Where to sample birds and some more stuff

Again, H5N1 is rewriting the book. Influenza A is usually thought of as an intestinal disease of birds. Surveillance and monitoring, therefore, has been carried out by sampling bird feces and cloacal (rectal) swabs. In a meeting in Singapore, however, the dean of flu virologists, Robert Webster of St. Jude's Children's Hospital in Memphis, is now reporting there are much higher H5N1 viral loads in the upper respiratory tract of birds than in the intestines. This is work done jointly with Albert Osterhaus in The Netherlands. It has led to changes in recommendations for detecting the virus in birds:

The Food and Agriculture Organization of the United Nations and a WHO research advisory group both have recommended that scientists swab animals' upper airways for bird flu virus.

The FAO recommends both tracheal and rectal testing of infected birds on its Web site. The agency will change the Web site to emphasize airway testing for H5N1, said Peter Roeder, an animal health officer who helped Indonesia set up its bird surveillance.

"This virus behaves very differently from other avian influenza viruses and its presence in the trachea is one of the characteristics we've had to take into account," Roeder said today in a telephone interview. "Perhaps we should make a bigger splash about it." (John Jauerman, Bloomberg)

So its no longer enough to take samples for virus from feces or the cloaca. We have to do the mouth and upper respiratory tract as well, logistically more difficult. The virus doesn't want to make our scientific lives any easier than it makes our biological lives.

Oh, and there was also this, in Lauerman's report of the Singapore meeting which will go on until Thursday:

Potentially dangerous new mutations that might give H5N1 the ability to spread among people are cropping up in birds, and perhaps other species including cats and dogs, said Ron Fouchier, also an Erasmus virologist, at the conference.

"We've been hearing about hundreds of reports of dead cats from Indonesia," Fouchier said today in an interview. "We've also had several reports of infected dogs from countries of the former Soviet Republic."

Thanks for telling us. What else do you know? Dangerous new mutations? Excuse, me. Do you mind telling us what that's about? This is the internet age. We are past the point where you can try to make your life easier by keeping it in within a close circle.

Unless, of course, your intention is to completely destroy your own credibility and trust.

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Boy, where to even begin to start on this one is the question...

This question/observation might be more for Niman or someone who supports his theories: IF the above means the virus has CHANGED to now be found more infective in the upper respiratory tract of birds, does that signify that there has been recombination or reassortment with perhaps a human virus which normally does attach more easily to cell sites in the upper respiratory tract? (as per your 4 part science of influenza series)

By mary in hawaii (not verified) on 13 Dec 2006 #permalink

Niman has been saying since the Karo cluster that the human and chicken sequences don't match. Over and over he posts travel histories of polymorphisms showing that the bird forms are acquiring mammalian polymorphisms that allow the virus to live at lower temperatures and higher in the respiratory tract. These changes aren't new, they happened months ago. But there has been little new sequence data released from Indonesia, and it isn't known whether they sample anything but chickens and people.

I dont remember any report stating that hundreds of cats have died. Have I missed something, or has this information been hidden? could this explain the culling of dogs in South Korea, assuming they had access to this information.

What can we deduce from these deaths? Are the cats a potential cause of some of the infections in humans that cant be traced to poultry? Lastly would the fact that cats are a resevior increase the chance of the virus mutating into a form that can transmit easily in humans?

Wet dirt: I am quite aware of the changes in genetic sequence Niman has been posting. That is not the point I was making.I do not think that these genetic changes Niman has tracked are necessarily the same thing as actually finding high viral loads in the respiratory tract of birds, indicating that these DNA changes have actually caused a significant change in the bird's infectivity. My question is whether this adds some proof and weight to Niman's theories and observations. And if recombination is the method, then might the human viruses that switched this receptor site DNA sequence with the avian H5N1 be found to be more infective in the digestive tract of humans?

By mary in hawaii (not verified) on 13 Dec 2006 #permalink

Janetn-I am not aware of "hundreds" of animals dying other than birds. I am aware that along the road to Kano Reservoir that there were "scores" (what in hell is a score) of dead scavengers such as hyenas and the indigenous dogs of the area that ate dead and dying waterfowl. I think if I recall it was something like 50,000 birds that croaked and they never even cleaned them up.

The infected dog/cat thing in numbers isnt so far in any OIE report that I have seen. I do know that a bulletin was sent out months? or many weeks ago that local veterinarians were to be on the lookout for sick animals.

On the other hand if I read the last blurb from these guys right, a mouse or rat will eat something that is infected and amplify the bug in their systems by about 5000 times. Kills a bunch of them (just as plague did) but one or two survive and you have whole colony of endemically infected mice and rats from just one survivor. Dogs and cats I think it just flyswatters them outright and kills within days. Plenty of time to infect a family or two.

Niman has esconced for MONTHS that H5 has been aquiring more and more mammal polymorphs. If you have been reading what he has been posting and pulling the books out on how to read the sequences even I could see it. I couldnt attribute more than 9 or 10 to mammals due to lack of education but it was there as the "people" who define what is mammal and what is bird have baselines established. This aint reading for the weak of heart. Its long and tedious and I have been trying to understand it for a year. I guess what you really need to look for is words like 2006-Cat xxxx and the changes, or 2006-Dog- location dog, pig etc..

Any of those start popping up more than birds then I think the die is cast. Those sequences are out there but Henry would be better to speak to on this as he pounces on everything they release. He goes into a silent mode on his posts during that time when he is analyzing the data. Too damned many little letters to follow and I dont know how he does it day in and day out.

Russian dogs? What Russian dogs?

By M. Randolph Kruger (not verified) on 13 Dec 2006 #permalink

I don't have any other info than what I posted. I have no idea what Fouchier is talking about, but I'd sure like to know. Regarding the mutations, I also don't know what he is referring to, whether they are already known or new. So it's kind of useless to speculate at this point. If you have any actual information, of course, it would be welcome.

I first heard cats mentioned in Declan Butler's blog - try googling "aargh plop". He also wrote a piece about it in Nature I think. AFAIK, dogs have only recently started to be mentioned, also just anecdotally - eg Why the massive dog cull in China - is it really rabies or "something else"? And then South Korea started culling cats and dogs in the context of bird flu outbreaks. Nothing official based on tests etc.

By Shy reader (not verified) on 13 Dec 2006 #permalink

In the context with which virologist Fouchier mentions the dead dogs and cats: "Potentially dangerous new mutations that might give H5N1 the ability to spread among people are cropping up in birds," and "We've been hearing about hundreds of reports of dead cats..." The impression given is that this is current and ongoing. (use of present tense 'are cropping up' and 'We've been hearing...')

The fact that WE haven't been hearing anything is no surprise. We've been pretty much cut off from info from Indonesia. Right now on fluwikie Indonesia thread there are translations indicating presently around 9 people are ill awaiting tests for bird flu, and 1 has died in the past few days. Where are the stories on "news now" and "bird flu breaking news", Reuters, CIDRAP or any other news source? The news is confined to local media and only accessed via those translator machines...but does that mean it is questionable and unreliable? Are we biased towards believing only our major, English speaking news media...even though we know we have been lied to and misled by these same news sources time and again on all sorts of important issues for the sake of political expediency, economics and other reasons?

By mary in hawaii (not verified) on 14 Dec 2006 #permalink

Hi all,

I decided to weigh in on this situation, since I have a strong opinion about what is going on. I don't know if it is accurate, but it is my opinion, none-the-less.

BTW, Kruger, a score is the number 20 (as in "Four score and seven years ago...").

Anyway, the theory about the transformation of H5N1 (or any influenza virus) has always been that the disease would mutate into a form that could easily infect humans, but would then not be able to infect birds. I don't think anyone has really considered the intermediate steps in that process.

The disease is (mostly) intestinal in birds, but (mostly) respiratory in humans. This is, for the most part because of the differences in the relevant receptors between people and birds. As the virus becomes more adapted to humans, the theory is that it will become less adapted to birds. I suspect that this means that the site of infection will likely change to one that is more compatible with humans than with birds (i.e., the upper respiratory tract). It also means that fewer birds will become infected, since the disease is not longer "well adapted" to them. But neither is it well adapted to humans. At some point, it will either have to make the jump directly to humans, or infect an intermediate vector (likely a mammal) where it can finish the process of conversion into a mammalian virus, before moving into humans.

Pigs are a good possibility for this, because they have large numbers of both types of receptors, but most other mammals have varying degrees of this receptor mix. I'm not sure where cats and dogs fit on the scale.

There has been "background" talk for several years about cats and dogs becoming infected. The disease killed a number of tigers in the Bangkok zoo in 2004. There is at least one scientific journal article out where scientists found a large number of both cats and dogs that had sero-converted, and one of the dogs was still shedding virus at the time of the study.

My guess is that even if Niman is not exactly right on the money here, he is still fairly close. And my advice, for whatever little it's worth, is that scientists should start not only looking in bird noses and mouths, but also should start checking mammals (especially cats and dogs) in areas where the disease is endemic. This should give us a better idea of what exactly is going on.

Oh, and another BTW to Kruger... hyenas are carnivores like both cats, dogs, and bears. However, whereas bears are more closely related to dogs, hyenas are more closely related to cats.

Cheers, all!

Lenn: This has been discussed pretty thoroughly here, Fluwikie and several other sites, so the background is pretty familiar. You present the conventional view (as of 6 months ago, maybe) but a lot has happened since then, especially in the receptor area. The Niman controversy is what drives genetic variation and I don't want to argue about it as it isn't my concern. Regarding receptors, we don't know where the alpha 2,3s are in humans. Matrosovich's work finds them in ciliated cells which are in the upper tract. The papers in Nature and Science that implicated the lower tract as site of infection didn't measure the receptors but rather the presence of the virus. So that is still uncertain and there is more to it than the receptors anyway. I did a series of posts on glycoproteins which you can find with a search in the Google search box using "Influenza Science" I think. Note also the post here from the other day on intestinal versus respiratory infection in birds from the Singapore meeting. H5N1 may be an exception (as usual).

Thanks Revere. As hard as I try to keep up, and it seems that I'm still behind the times :-(

Also, I read somewhere in scientific papers that two places in humans that are known to have the 2,3 receptors are the eyes and deep in the lungs at the connection between the alveoli and bronchils. I don't know if this is correct, but since you mentioned it, I thought I'd mention it.

Lenn: Yes, it's correct, but there are many other possibilities. Mucus, for example, has 2,3 sialic acid in it, which may be one of the ways it protects us. The cells deep in the lung where the virus lives are the type II pneumocytes but we don't know much about the receptors (the assay was for the virus, not the receptors). We don't know about the g.i. tract, either, for example, or many other tissues. So much of what is said in the textbooks is either out of date or was conjecture that became set in stone.