U.S. study defines two clear bird flu strains (2 people dead 14 infected- Azerbaijan)

ATLANTA, March 20 (Reuters) - The H5N1 strain of bird flu in humans has evolved into two separate strains, U.S. researchers reported on Monday, which could complicate developing a vaccine and preventing a pandemic.

One strain, or clade, made people sick in Vietnam, Cambodia and Thailand in 2003 and 2004 and a second, a cousin of the first, caused the disease in people in Indonesia in 2004.

Two clades may share the same ancestor but are distinct -- as are different clades, or strains, of the AIDS virus, the team from the U.S. Centers for Disease Control and Prevention found.

"Back in 2003 we only had one genetically distinct population of H5N1 with the potential to cause a human pandemic. Now we have two," said the CDC's Rebecca Garten, who helped conduct the study.

Speaking to the International Conference on Emerging Infectious Diseases in Atlanta, Garten said the pool of H5N1 candidates with the potential to cause a human influenza pandemic is getting more genetically diverse, which makes studying the virus more complex and heightens the need for increased surveillance.

"As the virus continues its geographic expansion, it is also undergoing genetic diversity expansion," Garten said in a statement.

The H5N1 strain of bird flu has spread across Europe, Africa and parts of Asia and killed about 100 people worldwide and infected about 180 since it re-emerged in 2003.

Although it is difficult to catch bird flu, people can become infected if they come into close contact with infected birds. Scientists fear the virus could mutate into a form that could pass easily between humans, triggering a pandemic in which millions could die.

"Only time will tell whether the virus evolves or mutates in such a way that it can be transmitted from human to human efficiently," Garten said.

The U.S. Health and Human Services Department has already recognized the two strains and approved the development of a second H5N1 vaccine based on the second clade.

Several companies are working on H5N1 vaccines experimentally, although current formulations are not expected to protect very well, if at all, against any pandemic strain.

A vaccine against a pandemic flu strain would have to be formulated using the actual virus passing from person to person.

For their study, Garten and colleagues analyzed more than 300 H5N1 virus samples taken from both infected birds and people 2003 through the summer of 2005.

The majority of the viruses, including all the human cases, belonged to genotype Z. Now there are two clades of the Z genotype. There were also small numbers of viruses in birds that were genotype V or W or recently identified genotype G.

Preparing for a Pandemic

An Expert Goes Over the Must-Haves if Bird Flu Cripples the Country

March 14, 2006 — - Over the weekend, the government told Americans to start storing canned foods and powdered milk under their beds as the prospect of a deadly bird flu outbreak approaches the United States. The fear is that the bird flu will turn into a pandemic and drastically alter the course of American life for a time.

The Red Cross says that if there's a pandemic, we need to prepare for 10 days of being stuck in our homes, and that we may be without power and water during that time. In the event of a bird flu pandemic, Americans should plan for interruptions or delays in other services: Banks might close, hospitals could be overwhelmed, and postal service could be spotty. Experts also say that people need to begin stocking up on extra food and supplies like protective masks, flashlights, portable radios, batteries and matches.

"When you go to the store and buy three cans of tuna fish, buy a fourth and put it under the bed. When you go to the store to buy some milk, pick up a box of powdered milk, put it under the bed," said Health and Human Services Secretary Mike Leavitt. "When you do that for a period of four to six months, you are going to have a couple of weeks of food. And that's what we're talking about."

Previous pandemics occurred in 1918, 1957 and 1968, and the worst waves of illness seem to pass through communities in a matter of six weeks to eight weeks. Computer models suggest about 30 percent of people could be infected, but not all at the same time.

In the event of a pandemic, people must practice what the health officials call "social distancing," or keeping away from other people's germs. Schools and day-care centers could be closed, sporting events and other large gatherings could be canceled, and shaking hands could become socially unacceptable, at least for a while.

Darlene Washington, the director of disease prevention education at the American Red Cross, came to "Good Morning America" to go over some of the must-haves in the event of a bird flu pandemic.

Water

"We recommend that each member of your family has a gallon of water for each day, so a family of four needs to have 40 gallons of water available and you need that much water stored because there's a chance that your water will get cut off if there's a pandemic," Washington said. "Workers may not be able to make it, and plants may stop operating. Your family will need to drink water and for hygiene, for brushing their teeth and washing their hands."

Food

"You need foods that will not spoil," Washington said. "So you need canned foods like tuna. You also need to get foods that you don't have to heat, because just like your water, your powers may go out, too. In addition, to things like canned tuna, you should start storing peanut butter, protein, bars, crackers. Again, foods that have a long shelf life and that don't need to be heated. Make sure you have enough formula and baby food to get through that 10 days. You have to plan for every member of your family and that includes your pets. So get extra dog food or cat food, and make sure you have extra water for your pets. You need a 10-day supply for everyone."

Power Outages

"Stores are going to run out of what you need, too," Washington said. "So that's why you need to stock up now. And we encourage families to have supplies on hand like flashlights and batteries, matches. Hand-cranked or battery-operated radios, and a manual can opener, because you are going to need to open all those cans of food. And this may not seem important but you must get activities for your children and yourself, games, coloring books, cards."

Cleaning Supplies

"You have to have all those on hand to keep your home clean and to have receptacles for all your trash," she said. "You probably won't have trash service and you need to account for that. You need to make sure to have paper towels, toilet paper and soap. Everything you need to keep your home clean and practice good hygiene."

Medication

"You need to get an additional 10 days of all your prescription medications," Washington said. "You should also have over-the-counter, fever-reducing medications; medications for upset stomach; and cold and flu medication. You'll also want to have fluids like Gatorade and Pedialite, which have electrolytes and will help a family member rehydrate if they get sick. Also, keep a few thermometers around in case someone gets sick."

If a Family Member Gets Sick …

"The first thing is to strengthen your hand washing and to have the infected family member cover his mouth when he coughs," she said. "You should also keep that person isolated in a certain part of the house and identify a family member who will help him. You may have to take turns."

(I wonder what 'wonderous event' is gonna happen after ten days. I noticed that part was missing.)

As always excellent comments.

The more virulent and far more dangerous pandemic strain and subtype will likely acquire mammalian polymorphisms rather than attaining human specificity through a recombination event. Recombination although anticipated and not desired does not scare me as much as the highly virulent H5Ni subtype with acquired mammalian specificity."

If you don't mind I would like to expand a bit on the topic for those posters who roll their eyes when these terms are bandied about.

++++++++++++

H5N1 has been changing in a way that helps it infect humans. These changes are called mammalian polymorphisms.

These changes increase the efficiency of H5N1 in attaching to human receptors.

In Turkey we saw large number of cases and increased size of familial clusters indicated transmission to humans was more efficient than had been seen previously.

Virus from one of the patients shows mutations at the receptor-binding site. One of the mutations has been seen previously in viruses isolated from a small outbreak in Hong Kong in 2003.

And most importantly research has indicated that the Hong Kong 2003 viruses bind preferentially to human cell receptors more so than to avian cell receptors.

H5N1 has been evolving by capturing mammalian polymorphisms and these acquisitions are leading to more efficient transmission of H5N1 to humans.

If you are with me so far, then lets look at some more terminology.

Analysis has shown that, compared to previous H5N1 isolates, 20042005 isolates share several amino acid changes - these changes may modulate antigenicity and perhaps other biological functions.

For example, an isolate (VN/JP12-2/05) showed a change from serine to asparagine at position 223 of the HA1 (S223N) that may affect receptor-binding specificity.

The S227N (also called S223N) poymorphism was found in an isolate from a fatal Turkish case.

This change is of concern because it allows H5N1 to grow efficiently at 34 C, the temperature of a human nose in the winter.

The fixing of S227N in the bird population is obviously a cause for concern.

++++++++++++++++++++

Now back to the points at hand.

Our discussion, which may seem a bit esoteric to others, is about these continued changes which (in theory) may lead to a H5N1 that can easily move from human to human - without an avian host.

The question is:

1. Will this pandemic shift occur as a result of a recombinant event where H5N1 and a common human flu virus (with loose morals and a weakness for banana daiquiris) spend some quality time together in a co-infected host.

2. Or will H5N1 acquire (in its world travels) a pandemic mammalian polymorphism that makes it a killer.

Please feel free to correct any errors or restate my cocktail hour summations.

Oh - I have no idea which is the correct answer.

Egypt reports third human bird flu case

CAIRO, March 20 (Reuters) - Egypt said on Monday a third suspected human case of bird flu had been discovered and the woman infected was in hospital.

She is the third infected person
Egypt has reported in three days.
All are from Qaloubiyah governorate, about 40 km (25 miles) north of Cairo.

A man admitted to hospital on Sunday recovered after being administered Tamiflu, but a woman died on Friday despite receiving the drug.

Initial tests in the two cases had shown virus infection, but authorities are awaiting further tests for final confirmation.
The state-run MENA news agency did not say whether the woman in the latest case had been tested for the bird flu virus.

"It was proven that she had handled infected birds and slaughtered some of these birds 15 days ago," MENA quoted Health Minister Hatem el-Gabali as saying.

Tamiflu is one of the most effective ways of treating humans with bird flu, which has spread across Europe, Africa and parts of Asia, and killed more than 90 people worldwide since 2003.

The highly pathogenic H5N1 bird flu virus was first found in birds in Egypt last month. So far, 17 of Egypt's 26 governorates and the city of Luxor have reported cases in birds.

http://www.alertnet.org/thenews/newsdesk/L20354196.htm

This work supports your thesis.

MA

Small Possible Mutation Vectors with H5 Avian Viruses Shown [/B]
Small Possible Mutation Vectors with H5 Avian Viruses Shown
A team of researchers have identified a probable way for the Avian Flu virus to become human to human transmissible. They have found that small chemical "bindings" can change readily, and give the virus the ability to take hold in the human respiratory tract, whereas now it is mostly limited to avian digestive tracts, which is why it has not yet reached human pandemic levels.

News release from Scripps Research Institute:

"Scientists at The Scripps Research Institute, the Centers for Disease Control, and the Armed Forces Institute of Pathology have identified what the researchers described as a possible pathway for a particularly virulent strain of the avian flu virus H5N1 "to gain a foothold in the human population."

The H5N1 avian influenza virus, commonly known as "bird flu," is a highly contagious and deadly disease in poultry. So far, its spread to humans has been limited, with 177 documented severe infections, and nearly 100 deaths in Indonesia, Vietnam, Thailand, Cambodia, China, Iraq, and Turkey as of March 14, 2006, according to the World Health Organization.

"With continued outbreaks of the H5N1 virus in poultry and wild birds, further human cases are likely," said Ian Wilson, Scripps Research professor of molecular biology and head of the laboratory that conducted the recent study.

"The potential for the emergence of a human-adapted H5 virus, either by re-assortment or mutation, is a clear threat to public health worldwide."

Of the H5N1 strains isolated to date, the researchers looked at A/Vietnam/1203/2004 (Viet04), one of the most pathogenic H5N1 viruses studied so far. The virus was originally isolated from a 10-year-old Vietnamese boy who died from the infection in 2004. The hemagglutinin (HA) structure from the Viet04 virus was found to be closely related to the 1918 virus HA, which caused some 50 million deaths worldwide.

Using a recently developed microarray technology—hundreds of microscopic assay sites on a single small surface—the study showed that relatively small mutations can result in switching the binding site preference of the avian virus from receptors in the intestinal tract of birds to the respiratory tract of humans.These mutations, the study noted, were already "known in [some human influenza] viruses to increase binding for these receptors."
The study was published on March 16, 2006 by ScienceXpress, the advance online version of the journal Science.

Receptor specificity for the influenza virus is controlled by the glycoprotein hemagglutinin (HA) on the virus surface. These viral HAs bind to host cell receptors containing complex glycans—carbohydrates—that in turn contain terminal sialic acids.

Avian viruses prefer binding to a2-3-linked sialic acids on receptors of intestinal epithelial cells, while human viruses are usually specific for the a2-6 linkage on epithelial cells of the lungs and upper respiratory tract.
Such interactions allow the virus membrane to fuse with the membrane of the host cell so that viral genetic material can be transferred to the cell.

The switch from a2-3 to a2-6 receptor specificity is a critical step in the adaptation of avian viruses to a human host and appears to be one of the reasons why most avian influenza viruses, including current avian H5 strains, are not easily transmitted from human-to-human following avian-to-human infection. However, the report did suggest that "once a foothold in a new host species is made, the virus HA can optimize its specificity to the new host."

"Our recombinant approach to the structural analysis of the Viet04 virus showed that when we inserted HA mutations that had already been shown to shift receptor preference in H3 HAs to the human respiratory tract, the mutations increased receptor preference of the Viet04 HA towards specific human glycans that could serve as receptors on lung epithelial cells," Wilson said. "The effect of these mutations on the Viet04 HA increases the likelihood of binding to and infection of susceptible epithelial cells."

The study was careful to note that these results reveal only one possible route for virus adaptation. The study concluded that other, as yet "unidentified mutations" could emerge, allowing the avian virus to switch receptor specificity and make the jump to human-to-human transmission.

The glycan microarray technology, which was used to identify the mutations that could enable adaptation of H5N1 into the human population in the laboratory, could also be used to help identify new active virus strains in the field by monitoring changes in the receptor binding preference profile where infection is active, according to Jeremy M. Berg, the director of the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health (NIH). The glycan microarray was developed by The Consortium for Functional Glycomics, an international group led by Scripps Research scientists and supported by the NIGMS.

"This technology allows researchers to assay hundreds of carbohydrate varieties in a single experiment," Berg said. "The glycan microarray offers a detailed picture of viral receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza, and could prove invaluable in the early identification of emerging viruses that could cause new epidemics."

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