indonesia in 2005. Recent avian and human isolates are predominantly genotype Z viruses but additional avian isolates of genotype V and Z/W reassortants are also circulating. The hemagglutinin (HA) gene has evolved considerably since 2003 into distinct clades (1, 1’ and 2). Human and avian isolates from
Vietnam, Thailand, Cambodia, Malaysia and Laos are genotype Z and have a clade 1 HA. Viruses with clade 2 HA belong to genotypes Z, V or Z/W reassortants and are responsible for the recent outbreaks of avian influenza in Indonesia, China, Japan, South Korea, Vietnam and Eastern Europe andhuman cases in Indonesia. Clade 2 HA can be further subdivided into at least 6 subclades (2A-F) with distinct amino acid motifs and the potentialfor different antigenic profiles. Positive selection analysis of all H5N1 HA showed that amino acids corresponding to two major antigenic sites are under selective pressure (Garten, R. Analysis of H5N1 Influenza Viruses from Humans and Birds Between 2003 and 2005 Reveals an Increase in the Spectrum of Viruses with Pandemic Potential. ICEID2006 Abstractref)
http://focosi.immunesig.org/pathoviruses_influenzaA.html#H5
Hmmm... Interesting post.
Research on H5N1 began in 1961. On cats.
There were a number of reports last year of H5N1 in various mammals, mostly predators. It was thought they had probably eaten infected birds.
The genetic sequences recently found in humans are not matching up with those found in birds. This is leading to speculation that H5N1 has an animal reservoir (host?) other than birds. (Cats??)
Interesting.
It gets better. Newcastle wiped out many chickens and ducks in California in 1976. I was there, and hence my interest in this round of "bird flu". Cats also died during that outbreak. In the event that cats are identified as the mammalian jump, this could explain the Egyptian cluster.
"
Avian H5N1 influenza in cats.
Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, Osterhaus A.
Department of Virology, Erasmus Medical Center, 3015 GE Rotterdam, Netherlands. t.kuiken@erasmusmc.nl
During the 2003 to 2004 outbreak of avian influenza A (H5N1) virus in Asia, there were anecdotal reports of fatal infection in domestic cats, although this species is considered resistant to influenza. We experimentally inoculated cats with H5N1 virus intratracheally and by feeding them virus-infected chickens. The cats excreted virus, developed severe diffuse alveolar damage, and transmitted virus to sentinel cats. These results show that domestic cats are at risk of disease or death from H5N1 virus, can be infected by horizontal transmission, and may play a role in the epidemiology of this virus.
PMID: 15345779 [PubMed - indexed for MEDLINE]"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15345779
AI means Avian Influenza.
"„X D. bivalent Avian influenza/Newcastle disease vaccine, has been developed by the Harbin Veterinary
Research Institute in northeast China's Heilongjiang Province and quickly put into production before thorough bio-safety studies.
The new vaccine is safer, more convenient to use and cannot kill newborn chicks, attributes that made it more attractive to farmers than a vaccine they were already using.
The vaccine can be injected, given as nasal spray or as eye drops, or put into water supplies and immunizes birds against bird flu and Newcastle disease.
China will produce 1 billion doses by the end of 2005. Production of the live vaccine costs 20% as much as inactivated vaccines on the market, has a longer shelf life of 18 months, and 70-80% effectiveness.
The Chinese bivalent vaccine might be related to a previously published paper on experimental recombinant NCD/AI vaccine.
A recombinant vaccine (rNDV-AIV-H7) was constructed by using a lentogenic paramyxovirus type 1 vector (Newcastle disease virus [NDV] B1 strain, similar to LaSota) with insertion of the hemagglutinin (HA) gene from avian influenza virus (AIV) A/chicken/NY/13142-5/94 (H7N2).
The recombinant virus had stable insertion and expression of the H7 AIV HA gene as evident by detection of HA expression via immunofluorescence in infected Vero cells.
The rNDV-AIV-H7 replicated in 9-10 day embryonating chicken eggs and exhibited hemagglutinating activity from both NDV and AI proteins that was inhibited by antisera against both NDV and AIV H7.
Groups of 2-week-old white Leghorn chickens were vaccinated with transfectant NDV vector (tNDV), rNDV-AIV-H7, or sterile allantoic fluid and were challenged 2 weeks later with viscerotropic velogenic NDV (vvNDV) or highly pathogenic (HP) AIV.
The sham-vaccinated birds were not protected from vvNDV or HP AIV challenge. The transfectant NDV vaccine provided 70% protection for NDV challenge but did not protect against AIV challenge.
The rNDV-AIV-H7 vaccine provided partial protection (40%) from vvNDV and HP AIV challenge.
The serologic response was examined in chickens that received 1 or 2 immunizations of the rNDV-AIV-H7 vaccine.
Based on hemagglutination inhibition and enzyme-linked immunosorbent assay (ELISA) tests, chickens that received a vaccine boost seroconverted to AIV H7, but the serologic response was weak in birds that received only one vaccination.
This demonstrates the potential for NDV for use as a vaccine vector in expressing AIV proteinsref. The Chinese scientists applied a similar approach starting with LaSota strain of NDV, inserting an H5 gene (from which virus strain?) instead of H7.
It would be helpful to obtain data on their work, particularly the methods and results of challenge trials, hopefully with better results than the ones obtained by the experimental rNDV-AIV-H7 vaccine."
We used bleach as a disinfectant when working around Newcastle flocks. After immunizing birds, all of the vials and implements were bleached and returned to the county ag agents in sealed containers. I contend that this is not the first encounter with avian flu.
Very interesting.
Wonder if anyone will notice the announcement in ten days or not.
You better keep that under your hat lest you incur the wrath of the global warming, bird flu, smallpox, Bush economy, ozone depletion, anti-nuke, gun control, dying oceans, anti-tobacco crowd.
If you point out the obvious, you undermine their arguments.
Thanks for the pings and the info. Your efforts are appreciated.
Very true. It's amazing how valuable common sense is. Unfortunately PC thinking and behavior will be our downfall, with more issues that potential pandemics.
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