The Chinese news agency Xinhua reported last week that scientists at the Wuhan Institute of Virology found H5N1 in the feces of sparrow, non-migratory urban birds two years ago (via Reuters). The brief news report only says the discovery followed an outbreak among poultry in nearby Henan province. It's not clear what took so long to report this or whether the H5N1 strain in sparrows differs from that in poultry.
Is this good or bad for public health?
It's hard to think of ways it could be good for public health to have another endemic source of a virus potentially capable of infecting humans in an animal species living in close proximity to people. It could, however, be neutral if the strain of H5N1 in sparrows was specially adapted to sparrows in ways that made it unsuitable to infect humans, or at least unsuitable for it to become easily transmissible. That is possible, and we don't understand the biology well enough to know if it is likely or unlikely.
This was underscored this week with publication of a paper in the Proceedings of the National Academy of Sciences indicating a new lineage of H5N1 has become dominant in southern China and spread to southeast Asia. The data suggest that China's program to vaccinate its entire stock of poultry has either failed because of the logistical difficulty or the vaccine is ineffective against the new strain:
"We don't know if the vaccine was wrong or if some birds were missed," [co-author Robert] Webster said. "That's the $60-million question."
Vaccinating poultry against H5N1 amounts to "a huge natural experiment," said Dr. Scott P. Layne, an epidemiologist at the UCLA School of Public Health. "By vaccinating we're manipulating the virus' evolution. Is that good, neutral or bad for us? Who knows?" (LA Times)
A mass vaccination program is said to have succeeded in Vietnam. I have my doubts about that, but if so, we don't know why it was successful there and not in China. The two obvious possibilities are that vaccinating all birds in Vietnam is easier than China; and/or that the Chinese vaccine was mismatched, faulty or ineffectively administered. In any event, the verdict remains out on mass poultry vaccination as a control measure.
The new strain seems better adapted to chickens than earlier ones:
The report, based on China's ongoing flu surveillance program, found that H5N1 became more prevalent from July 2005 to June 2006 compared with the previous 12 months. The researchers tested 53,220 birds in live poultry markets and found that 2.4% of them tested positive for any strain of H5N1, up from 0.9% a year earlier.
They found that ducks and geese were the most common carriers, and they were susceptible to bird flu year-round. Chickens tend to succumb only in the winter, but the researchers discovered cases in 11 out of the 12 months of their study, up from four out of 12 months the previous year. Overall, the peak flu season of October to March has been extended until June, the researchers found. (LA Times)
We can ask the same question about the emergence of this new strain in poultry as we did about the sparrows: is it a good or bad sign? Pretty much the same reasoning applies. It is hard to see how having the virus more widespread in birds for longer periods of time can be good for public health. At best, it is more or less neutral. Whatever the nature of the changes, so far it hasn't made the virus more transmissible from person to person, although the new strain can infect people.
Which leaves us here:
Dr. David Nabarro, who coordinates the United Nations' efforts against human and avian influenza, said the new data were a reminder that H5N1 was constantly evolving.
"I don't think it's a sign that we're getting any closer to pandemic flu," Nabarro said. "Frankly, I don't know how we're going to know when pandemic flu gets close. We're just going to get hit by it."
Maybe we should get ready -- just in case?
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How do you think this will affect the WHO Director-General nomination/appointment? Is Dr. Chan toast? I get the impression that not many people in the WHO are fans of China right now.
Nick,China will do whatever it want's to because it can and we should know this by now.Dr Chan's appointment will only be toast if Western political considerations decide so.And we probabably will not upturn China's decision because we want the trade.We will appease and lick arse and go to bed feeling guilty while knowing a deal has been done.If there is any part of this simple exposition that you do not understand,please sing out.
I'll post on the DG election later this weekend. This is a very complicated political mix. I don't think anyone knows right now how it will come out. At least I don't.
I find it more disturbing that the FJ-like strain had increased from being only 1% of all H5N1 positive samples in July-Sep 2005 to 95% in April-June 2006. This tells me that it is a very 'fit' virus, at least in ducks. That cannot possibly be good or neutral, given the fact that the few known human cases spread out to four corners of China are all caused by the same strain.
I also find it disturbing that Nabarro has changed his tune (again). It wasn't so long ago that he said we are living on 'God-given time'. http://www.fluwikie2.com/pmwiki.php?n=Forum.GojusNotesAndThoughts-SafeA…
Either he can't make up his mind, or he is under pressure because of his official position.
For his own credibility, he needs to get clear on how much he can speak frankly in his position and set a consistent standard. It is possible to interpret statements from officials constrained in their outspokenness; it's hard when their outspokenness fluctuates. Mixed messages are often worse than no message, IMHO. Dr Nabarro should take heed.
It is possible for birds to be co-infected with both H5N1 and Avian TB. In that case, which one presents the greatest danger to humans, considering that 2 million people die of TB per year, or one person every 15 seconds. TB is highly contagious, is an airborne disease, and is spreading all over the world. There needs to be more contributions from veterinarians to understand co-infections in birds, and their threat to humans. Veterinarians recommend that if birds are dying of Avian TB, that those taking care of them should not have HIV, have had radiation treatment for cancer, or have in general, weak immune systems.
It is well known birds can be co-infected with both TB and H5N1, and that birds can infect humans with TB.
Mycobacterium kansasii and certain forms of M. avium intercellualare are the commonest forms of non-human tuberculosis in human lungs.
Could a person become infected with both H5N1 and avian tuberculosis at the same time if the bird is co-infected? If so, which disease would kill the patient first? If the patient tested positive for H5N1, would the TB infection in the person be ignored. Could the TB then weaken the person's immune system, allowing the H5N1 to kill the patient?
anon22: It can be neutral if the changes that allow greater fitness for birds puts it "further away" in fitness distance from humans. Regarding Nabarro I have no opinion except to say that it should be permissible for someone to change his or her mind as we learn more. The problem with WHO is we can't be sure that changes in message are related to knowing more or other factors.
Anon-22... It would seem that our little friends in the East have once again hosed the world. Listen, its all about a working vaccine and they are worse than our own big Pharma. They get a vaccine and what wouldnt you pay for it to survive something like this? Webster has a vaccine in the freezer here in Memphis but he makes no bones about it, it could kill you just to take it because its so damned hot. Titer response off the scale but you would get just as sick as a dog that had H5. This is that reengineered gig you read about a few months ago. Great. But it aint vaccine. The Chinese want their person in there because that way they can skew the process.
Revere... those ships are on the move again.
I'm not sure what you mean by "Chickens tend to succumb only in the winter, but the researchers discovered cases in 11 out of the 12 months of their study, up from four out of 12 months the previous year." If you are saying they carry the virus 11 out of the 12 months but only become symptomatic and die during the winter, then (and I know this has been puzzled on re flu in general for years) WHY? Is it that the virus is UV sensitive, and higher levels kill it? It has already been suggested that it is temperature sensitive, but that would only be relative to airborne or other transmission methods outside the body of the host. What you seem to be saying is that the virus is "alive" and well inside the host homeotherm all year, where the temperature is stable, so what makes it suddenly "go off" in the winter? And what does that portend for us this winter, while it's quietly been making its way around into avian and mammalian hosts, perhaps ready to spring forth when the UV or whatever drops below a certain level, causing perhaps certain changes in the host's own immune system that have been keeping it at bay? I know, I know, you're going to tell me we have no idea what happens or why regarding the seasonality of the flu. I'm just throwing this out there as musings.
The Fujian sequences contain Qinghai sequuences. They are recombinants and wild birds are involved in the mixing and matching and include the tree sparrows which were reported some time ago
http://www.recombinomics.com/News/03060601/H5N1_Recombination_Guangdong…
http://www.recombinomics.com/News/10050603/H5N1_Recombination_Confirmat…
Comments posted serveral hours ago have not appeared.
Since the comments about the missing comments appeared immediately, it seems that the earlier comments are now "lost in space".
The comments were with regard to Qinghai sequences appearing in Fujian sequences via recombination.
Howdy Henry,
I'd very much like to read those comments and get a better picture of what's going on. Can you possibly repost!?!
Cheers:*) and Aloha pumehana -- Jon
Henry, Jon: I am traveling and only check the blog at intervals of many hours. For reasons unconnected with me or anything I have told the system to do it holds some of your comments for approval (I have never asked it to do that). I try to check periodically to see if any comments are being held and when I they are I almost invariably post them immediately. My apologies for the delay but there seems to be no way to stop this from happening. They are now up. Since there is a big time difference between where I am and the states it makes it more difficult..
Jon, The post did show up after a delay. The tree sparrow sequences were published last year, but the story behind the recombinants that have the tree sparrow sequences as parental strains have an interesting history. Those sequences were deposited at Genbank on Feb 28, 2005 and were releasd Feb 28, 2006. I assume that there were some significant problems getting the recomibinant sequences published, which remain unpublished.
It looks like the sequencers from Beijing Genome Institute resequenced the genes and relased those plus many supporting sequence (over 300) last month. The new sequences are full sequences for all 8 gene segments from isolates collected in northern China between 1997 and 2004. These sequences have MANY examples of clear-cut recombination and allow the evolution of H5N1 in China to be traced.
Included are sequences from 1997 with the 20 aa deltion in NA. This deletion distinguishes the Z+ gentotype from the Z genotype. In previously released sequences the deletion showed up in 2003, but these sequences indicate it was present in northern China in 1997.
Moreover, 1997 sequences have large regions of identity with low path sequences from Hong Kong in the 1970's, again highlighting the central role of low path wild wird isolates, as well as recombiantion.
Showing the evolution and recombination has been difficult because of the large number of H5N1 partial sequences submitted by St Jude and Hong Kong University. Although they claim the record for sequencing the largest number of H5N1 isolates, they also hold the record for loading up the data base with partial sequences.
The data from Beijing strongly suggests that the gaping holes contain OBVIOUS examples of recombination. These withheld sequnece go back to 2000 and the submitted patials have been published long ago, yet the database holes remain.
Moreover, St Jude used the NIAID flu sequencing program to generate full sequences of all 8 gene segments of low path bird as well as human isolates, but they have yet to fill in any H5N1 holes, and the list of sequences at TIGR not completed also has no H5N1 sequences from St Jude.
It will be interesting to see exactly what has been withheld for the past several years, long after publication. I suspect the data will put the final nails in the "random mutation" coffin and raise questions about why such convincing data was withheld for so long.