Questions raised by latest Indonesian case

To me, Revere's work on this Blog site is absolutely of critical importance. He never ceases to amaze me by his profound understanding of public health in general, and bird flu in particular.
His section 3 entitled "Other infected animals (dogs)." and especially his statement:
"But the question goes beyond that, to questions of other animal reservoirs of the virus."
Henry Niman also mentioned today to need to investigate mammalian reservoirs of H5N1, as well as wild birds.
For me, Section 3 demonstrates, beyond any doubt that Revere is a scientist who carefully considers all the evidence in an impartial manner, using the scientific method, and applies his skill and knowlege to the protection of human life.

Cat eats chicken, mosquito (flea, etc.) bites cat, mosquito bites human?
Dog, etc.? Other animal?
Sick animal drinks water, human gets water from same source?

revere,

what do you think about the latest paper coming out of Japan about the isolation of HP H5N1 in blowflies near poultry farms with outbreaks?

http://www.ajtmh.org/cgi/content/abstract/75/2/327

anon_22,
This just confirms a field research study in Java by a university in Indonesia. in which it was determined that near poultry sites, where chickens were infected, the flies were also infected with H5N1.
If it is scientifically proved beyond a doubt flies are a vector for bird flu, cat flu, pig flu, rat flu, dog flu, or human H5N1 H2H flu, etc.; then in my profound scientific judgment ( I am not a scientist, but only an observer of the coming nuclear destruction of Iran). I would like to suggest we must immediately cull all the flies on the planet, especially the big blow flies, and maybe all mosquitos and knats. First we must isolate all flies that are H5N1 positive; and then shoot them with a shotgun. Vice President Cheney can be our leader, since he is an expert marksman.
For those of you who are experts on H5N1 human flu, if flies are a vector to humans of H5N1, will we be able to control human infections of H5N1? I think the answer is no. What do you think?
And if H5N1 mutates into several different kinds of mammals, such as dogs, cats, rats, pigs, etc.; how do we stop a possbile pandemic? Do we cull all of these mammals also?

anon_22,
I forgot to mention there would be one very omnimous result, if flies are discovered to be the main vector to humans of H5N1. And that is: it would have to be called fly flu. Try pronouncing fly flu really fast ten times. Do you now realize what an omnimous result that would be?
Since I think rats are the main vector, although there could easily be multiple vectors; I still think rat flu sounds better.

Sorry, it is ominous.

anon22, william, etc.: I saw the blowfly paper and have no particular reaction to it. What it shows is that they are mechanical carriers of the virus. This isn't surprising at all. A bigger issue would be if they were actually infected with the virus, i.e., that the virus replicated in them. The chances of a fly or mosquito being efficient vectors for the disease is very slight, IMO. The viremia that could be caused by a mospuito bite would not likely be efficient as a mode of transmission, nor do we know the virus is even viable after passing through a flyu or mosquito. Flies carry a huge number of viruses and bacteria but transmit very few, and most of those are enteric bacteria or viruses. This is not something I lose a lot of sleep over.

Hair gel, however, that's something else.

IMO the snide comment that "The religious right, for example, does not agree with the right to refuse treatment and wishes to impose that demur on the rest of us, but that's another story." is silly as well as wrong. Setting aside the Shivo case about which reasonable people might make an arugment, exactly where is the "religious right" (whoever they are) saying that anyone cannot refuse medical treatment? Any examples? Opposition to physician assisted suicide is opposition to an action. Such opposition has nothing to do with people refusing further medical treatment. The only thing I can think of where someone is being prohibited from refusing treatment is a case in Viginia where state child protective workers (perhaps they are democrats) are attempting to have the courts force cancer treatment on a sixteen year old who doesn't want further treatment. In any event I would be interested in seeing where the right wing religious are attemtpting to prohibit anyone from refusing medical treatment.

BTW - my comment above should not be construed to detract from Revere's excellent material on H5N1 - that I follow "religiously" :-)

revere,

Thanks! This just confirms my own thinking that mechanical vector is not the same as a host. So it isn't any more serious than a hygiene problem.

Well, there's hair gel, and there's hair gel, you know.

I'm trying to figure out whether lipstick counts as liquid or liquid-like substance. I gotta go look up some papers. Now where would one find information like that?...

anon_22 - Yesterday the Transprtation Security Administration (TSA) approved lipstick for carry-on luggage. http://news.yahoo.com/s/ap/20060813/ap_on_re_us/terror_plot_security_9.

Revere - I'm suprised that the Indo government is letting patients infected with the H5N1 virus to go home. The potential for this virus to become a pandemic seems to be rising on a daily basis (especially in Indonesia). I personaly believe the start of the pandemic is going to be soon if it hasn't already begun. Every person infected with the virus could potentially be infected with a pandemic strain and these people can't be out among the general population. At this time a person infected shouldn't have the right to decide whether or not they want to be isolated. A person that has the potential to harm the public by being in contact with the public should be forced into isolation IMO. I'm amazed that these patients in Indonesia are allowed to leave the hospital. And I'm a liberal Democrat.

Revere:

I take your point about blowflies only being able to move virus from place to place and not produce more virons but did you also see the PRRSV paper (link & abstract in the Economist thread). In this case the mosquitoes were feeding on infected pigs and then infecting other pigs. I do not know how different PRRSV is in its biology - from H5N1 - but this would seem to show mosquitos as a viable transmission mechanism (possibly an alternative explanation of H2H in clusters) although they could not be the missing host reservoir for the RES cleavage cases.

It was reported today authorities in Thailand have found 46 people in a single 24 hour period with bird flu symptoms, and another 100 waiting for test results. The Thai government has now allocated funding for 100 quarantine rooms.
Does anyone still remember when, in the past, during any one week period, there were on average, reports in the world of 2 or 3 patients with bird flu symptoms; and clusters of even 2 people were infrequent? And there might be one or two deaths per week from bird flu.
And now, in only one country, there are 46 people with symptoms in only 24 hours. The virus now seems to be infecting humans at almost the speed of light. The momentum of these infections is increasing almost by the hour.
Will tomorrow the authorities in Thailand report 100 new bird flu patients in the next 24 hour period? And perhaps 300 per 24 hour period by the end of the month?
The number of deaths in Asia per week also appears to be increasing rapidly.
What does all of this signify?

William, It appears to me that Thailand is reporting everyone that has any flu symtoms, even mild cases and testing them all. I'll be very concerned when I see a bunch of suspect cases coming back positive. These suspected numbers have been going up and down for a couple of weeks now but we haven't seen any positives except for the two fatal cases. Thailand is concerning but I'm still more concerned with what's going on in Indonesia. Two deaths and another infected from the same area in the past week. I'm afraid something bad is brewing in Indonesia. I hope I'm wrong.

Tim B,
"Two deaths and another infected from the same area in the past week. I'm afraid something bad in brewing in Indonesia.
I hope I am wrong."
In all humility I too hope you are wrong, but as you say, the situation in Indonesia is bad. And it may soon get worse.

Revere,
In the question you posed, '2. The probable existence of undiagnosed cases.' ; Do you truly think that might be the case? I ask, because the question has come up time and time again, and it is the one question I follow closely. As I know you are aware, the seroprevalence studies do not show that there are undiagnosed cases. That said, I am quite sure they would be some. Somewhere. But from an epidemiological viewpoint, I am also relatively confident that the known patient contacts were tested. In all the studies I have seen, there does not appear to be a substantive amount of mild cases going unnoticed.

In Feb, I attended the Florida Pandemic Summit. Julie Gerberding (CDC) stated that the CDC had hoped there would be some mild unreported cases. This, of course, would lower the CFR. She said (her words), that the 'studies have failed to show there were any mild unreported cases'.

And since then, (actually right about that time). Indonesian cases / cluster occurred. There was a big push toward getting seroprevalence testing at that time. My understanding is they did complete the testing,,,, and have not yet released the results.

Do you , by chance, happen to know the results of the seroprevalence testing? Or my question to you then would be,,,,. Are people just wishful thinking?

I am more inclined to think there are problems with the testing / test kits�.. Misdiagnosed cases would be higher on my list also. (Those that are not tested at all). But, points to ponder are,,,.. if testing is negative for known patient contacts, then it is still not easily spread. If it is being misdiagnosed as other diseases, (therefore not tested for H5N1) then we still have a problem.

Revere says "cats eating infected meat have become infected and are able to spread the disease horizontally (from cat to cat)."...and a bit later in paragraph speaks of again raising "the issue of infection via the gastrointestinal route."

I know I've beat this dead horse before, but the issue of infection route is still troubling to me. Infection by the gastrointestinal route or via infected blood from the meat source passing into the bloodstream of the new host through sores in the mouth or other openings (eyes, mucous membranes etc) is obvious. Cat eats infected bird, cat gets sick. But how is the same virus then transmitted from cat to cat? Or for that matter from bird to bird? Is it distributed as an aerosol, sneezed or coughed into the air from the infected animal and breathed into the new host? I mean, the cats don't eat each other, nor do the chickens, so at that point the gastrointestinal or blood to blood transmission is out. And also, when it passes from the gastrointestinal tract or blood stream to the lungs, where it seems to have its primary attachment sites, does it mutate at all along the way to be able to do so?..Anyone have a hypothesis to share?

Tim B I tend to agree with you that isolation of infected people is a good idea, in terms of preventing further spread and reducing the chances of a person passing on a possible pandemic or mutated virus. But I'm not sure making hospital isolation mandatory at this point is a good idea. First of all, there's the likelihood that if a given version of the virus is transmissable between humans, it could be transmissable before a person even shows symptoms. Then there's the added time, hours or days, between when a person falls sick and when they realize it's serious enough to seek medical care.

Meanwhile, if people who are seriously ill, (or their caretakers), believe they don't have H5N1, or that they will be more likely to survive outside the hospital, or they'd just rather die at home, then even fewer people will seek medical care. Would you go to the doctor if you believed it could result in you being imprisoned against your will? I think instituting a policy of forcible hospital isolation at this stage could backfire. It sounds like doctors are monitoring this boy, and hopefully not allowing him to travel or see too many people, and that may be the best we can hope for.

How many times have we heard of families were someone dies, and then a subsequent relative is admitted with bird flu? How many people die (or not) and are never known to have been H5N1 cases?

On the topic of unrecognized infections... Revere, last I heard, populational studies of people near to outbreaks in birds or cases in humans hadn't been found to have H5N1 antibodies, which we were told meant there probably weren't asymptomatic cases. But your suggestion of symptomatic cases sounds more than plausible. Has anyone gone back and and tested pneumonia patients for antibodies to H5N1?

Without a doubt its a mess on this one.I distinctly remember a few months ago that the theory was kicked out that it wasnt just birds any longer. Our much beloved WHO said by golly if they have bird flu then them sumbitches have to have dead birds near them. Okay, so that ones debunked but its still the criteria. They aint reporting diddly and Dr. Hideki said it last month that Indonesia is a complete H5N1 petting zoo. He was there for the earthquake and said then that people had pneumonia and were sitting around and dying from it. It was chalked off to everything but H5N1. I just dont get the vibe and conspiracy theory be damned they are clearly witholding information all over this planet. When they release it, it will be with a big scream that they have H5N1 and a request to send money and medical help.

Good luck Indonesia and Thailand. Ground zero for the Bird Bio Bomb.

floridagirl, caia: My reasoning here is independent of the seroprevalence studies, which are few and very limited. It is that there are hundreds of thousands of pneumonia cases in Indon and elsewhere that are never worked up diagnostically. It would be very surprising if there weren't human cases in that crowd.

m.i.h.: I'm afraid I always sing the same song here. We don't know the sources and modes of transmission of this virus with any certainty. We don't know if there are cells in the intestinal tract with the proper receptors and other conditions that would allow infection there. If there are, we don't know what the next step is. Does the virus migrate via the lymph system to elsewhere until it finds other tissues hospitable to it (like in the respiratory tract)? If so, it could enter via the g.i. tract and still infect others via the respiratory tract. Or, via the fecal oral route. I think speculating abouty this is useful for experimental hypotheses but not at the moment for prevention because we know too little to base a reasonable strategy. We need more intensive work on the problem and that takes time. It would have been good if we'd started years earlier, but we didn't. Misplaced priorities do kill people.

isolation: Isolation of infective people makes sense and usually isn't highly controversial. However at the moment this isn't considered a very contagious disease. The gov't of Indonesia is not really in control of things anyway so enforcing isolation is probably not in the cards for them. They are relatively impotent.

M.Randolph Kruger,
"Our much beloved WHO said by golly if they have bird flu then them sumbitches have to have dead birds near them. Okay, so that ones debunked but its still the criteria."
The above statement contains all the ingredients of tragedy. In 2 short sentences you have summarized perfectly the situation.
This is tragic in the sense WHO and public health officials in Asia are loosing valuable time and directing all human energy in the search of sick chickens as the source of human H5N1 infections, when the real source is probably in a mammal, or mammals.
It is not only tragic for the innocent victims of H5N1 in Asia, but also for us. Because this misguided attempt to control H5N1 human infections may lead to the death of people all over the world, including in the US; if, as it now appears it may soon occur; an H5N1 pandemic develops.
What these public health officials and WHO are now doing may result in your death here in the US.

You would think that they would want to answer these questions not out of fear or paranoi but out of...pure scientific interest...this is both a perplexing and highly interesting problem...

...and in the answer lies the future of influenza research and development and could be a font of knowledge in respect to other emerging diseases as well...

...in other words, a once in a life-time opportunity!!

If we use the 5% MR then to a first approximation, about 6-7% of all patients have H5N1 with the rest having seasonal flu. That's a significant number if several thousand in Indo have "the flu."

Revere: I think it's more than a hypothetical question for research and experimentation. It's a clue, a big one. Infection is obviously not just via the gastrointestinal tract and blood to body fluid, but also by some other means. The big question is what is that other means? Discovering that mode of transmission is the key to prevention of further spread, especially among mammalian hosts including humans. It isn't that hard for humans to prevent infection via the GI tract or blood to blood route: proper precautions in the handling of infected animals of any kind can take care of that. But if we don't find out the other route, we are screwed. This is not just speculation for the sake of knowledge or mental exercise. How do infected cats pass the disease from one to the next? Not that hard to study, test, and find out.

Good points Mary, it seems that the fecal/oral route could be a 'prepandemic phase' of virus spread possibly causing limited clusters of disease while it works on the process of developing a more efficient means of transmission.

http://www.eurekalert.org/pub_releases/2006-01/ajop-aiv011306.php

Avian influenza virus in mammals spreads beyond the site of infection to other organ systems

Researchers at Erasmus Medical Center have demonstrated systemic spread of avian influenza virus in cats infected by respiratory, digestive, and cat-to-cat contact. The paper by Rimmelzwaan et al., "Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts," appears in the January issue of The American Journal of Pathology and is accompanied by a commentary.
Avian influenza (H5N1) is of great concern because of the current outbreaks in Asia and the potential for pandemic spread. This virus is highly contagious in birds and spreads easily due to the agricultural and migratory nature of the bird species infected, including poultry, water fowl, and other migratory species (See commentary by Brown for more information). While spread of avian influenza from bird to man is known to occur, as first reported during the 1997 Hong Kong outbreak, human-to-human spread is extremely rare. Thus, the disease events that take place during mammal-to-mammal spread are not well characterized.

To assess the spread of H5N1 influenza virus in mammalian hosts, Rimmelzwaan et al. examined cats infected via the respiratory tract, via the digestive tract (by feeding on infected chicks), or by close contact with respiratory-infected cats . The researchers, led by Dr. Thijs Kuiken, then examined mucous membranes (throat, nasal, and rectal swabs) and organ systems (respiratory, digestive, nervous, cardiovascular, urinary, lymphoid, and endocrine) for the presence of virus and viral protein.

As expected, all cats were infected with H5N1 virus and exhibited clinical signs of disease (fever, lethargy, labored breathing, etc.), and virus was detected in throat, nasal, and rectal swabs, regardless of the original site of infection. Most interesting, virus spread throughout the organ systems with virus being found in respiratory and digestive tracts, liver, kidney, heart, brain, and lymph nodes. Furthermore, examination of infected tissues revealed cellular damage at sites containing viral proteins, providing an explanation for the increased severity of disease in humans.

These data underscore the potential for influenza virus to spread not only from the respiratory tract but also from the digestive and urinary tracts, greatly increasing the possible routes of mammalian transmission. Systemic disease has long been known to occur in birds, with the fecal-oral route of transmission being most important. However, this is the first demonstration of systemic replication in cats, providing a cautionary tale for humans regarding how influenza is spread and how the disease presents itself.

Rimmelzwaan and colleagues caution that because of the systemic nature of avian influenza, "H5N1 virus infection needs to be included in the differential diagnosis of a broader range of clinical presentations than is currently done." In addition better understanding of the mechanisms of spread, including possible fecal-oral route in humans, "may limit the risk of H5N1 virus developing into a pandemic influenza virus."

Kent. I read the paper, too. Some good points here. Question: Is the PPV/NPV of the current PCR tests changing as the virus continues to evolve? I've heard more than a few people say that this is a possibility--i.e., we're having false negatives, but i've not seen any data on the subject.

The cluster in Garut has grown to nine and it looks like the H5N1 sequence has changed.

Media is definitely missing the boat

http://www.recombinomics.com/News/08170606/H5N1_Garut_Sequence.html

At the Flu Clinic, I've just posted that imho the vector of transmission is the DOG.

I'll repeat here my observations. Hopefully someone with science smarts will do a quick sequencing of the dogs in Garut.
http://www.curevents.com/vb/showthread.php?t=56442

GR: It is my clear, first hand knowledge that in Java it is common for the country people to raise dogs in cages and to eat them just as country folk in the US eat rabbits. The Jakarta Post article states unequivocally that the residents of Garut fed the chickens to the dogs. Those are not pet dogs; those are protein source dogs which are raised in backyard cages and are eaten as delicacy and on festive occasions. The human interaction with the dogs include feeding and cage cleaning as well as all steps in the butchering process. The answer to this outbreak in Garut lies here, imho. The necessity to immediately slaughter all dogs in the region is obvious. We now are witnessing mammal to mammal transmission. The leap to mammals is now completed. Whether this strain will become pandemic I do not know. However, the first step in the two step process has now obviously occurred. [snip]

>My posting above is based on Siam's insight at FT. I've just fleshed it out.
Siam posted: Re: New H5N1 in Garut
This is the same area that they fed the dead chickens to the dogs. I wonder if it could be that simple??

>Niman posted at Recombinomics this:
>The cluster in Garut is alarming. The number of confirmed or suspect cases ijas quickly grown to nine and six of the cases have already died. Moreover, within the larger cluster are smaller clusters including two cousins in one hamlet and an index case, her mother, and two neighbors in another hamlet. All secondary cases attended the funeral of the index case for that hamlet.
http://www.recombinomics.com/News/0...t_Sequence.html

GR: Here's the clue: At the funeral, the hosts served DOG, along with other foods. As "chicken" would have not been the meat of choice, dog would have sufficed nicely as a welcomed substitute. I'll take that bet.

>More...

The reason that the virulence is so high is because this virus has now adapted to mammals in the caged dogs. Hence, a lateral, mammal to mammal infection transmission is for this virus a piece of cake.

>The obvious question is why the dogs did not die, or have not been observed as having sickened and died? Is it possible that the moment the dogs have shown illness they've been and are being slaughtered and eaten? Moreover, would not all the dogs wh were fed the hundreds of dead chickens have sickened? I still stick to my guns, just call me W Jr, and assert that it's the DOG who's the animal vector of the moment.

BTW, dog as a food source is ubiquitous in Indonesia. When I was in Java, I was offered dog as a dinner item as I was considered at that time as an honored guest in the house of a lower upper class family in a town whose name has been by me long forgotten.

From Wikipedia:
In Indonesia, eating dog meat is usually associated with people from the Batak culture, who cook a traditional dish named saksang that is like a dog-meat stew.[citation needed] The Minahasa are also well-known for eating dog, which is considered a festive dish and usually reserved for special occasions like weddings and Christmas. However dogs are not consumed by the muslim population of Indonesia, as dogs are carnivorous and are haraam under Muslim dietary laws.

Email from the Director General of Indonesia's Nat'l Institute of Health Research and Development division, August 17, 2006

Indonesian Official Comment on Release of Sequences
received by email from Triono Soendoro, M.D., Ph.D
From the Director General of National Institute of Health Research and Development, Indonesia

Triono Soendoro, M.D., Ph.D
DG of NIHR&D

----- Original Message -----
From: triono soendoro
To: [Gaudia Ray]
Sent: Thursday, August 17, 2006 7:08 PM
Subject: Re: Thank you for posting Indonesian sequences

Dear [Gaudia Ray],

The Indonesian Government through MOH would like the world know that we are working together with all scientists in the world so that AI can be solved together. The interest of public health is far more important than the interest of any scientist including our sceintist in Indonesia. This is the foundation of Indonesian government rationale. In addition, we have been accused for hiding the DNA sequence of AI but as you know that the DNA sequence has been done in Hongkong and CDC Atlanta not in our lab in Indonesia. CDC Atlanta division of Avian Influenza will make our DNA sequence public. I believe they have done so.

As of last month all future DNA sequence will be open for public and all scientist. Please informed everyone accordingly

Triono Soendoro, M.D., Ph.D

DG of NIHR&D

Gaudia Ray wrote:
Terima kasi for posting the Indonesian sequences of H5N1.

There are thousands of people who are watching the development of avian influenza, and the information you are sharing is helping us to "see", as a group, what is happening.

The readers of www.flutrackers.com, www.thefluclinic.com, and www.fluwikie.com I am sure all thank you and the Indonesian Ministry of Health for being brave and responsible world citizens.

We are concerned that the polymorphisms in chickens and wild birds are different from the polymorphisms found in the human samples of H5N1 recently made public. This issue is not explainable by saying that the disease is caused by chicken/bird to human contact.

It appears well within reasonably probability that avian influenza has found a mammalian host which is now a vector. Nobody knows what that mammal may be. There is some speculation that it is the cat, or it is animal feces which touches something like a soccerball and then the children touch that ball. This is merely speculation.

We the readers encourage your government to continue to be bold and in the leadership position.

This is a very dangerous disease and if it becomes Phase 5 pandemic, it will be the assure destruction of millions of lives and enormous economic ruin worldwide.

Again, thank you for your vision and leadership.

Gaudia Ray
Ojai, California USA

Kent and Marissa,

thank you for taking time to answer so thoroughly the concerns I raised about the different possible modes of transmission and infection of this particular virus. The data you provided on the way it spreads within the mammalian host to infect all kinds of cells throughout the body, regardless of the original mode of transmission or site of infection, is truly alarming. Yet at the same time it again raises big question marks. My layperson's understanding is that this RNA virus is composed of 8 separate genetic strands, each coding for a different protein. I'm guessing that most of these proteins would be components of the protein coat, some containing the sites that allow it to specifically bind to certain attachment sites on a host cell, while a few would be involved in the replication processes inside the host cell? I read sometime ago that a certain slight genetic change in one of those proteins makes it able to bind at a different site on a respiratory tract cell higher up in the airway, rather than at the lower site. So this explains the protein function of one of those 8 gene sequences. But H5N1's ability to infect so many different types of cells makes it seem that this virus perhaps has managed to develop, despite its very limited array of proteins, the ability to bind to a number of different cell attachment sites within mammalian hosts. Or perhaps it has one very general, very generic type of attachment protein that is common to and binds with a wide range of cells. (Most viruses - from my understanding - are pretty specific regarding the type of cell to which they will bind and infect.) One might start to ponder, then, what kind of attachment sites all these diverse cells would have in common, and then look for the sequences in the H5N1 nucleic acids that would correspond. Another avenue for trying to discover the nature of this "magic sequence" (presuming there is one) would be to compare the Low Path H5N1 sequences with the High Path ones. Where they differ may be the key.

Hi Marissa, I haven't seen any data on how the various tests sensitivity, specificity, positive predictive value, or negative predictive value vary with the different strains of the virus but would definitely be very important information.

While you wonderful "pointy heads" ponder the mysteries of the virus,I fume about the impact on us of poor 3rd world peasants and their "animal husbandry" practices, because of the corrupt and ignorant negligence of their Governments. Take Indonesia for example...on second thoughts,don't.

kent, marissa: Just a reminder. Sensitivity and specificity are attributes of a test. When one goes up, the other (usually) goes down. But PPV and NPB are attributes of the test AND the tested population. For exactly the same test, PPV and NPV can be very different in two populations, depending on the prevalence of the tested-for condition.

The catch here is that to determine sensitivity and specificity of a test you need some gold standard. That requires a great deal of additional investment since everything has to be done again by a method you feel is reliable enough to be the standard and then, the sensitivity and specificity will only be relative to that method. If you are satisified your gold standard is really gold, then you are estimating sensitivity and specificity as we tend to assume it.

Revere, thanks for the reminder--my guess is that it's an issue about sensitivity, i.e., less sensitive toward the newer subtypes. What's the gold standard for H5N1?

Mary, it's the HA gene that controls this function and has been well studied. The problem is that from strain to strain, I don't think the same genetic markers apply. Its complicated and unlikely to become unraveled without serious supercomputer modeling.